Pharmaceutical and diagnostic compositions containing nucleic acids and corresponding proteins entitled 282p1g3

Pharmaceutical and Diagnostic Compositions Containing Nucleic Acids and Corresponding

Proteins Entitled 282P1G3

FIELD OF THE INVENTION

The invention described herein relates to genes and their encoded proteins, termed 282P1G3, expressed in certain cancers, and to diagnostic and therapeutic compositions useful in the management of cancers that express 282P1G3. it is to be noted that only subject matter embraced in the scope of the claims appended hereto, whether in the manner defined in the claims or in a manner similar thereto and involving the main features as defined in the claims, is intended to be included in the scope of the present invention, while subject matter described and exemplified to provide background and better understanding of the invention, is not intended for inclusions as part of the present invention.

The present application is divided from Israel Specification No. 166,531 filed January 27th, 2005 and antedated May 9th, 2003. In order that the invention may be better understood and appreciated, description from Israel Specification No. 166,531 is included herein, it being understood that this is for background purposes only, the subject matter of Israel Specification 166,531 being specifically disclaimed and not forming a part of the present invention. 1

BACKGROUND OF THE INVENTION

Cancer is the second leading cause of human death next to coronary disease. Worldwide, millions of people die from cancer every year. In the United States alone, as reported by the American Cancer Society, cancer causes the death of wet1, over a half-miiiion people annually, with over 1.2 million new cases diagnosed per year. While deaths from heart disease have been decfining significantly, those resulting from cancer generally are on the rise. In the early part of the next century, cancer is predicted to become the leading cause of death.

Worldwide, several cancers stand out as the leading killers. In particular, carcinomas of toe lung, prostate, breast, colon, pancreas, and ovary represent the primary causes of cancer death. These and virtually all other carcinomas share a-common lethal feature. With very few exceptions, metastatic disease from a carcinoma is fata!. Moreover, even for those cancer patients who initially survive their primary cancers, common experience has shown that their lives are dramatically altered. Many cancer patients experience strong anxieties driven by the awareness of toe potential for recurrence or treatment failure. Many cancer patients experience physical debilitations following'treatment Furthermore, many cancer patients experience a recurrence.

Worldwide, prostate cancer is the fourth most prevalent cancer in men. In North America and Northern Europe, it is by far the most common cancer in males and is the second‘leading cause of cancer death in men. In the United States alone, well over 30,000 men die annually of this disease - second only to lung cancer. Despite the magnitude of these figures, there is still no effective treatment for metastatic prostate cancer. Surgical prostatectomy, radiation therapy, hormone ablation therapy, surgical castration and chemotherapy continue to be toe main treatment modalities.

Unfortunately, these treatments are ineffective for many and are often associated with undesirable consequences.

On toe diagnostic front, the lack of a prostate tumor marker that can accurately detect eariy-stage, localized tumors remains a significant fimitation In toe diagnosis and management of this disease. Although toe serum prostate specific antigen (PSA) assay has been a very useful tool, however its specificity and general utility is widely regarded as lacking in · several important respects. 1a

Progress in identifying additional specific markers for prostate cancer has been improved by the generation of prostate cancer xenografts that can recapitulate different stages of the disease in mice. The LAPC (Los Angeles Prostate Cancer) xenografts are prostate cancer xenografts that have survived passage in severe combined immune deficient (SCID) mice and have exhibited the capacity to mimic the transition from androgen dependence to androgen independence (Klein ef al., 1997, Nat. Med. 3:402). More recently identified prostate cancer markers include PCTA-1 (Su ef al., 1996, Proc. Natl. Acad. Sci. USA 93:7252), prostate-specific membraee (PSM) antigen (Pinto ef al., Clin Cancer Res 1996 Sep 2 (9): 1445-51), STEAP (Hubert, ef al, Proc Nat! Acad Sci USA. 1999 Dec 7; 96(25): 14523-8) and prostate stem cell antigen (PSCA) (Reiter ef a/., 1998, Prop. Natl. Acad. Sci. USA 95:1735).

While previously identified markers such as PSA, PSM, PCTA and PSCA have facilitated efforts to diagnose and treat prostate cancer, there ie need for the identification of additional markers and therapeutic targets for prostate and related cancers in order to further improve diagnosis and therapy.

Rena! cel! carcinoma (RCC) accounts for approximately 3 percent of adult malignancies. Once adenomas reach a diameter of 2 to 3 cm, malignant potential exists. In the adult, the two principal malignant renal tumors are renal cell adenocarcinoma and transitional cell carcinoma of the renal pelvis or ureter. The incidence of renal cell adenocarcinoma is estimated at more than 29,000 cases in the United States, and more than 11,600 patients died of this disease in 1998. Transitional cell carcinoma is less frequent, with an incidence of approximately 500 cases per year in the United States.

Surgery has been the primary therapy for renal cell adenocarcinoma for many decades. Until recently, metastatic disease has been refractory to any systemic therapy. With recent developments in systemic therapies, particularly immunotherapies, metastatic renal cell carcinoma may be approached aggressively in appropriate patients with a possibility -of durable responses. Nevertheless, there is a remaining need for effective therapies for these patients. 01 ai! new cases of cancer in -the United State®, bladder cancer represents approximately 5 percent in men (fifth most common neoplasm) and 3 percent in women (eighth most common neoplasm). The incidence is increasing slowly, concurrent with an increasing older population. In 1998, there was an estimated 54,500 cases, including 39,500 i« men and 15,000 in women. The age-adjusted incidence in the United States is 32 per 100,000 for men and eight per 100,000 in women. The historic male/female ratio of 3:1 may be decreasing related to smoking patterns in women. There were an estimated 11,000 deaths from bladder cancer in 1998 (7,800 in men and 3,900 in women). Bladder cancer incidence and mortality strongly increase with age and will be an increasing problem as the population becomes more elderly.

Most bladder cancers recur in the bladder. Bladder cancer is managed with a combination of transurethral ,. resection of the bladder (TUR) and intravesical chemotherapy or immunotherapy. The multifocal and recurrent nature of bladder cancer points out the limitations of TUR. Most muscle-invasive cancers are not cured by TUR alone. Radical cystectomy and urinary diversion is the most effective means to eliminate the cancer but carry an undeniable impact on urinary and sexual function. There continues to be a significant need for treatment modalities that are beneficial for bladder capcer patients.

An estimated 130,200 cases of colorectal cancer occurred in 2000 in the United States, including 93,800 cases of colon cancer and 36,400 of rectal cancer. Colorectal cancers are the third most common cancers in men and women. Incidence rates declined significantly during 1992-1996 (-2.1% per year). Research suggests that these declines have been due to increased screening and polyp removal, preventing progression of polyps to invasive cancers. There were-an estimated 56,300 deaths (47,700 from colon cancer, 8,600 from rectal cancer) in 2000, accounting for about 11% of all U.S. cancer deaths.

At present, surgery is the most common form of therapy for colorectal cancer, and for cancers that have not spread, it is frequently curative. Chemotherapy, or chemotherapy plus radiation, is given before or after surgery to most patients whose cancer has deeply perforated the bowel wall or has spread to the lymph nodes. A permanent colostomy 2 (creation of an abdominal opening for elimination of body wastes) is occasionally needed for colon cancer and is infrequently required for recta! cancer. There continues to be a need for effective diagnostic and treatment modalities for colorectal cancer.

There were an estimated 164,100 new cases of lung and bronchial cancer in 2000, accounting for.14% of all U.S. cancer diagnoses. The incidence rate of lung and bronchial cancer is declining significantly in men, from a high of 86.5 per 100,T)00 in 1984 to 70.0 in 1996. In the 1990s, the rate of increase among women began to slow, in 1996,The incidence rate in women was 42.3 per 100,000.

Lung and bronchial cancer caused an estimated 156,900 deaths in 2000, accounting for 28% of all cancer deaths. During 1992-1996, mortality from lung cancer declined significantly among men (-1.7% per year) while rates for women were stiil significantly increasing (0.9% per year). Since 1987, more women have died each year of lung cancer than breast cancer, which, for over 40 years, was the majoT cause of cancer death in women. Decreasing lung cancer incidence and mortality rates most likely resulted from decreased smoking rates over the previous 30 years; however, decreasing smoking patterns among women lag behind those of men. Of concern, although the declines in adult tobacco use have slowed, tobacco use in youth is increasing again.

Treatment options for lung and bronchial cancer are determined by the type and stage of the cancer and include surgery, radiation therapy, and chemotherapy. For many localized cancers, surgery is usually the treatment of choice. Because the disease has usually spread by the time it is discovered, radiation thq^apy and chemotherapy are often needed in combination with surgery. Chemotherapy aione or combined with radiation is the treatment of choice for small cell lung canceq on this regimen, a large percentage of patients experience remission, which in some cases is long lasting. There is however, an ongoing need for effective treatment and.diagnostic appcoacnes for lung and bronchiakcancers.

An estimated 182,800 new invasive cases of breast cancer were expected to occur among women in the United States during 2000. Additionally, about 1,400 new cases of breast cancer were expected to be diagnosed in men in 2000. After increasing about 4% per year in the 1980s, breast cancer incidence rates in women have leveled off in the 1990s to •ebout 110.6 cases per 100,000. in the U.S. aione, there were an estimated 41,200 deaths (40,800 women, 400 men) in 2000 due to breast cancer. Breast cancer ranks second among cancer deaths in women. According to the most recent data, mortality rates declined significantly during 1992-1996 with the largest decreases in younger women, both white and black. These decreases were probably the result of earlier detection and improved treatment

Taking into account the medical circumstances and the patient's preferences, treatment of breast cancer may involve lumpectomy (local removal of the tumor) and removal of the lymph nodes'under the arm; mastectomy (sftrgicai removal of the breast) and removal of the lymph nodes under the arm; radiation therapy; chemotherapy; or hormone therapy. Often, two or more methods are used in combination. Numerous studies have shown that, for early stage disease, long-term survival rates after lumpectomy plus radiotherapy are similar to survival rates after modified radical mastectomy. Significant advances in reconstruction techniques provide several options for breast reconstruction after mastectomy. Recently, such reconstruction has been done at the same time as the mastectomy.

Local excision of ductal carcinoma in situ (DCiS) with adequate amounts of surrounding normal breast tissue may prevent the local recurrence of the DCIS. Radiation to the breast and/or tamoxifen may reduce the chance of DCIS occurring in the remaining breast tissue. This is important because DOS, if left untreated, may develop into invasive breast cancer. Nevertheless, there are serious side effects or sequelae to these treatments. There is, therefore, a need for efficacious breast cancer treatments.

There were an estimated 23,100 new cases of ovarian cancer in the United States in 2000. it accounts for 4% of ail cancers among women and ranks second among gynecologic cancers. During 1992-1996, ovarian cancer incidence 3 rates were significantly declining. Consequent to ovarian cancer, there were an estimated 14,000 deaths in 2000. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Surgery, radiation therapy, and chemotherapy are treatment options for ovarian cancer. Surgery usually includes the removai of one or both ovaries, the faltopian tubes (saipingo-oophorectomy), and the uterus (hysterectomy). In some very early tumors, only the involved ovary will be removed, especially in young women who wish to have children. In advanced disease, an attempt is made to remove all intra-abdominal disease to enhance the effect of chemotherapy. There continues to be an important need for effective treatment options for ovarian cancer.

There were an estimated 28,300 new cases of pancreatic cancer in the United States in 2000. Over the past 20 years, rates of pancreatic cancer have declined in men. Rales among women have remained approximately Constant but may be beginning to decline. Pancreatic cancer caused an estimated 28,200 deaths in 2000 in the United States. Over the past 20 years, there has been a slight but significant decrease in mortality rates among men (about -0.9% per year) while rates have increased slightly among women.

Surgery, radiation therapy, and chemotherapy are treatment options for pancreatic cancer. These treatment options can extend survival and/or relieve'symptoms in many patiBnts but are not likely to produce a cure for most There is a significant need for additional therapeutic and diagnostic options for pancreatic cancer. 4

In Israel Specification No. 166,531, there is described and claimed an isolated polynucleotide that encodes a 282P1G3 protein, wherein the polynucleotide comprises the sequence of SEQ ID NQ:2, from nucleotide residue number 272 through nucleotide residue number 3946.

SUMMARY OF THE INVENTION

The present invention provides an isolated antibody or fragment thereof that immunospecifically binds to an epitope on a 282P1G3 protein encoded by the polypeptide sequence set forth in SEQ ID NO:3.

The present invention also provides a vector comprising a polynucleotide encoding a single chain monoclonal antibody according to claims 4 or 5. 5

BRIEF DESCRIPTION OF THE FIGURES

Figure 1. The 282P1G3 SSH sequence of 321 nucleotides.

Figure 2. A) The cDNA and amino acid sequence of 282P163 variant 1 (aiso called “282P1G3 ν.Γ or "282P1G3 variant Γ) is shown in Figure 2A. The start methionine is underlined. The open reading frame extends from nucleic acid 272-3946 .including the stop codon. B) The cDNA and amino acid sequence of 282P1G3 variant 2 (aiso called “282P1G3 v.2") is shown in Figure 2B. The codon for the start methionine is underlined.· The open reading frame extends from nucleic acid 272-3787 including the stop codon. C) The cDNA and amino acid sequence of 282P1G3 variant 3 (also called “282P1G3 v.3") is shown in Figure 2C. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-2953 including the stop codon. D) The cDNA and amino acid sequence of 282P1G3 variant 4 (aiso called “282P1G3 v.4") is shown in Figure 2D. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-3625 including the stop codon. E) The cDNA and amino acid sequence of 282P1G3 variant 5 (also called “282P1G3 v.5") is shown in Figure 2E. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-3898 including the stop codon. F) The cDNA and amino acid sequence of 282P1G3 variant 6 (also called “282P1G3 v,6") is shown in Rgure 2F. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-3823 including the stop codon. G) The cDNA and amino acid sequence of 282P1G3 variant 7 (also called “282P1G3 v.7”) is shown in Rgure 2G. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-3982 including the stop codon. H) The cDNA and amino acid sequence of 282P1G3 variant 8 (also called “282P1G3 v.8”) is shown in Rgure 2H. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-3859 including the stop codon. I) The cDNA and amino acid sequence of 282P1G3 variant 28 (also called “282P163 v.28”) is shown in Figure 21. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 192-3888 including the stop codon. J) The cDNA and amino acid sequence of 282P1G3 variant 14 (also called “282P1G3 v.14") is shown in Figure 2J. The codon for the start methionine is underlined. The open reading frame extends from nucleic acid 272-3946 including the stop codon. 6 K) SNP variants of 282P1G3 v.1. 282P1G3 v.9 through v.25. The 282P1G3 v.9 through v.23 proteins have 1224 amino acids. Variants 282P1G3 v.9 through v.25 are variants with single nucleotide difference from 282P1G3 v.1. 282P1G3 v.9, v.10, v.11, v.24 and v.25 proteins differ from 282P1G3 v.1 by one amino acid. 282P1G3 v.12 through v.23, v.26 and v.27 code for the same protein as v.1. Though these SNP variants are shown separately, they can also occur in any combinations and in any of the transcript variants listed above in Figures 2A through 21.

Figure 3. A) The amino acid sequence of 282P1G3 v.1 is shown in Figure 3A; it has 1224 amino acids. B) The amino acid sequence of 282P1G3 v.2 is shown in Figure 3B; it has 1171 amino acids. C) The amino acid sequence of 282P1G3 v.3 is shown in Figure 3C; it has 893 amino acids. D) The amino acid sequence of 282P1G3 v.4 is shown in Figure 3D; it has 1117 amino acids. E) The amino acid sequence of 282P1G3 v.5 is shown in Figure 3E; it has 1208 amino acids. F) The amino acid sequence of 282P1G3 v.S is shown in Figure 3F; it has 1183 amino acids. G) The amino acid sequence of 282P1G3 v.7 is shown in Figure 3G; it has 1236 amino acids. H) The amino acid sequence of 282P1G3 v.8 is shown in Figure 3H; it has 1195 amino acids. I) The amino acid sequence of 282P1G3 v.9 is shown in Figure 3I; it has 1224 amino acids. J) The amino acid sequence of 282P1G3 v.10 is shown in Figure 3J; it has 1224 amino acids. K) The amino acid sequence of 282P1G3 v.11 is shown in Figure 3k; it has 1224 amino acids. L) The amino acid sequence of 282P1G3 v.24 is shown in Figure 3L; it has 1224 amino acids. M) The amino acid sequence of 282P1G3 v.25 is shown in Figure 3M; it has 1224 amino acids.

As used herein, a reference to 282P1G3 includes all variants thereof, including those shown in Figures 2,3,10, and 11, unless the context clearly indicates otherwise.

Figure 4. Figure 4A: Alignment of 282P1G3 with human close homolog of L1 (gi 27894376). Figure 4B:

Alignment of 282P1G3 with mouse dose homolog of L1 (gi6680936).

Figure 5. Figures 5(a)-(c): Hydrophilicity amino acid profile of 282P1G3v.1, v.3, and v.7 determined by computer algorithm sequence analysis using the method of Hopp and Woods (Hopp T.P., Woods K.R., 1981. Proc. Natl. Acad. Sci, U.S.A. 78:3824-3828) accessed on the Protscale website located on the World Wide Web at (expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server.

Figure 6. Figures 6(a)-(c); Hydropathicity amino acid profile of 282P1G3v.1, v.3, and v.7 determined by computer algorithm sequence analysis using the method of Kyte and Doolittle (Kyte J„ Doolittle R.F., 1982. J. Mol. Biot: 157:105-132) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server.

Figure 7. Figures 7(a)-(c): Percent accessible residues amino acid profile of 282P1G3v.1, v.S, and v.7 determined by computer algorithm sequence analysis using the method of Janin (Janin J., 1979 Nature 277:491-492) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server.

Figure 8. Figures 8(a)-(c): Average flexibility amino acid profile of 282P1G3v.1, v.3, and v.7 determined by computer algorithm sequence analysts using the method of Bhaskaran and Ponnuswamy (Bhaskaran R., and Ponnuswamy P.K., 1988. InL J. Pept. Protein Res. 32:242-255) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscale.pl) through the ExPasy molecular biology server.

Figure 9. Figures 9(a)-(c): Beta-turn amino acid profile of 282P1G3v.1, v.S, and v.7 determined by computer algorithm sequence analysts using the method of Deleage and Roux (Deleage, G., Roux B. 1987 Protein Engineering 1:289- 7 294) accessed on the ProtScale website located on the World Wide Web at (.expasy.ch/cgi-bin/protscaie.pl) through the ExPasy molecular biology server.

Figure 10. Schematic alignment of SNP variants of282P1G03 v.1. Variants 282P1G03 v.9 through v.27are variants with single nucleotide difference from v.1. Variant v.14 inserted a T between 4635 and 4636 of v.1. Though these SNP variants are shown separately, they can also occur in any combinations and in any transcript variants as shown in Fig. 12, e.g. v.2, that contains the bases. Numbers correspond to those of 282P1G03 v.1. Black box shows the same sequence as 282P1G03 v. 1. SNPs are indicated above the box.

Figure 11. Schematic alignment of protein variants of 282P1G03. Protein variants are named to correspond to nucleotide variants. Variants v.2 through v.8 were translated from splice variants. Variants v.7 and v.8 had an insertion of 12 amino acids. Variants v.9 through v.11, v.24, and v.25 were translated from SNP variants. Nucleotide variants 282P1G03 v.12 through v.23 coded for the same protein as v.1. Single amino acid differences among the proteins translated from SNP variants were indicated above the boxes. Black boxes represent the same sequence as 282P1G03 v.1. Numbers underneath the box correspond to positions in 282P1G03 v.1.

Figure 12. Structures of transcript variants of 282P1G03. Variant 282P1G03 v.2 through v.8 and v.28 are transcript variants of 282P1G03 v.1. Variant 282P1G03 v.3 deleted exons 22 through 27,3' portion of exon 21 and 5’ portion of exon 28 of variant 282P1G03 v.1. Variants v.2, v.4, v.5 and v.6 spliced out exon 25, exons 21-22, exon 8, and exon 5, respectively, in v.1. Variant 282P1G03 v.7 extended 36 bp at the 5’ end of exon 11 of variant 282P1G03 v.1. In addition to such an extension of 36 bp to exon 11 of v.1, variant 282P1G03 v.8 deleted exon 6 of variant 282P1G03 v.1. The 11 th potential exon had two forms: the longer form was 36 bp longer than the shorter form. The 21st and 28th potential exons could aiso have a long and a short form, as seen in v. 3. Poly A tails are not shown here. Numbers in “()” underneath the boxes correspond to those of 282P1G03 v.1. Lengths of introns and exons are not proportional.

Figure 13. Secondary structure and transmembrane domains prediction for 282P1G3B protein variants.

The secondary structure of 282P1G3B protein variants 1 through 8 (Figures 13A (SEQ ID NO: 199), 13B (SEQ ID NO: 200), 13C (SEQ ID NO: 201), 13D (SEQ ID NO: 202), 13E (SEQ ID NO: 203), 13F (SEQ ID NO: 204), 13G (SEQ ID NO: 205), and 13H (SEQ ID NO: 206) respectively) were predicted using the HNN - Hierarchical Neural Network method (NPS@: Network Protein Sequence Analysis TIBS 2000 March Vol. 25, No 3 [291 ]:147-150 Combet C., Blanchet C., Geourjon C. and Deleage G., http://pbiLibcp.fr/cgi-binZnpsa_automat.pl?page=npsa_nn.html), accessed from the ExPasy molecular biology server located on the World Wide Web at (.expasy.ch/tools/). This method predicts the presence and location of alpha helices, extended strands, and random coils from the primary protein sequence. The percent of the protein in a given secondary structure is also listed.

Figures 131,13K, 13M, 130,13Q, 13S, 13U, and 13W: Show schematic representations of the probability of existence of transmembrane regions and orientation of 282P1G3B variants 1 through 9, respectively, based on the TMpred algorithm of Hofmann and Stoffel which utilizes TMBASE (K. Hofmann, W. Stoffel. TMBASE - A database of membrane spanning protein segments Biol. Chem. Hoppe-Seyler 374:166,1993). Figures 13J, 13L, 13N, 13P, 13R, 13T, 13V, and 13X: Show schematic representations of the probability of the existence of transmembrane regions and the extracellular and intracellular orientation of282P1G3B variants 1 through 9, respectively, based on theTMHMM algorithm of Sonnhammer, von Heijne, and Krogh (Erik L.L. Sonnhammer, Gunnar von Heijne, and Anders Krogh: A hidden Markov model for predicting transmembrane helices in protein sequences. In Proc. of Sixth InL Conf, on Intelligent Systems for Molecular Biology, p 175-182 Ed J. Glasgow, T. Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen Menlo Park, CA: AAAI Press, 1998). The TMpred and TMHMM algorithms are accessed from the ExPasy molecular biology server located on the World Wide Web at (.expasy.ch/tools/). 8

Figure 14. 282P1G3 Expression by RT-PCR. First strand cDNA was prepared from (A) vital poo! 1 (liver, lung and kidney), vital pool 2 (pancreas, colon and stomach), normal pancreas, ovary cancer pool, and pancreas cancer pool; (B) normal stomach, normal brain, normal heart, normal liver, normal skeletal muscle, normal testis, normal prostate, normal bladder, normal kidney, normal colon, normal lung, normal pancreas, and a pool of cancer specimens from pancreas cancer patients, ovary cancer patients, and cancer metastasis specimens. Normalization was performed by PCR using primers to actin. Semi-quantitative PCR, using primers to 282P1G3, was performed at 26 and 30 cycles of amplification. (A) Expression of 282P1G3 was detected in ovary cancer poo!, pancreas cancer pool vital pool 1, but not in vital pool 2 nor in normal pancreas. (B) Samples were run on an agarose gel, and PCR products were quantitated using the Alphalmager software. Results show strong expression in pancreas cancer, ovary cancer, cancer metastasis, and norma! brain compared to all other normal tissues tested.

Figure 15. 282P1G3 expression in normal tissues. Two multiple tissue northern blots (Clontech) both with 2 ug of mRNWlane were probed with the 282P1G3 sequence. Size standards in kilobases (kb) are indicated on the side. Results show expression of an approximately 9-1 Qkb 282P1G3 transcript in normal brain, but not in any other normal tissue tested.

Figure 16. Expression of 282P1G3 in Pancreas Cancer Patient Specimens. RNA was extracted from pancreas cancer cell lines (CL), norma! pancreas (N), and pancreas cancer patient tumor (T). Northern blots with 10ug of total RNA were probed with the 282P1G3 DNA probe. Size standards in kilobases are on the side. Results show expression of 282P1G3 in pancreas cancer patient tumor specimen but not in the cell lines nor in the normal pancreas.

Figure 17. Expression of 282P1G3 in Ovary Cancer Patient Specimens. RNA was extracted from ovary cancer cell lines (CL), normal ovary (N), and ovary cancer patient tumor (T). Northern blots with 1Qug of total RNA were probed with the 282P1G3 DNA probe. Size standards in kilobases are on the side. Results show expression of 282P1G3 in ovary cancer patient tumor specimen but not in the cel! lines nor in the normal ovary.

Figure 18. Expression of 282P1G3 in Lymphoma Cancer Patient Specimens. RNA was extracted from peripheral blood lymphocytes, cord blood isolated from normal individuals, and from lymphoma patient cancer specimens. Northern blots with 10ug of total RNA were probed with the 282P1G3 sequence. Size standards in kilobases are on the side. Results show expression of 282P1G3 in lymphoma patient specimens but not in the normal blood cells tested.

Figure 19. 282P1G3 Expression in 293T Cells Following Transfection of 282P1 G3.pcDNA3.1/MycHis Construct. The complete ORF of 282P1G3 v.2 was cloned into the pcDNA3.1/MycHis construct to generate 282P1G3.pcDNA3.1/MycHis. 293T cells were transfected with either 282P1G3.pcDNA3.1/MycHis or pcDNA3.1/MycHis vector control. Forty hours later, cell lysates were collected. Samples were run on an SDS-PAGE acrylamide gel, blotted and stained with anti-his antibody. The blot was developed using the ECL chemiluminescence kit and visualized by autoradiography. Results show expression of 282P1G3 from the 282P1G3.pcDNA3.1/MycHis construct in the lysates of transfected cells.

Figure 20. 282P1G3 Expression in 293T Ceils Following Transfection of 282P1G3.pcDNA3.1/MycHis Construct The extracellular domain, amino acids 26-1043, of 282P1G3 v.2 was cloned into the pTag5 construct to generate 282P1G3.pTag5.293T cells were transfected with 282P1G3.pTag5 construct. Forty hours iater, supernatant as well as cell lysates were collected. Samples were run on an SDS-PAGE acrylamide gel, blotted and stained with anti-his antibody. The blot was developed using the ECL chemiluminescence kit and visualized by autoradiography. Results show expression and secretion of 282P1G3 from the 282P1G3.pTag5 transfected celis.

DETAILED DESCRIPTION OF THE INVENTION

Outline of Sections I. ) Definitions II. ) 282P1G3 Polynucleotides 9

Il A} Uses of 282P1G3 Polynucleotides II. A.1.) Monitoring of Genetic Abnormalities HA2.) Antisense Embodiments ILA.3.) Primers and Primer Pairs H.A.4.) Isolation of 282P1G3-Encoding Nucleic Acid Molecules HAS.) Recombinant Nucleic Acid Molecules and Host-Vector Systems III. ) 282P1G3-related Proteins III A) Motif-bearing Protein Embodiments lll.B.) Expression of 282P1G3-related Proteins ill.C.) Modifications of 282P1 G3-related Proteins III.D.) Uses of 282P1G3-re!ated Proteins IV. ) 282P1G3 Antibodies V. ) 282P1G3 Cellular Immune Responses VI. ) 282P1G3 Transgenic Animals VII. ) Methods for the Detection of 282P1G3 VIII. ) Methods for Monitoring the Status of 282P1G3-related Genes and Their Products IX. ) Identification of Molecules That Interact With 282P1G3 X. ) Therapeutic Methods and Compositions X.A.) Anti-Cancer Vaccines X.B.) 282P1G3 as a Target for Antibody-Based Therapy X.C.) 282P1G3 as a Target for Cellular Immune Responses X.C.1. Minigene Vaccines X.C.2. Combinations of CTL Peptides with Helper Peptides X.C.3. Combinations of CTL Peptides with T Cell Priming Agents X.C.4. Vaccine Compositions Comprising DC Pulsed with CTL and/or HTL Peptides X.D.) Adoptive immunotherapy X.E.) Administration of Vaccines for Therapeutic or Prophylactic Purposes XL) Diagnostic and Prognostic Embodiments of 282P1G3. XII.) Inhibition of 282P1G3 Protein Function X11.A.) Inhibition of 282P1G3 With Intracellular Antibodies Xli.B.) Inhibition of 282P1G3 with Recombinant Proteins XII.C.) Inhibition of 282P1G3 Transcription or Translation X1I.D.) General Considerations for Therapeutic Strategies

Xl!!.) Identification, Characterization and Use of Modulators of 282P1G3 XIV.) KITS/Articles of Manufacture L)_Definitions:

Unless otherwise defined, all terms of art, notations and other scientific terms or terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantia! difference over what is generally understood in the art. Many of the techniques and procedures described or referenced herein are well understood and 10 commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd. edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and/or parameters unless otherwise noted.

The terms “advanced prostate cancer", “locally advanced prostate cancer", “advanced disease’ and “locally advanced disease" mean prostate cancers that have extended through the prostate capsule, and are meant to include stage C disease under the American Urological Association (AUA) system, stage C1 - C2 disease under the Whitmore-Jewett system, and stage T3 - T4 and N+ disease under the TNM (tumor, node, metastasis) system. In general, surgery is not recommended for patients with locally advanced disease, and these patients have substantially less favorable outcomes compared to patients having clinically localized (organ-confined) prostate cancer. Locally advanced disease is clinically identified by palpable evidence of induration beyond the lateral border of the prostate, or asymmetry or induration above the prostate base. Locally advanced prostate cancer is presently diagnosed pathologically following radical prostatectomy if the tumor invades or penetrates the prostatic capsule, extends into the surgical margin, or invades the seminal vesicles. “Altering the native glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence 282P1G3 (either by removing the underlying glycosylation site or by deleting the glycosylation by chemical and/or enzymatic means), and/or adding one or more glycosylation sites that are not present in the native sequence 282P1G3. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, involving a change in the nature and proportions of the various carbohydrate moieties present

The term “analog’ refers to a molecule which is structurally similar or shares similar or corresponding attributes with another molecule (e.g. a 282P1 G3-related protein). For example, an analog of a 282P1G3 protein can be specifically bound by an antibody or T cell that specifically binds to 282P1G3.

The term “antibody” is used in the broadest sense. Therefore, an “antibody” can be naturally occurring or man-made such as monoclonal antibodies produced by conventional hybridoma technology. Anii-282P1G3 antibodies comprise monoclonal and polyclonal antibodies as well as fragments containing the antigen-binding domain and/or one or more complementarity determining regions of these antibodies.

An'“antibody fragment” is defined as at least a portion of the variable region of the immunoglobulin molecule that binds to its target, i.e., the. antigen-binding region. In one embodiment it specifically covers single anti-282P1G3 antibodies and clones thereof (including agonist, antagonist and neutralizing antibodies) and anti-282P1G3 antibody compositions with polyepitopic specificity.

The term “codon optimized sequences” refers to nucleotide sequences that have been optimized for a particular host species by replacing any codons having a usage frequency of less than about 20%. Nucleotide sequences that have been optimized for expression in a given host species by elimination of spurious polyadenylation sequences, elimination of exon/intron splicing signals, elimination of transposon-like repeats and/or optimization of GC content in addition to codon optimization are referred to herein as an "expression enhanced sequences.” A “combinatorial library" is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical "building blocks" such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide (e.g., mutein) library, is formed by combining a set of chemical building blocks called amino acids in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound). Numerous chemical compounds are synthesized through such combinatorial mixing of chemical building blocks (Gallop et al., J. Med. Chem. 37(9): 1233-1251 (1994)). 11

Preparation and screening of combinatorial libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Patent No. 5,010,175, Furka, PepL ProL Res. 37:487-493 (1991), Houghton et al., Nature, 354:84-88 (1991)), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio- oligomers (PCT Publication WO 92/00091), benzodiazepines (U.S.

Pat No. 5,288,514), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs et at, Proc. Nat Acad. Sci. USA 90:6909-6913 (1993)), vinylogous polypeptides (Hagihara et at, J. Amer. Chem. Soc. 114:6568 (1992)), nonpeptidal peptidomimetics with a Beta-D-Glucose scaffolding (Hirschmann et at, J. Amer. Chem. Soc. 114:9217-9218 (1992)), analogous organic syntheses of small compound libraries (Chen et at, J. Amer. Chem. Soc. 116:2661 (1994)), oligocarbarnates (Cho, et at, Science 261:1303 (1993)), and/or peptidyl phosphonates (Campbel! et at, J. Org. Chem. 59:658 (1994)). See, generally, Gordon et at, J. Med. Chem. 37:1385 (1994), nucleic acid libraries (see, e.g., Stratagene, Corp.), peptide nucleic acid libraries (see, e.g., U.S. Patent 5,539,083), antibody libraries (see, e.g., Vaughn et at, Nature Biotechnology 14(3): 309-314 (1996), and carbohydrate libraries (see, e.g., Liang et at, Science 274:1520-1522 (1996), and U.S. Patent No. 5,593,853), and small organic molecule libraries (see, e.g., benzodiazepines, Baum, C&EN, Jan 18, page 33 (1993); isoprenoids, U.S. Patent No. 5,569,588; thiazolidinones and metathiazanones, U.S. Patent No. 5,549,974; pyrrolidines, U.S. Patent Nos. 5,525,735 and 5,519,134; morphoiino compounds, U.S. Patent No. 5,506,337; benzodiazepines, U.S. Patent No. 5,288,514; and the like).

Devices for the preparation of combinatorial libraries are commercially available (see, e.g., 357 NIPS, 390 NIPS, Advanced Chem Tech, Louisville KY; Symphony, Rainin, Woburn, MA; 433A, Applied Biosystems, Foster City, CA; 9050,

Plus, Millipore, Bedford, NIA). A number of well-known robotic systems have also beertdeveloped for solution phase chemistries. These systems include automated workstations such as the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymafe H, Zymark Corporation, Hopkinton, Mass.; Orca, Hewlett-Packard, Palo Alto, Calif.), which mimic the manual synthetic operations performed by a chemist Any of the above devices are suitable for use with the present invention. The nature and implementation of modifications to these devices (if any) so that they can operate as discussed herein will be apparent to persons skilled in the relevant art. in addition, numerous combinatorial libraries are themselves commercially available (see, e.g., ComGenex, Princeton, NJ; Asinex, Moscow, RU; Tripos, Inc., St Louis, MO; ChemStar, Ltd, Moscow, RU; 3D Pharmaceuticals, Exton, PA; Martek Biosciences, Columbia, MD; etc.).

The term “cytotoxic agent” refers to a substance that inhibits or prevents the expression activity of cells, function of cells and/or causes destruction of cells. The term is intended to include radioactive isotopes chemotherapeutic agents, and toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and/or variants thereof. Examples of cytotoxic agents include, but are not limited to auristatins, auromycins, maytansinoids, yttrium, bismuth, ricin, ricin A-chain, combrestatin, duocarmycins, dolostatins, doxorubicin, daunorubicin, taxol, cisplatin, cc1065, ethidium bromide, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin, diphtheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, modeccin A chain, alpha-sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, Sapaonaria officinalis inhibitor, and glucocorticoid and other chemotherapeutic agents, as well as radioisotopes such as At211,1131,1125, Y30, Re186, Re188, Sm153, Bi212or213, P32 and radioactive isotopes of Lu including Lu177. Antibodies may also be conjugated to an anticancer pro-drug activating enzyme capable of converting the pro-drug to its active form.

The “gene product” is sometimes referred to herein as a protein or mRNA. For example, a “gene product of the invention” is sometimes referred to herein as a "cancer amino acid sequence", “cancer protein", “protein of a cancer listed in Table Γ, a "cancer mRNA", “mRNA of a cancer listed in Table Γ, etc. In one embodiment, the cancer protein is encoded by a nucleic acid of Figure 2. The cancer protein can be a fragment, or alternatively, be the full-length protein to the fragment 12 encoded by the nucleic acids of Figure 2. In one embodiment, a cancer amino acid sequence is used to determine sequence identity or similarity. In another embodiment, the sequences are naturally occurring allelic variants of a protein encoded by a nucleic acid of Figure 2. In another embodiment, the sequences are sequence variants as further described herein. "High throughput screening’’ assays for the presence, absence, quantification, or other properties of particular nucleic acids or protein products are well known to those of skill in the art Similarly, binding assays and reporter gene assays are similarly well known. Thus, e.g., U.S. Patent No. 5,559,410 discloses high throughput screening methods for proteins; U.S. Patent No. 5,585,639 discloses high throughput screening methods for nucleic acid binding (i.e., in arrays); while U.S. Patent Nos. 5,576,220 and 5,541,061 disclose high throughput methods of screening for ligand/antibody binding.

In addition, high throughput screening systems are commercially available (see, e.g., Amersham Biosciences, Piscataway, NJ; Zymark Corp., Hopkinton, MA; Air Technical industries, Mentor, OH; Beckman Instruments, Inc. Fullerton, CA; Precision Systems, Inc., Natick, MA; etc.). These systems typically automate entire procedures, including all sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the micropiate in detector(s) appropriate for the assay. These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems. Thus, e.g., Zymark Corp, provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.

The term “homolog" refers to a molecule which exhibits homology to another molecule, by for example, having sequences of chemical residues that are the same or similar at corresponding positions. “Human Leukocyte Antigen” or “HLA” is a human class i or ciass il Major Histocompatibility Complex (MHC) protein (see, e.g., Stites, et a!., Immunology, 8th Eq., Lange Publishing, Los Altos, CA (1994).

The terms “hybridize”, “hybridizing”, “hybridizes" and the like, used in the context of polynucleotides, are meant to refer to conventional hybridization conditions, preferably such as hybridization in 50% formamide/6XSSC/0.1% SDS/10O pg/ml ssDNA, in which temperatures for hybridization are above 37 degrees C and temperatures for washing in 0.1XSSC/0.1% SDS are above 55 degrees C.

The phrases "isolated" or "biologically pure" refer to material which is substantially or essentially free from components which normally accompany the material as it is found in its native state. Thus, isolated peptides in accordance with the invention preferably do not contain materials normally associated with the peptides in their in situ environment For example, a polynucleotide is said to be “isolated" when it is substantially separated from contaminant polynucleotides that correspond or are complementary to genes other than the 282P1G3 genes or that encode polypeptides other than 282P1G3 gene product or fragments thereof. A skilled artisan can readily employ nucleic acid isolation procedures to obtain an isolated 282P1G3 polynucleotide. A protein is said to be “isolated," for example, when physical, mechanical or chemical methods are employed to remove the 282P1G3 proteins from cellular constituents that are normally associated with the protein. A skilled artisan can readily employ standard purification methods to obtain an isolated 282P1G3 protein. Alternatively, an isolated protein can be prepared by chemical means.

The term “mammal” refers to any organism classified as a mammal, including mice, rats, rabbits, dogs, cats, cows, horses and humans. In one embodiment of the invention, the mammal is a mouse, in another embodiment of the invention, the mammal is a human.

The terms “metastatic prostate cancer" and “metastatic disease” mean prostate cancers that have spread to regional lymph nodes or to distant sites, and are meant to include stage D disease under toe AUA system and stage TxNxM+ under toe TNM system. As is toe case with locally advanced prostate cancer, surgery is generally not indicated for patients with metastatic disease, and hormonal (androgen ablation) therapy is a preferred treatment modality. Patients with 13 metastatic prostate cancer eventually develop an androgen-refractory state within 12 to 18 months of treatment initiation. Approximately half of these androgen-refractory patients die within 6 months after developing that status. The most common site for prostate cancer metastasis is bone. Prostate cancer bone metastases are often osteoblastic rather than osteolytic (i.e., resulting in net bone formation). Bone metastases are found most frequently in the spine, followed by the femur, peivis, rib cage, skull and humerus. Other common sites for metastasis include lymph nodes, lung, liver and brain. Metastatic prostate cancer is typically diagnosed by open or laparoscopic pelvic lymphadenectomy, whole body radionuclide scans, skeletal radiography, and/or bone lesion biopsy.

The term “modulator" or "test compound" or "drug candidate" or grammatical equivalents as used herein describe any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the cancer phenotype or the expression of a cancer sequence, e.g., a nucleic acid or protein sequences, or effects of cancer sequences (e.g., signaling, gene expression, protein interaction, etc.) In one aspect, a modulator will neutralize the effect of a cancer protein of the invention. By "neutralize" is meant that an activity of a protein is inhibited or blocked, along with the consequent effect on the cell. In another aspect, a modulator will neutralize the effect of a gene, and its corresponding protein, of the invention by normalizing levels of said protein. In preferred embodiments, modulators alter expression profiles, or expression profile nucleic acids or proteins provided herein, or downstream effector pathways. In one embodiment, the modulator suppresses a cancer phenotype, e.g. to a normal tissue fingerprint In another embodiment, a modulator induced a cancer phenotype. Generally, a plurality of assay mixtures is run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i.e., at zero concentration or below the level of detection.

Modulators, drug candidates or test compounds encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 Daltons, Preferred small molecules are less than 2000, or less than 1500 or less than 1000 or less than 500 D. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or poiyaromatic structures substituted with one or more of toe above functional groups. Modulators also comprise biomolecules such as peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof. Particularly preferred are peptides. One class of modulators are peptides, for example of from about five to about 35 amino acids, with from about five to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. Preferably, the cancer modulatory protein is soluble, includes a non-transmembrane region, and/or, has an Il-terminal Cys to aid in solubility. In one embodiment, the C-ferminus of the fragment is kept as a free acid and the N-terminus. is a free amine to aid in coupling, i.e., Io cysteine. In one embodiment, a cancer protein of the invention is conjugated to an immunogenic agent as discussed herein. In one embodiment, the cancer protein is conjugated to BSA. The peptides of the invention, e.g., of preferred lengths, can be linked to each other or to other amino acids to create a longer peptide/protein. The modulatory peptides can be digests of naturally occurring proteins as is outlined above, random peptides, or "biased" random peptides, in a preferred embodiment, peptide/protein-based modulators are antibodies, and fragments thereof, as defined herein.

Modulators of cancer can also be nucleic acids. Nucleic acid modulating agents can be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. For example, digests of prokaryotic or eukaryotic genomes can be used in an approach analogous to that outlined above for proteins. 14

The term “monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the antibodies comprising the population are identical except for possible naturally occurring mutations that are present in minor amounts. A “motif, as in biological motif of a 282P1 G3-reiated protein, refers to any pattern of amino acids forming part of the primary sequence of a protein, that is associated with a particular function (e.g. protein-protein interaction, proiein-DNA interaction, etc) or modification (e.g. that is phosphoryiated, glycdsylated or amidated), or localization' (e.g. secretory sequence, nuclear localization sequence, etc.) or a sequence that is correlated with being immunogenic, either humorally or cellulariy. A motif can be either contiguous or capable of being aligned to certain positions that are generally correlated with a certain function or property. In the context of HLA motifs, “motif refers to the pattern of residues in a peptide of defined length, usually a peptide of from about 8 to about 13 amino acids for a class I HLA motif and from about 6 to about 25 amino acids for a class II HLA motif, which is recognized by a particular HLA molecule. Peptide motifs for HLA binding are typically different for each protein encoded by each human HLA allele and differ in the pattern of the primary and secondary anchor residues. A “pharmaceutical excipient” comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservative, and the like. “Pharmaceutically acceptable" refers to a non-toxic, inert, and/or composition that is physiologically compatible with humans or other mammals.

The term “polynucleotide" means a polymeric form of nucleotides of at least 10 bases or base pairs in length, either ribonucleotides or deoxynucleotides or a modified form of either type of nucleotide, and is meant to include single and double stranded forms of DNA and/or RNA. in the art, this term if often used interchangeably with “oligonucleotide”. A polynucleotide can comprise a nucleotide sequence disclosed herein wherein thymidine (T), as shown for example in Figure 2, can also be uracil (U); this definition pertains to the differences between the chemical structures of DNA and RNA, in particular the observation that one of the four major bases in RNA is uracil (U) instead of thymidine (T).

The term “polypeptide” means a polymer of at least about 4,5,8,7, or 8 amino acids. Throughout the specification, standard three letter or single letter designations for amino acids are used. In the art, this term is often used interchangeably with “peptide" or “protein".

An HLA “primary anchor residue” is an amino add at a specific position along a peptide sequence which is understood to provide a,contact point between the immunogenic peptide and the HLA molecule. One to three, usually two, primary anchor residues within a peptide of defined length generally defines a “motif for an immunogenic peptide. These residues are understood to fit in close contact with peptide binding groove of an HLA molecule, with their side chains buried in specific pockets of the binding groove, in one embodiment, for example, the primary anchor residues for an HLA class I molecule are located at position 2 (from the amino terminal position) and at the carboxyi terminal position of a 8,9,10,11, or 12 residue peptide epitope in accordance with the invention. Alternatively, in another embodiment, the primary anchor residues of a peptide binds an HLA class Ii molecule are spaced relative to each other, rather than to the termini of a peptide, where the peptide is generally of at least 9 amino acids in length. The primary anchor positions for each motif and supermotif are set forth in Table IV. For example, analog peptides can be created by altering the presence or absence of particular residues in the primary and/or secondary anchor positions shown in Table !V. Such analogs are used to modulate the binding affinity and/or population coverage of a peptide comprising a particular HLA motif or supermotif. “Radioisotopes” include, but are not limited to the following (non-limiting exemplary uses are also set forth);

Examples of Medical isotopes: isotope Description of use

Actinium-225 See Thorium-229 (Th-229) 15 (AC-225)

Actinium-227 (AC-227)

Bismuth-212 (Bi-212)

Bismuth-213 (Bi-213)

Cadmium-109 (Cd-109)

Cobait-50 (Co-60)

Parent of Radium-223 (Ra-223) which is an alpha emitter used to treat metastases in the skeleton resulting from cancer (i.e., breast and prostate cancers), and cancer radioimmunotherapy

See Thorium-223 (Th-228)

See Thorium-229 (Th-229)

Cancer detection

Radiation source for radiotherapy of cancer, for food irradiators, and for sterilization of medical supplies

Copper-64 (Cu-64)

Copper-67 (Cu-67) A positron emitter used for cancer therapy and SPECT imaging

Beta/gamma emitter used in cancer radioimmunotberapy and diagnostic studies (i.e., breast and colon cancers, and lymphoma)

PyKiS)™ dancer radioimmunotherapy

Erbium-169 Rheumatoid arthritis treatment, particularly for the small joints associated with fingers and (Er-169) toes

Europium-152 (Eu-152)

Radiation source for food irradiation and for sterilization of medical supplies

Europium-154 (Eu-154)

Radiation source for food irradiation and for sterilization of medical supplies

Gadolinium-153 (Gd-153)

Gold-198 (Au-198)

Osteoporosis detection and nuclear medical quality assurance devices implant and intracavity therapy of ovarian, prostate, and brain cancers

Holmium-166 Multiple myeloma treatment in targeted skeletal therapy, cancer radioimmunotherapy, bone (Ho-166) marrow ablation, and rheumatoid arthritis treatment

Osteoporosis detection, diagnostic imaging, tracer drugs, brain cancer treatment,

Iodine-125 radiolabeling, tumor imaging, mapping of receptors in the brain, interstitial radiation therapy, (1-125) brachytherapy for treatment of prostate cancer, determination of glomerular filtration rate (GFR), determination of plasma volume, detection of deep vein thrombosis of the legs

Thyroid-function evaluation, thyroid disease detection, treatment of thyroid cancer as well as lodine-131 other non-maiignant thyroid diseases (i.e., Graves disease, goiters, and hyperthyroidism), (1-131) treatment of leukemia, lymphoma, and other forms of cancer (e.g., breast cancer) using ’ radioimmunotherapy iridium-192 Brachytherapy, brain and spinal cord tumor treatment, treatment of blocked arteries (i.e., (lr-192) arteriosclerosis and restenosis), and implants for breast and prostate.tumors

Lutetium-177 Cancer radioimmunotherapy and treatment of blocked arteries (i.e., arteriosclerosis and (Lu-177) restenosis)

Parent of Technetium-99m (Tc-99m) which is used for imaging the brain, liver, lungs, heart, Molybdenum-99 and other organs. Currently, Tc-99m is the most widely used radioisotope used for diagnostic (Mo-99) imaging of various cancers and diseases involving the brain, heart, liver, lungs; aiso used in detection of deep vein thrombosis of the tegs

Osmium-194 (Os-194)

Palladium-103 (Pd-103)

Platinum-195m (Pt-195m)

Phosphorus-32

Cancer radioimmunotherapy

Prostate cancer treatment .

Studies on biodistribufon and metabolism of cisplatin, a chemotherapeutic drug Polycythemia rubra vera (blood cel! disease) and leukemia treatment, bone cancer 16 (P-32)

Phosphorus-33 (P-33)

Radium-223 (Ra-223)

Rhenium-186 (Re-186)

Rhenium-188 (Re-188)

Rhodium-105 (Rh-105)

Samarium-145 (Sm-145)

Samarium-153 (Sm-153)

Scandium-47 (Sc-47)

Selenium-75 (Se-75)

Strontium-85 (Sr-85)

Strontium-89 (Sr-89)

Yttrium-91 (Y-91) diagnosis/treatment; colon, pancreatic, and liver cancer treatment; radiolabeling nucleic acids for in vitro research, diagnosis of superficial tumors, treatment of blocked arteries (i.e., arteriosclerosis and restenosis), and intracavity therapy

Leukemia treatment, bone disease diagnosis/treatment, radiolabeling, and treatment of blocked arteries (i.e., arteriosclerosis and restenosis)

See Actinium-227 (Ac-227)

Bone cancer pain relief, rheumatoid arthritis treatment, and diagnosis and treatment of lymphoma and bone, breast, colon, and liver cancers using radioimmunotherapy

Cancer diagnosis and treatment using radioimmunotherapy, bone cancer pain relief, treatment of rheumatoid arthritis, and treatment of prostate cancer Cancer radioimmunotherapy

Ocular cancer treatment

Cancer radioimmunotherapy and bone cancer pain relief

Cancer radioimmunotherapy and bone cancer pain relief

Radiotracer used in brain studies, imaging of adrenal cortex by gamma-scintigraphy, lateral locations of steroid secreting tumors, pancreatic scanning, detection of hyperactive parathyroid glands, measure rate of bile acid loss from the endogenous pool

Bone cancer detection and brain scans

Bone cancer pain relief, multiple myeloma treatment, and osteoblastic therapy

Technetium-99m (Tc-39rn)

Thorium-228 (Th-228)

Thorium-229 (Th-229)

Thulium-170 (Tm-170)

Tin-117m (Sn-117m)

Tungsten-188 (W-188)

Xenon-127 (Xe-127)

Ytterbium-175 (Yb-175)

Yttrium-90 (Y-90)

See Molybdenum-99 (Mo-99)

Parent of Bismuth-212 (Bi-212) which is an alpha emitter used in cancer radioimmunotherapy

Parent of Actinium-225 (Ac-225) and grandparent of Bismuth-213 (Bi-213) which are alpha emitters used in cancer radioimmunotherapy

Gamma source for blood irradiators, energy source for implanted medical devices

Cancer immunotherapy and bone cancer pain relief

Parent for Rhenium-188 (Re-188) which is used for cancer diagnostics/treatment, bone cancer pain relief, rheumatoid arthritis treatment, and treatment of blocked arteries (i.e„ arteriosclerosis and restenosis)

Neuroimaging of brain disorders, high resolution SPECT studies, pulmonary function tests, and cerebral blood flow studies Cancer radioimmunotherapy

Microseeds obtained from irradiating Yttrium-89 (Y-89) for liver cancer treatment A gamma-emitting label for Yttrium-90 (Y-90) which is used for cancer radioimmunotherapy (i.e., lymphoma, breast, colon, kidney, lung, ovarian, prostate, pancreatic, and inoperable liver cancers) 17

By "randomized" or grammatical equivalents as herein applied to nucleic acids and proteins is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. These random peptides (or nucleic acids, discussed herein) can incorporate any nucleotide or amino acid at any position. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible / combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.

In one embodiment, a library is “fully randomized,” with no sequence preferences or constants at any position. In another embodiment, the library is a “biased random” library. That is, some positions within the sequence either are held constant, or are selected from a limited number of possibilities. For example, the nucleotides or amino acid residues are randomized within a defined class, e.g., of hydrophobic amino acids, hydrophilic residues, stericaily biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-iinking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc., or to purines, etc. A “recombinant" DNA or RNA molecule is a DNA or RNA molecule that has been subjected to molecular manipulation in vitro.

Non-limiting examples of small molecules include compounds that bind or interact with 282P1G3, ligands including hormones, neuropeptides, chemokines, odorants, phospholipids, and functional equivalents thereof that bind and preferably inhibit 282P1G3 protein function. Such non-limiting small molecules preferably have a molecular weight of less than about 10 kDa, more preferably below about 9, about 8, about 7, about 6, about 5 or about 4 kDa. In certain embodiments, small molecules physically associate with, or bind, 282P1G3 protein; are not found in naturally occurring metabolic pathways; and/or are more soluble in aqueous than non-aqueous solutions “Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured nucleic acid sequences to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature that can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubei et al., Current Protocols in Molecular Biology, Wiley Interscience Publishers, (1995). “Stringent conditions" or “high stringency conditions”, as defined herein, are identified by, but not limited to, those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1 % sodium dodecyl sulfate at 50°C; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1 % polyvinylpyrroiidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42 °C; or (3) employ 50% formamide, 5 x SSC (0.75 M NaCI, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1 % sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 pg/ml), 0.1% SDS, and 10% dextran sulfate at 42 °C, with washes at 42°C in 0.2 x SSC (sodium chloride/sodium. citrate) and 50% formamide at 55 °C, followed by a high-stringency wash consisting of 0.1 x SSC containing EDTA at 55 °C. "Moderately stringent conditions" are described by, but not limited to, those in Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent than those described above. An example of moderately stringent conditions is overnight incubation at 37°C in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x 18

Denhardt's solution, 10% dexiran sulfate, and 20 mg/mL denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50°C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like.

An HLA “supermotiP is a peptide binding specificity shared by HLA molecules encoded by two or more HLA alleles. Overall phenotypic frequencies of HLA-supertypes in different ethnic populations are set forth in Table IV (F). The non-iimiting constituents of various supetypes are as follows: A2: A*0201, A*0202, A*0203, A*0204, A* 0205, A*0206, A*6802, A*6901, A*0207 A3: A3, A11, A31, A*3301, A*6801, ΑΌ301, ΑΊ101, A‘3101 B7: B7, B"3501-03, B*51, B*53G1, B*5401, B*5501, B*5502, B*5601, B*6701, B7801, B‘0702, B*5101, B*5602 B44: B*3701, B*4402, B*4403, B*60 (B*4001), B61 (B’4006)

Al: A*0102, A*2604, A"3601, A*4301, A’8001 A24: A*24, A*30, A*2403, A*2404, A’3002, A*3003 B27: ΒΊ401-02, ΒΊ503, ΒΊ509, ΒΊ510, B*1518, 8*3801-02, B*3901, B*3902, B*3903-04, B*4801-02, B7301, B*2701-08 -B58: B*1516, ΒΊ517, B*5701, B’5702, B58 B62: B*4601. B52, B*1501 (B62), B*15Q2 (B75), ΒΊ513 (B77)

Calculated population coverage afforded by different HLA-supertype combinations are set forth in Table IV (G).

As used herein “to treat” or “therapeutic" and grammatically related terms, refer to any improvement of any consequence of disease, such as prolonged survival, less morbidity, and/or a lessening of side effects which are the byproducts of an alternative therapeutic modality; full eradication of disease is not required. A “transgenic animal" (e.g., a mouse or rat) is an animal having cells that contain a transgene, which transgene was introduced into the animal or an ancestor of the animal at a prenatal, e.g., an embryonic stage. A “transgene" is a DNA. that is integrated into the genome of a cell from which a transgenic animal develops.

As used herein, an HLA or cellular immune response “vaccine” is a composition that contains or encodes one or more peptides of the invention. There are numerous embodiments of such vaccines, such as a cocktail of one or more individual peptides; one or more peptides of the invention comprised by a polyepitopic peptide; or nucleic acids that encode such individual peptides or polypeptides, e.g., a minigene that encodes a poiyepitopic peptide. The “one or more peptides” can include any whole unit integer from 1-150 or more, e.g., at least 2,3,4,5,6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33,34, 35, 36, 37, 38, 39, 40,41,42, 43, 44, 45, 46, 47, 48,49,50, 55, 60,65,70,75,80,85,90,95,100,105,110,115,120,125,130,135,140,145, or 150 or more peptides of the invention.

The peptides or polypeptides can optionally be modified, such as by lipidation, addition of targeting or other sequences. HLA class! peptides of the invention can be admixed with, or linked to, HLA class ii peptides, to facilitate activation of both cytotoxic T lymphocytes and helper T lymphocytes. HLA vaccines can also comprise peptide-pulsed antigen presenting ceils, e.g., dendritic celis.

The term “variant” refers to a molecule that exhibits a variation from a described type or norm, such as a protein that has one or more different amino acid residues in the corresponding posifion(s) of a specifically described protein (e.g. the 282P1G3 protein shown in Figure 2 or Figure 3. An analog is an example of a variant protein. Splice isoforms and single nucleotides polymorphisms (SNPs) are further examples of variants.

The “282P1G3-related proteins” of the invention include those specifically identified herein, as well as allelic variants, conservative substitution variants, analogs and homoiogs that can be isolated/generated and characterized without undue experimentation following the methods outlined herein or readily available in the art. Fusion proteins Shat combine parts of different 282P1G3 proteins or fragments thereof, as well as fusion proteins of a 282P1G3 protein and a heterologous polypeptide 19 are also included. Such 282P1G3 proteins are collectively referred to as the 282P1G3-related proteins, the proteins of the invention, or 282P1G3. The term “282P1G3-related protein” refers to a polypeptide fragment or a 282P1G3 protein sequence of 4, 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25, or more than 25 amino acids; or, at least 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 85, 90, 95,100,105,110,115,120,125,130,135,140,145,150,155,160,165,170,175,180, 185,190,195, 200, 225,250,275, 300, 325, 350, 375, 400, 425,450,475, 500, 525, 550, 575, or 576 or more amino acids. IL) 282P1G3 Polynucleotides

One aspect of the invention provides polynucleotides corresponding or complementary to all or part of a 282P1G3 gene, mRNA, and/or coding sequence, preferably in isolated form, including polynucleotides encoding a 282P1 G3-related protein and fragments thereof, DNA, RNA, DNA/RNA hybrid, and related molecules, polynucleotides or oligonucleotides complementary to a 282P1G3 gene or mRNA sequence or a part thereof, and polynucleotides or oligonucleotides that hybridize to a 282P1G3 gene, mRNA, or to a 282P1G3 encoding polynucleotide (collectively, “282P1G3 polynucleotides”).

In all instances when referred to in this section, T can also be U in Figure 2.

Embodiments of a 282P1G3 polynucleotide include: a 282P1G3 polynucleotide having the sequence shown in Figure 2, the nucleotide sequence of 282P1G3 as shown in Figure 2 wherein T is U; at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in Figure 2; or, at least 10 contiguous nucleotides of a polynucleotide having the sequence as shown in Figure 2 where T is U. For example, embodiments of 282P1G3 nucleotides comprise, without limitation: (I) a polynucleotide comprising, consisting essentially of, or consisting of a sequence as shown in Figure 2, wherein T can also be U; (II) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2A, from nucleotide residue number 272 through nucleotide residue number 3946, including the stop codon, wherein T can also be U; (III) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2B, from nucleotide residue number 272 through nucleotide residue number 3787, including the stop codon, wherein T can also be U; (IV) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2C, from nucleotide residue number 272 through nucleotide residue number 3953, including the a stop codon, wherein T can also be U; (V) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2D, from nucleotide residue number 272 through nucleotide residue number 3625, including the stop codon, wherein T can also be U; (VI) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2E, from nucleotide residue number 272 through nucleotide residue number 3898, including the stop codon, wherein T can also be U; (VII) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2F, from nucleotide residue number 272 through nucleotide residue number 3823, including the stop codon, wherein T can also be U; 20 (VIII) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 2G, from nucleotide residue number 272 through nucleotide residue number 3982, including the stop codon, wherein T can also be U; (IX) a polynucleotide comprising, consisting essentialiy of, or consisting of the sequence as shown in Figure 2H, from nucleotide residue number 272 through nucleotide residue number 3859, including the stop codon, wherein T can also be II; (X) a polynucleotide comprising, consisting essentially of, or consisting of the sequence as shown in Figure 21, from nucleotide residue number 192 through nucleotide residue number 3866, including the stop codon, wherein T can aiso be U; (XI) a polynucleotide that encodes a 282P1 G3-related protein that is at least 90, 91, 92, 93,94, 95, 96, 97, 98,99 or 100% homologous to an entire amino acid sequence shown in Figure 2A-J; (XII) a polynucleotide that encodes a 282P1 G3-related protein that is at least 90, 91, 92,93,94, 95, 96,97, 98,99 or 100% identical to an entire amino acid sequence shown in Figure 2A-J; (XIII) a polynucleotide that encodes at least one peptide set forth in Tables VIII-XX1 and XXIi-XLIX; (XIV) a polynucleotide that encodes a peptide region of at least 5, 6,7,8,9,10,11,12,13,14,15,16,17,18, 19,20,21, 22,23,24,25,26,27, 28,29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figures 3A and 3I-3M in any whole number increment up to 1224 that includes at least 1, 2, 3,4, 5,6,7, 8,9,10,11,12,13,14,15,16, 17,18,19, 20, 21,22,23,24, 25, 26,27,28, 29,30, 31, 32, 33, 34, 35 amino acid positions) having a value greater than 0.5 in the Hydrophiticity profile of Figure 5; (XV) a polynucleotide that encodes a peptide region of at least 5, 6, 7,8,9,10,11,12,13,14,15,16.17,18, 19,20, 21, 22,23,24, 25,26,27,28,29,30, 31,32,33,34,35 amino acids of a peptide of Figure 3A and 31-3M in any whole number increment up to 1224 that includes 1,2,3,4,5, 6,7, 8,9,10,11,12,13,14, 15,16,17,18,19, 20, 21, 22, 23, 24,25, 25, 27, 28, 29,30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XVI) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23,24,25, 26,27,28,29, 30, 31, 32, 33,34, 35 amino acids of a peptide of Figure 3A and 3I-3M in any whole number increment up to 1224 that includes 1, 2,3,4,5, 6, 7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24,25, 26,27,28,29,30,31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XVII) a polynucleotide that encodes a peptide region of at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21,22,23,24, 25,26,27,28,29, 30,31, 32,33,34,35 amino acids of a peptide of Figure 3A and 31-3M in any whole number increment up to 1224 that includes 1, 2, 3, 4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22,23,24,25,26,27,28,29,30, 31,32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Fgure 8; (XVI!I) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20,21, 22,23,24,25,26,27,28, 29, 30, 31, 32, 33, 34,35 amino acids of a peptide of Figure 3A and 3I-3M in any whole number increment up to 1224 that includes 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23,24,25,26,27,28,29,30,31,32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; 21 (XIX) a polynucleotide that encodes a peptide region of at least 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32,33, 34, 35 amino acids of a peptide of Figure 3B in any whole number increment up to 1171 that includes 1, 2,3, 4, 5, 6, 7, 8, 9,10,11,12,13, 14,15,16,17,18,19, 20,21, 22, 23,24, 25,26,27,28,29,30,31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophiiicity profile of Figure 5; (XX) a polynucleotide that encodes a peptide region of at least 5, 6,7,8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21,22,23,24,25, 26,27,28,29,30,31,32,33,34,35 amino acids of a peptide of Figure 3B in any whole number increment up to 1171 that includes 1, 2,3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21,22, 23, 24, 25, 26, 27,28, 29, 30,31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XX!) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28,29,30, 31, 32, 33,34, 35 amino acids of a peptide of Figure 3B in any whole number increment up to 1171 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24,25,26,27,28,29,30,31, 32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXII) a polynucleotide that encodes a peptide region of at least 5,6, 7,8, 9,10,11,12,13,14,15,16,17,18, 19,20,21,22,23,24,25, 26,27,28, 29,30,31,32, 33,34,35 amino acids of a peptide of Figure 3B in any whole number increment up to 1171 that includes 1, 2,3, 4,5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23,24,25,26,27,28,29,30,31, 32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXIII) a polynucleotide that encodes a peptide region of at least 5, 6,7,8, 9,10,11,12,13,14,15,16,17,18, 19, 20,21,22,23, 24,25,26,27,28,29,30,31,32, 33,34,35 amino acids of a peptide of Figure 3B in any whole number increment up to 1171 that includes 1, 2, 3, 4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23,24, 25, 26,27,28,29,30, 31, 32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9 (XXIV) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27,28, 29,30,31, 32, 33, 34, 35 amino acids of a peptide of Figure 3C in any whole number increment up to 893 that includes 1, 2,3,4, 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20,21,22, 23, 24,25, 26,27,28,29,30, 31,32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophiiicity profile of Figure 5; (XXV) a polynucleotide that encodes a peptide region of at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21,22,23, 24,25, 26,27,28,29,30,31,32,33, 34, 35 amino acids of a peptide of Figure 3C in any whole number increment up to 893 that includes 1,2,3,4, 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, 20,21, 22, 23,24,25,26,27,28,29, 30,31,32,33,34,35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XXV!) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21,22,23,24,25, 26, 27,28,29,30, 31,32, 33, 34, 35 amino acids of a peptide of Figure 3C in any whole number increment up to 893 that includes 1,2,3,4,5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23, 24, 25,26,27,28,29, 30,31,32,33,34, 35 amino acid position(s) having a value greater than 0.5 in the

Percent Accessible Residues profile of Figure 7; 22 (XXVII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33,34,35 amino acids of a peptide of Figure 3C in any whole number increment up to 893 that includes 1, 2,3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the

Average Flexibility profile of Figure 8; (XXVII!) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21, 22, 23, 24,25, 26,27,28, 29,30, 31,32,33,34, 35 amino acids of a peptide of Figure 3C in any whole number increment up to 893 that includes 1,2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13/14,15,16,17,18,19,20, 21, 22, 23,24, 25, 26, 27, 28,29,30,31, 32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9 (XXIX) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21, 22, 23, 24,25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3D in any whole number increment up to 1117 that includes 1, 2, 3,4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17, 18,19, 20, 21, 22, 23,24,25, 26,27, 28,29, 30, 31,32,33,34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophiiicity profile of Figure 5; (XXX) a polynucleotide that encodes a peptide region of at least 5, 6, 7,8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21,22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3D in any whole number increment up to 1117 that includes 1, 2, 3,4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24, 25, 26, 27, 28,29,30, 31,32,33,34, 35 amino acid position^) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XXXi) a polynucleotide that encodes a peptide region of at least 5,6,7,8,9,19,11,12,13,14,15,16,17,18, 19,20, 21, 22,23,24,25, 26, 27,28, 29,30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3D in any whole number increment up to.1117 that includes 1, 2,3, 4, 5, 6, 7, 8, 9, 10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25, 26, 27, 28. 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXXII) a polynucleotide that encodes a peptide region of at least 5, 6,7,8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3D in any whole number increment up to 1117 that includes 1, 2, 3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23,24, 25,26, 27,28, 29,30, 31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXXIII) a polynucleotide that encodes a peptide region of at least 5, 6,7,8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21, 22,23, 24,25,26, 27,28,29,30,31, 32,33,34, 35 amino acids of a peptide of Figure 3D in any whole number increment up to 1117 that includes 1,2,3,4,5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23,24,25,26, 27,28, 29,30, 31,32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9 (XXXIV) a polynucleotide that encodes a peptide region of at least 5, 6,7,8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21,22,23, 24,25,26, 27,28, 29, 30,31, 32,33, 34, 35 amino acids of a peptide of Figure 3E in any whole number increment up to 1208 that includes 1,2, 3,4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23,24, 25,26,27,28,29,30, 31,32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the

Hydrophiiicity profile of Figure 5; 23 (XXXV) a polynucleotide that encodes a peptide region of at feast 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22,23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acids of a peptide of Figure 3E in any whole number increment up to 1208 that includes 1, 2, 3,4, 5,6,7, 8, 9,10,11,12,13, 14,15,16, 17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the

Hydropathicity profile of Figure 6; (XXXV!) a polynucleotide that encodes a peptide region of at least 5, 6,7,8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21,22,23, 24, 25,26, 27, 28, 29,30, 31,32,33,34, 35 amino acids of a peptide of Figure 3E in any whole number increment up to 1208 that includes 1, 2, 3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXXVII) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3E in any whole number increment up to 1208 that includes 1, 2,3, 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24,25, 26, 27,28,29, 30,31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXXVIII) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35 amino acids of a peptide of Figure 3E in any whole number increment up to 1208 that includes 1, 2, 3, 4, 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a vaiue greater than 0.5 in the Beta-turn profile of Figure 9 (XXXIX) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21,22,23,24; 25,26,27,28,29,30,31,32,33,34,35 amino acids of a peptide of Figure 3F in any whole number increment up to 1183 that includes 1, 2,3,4, 5, 6, 7, 8, 9,10, 11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23,24, 25, 26,27, 28, 29, 30,31,32,33, 34, 35 amino acid posifion(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XL) a pojynucleotide that encodes a peptide region of at least 5, 6,7,8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21,22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acids of a peptide of Figure 3F in any whole number increment up to 1183 that includes 1, 2,3, 4,5, 6, 7, 8,9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24,25, 26,27,28, 29,30,31,32, 33,34,35 amino acid position(s) having a vaiue less than 0.5 in the Hydropathicity profile of Figure 6; (XL!) a polynucleotide that encodes a peptide region of at least 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20,21,22,23, 24, 25,26, 27,28, 29,30,31,32,33,34,- 35 amino acids of,a peptide of Figure 3F in any whole number increment up to 1183 that includes 1,2,3,4,5, 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25, 26,27, 28,29, 30,31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XLII) a polynucleotide that encodes a peptide region of at least 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22,23, 24,25,26, 27,28,29, 30,31, 32,33,34, 35 amino acids of a peptide of Figure 3F in any whole number increment up to 1183 that includes 1, 2, 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23, 24, 25, 26,27,28,29,30, 31,32,33, 34,35 amino acid position(s) having a vaiue greater than 0.5 in the

Average Flexibility profile of Figure 8; 24 (XLIII) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acids of a peptide of Figure 3F in any whole number increment up to 1183 that includes 1, 2, 3,4, 5, 6, 7,8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta- turn profile of Figure 9 (XLIV) a polynucleotide that encodes a peptide region of at least 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19,20, 21, 22, 23, 24,25,26,27, 28,29,30, 31,32,33, 34,35 amino acids of a peptide of Figure 3G in any whole number increment up to 1236 that includes 1,2, 3,4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23,24, 25, 26, 27,28, 29, 30, 31,32,33,34, 35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XLV) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3G in any whole number increment up to 1236 that includes 1, 2, 3, 4, 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30,31, 32,33,34,35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XLVI) a polynucleotide that encodes a peptide region of at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35 amino acids of a peptide of Figure 3G in any whole number increment up to 1236 that includes 1,2, 3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21, 22, 23,24,25, 26, 27, 28, 29,30,31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XLVII) a polynucleotide that encodes a peptide region of at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18, 19,20, 21,22, 23, 24, 25, 26,27, 28,29,30,31,32,33, 34,35 amino acids of a peptide of Figure 3G in any whole number increment up to 1236 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the

Average Flexibility profile of Figure 8; (XLVtlt) a polynucleotide that encodes a peptide region of at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18, 19,20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a peptide of Figure 3G in any whole number increment up to 1236 that includes 1,2, 3,4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30,31, 32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9 (XL1X) a polynucleotide that encodes a peptide region of at least 5,6,7,8,9,10,,11,12,13,14,15,16,17,18, 19, 20, 21,22,23,24, 25, 26,27,28,29, 30,31, 32,33, 34, 35 amino acids of a peptide of Figure 3Ein any whole number increment up to 1208 that includes 1,2,3,4, 5,6,7,8, 9,10,11,12,13,14,15,16,17,18,19, 20,21,22, 23,24,25,26, 27,28,29,30,31,32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (L) a polynucleotide that encodes a peptide region of at least 5, 6,7,8,9,10,11,12,13,14,15,16,17,18, 19,20, 21,22,23, 24,25,26,27, 28,29, 30, 31,32,33, 34, 35 amino acids of a peptide of Figure 3H in any whole number increment up to 1195 that includes 1,2, 3, 4, 5, 6, 7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23,24, 25,26, 27,28,29, 30, 31,32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the

Hydropathicity profile of Figure 6; 25 (L!) a polynucleotide that encodes a peptide region of at least 5, 6, 7, 8, 9,10, 11,12,13,14,15,16,17,18, 19, 20,21,22, 23, 24, 25, 26,27, 28,29, 30, 31, 32, 33,34, 35 amino acids of a peptide of Figure 3H in any whole number increment up to 1195 that includes 1,2, 3, 4,5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the

Percent Accessible Residues profile of Figure 7; (Lli) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31,32, 33, 34, 35 amino acids of a peptide of Figure 3H in any whole number increment up to 1195 that includes 1,2, 3,4, 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (Lilt) a polynucleotide that encodes a peptide region of at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29,30, 31,32, 33, 34, 35 amino acids of a peptide of Figure 3H in any whole number increment up to 1195 that includes 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21, 22, 23, 24, 25,26, 27,28, 29,30,31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9 (LIV) a polynucleotide that is fully complementary to a polynucleotide of any one of (l)-(LllI). (LV) a peptide that is encoded by any of (I) to (LIV); and (LVI) a composition comprising a polynucleotide of any of (l)-(LIV) or peptide of (LV) together with a pharmaceutical excipient and/or in a human unit dose form. (LVil) a method of using a polynucleotide of any (l)-(LiV) or peptide of (LV) or a composition of (LVI) in a method to modulate a cell expressing 282P1G3, (LVIII) a method of using a polynucleotide of any (l)-(LIV) or peptide of (LV) or a composition of (LVI) in a method to diagnose, prophyiax, prognose, or treat an individual who bears a cell expressing 282P1G3 (LIX) a method of using a polynucleotide of any (l)-(LlV) or peptide of (LV) or a composition of (LVI) in a method to diagnose, prophyiax, prognose, or treat an individual who bears a cell expressing 282P1G3, said ceil from a cancer of a tissue listed in Table I; (LX) a method of using a polynucleotide of any (l)-(LIV) or peptide of (LV) or a composition of (LVi) in a method to diagnose, prophyiax, prognose, or treat a a cancer; (LXI) - a method of using a polynucleotide of any (I)-(LIV) or peptide of (LV) or a composition of (LVi) in a method to diagnose, prophyiax, prognose, or treat a a cancer of a tissue listed in Table l; and, (LXIi) a method of using a polynucleotide of any (I)-(LIV) or peptide of (LV) or a composition of (LVI) in a method to identify or characterize a modulator of a cell expressing 282P1G3.

As used herein, a range is understood to disclose specifically ail whole unit positions thereof.

Typical embodiments of the invention disclosed herein include 282P1G3 polynucleotides that encode specific portions of 282P1G3 mRNA sequences (and those which are compiementary to such sequences) such as those that encode the proteins and/or fragments thereof, for example: . (a) 4, 5,6,7, 8,9,10,11,12,13,14,15,16,17, 18,19,20, 21, 22, 23, 24, 25,30,35,40,45, 50, 55,60, 65,70, 75,80, 85, 90, 95,100,105,110,115,120,125,130,135,140,145,150,155,160,165,170,175,180,185,190,195, 200, 26 225, 250, 275, 300, 325, 350, 375,400, 425,450, 475,500,525, 550, 575,600,625,650,675,700,725,750,775, 800, 825, 850, 875,900, 925, 950,975,1000,1025,1050,1075,1100,1125,1150,1175,1200,1210,1220, and 1224 or more contiguous amino acids of 282P1G3 variant 1; the maximal lengths relevant for other variants are: variant 2,1171 amino acids; variant 3, 893 amino acids, variant 4,1117 amino acids, variant 5,1208 amino acids, variant 6,1183 amoni acids, variant 7,1236 amoni acids, variant 8,1195 amino acids, variant 9,1224 amino acids, variant 10,1224 amino acids, variant 11,1224 amino acids, variant 24,1224 amino acids, and variant 25,1224 amino acids.

For example, representative embodiments of the invention disclosed herein include: polynucleotides and their encoded peptides themselves encoding about amino acid 1 to about amino acid 10 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 10 to about amino acid 20 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 20 to about amino acid 30 of the 282P1G3 protein shown· in Figure 2 or Figure 3, polynucleotides encoding about amino acid 30 to about amino acid 40 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 40 to about amino acid 50 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 50 to about amino acid 60 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 60 to about amino acid 70 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 70 to about amino acid 80 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 80 to about amino acid 90 of the 282P1G3 protein shown in Figure 2 or Figure 3, polynucleotides encoding about amino acid 90 to about amino acid 100 of the 282P1G3 protein shown in Figure 2 or Figure 3, in increments of about 10 amino acids, ending at the carboxyl terminal amino acid set forth in Figure 2 or Figure 3. Accordingly, polynucleotides encoding portions of the amino acid sequence (of about 10 amino acids), of amino acids, 100 through the carboxyl terminal amino acid of the 282P1G3 protein are embodiments of ine invention. Wherein it is understood that each particular amino acid position discloses that position plus or minus five amino acid residues.

Polynucleotides encoding relatively long portions of a 282P1G3 protein are also within the scope of the invention. For example, polynucleotides encoding from about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20, (or 30, or 40 or 50 etc.) of the 282P1G3 protein "or variant” shown in Figure 2 or Figure 3 can be generated by a variety of techniques well known in the art. These polynucleotide fragments can include any portion of the 282P1G3 sequence as shown in Figure 2.

Additional illustrative embodiments of the invention disclosed herein include 282P1G3 polynucleotide fragments encoding one or more of the biological motifs contained within a 282P1G3 protein “or variant” sequence, including one or more of the motif-bearing„subsequences of a 282P1G3 protein “or variant" set forth in Tables Vill-XXl and XXII-XLIX. In another embodiment, typical polynucleotide fragments of the invention encode one or more of the regions of 282P1G3 protein or variant that exhibit homology to a known molecule. In another embodiment of the invention, typical polynucleotide fragments can encode one or more of the 282P1G3 protein or variant N-glycosylation sites, cAMP and cGMP-dependent protein kinase phosphorylation sites, casein kinase II phosphorylation sites or N-myristoylation site and amidation sites.

Note that to determine the starting position of any peptide set forth in Tables Vlll-XXi and Tables XXII to XLIX (collectively HLA Peptide Tables) respective to its parental protein, e.g., variant 1, variant 2, etc., reference is made to three factors: the particular variant, the length of the peptide in an HLA Peptide Table, and the Search Peptides listed in Table VIL Generally, a unique Search Peptide is used to obtain HLA peptides for a particular varianL The position of each Search Peptide relative to its respective parent molecule is listed in Table VII. Accordingly, if a Search Peptide begins at position “X”, one must add the value "X minus 1 ’ to each position in Tables VSil-XXI and Tables XXII-IL to obtain the actual position of the HLA peptides in their parental molecule. For example if a particular Search Peptide begins at position 150 of its parental molecule, one must add 150 -1, i.e., 149 to each HLA peptide amino acid position to calculate the position of that amino acid in the parent molecule. ILA.) Uses of 282P1G3 Polynucleotides 27 11.A.1.) Monitoring of Genetic Abnormalities

The polynucleotides of the preceding paragraphs have a number of different specific uses. The human 282P1G3 gene maps to the chromosomal location set forth in the Example entitled "Chromosomal Mapping of 282P1G3." For example, because the 282P1G3 gene maps to this chromosome, polynucieotides that encode different regions of the 282P1G3 proteins are used to characterize cytogenetic abnormalities of this chromosomal locale, such as abnormalities that are identified as being associated with various cancers. In certain genes, a variety of chromosomal abnormalities including rearrangements have been identified as frequent cytogenetic abnormalities in a number of different cancers (see e.g. Krajinovic etal., Mutat. Res. 382(3-4): 81-83 (1998); Johansson et a!., Blood 86(10): 3905-3914 (1995) and Finger etal., P.NAS. 85(23): 9158-9162 (1988)). Thus, polynucleotides encoding specific regions of the 282P1G3 proteins provide new tools that can be used to delineate, with greater precision than previously possible, cytogenetic abnormalities in the chromosomal region that encodes 282P1G3 that may contribute to the malignant phenotype. In this context, these polynucleotides satisfy a need in the art for expanding the sensitivity of chromosomal screening in order to identify more subtle and less common chromosomal abnormalities (see e.g. Evans etal., Am. J. Obstet. Gynecol 171(4): 1055-1057 (1994)).

Furthermore, as 282P1G3 was shown to be highly expressed in prostate and other cancers, 282P1G3 polynucleotides are used in methods assessing the status of 282P1G3 gene products in normal versus cancerous tissues. Typically, polynucleotides that encode specific regions of the 282P1G3 proteins are used to assess the presence of perturbations (such as deletions, insertions, point mutations, or alterations resulting in a loss of an antigen etc.) in specific regions of the 282P1G3 gene, such as regions containing one or more motifs. Exemplary assays include both RT-PCR assays as well as-singie-strand conformation polymorphism (SSCP) analysis (see, e.g., Marrogi ef al., J. Cutan. Pathol. 26(8): 369-378 (1999), both of which utilize polynucleotides encoding specific regions of a protein to examine these regions within the protein. 1I.A.2.) Antisense Embodiments

Other specifically contemplated nucleic acid related embodiments of the invention disclosed herein are genomic DNA, cDNAs, ribozymes, and antisense molecules, as we!! as nucleic acid molecules based on an alternative backbone, or including alternative bases, whether derived from natural sources or synthesized, and include molecules capable of inhibiting the RNA or protein expression of 282P1G3. For example, antisense molecules can be RNAs or other molecules, including peptide nucleic acids (PNAs) or non-nucleic acid molecules such as phosphorothioate derivatives that specifically bind DNA or RNA in a base pair-dependent manner. A skilled artisan can readily obtain these classes of nucleic acid molecules using the 282P1G3 polynucleotides and polynucleotide sequences disclosed herein.

Antisense technology entails the administration of exogenous oligonucleotides that bind to a target polynucleotide located within the cells. The term "antisense" refers to the fact that such oligonucleotides are complementary to their intracellular targets, e.g., 282P1G3. See for example, Jack Cohen, Oligodeoxynucleotides, Antisense Inhibitors of Gene Expression, CRC Press, 1989; and Synthesis 1:1-5 (1988). The 282P1G3 antisense oligonucleotides of the present invention include derivatives such as S-oligonucleotides (phosphorothioate derivatives or S-oligos, see, Jack Cohen, supra), which exhibit enhanced cancer cel! growth inhibitory action. S-oligos (nucleoside phosphorothioates) are isoelectronic analogs of an oligonucleotide (O-oligo) in which a nonbridging oxygen atom of the phosphate group is replaced by a sulfur atom. The S-oligos of the present invention can be prepared by treatment of the comesponding O-oligos with 3H-1,2-benzodithiol one-1,1-dioxide, which is a sulfur transfer reagent See, e.g., Iyer, R. P. eta!., J. Org. Chem. 55:4693-4698 (1990); and Iyer, R. P. ef al., J. Am. Chem. Soc. 112:1253-1254 (1990). Additional 282P1G3 antisense oligonucleotides of the present invention include morpholino antisense oligonucleotides known in the art (see, e.g., Partridge ef a/., 1996, Antisense & Nucleic Acid Drug Development 6:169-175). 28

The 282P1G3 antisense oligonucleotides of the present invention typically can be RNA or DNA that is complementary to and stably hybridizes with the first 100 5' codons or last 100 3’ codons of a 282P1G3 genomic sequence or the corresponding mRNA Absolute complementarity is not required, although high degrees of complementarity are preferred. Use of an oligonucleotide complementary to this region allows for the selective hybridization to 282P1G3 mRNA and not to mRNA specifying other regulatory subunits of protein kinase. In one embodiment, 282P1G3 antisense oligonucleotides of the present invention are 15 to 30-mer fragments of the antisense DNA molecule that have a sequence that hybridizes to 282P1G3 mRNA. Optionally, 282P1G3 antisense oligonucleotide is a 30-mer oligonucleotide that is complementary to a region in the first 10 5' codons or last 10 3' codons of 282P1G3. Alternatively, the antisense molecules are modified to employ ribozymes in the inhibition of 282P1G3 expression, see, e.g., L A. Couture & D. T. Stinchcomb;

Trends Genet 12: 510-515 ¢1996). I1.A.3.) Primers and Primer Pairs

Further specific embodiments of these nucleotides of the invention include primers and primer pairs, which allow the specific amplification of polynucleotides of the invention or of any specific parts thereof, and probes that selectively or specifically hybridize to nucleic acid molecules of the invention or to any part thereof. Probes can be labeled with a detectable marker, such as, for example, a radioisotope, fluorescent compound, bioiuminescent compound, a chemiluminescent compound, metal chelator or enzyme. Such probes and primers are used to detect the presence of a 282P1G3 polynucleotide in a sample and as a means for detecting a cell expressing a 282P1G3 protein.

Examples of such probes include polypeptides comprising all or part of the human 282P1G3 cDNA sequence shown in Figure 2. Examples of primer pairs capable of specifically amplifying 282P1G3 mRNAs are also described in the Examples. As will be understood by the skilled artisan, a great many different primers and probes can be prepared based on the sequences provided herein and used effectively to amplify and/or detect a 282P1G3 mRNA

The 282P1G3 polynucleotides of the invention are useful for a variety of purposes, including but not limited to their t use as probes and primers for the amplification and/or detection of the 282P1G3 gene(s), mRNA(s), or fragments thereof; as reagents for the diagnosis and/or prognosis of prostate cancer and other cancers; as coding sequences capable of directing the expression of 282P1G3 polypeptides; as tools for modulating or inhibiting the expression of the 282P1G3 gene(s) and/or translation of the 282P1G3 transcript(s); and as therapeutic agents.

The present invention includes the use of any probe as described herein to identify and isolate a 282P1G3 or 282P1G3 related nucleic acid sequence from a naturally occumng source, such as humans or other mammals, as well as the isolated nucleic acid sequence per se, which would comprise all or most of the sequences found in the probe used. II.A.4.) Isolation of 282P1G3-Encoding Nucleic Acid Molecules

The 282P1G3 cDNA sequences described herein enable She isolation of other polynucleotides encoding 282P1G3 gene produces), as well as the isolation of polynucleotides encoding 282P1G3 gene product homologs, alternatively spliced isoforms, allelic variants, and mutant forms of a 282P1G3 gene product as well as polynucleotides that encode analogs of 282P1G3-related proteins. Various molecular cloning methods that can be employed to isolate toil length cDNAs encoding a 282P1G3 gene are well known (see, for example, Sambrook, J. et a/., Molecular Cloning: A Laboratory Manual, 2d edition, Cold Spring Harbor Press, New York, 1989; Current Protocols in Molecular Biology. Ausubel et at., Eds., Wiley and Sons, 1995). For example, lambda phage cloning methodologies can be conveniently employed, using commercially available cloning systems (e.g., Lambda ZAP Express, Stratagene). Phage clones containing 282P1G3 gene cDNAs can be identified by probing with a labeled 282P1G3 cDNA or a fragment thereof. For example, in one embodiment, a 282P1G3 cDNA.(e.g., Figure 2) or a portion thereof can be synthesized and used as a probe to retrieve overlapping and toll-length cDNAs corresponding to a 282P1G3 gene. A 282P1G3 gene itself can be isolated by screening genomic DNA libraries, bacterial artificial chromosome libraries (BACs), yeast artificial chromosome libraries (YACs), and the like, with 282P1G3 DNA probes or primers. 29 II.A.5.) Recombinant Nucleic Acid Molecules and Host-Vector Systems ' The invention also provides recombinant DNA or RNA molecules containing a 282P1G3 polynucleotide, a fragment, analog or homologue thereof, including but not limited to phages, plasmids, phagemids, cosmids, YACs, BACs, as well as various vira! and non-viral vectors well known in the art, and cells transformed or transfected with such recombinant DNA or RNA molecules. Methods for generating such molecules are well known (see, for example, Sambrook ef al., 1989, supra).

The invention further provides a host-vector system comprising a recombinant DNA molecule containing a 282P1G3 polynucleotide, fragment, analog or homologue thereof within a suitable prokaryotic or eukaryotic host cell. Examples of suitable eukaryotic host cells include a yeast ceil, a plant cell, or an animal cell, such as a mammalian cell or an insect cell (e.g., a baculovirus-infectible ceil such as an Sf9 or HighFive cell). Examples of suitable mammalian cells include various prostate cancer cell lines such as DU145 and TsuPrl, other transfectable or transducible prostate cancer ceii lines, primary cells (PrEC), as well as a number of mammalian ceils routinely used for the expression of recombinant proteins (e.g., COS, CHO, 293, 293T cells). More particularly, a polynucleotide comprising the coding sequence of 282P1G3 or a fragment, analog or homolog thereof can be used to generate 282P1G3 proteins or fragments thereof using any number of host-vector systems routinely used and widely known in the art. A wide range of host-vector systems suitable for the expression of 282P1G3 proteins or fragments thereof are available, see for example, Sambrook ef al., 1989, supra; Current Protocols in Moiecuiar Biology, 1995, supra). Preferred vectors for mammalian expression include but are not limited to pcDNA 3.1 myc-His-tag (Invitrogen) and the retroviral vector pSRatkneo (Muller ef al., 1991, MCB 11:1785). Using these expression vectors, 282P1G3 can be expressed in several prostate cancer and non-prostate cell lines, including for example 293, 293T, rat-1, NIH 3T3 and TsuPrl. The host-vector systems of the invention are useful for the production of a 282P1G3 protein or fragment thereof. Such host-vector systems can be employed to study the functional properties of 282P1G3 and 282P1G3 mutations or analogs.

Recombinant human 282P1G3 protein or an analog or homoiog or fragment thereof can be produced by mammalian cells transfected with a construct encoding a 282P1 G3-related nucleotide. For example, 293T cells can be transfected with an expression plasmid encoding 282P1G3 or fragment, analog or homolog thereof, a 282P1G3-related protein is expressed in the 293T ceils, and the recombinant 282P1G3 protein is isolated using standard purification methods (e.g., affinity purification using anti-282P1 G3 antibodies), in another embodiment, a 282P1G3 coding sequence is subcloned into the retroviral vector pSRccMSVtkneo and used to infect various mammalian cell lines, such as NIH 3T3, TsuPrl, 293 and rat-1 in order to establish 282P1G3 expressing ceil fines. Various other expression systems wel! known in the art can also be employed. Expression constructs encoding a leader peptide joined in frame to a 282P1G3 coding sequence can be used for the generation of a secreted form of recombinant 282P1G3 protein.

As discussed herein, redundancy in the genetic code permits variation in 282P1G3 gene sequences. In particular, it is known in the art that specific host species often have specific codon preferences, and thus one can adapt the disclosed sequence as preferred for a desired host. For example, preferred analog codon sequences typically have rare codons (i.e., codons having a usage frequency of less than about 20% in known sequences of the desired host) replaced with higher frequency codons. Codon preferences for a specific species are calculated, for example, by utilizing codon usage tables available on the INTERNET such as at URL dna.affrc.go.jp/~nakamura/codon.htmL

Additional sequence modifications are known to enhance protein expression in a cellular host These include elimination of sequences encoding spurious polyadenylation signals, exon/intron splice site signals, transposon-iike repeats, and/or other such well-characterized sequences that are deleterious to gene expression. The GC content of the sequence is adjusted to levels average for a given cellular host, as calculated by reference td known genes expressed in the host ceii. Where possible, the sequence is modified to avoid predicted hairpin secondary mRNA structures. Other useful modifications include the addition of a translational initiation consensus sequence at the start of the open reading frame, as described in 30

Kozak, Mol. Cell Biol., 9:5073-5080 (1989). Skilled artisans understand that the general rule that eukaryotic ribosomes

initiate translation exclusively at the 5' proximal AUG codon is abrogated only under rare conditions (see, e.g., Kozak PNAS 92(7): 2662-2666, (1995) and Kozak NAR 15(20); 8125-8148 (1987)). HI.)_282P1G3-related Proteins

Another aspect of the present invention provides 282P1G3-related proteins. Specific embodiments of 282P1G3 proteins comprise a polypeptide having all or part of the amino acid sequence of human 282P1G3 as shown in Figure 2 or Figure 3. Alternatively, embodiments of 282P1G3 proteins comprise variant, homolog or analog polypeptides that have alterations in the amino acid sequence of 282P1G3 shown in Figure 2 or Figure 3.

Embodiments of a 282P1G3 polypeptide include: a 282P1G3 polypeptide having a sequence shown in Figure 2, a peptide sequence of a 282P1G3 as shown in Figure 2 wherein T is U; at least 10 contiguous nucleotides of a polypeptide having the sequence as shown in Figure 2; or, at least 10 contiguous peptides of a polypeptide having the sequence as shown in Figure 2 where T is U. For example, embodiments of 282P1G3 peptides comprise, without limitation: (I) a protein comprising, consisting essentially of, or consisting of an amino acid sequence as shown in

Figure 2A-J or Figure 3A-M; (It) a 282P1G3-reIated protein that is at least 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% homologous to an entire amino acid sequence shown in Figure 2A-J or 3A-M; (III) a 282P1G3-related protein that is at ieast 90,91, 92,93, 94,95, 96, 97,98, 99 or 100% identical loan entire amino acid sequence shown in Figure 2A-J or 3A-M; (IV) a protein that comprises at least one peptide set forth in Tables VIII to XLIX, optionally with a proviso that it is not an entire protein of Fgure 2; (V) a protein that comprises at least one peptide set forth in Tables VIll-XXl, collectively, which peptide is also set forth in Tables XXii to XLIX, collectively, optionally with a proviso that it is not an entire protein of Figure 2; (V!) a protein that comprises at least two peptides selected from the peptides set forth in Tables Vlll-XLIX, optionally with a proviso that it is not an entire protein of Figure 2; (Vll) a protein that comprises at least two peptides selected from the peptides set forth in Tables VIII to XLIX collectively, with a proviso that the protein is not a contiguous sequence from an amino acid sequence of Fgure 2; (Vlll) " a protein that comprises at least one peptide selected from the peptides set forth in Tables VIll-XXl; and at least one peptide selected from the peptides set forth in Tables XXII to XLIX, with a proviso that the protein is not a contiguous sequence from an amino acid sequence of Figure 2; (IX) a polypeptide comprising at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20,21, 22, 23, 24, 25, 26, 27,28,29,30,31,32,33,34,35 amino acids of a protein of Figure 3A, 31-3M in any whole number increment up to 1224 respectively that includes at least 1, 2,3,4,5, 6,7,8,9,10,11,12,13,14,15,16,17,18, 19, 20, 21,22,23, 24,25,26,27,28,29,30,31, 32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (X) a polypeptide comprising atleast 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20,21, 22, 23,24, 25,26, 27, 28, 29, 30,31,32,33,34,35 amino acids of a protein of Fgure 3A, 3I-3M, in any whole number increment up to 1224 respectively that includes at ieast at least 1, 2,3, 4,5, 6,7,8,9,10,11,12,13,14,15,16, 31 WU ZUU4/U1O 1 J-t 17,18,19,20, 21,22, 23,24, 25, 26, 27,28, 29, 30,31,32,33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (X!) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25.28.27, 28,29,30,31,32, 33, 34,35 amino acids of a protein of Figure 3A, 31-3M, in any whole number increment up to 1224 respectively that includes at least at least 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16, 17,18,19,20,21,22,23,24, 25,26, 27, 28,29, 30,31,32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XII) a polypeptide comprising at least 5, 8, 7, 8, 9,10,11,12,13, 14,15,16,17,18,19, 20, 21, 22, 23,24, 25,26, 27, 28,29,30, 31, 32,33, 34,35 amino acids of a protein of Figure 3A, 3I-3M, in any whole number increment up to 1224 respectively that includes at least at least 1, 2, 3,4, 5, 6, 7, 8, 9,10, 11,12,13,14,15,16, 17,18,19,20,21,22,23, 24,25,26, 27, 28, 29,30, 31,32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (Xlll) a polypeptide comprising at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23, 24, 25,26, 27,28,29,30,31,32,33,34, amino acids of a protein of Figure 3A, 3I-3M in any whole number increment up to 1224 respectively that includes at least at least 1,2,3,4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23,24, 25,26', 27, 28, 29,30,31, 32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XIV) a polypeptide comprising at least 5,6,7.8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23, 24,' 25.26.27, 28,29, 30,31,32, 33,34,35 amino acids of a protein of Figure 3B, in any whole number increment up to 1171 respectively that includes at least 1, 2,3,4, 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24,25, 26,27,28,29, 30, 31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XV) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11, 12, 13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27,28,29,30,31, 32,33,34,35 amino acids of a protein of Figure 3B, in any whole number increment up to 1171 respectively that includes at least at least 1,2,3,4,5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22,23, 24,25,26,27, 28,29,30,31,32, 33, 34, 35 amino acid position(s) having a valueless than 0.5 in the Hydropathicity profile of Rgure 6; (XVI) a polypeptide comprising at least 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21, 22,23, 24, 25, 26,27,28,29,30,31,32,33, 34,35 amino acids of a protein of Figure 3B, in any whole number increment up to 1171 respectively that includes at least at least 1, 2,3,4,5,6,7, 8.9,10,11,12,13,14,15,16,17,18,19,20, 21, 22,23,24,25,26, 27,28, 29, 30, 31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XVI!) a polypeptide comprising at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21, 22,23,24, 25,26,27,28,29,30,31,32, 33,34,35 amino adds of a protein of'Figure 3B, in any whole number increment up to 1171 respectively that includes at least at least 1,2,3,4,5, 6, 7, 8, 9,10,11,12,13,1.4,15,16,17,18,19,20, 21, 22,23, 24,25, 26, 27,28,29,30,31, 32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Rgure 8; (XVIII) a polypeptide comprising at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, 20,21,22, 23,24, 25, 26,27,28,29,30, 31,32,33,34, amino acids of a protein of Figure 3B in any whole number increment up to 32 1171 respectively that includes at least at least 1, 2, 3,4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16, 17,18,19, 20, 21, 22, 23, 24, 25,26,27, 28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a vaiue greater than 0.5 in the Beta-turn profile of Figure 9; (XIX) a polypeptide comprising at least 5, 6,7,8, 9,10,11,12, '13,14,15,16,17,18,19,20,21,22,23,24,. 25,26, 27,28,29,30,31,32, 33,34,35 amino acids of a protein of Figure 3C, in any whole number increment up to 893 respectively that includes at least 1,2, 3,4,5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25, 26,27,28, 29, 30, 31,32, 33, 34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XX) a polypeptide comprising at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34,35 amino acids of a protein of Figure 3C, in any whole number increment up to 893 respectively that includes at least at least 1,2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24,25,26, 27,28,29, 30, 31,32, 33,34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XXI) a polypeptide comprising at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21,22,23, 24, 25.26, 27, 28,29,30,31,32,33,34,35 amino acids of a protein of Figure 3C, in any whole number increment up to 893 respectively that includes at least at least 1, 2, 3,4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23,24,25,26,. 27,28,29,30,31,32, 33,34,35 amino acid posifion(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXII) a polypeptide comprising at least 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23, 24, 25,26,27,28,29,30,31, -32,33,34,35 amino acids of a protein of Figure 3C, in any whole number increment up to 893 respectively that includes at least at least 1, 2,3,4, 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 21.22.23.24.25.26, 27,28,29,30,31, 32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile ofiFigure 8; (XXIil) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11, 12, 13,14,15,16, 17,18, 19,20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30,31, 32,33,34, amino acids of a protein of Figure 3C in any whole number increment up to 893 respectively that includes at least at least 1,2,3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21, 22,23,24, 25,26,27,28,29,30,31,32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XXIV) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25,26,27,28,29,30,31,32, 33,34,35 amino acids of a protein of Figure 3D, in any whole number increment up to 1117 respectively that includes at least 1, 2, 3,4, 5, 6, 7, 8, 9,10, 11,12,13,14,15,16, 17,18,19, 20, 21, 22, 23,24,25,26,27,28,29,30,31,32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XXV) a polypeptide comprising at least 5,6,7,8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26,27,28,29,30,31,32, 33,34,35 amino acids of a protein of Figure 3D, in any whole number increment up to 1117 respectively that includes at least at least 1,2,3,4, 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20, 21,22, 23, 24, 25,26, 27,28,29,30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; 33 (XXVI) a polypeptide comprising at least 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3D, in any whole number increment up to 1117 respectively that includes at least at least 1, 2,3,4,5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22. 23, 24, 25,26, 27, 28,29,30,31,32,33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXVII) a polypeptide comprising at least 5,6, 7,8, 9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23, 24, 25, 26, 27, 28, 29,30, 31,32, 33,34,35 amino acids of a protein of Figure 3D, in any whole number increment up to 1117 respectively that includes at least at least 1,2, 3,4,5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXVIII) a polypeptide comprising at least 5, 6,7,8,9,10,11,12,13,14( 15,16,17,18,19, 20,21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33,34, amino acids of a protein of Figure 3D in any whole number increment up to 1117 respectively that includes at least at least 1, 2, 3, 4,5, 6, 7, 8, 9,10,11,12,13,14,15,16, 17,18,19, 20, 21, 22,23,24,25,26,27, 28,29,30,31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XXIX) a polypeptide comprising at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 21, 22,23,24, 25, 26,27, 28,29,30, 31,32,33,34,35 amino acids of a protein of Figure 3E, in any whole number increment up to 1208 respectively that includes at least 1, 2,3,4,5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23.24.25.26, 27,28, 29,30,31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophiiicity profile of Figure 5; (XXX) a polypeptide comprising at least 5, 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32,33,34,35 amino acids of a protein of Figure 3E, in any whole number increment up to 1208 respectively that includes at least at least 1, 2, 3, 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24,25,26, 27,28,29,30,31,32,33, 34,35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6;

I (XXXI) a polypeptide comprising at least 5,6,7,8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22,23, 24, 25, 26, 27,28, 29,30,31, 32,33,34,35 amino acids of a protein of Figure 3E, in any whole number increment up to 1208 respectively that includes at least at least 1, 2,3,4,5, 5,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22,23, 24,25,26, 27, 28,29,30,31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXXII) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21,22, 23,24, 25, 26,27, 28, 29,30, 31, 32,33,34,35 amino acids of a protein of Figure 3E, in any whole number increment up to 1208 respectively that includes at least at least 1,2,3,4,5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20, 21, 22,23, 24,25,26, 27,28,29,30, 31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profiie of Figure 8; (XXXIII) a polypeptide comprising at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23, 24, 25.26, 27, 28,29,30,31,32,33,34, amino acids of a protein of Figure 3E in any whole number increment up to 1208 respectively that includes at least at least 1,2, 3,4, 5,6, 7,8, 9,10,11,12,13,14,15,16,17,18,19, 20,21, 22, 23, 24,25,26,27,28, 29,30,31,32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profiie of Figure 9; 34 (XXXiV) a polypeptide comprising at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, in any whole number increment up to 1183 respectively that includes at least 1, 2, 3,4, 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the

Hydrophilicity profile of Figure 5; (XXXV) a polypeptide comprising at least 5,6,7,8, 9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3F, in any whole number increment up to 1183 respectively that includes at least at least 1,2, 3,4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25,26, 27, 28, 29,30, 31, 32, 33, 34, 35 amino acid position(s) having a value less than 0:5 in the Hydropathicity profile of Figure 6; (XXXV!) a polypeptide comprising at least 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23,24, 25, 26, 27, 28, 29,30,31, 32, 33, 34,35 amino acids of a protein of Figure 3F, in any whole number increment up to 1183 respectively that includes af least at least 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 21,22, 23, 24, 25,26,27, 28, 29,30,31,32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XXXVII) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23,24, 25,26, 27, 28, 29,30,31, 32, 33, 34,35 amino acids of a protein of Figure 3F, in any whole number increment up to 1183 respectively that includes at least at least 1, 2,3,4, 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20, 21,22, 23, 24, 2j5,26,27, 28, 29, 30,31,32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XXXViil) a polypeptide comprising at least 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20,21, 22,23,24, 25,26, 27,28, 29,30, 31, 32,33, 34, amino acids of a protein of Figure 3F in any whole number increment up to 1183 respectively that includes at least at least 1,2, 3,4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19,20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XXXiX) a polypeptide comprising atieast 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 23,24, 25,26, 27, 28, 29,30,31,32,33, 34,35 amino acids of a protein of Figure 3G, in any whole number increment up to 1236 respectively that includes at least 1,2,3,4, 5,6,7, 8, 9,10,11,12,13,14,15,16,17,18,19,20,21, 22, 23, 24, 25, 26, 27, 28,29, 30,31, 32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophilicity profile of Figure 5; (XL) a polypeptide comprising at least 5, 6, 7, 8, 9,10,11,12,13,14,15, 16,17,18,19, 20,21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34,35 amino acids of a protein of Figure 3G, in any whole number increment up to 1236 respectively that includes at least at least 1, 2, 3, 4,5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23,24, 25, 26,27,28,29, 30,31,32,33, 34, 35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XLI) a polypeptide comprising atieast 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21, 22, 23, 24, 25,26, 27,28, 29,30, 31, 32,33, 34,35 amino acids of a protein of Figure 3G, in any whole number increment up to 1236 respectively that includes at least at least 1, 2, 3, 4,5, 6,7,8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23,24,25,26,27,28,29,30,31,32,33,34, 35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; 35 (XL1I) a polypeptide comprising at least 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21,22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35 amino acids of a protein of Figure 3G, in any whole number increment up to 1236 respectively that includes at least at least 1,2,3,4, 5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23, 24, 25, 26,27, 28, 29,30, 31,32, 33,34, 35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XLiil) a polypeptide comprising at least 5,6, 7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24, 25,26,27,28, 29, 30,31, 32, 33, 34, amino acids of a protein of Figure 3G in any whole number increment up to 1236 respectively that includes at least at least 1, 2, 3,4, 5, 6,7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 26, 27,28, 29, 30, 31, 32, 33, 34, 35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XLIV) a polypeptide comprising at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23, 24, 25,26,27, 28, 29,30,31,32, 33, 34,35 amino acids of a protein of Figure 3H, in any whole number increment up to 1195 respectively that includes at least 1, 2,3,4, 5, 6, 7, 8, 9,10,11,12, 13,14,15,16,17,18,19,20, 21, 22, 23,24, 25,26, 27,28,29, 30, 31,32, 33,34,35 amino acid position(s) having a value greater than 0.5 in the Hydrophiticity profile of Figure 5; (XLV) a polypeptide comprising at least 5,6, 7, 8, 9,10,11,12,13,14,15,16,17, 18,19, 20, 21,22, 23, 24, 25,26, 27,28, 29,30, 31, 32, 33, 34,35 amino acids of a protein of Figure 3H, in any whole number increment up to 1195 respectively that includes at least at least 1,2,3,4,5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21,22,23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34,35 amino acid position(s) having a value less than 0.5 in the Hydropathicity profile of Figure 6; (XLVI) a polypeptide comprising at least 5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24, 25, 26, 27,28, 29, 30,31,32,33, 34, 35 amino acids of a protein of Figure 3H, in any whole number increment up to 1195 respectively that includes at least at least 1,2,3,4, 5, 6,7,8,9,10,11,12,13,14,15,16,17,18,19,20, 21.22, 23, 24, 25, 28,27, 28, 29, 30, 31,32,33,34,35 amino acid position(s) having a value greater than 0.5 in the Percent Accessible Residues profile of Figure 7; (XLVII) a polypeptide comprising at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34,35 amino acids of a protein of Figure 3H, in any whole number increment up to 1195 respectively that includes at least at least 1,2,3,4,5, 6,7, 8,9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24,25,26, 27, 28, 29, 30, 31,32,33, 34,35 amino acid position(s) having a value greater than 0.5 in the Average Flexibility profile of Figure 8; (XLVII!) a polypeptide comprising at least 5,6,7, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23, 24, 25,26, 27,28, 29,30, 31,32, 33, 34, amino acids of a protein of Figure 3H in any whole number increment up to 1195 respectively that includes at least at least 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21, 22.23, 24,25,26,27,28,29, 30, 31, 32, 33, 34,35 amino acid position(s) having a value greater than 0.5 in the Beta-turn profile of Figure 9; (XLIX) a peptide that occurs at least twice in Tables Vltt-XX! and XXI! to XLIX, collectively; (L) a peptide that occurs at least three times in Tables V!ll-XXl and XX!I to XLIX, collectively; (Li) a peptide that occurs at least four times in Tables VIll-XXl and XXJi to XLIX, collectively; (LH) a peptide that occurs at least five times in Tables VllI-XXl and XXU to XLIX, collectively; 36 (LIII) a peptide that occurs at least once in Tables VIII-XXI, and at least once in tables XXII to XL1X; (LIV) a peptide that occurs at least once in Tables VIII-XXI, and at least twice in tables XXI! to XLIX; (LV) a peptide that occurs at least twice in Tables VIII-XXI, and at least once in tables XXII to XLIX; (LVI) a peptide that occurs at least twice in Tables VIII-XXI, and at least twice in tables XXII to XLIX; (LVII) a peptide which comprises one two, three, four, or five of the following characteristics, or an oligonucleotide encoding such peptide: i) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5, 0.6,0.7,0.8, 0.9, or having a value equal to 1.0, in the Hydrophilicity profile of Figure 5; ii) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or less than 0.5, 0.4,0.3, 0.2, 0.1, or having a value equal to 0.0, in the Hydropathicity profile of Figure 6; iii) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5,0.6,0.7,0.8, 0.9, or having a value equal to 1.0, in the Percent Accessible Residues profile of Figure 7; iv) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5,0.6, 0.7,0.8, 0.9, or having a value equal to 1.0, in the Average Flexibility profile of Figure 8; or, v) a region of at least 5 amino acids of a particular peptide of Figure 3, in any whole number increment up to the full length of that protein in Figure 3, that includes an amino acid position having a value equal to or greater than 0.5,0.6,0.7,0.8, 0.9, or having a value equal to 1.0, in the Beta-turn profile of Figure 9; (LVIII) a composition comprising a peptide of (l)-(LVII) or an antibody or binding region thereof together with a pharmaceutical excipient and/or in a human unit dose form. (LiX) a method of using a peptide of (I)-(LVII), or an antibody or binding region thereof or a composition of (LVIII) in a method to modulate a cell expressing 282P1G3, (LX) a method of using- a peptide of (i)-(LVI!) or an antibody or binding region thereof or a composition of (LVIII) in a method to diagnose, prophyiax, prognose, or treat an individual who bears a cell expressing 282P1G3 (LXI) a method of using a peptide of (l)-(LVII) or an antibody or binding region thereof or a composition (LVII!). in a method to diagnose, prophyiax, prognose, or treat an individual who bears a cell expressing 282P1G3, said cell from a cancer of a tissue listed in Table I; (LXII) a method of using a peptide of (I)-(LVI!) or an antibody or binding region thereof or a composition of (LVlii) in a method to diagnose, prophyiax, prognose, or treat a a cancer; (LXIII) a method of using a peptide of (l)-(LVH) or an antibody or binding region thereof or a composition of (LVIli) in a method to diagnose, prophyiax, prognose, or treat a a cancer of a tissue listed in Table I; and, (LXIV) a method of using a a peptide of (l)-(LVil) or an antibody or binding region thereof or a composition (LVIII) in a method to identify or characterize a modulator of a ceil expressing 282P1G3.

As used herein, a range is understood to specifically disclose all whole unit positions thereof. 37

Typical embodiments of the invention disclosed herein include 282P1G3 polynucleotides that encode specific portions of 282P1G3 mRNA sequences (and those which are complementary to such sequences) such as those that encode the proteins and/or fragments thereof, for example: (a) 4, 5, 6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24,25, 30, 35, 40,45, 50, 55, 60, 65,70, 75, 80, 85, 90, 95,100,105,110,115,120,125,130,135,140,145,150,155,160,165,170,175,180,185,190,195, 200, 225, 250, 275, 300, 325, 350, 375,400,425, 450, 475, 500, 525, 550, 575,600, 625, 650, 675, 700, 725, 750, 775, 800, 825, 850, 875, 900, 925, 950, 975,1000,1025,1050,1075,1100,1125,1150,1175,1200,1210,1215,1220, and 1224 or more contiguous amino acids of 282P1G3 variant 1; the maximal lengths relevant for other variants are: variant 2,1171 amino acids; variant 3/893 amino acids, variant4,1117 amino acids, variants, 1208 amino acids, variant6,1183 amino acids, variant 7,1236 amino acids, variant 8,1195 amino acids, variant 9,1224 amino acids, variant 10,1224 amino acids,, variant 11,1224 amino acids, variant 24,1224 amino acids, and variant 25,1224 amino acids. in general, naturally occurring allelic variants of human 282P1G3 share a high degree of structural identity and homology (e.g., 90% or more homology). Typically, allelic variants of a 282P1G3 protein contain conservative amino acid substitutions within the 282P1G3 sequences described herein or contain a substitution of an amino acid from a corresponding position in a homologue of 282P1G3. One class of 282P1G3 allelic variants are proteins that share a high degree of homology with at least a small region of a particular 282P1G3 amino acid sequence, but further contain a radical departure from the sequence, such as a non-conservative substitution, truncation, insertion or frame shift in comparisons of protein sequences, the terms, similarity, identity, and homology each have a distinct meaning as appreciated in the field of genetics. Moreover, orthology and paralogy can be important concepts describing the relationship of members of a given protein family in one organism to the members of the same family in other organisms.

Amino acid abbreviations are provided in Table II. Conservative amino acid substitutions can frequently be made In a protein without altering either the conformation or the function of the protein. Proteins of the invention can comprise 1,2, 3, 4,5, 6,7, 8,9,10,11,12,13,14,15 conservative substitutions. Such changes include substituting any of isoleucine (1), valine (V), and leucine (L) for any other of these hydrophobic amino acids; aspartic acid (D) for glutamic acid (E) and vice versa; glutamine (Q) for asparagine (N) and vice versa; and serine (S) for threonine (T) and vice versa. Other substitutions can also be considered conservative, depending on the environment of the particular amino acid and its role in the three-dimensional structure of the protein. For example, glycine (G) and alanine (A) can frequently be interchangeable, as can alanine (A) and valine (V). Methionine (M), which is relatively hydrophobic, can frequently be interchanged with ieucine and isoleucine, and sometimes with valine. Lysine (K) and arginine (R) are frequently interchangeable in locations in which the significant feature of the amino acid residue is its charge and the differing pK's of these two amino acid residues are not significanL Still other changes can be considered "conservative” in particular environments (see, e.g. Table 111 herein; pages 13-15 “Biochemistry" 2nd ED. Lubert Stryer ed (Stanford University); Henikoff ef a/., PNAS1992 Vo! 89 10915-10919; Lei et al., J Biol Chem 1995 May 19; 270(20):11882-6).

Embodiments of the invention disclosed herein include a wide variety of art-accepted variants or analogs of 282P1G3 proteins such as polypeptides having amino acid insertions, deletions and substitutions. 282P1G3 variants can be made using methods known in the art such as site-directed mutagenesis, alanine scanning, and PCR mutagenesis. Site-directed mutagenesis (Carter ef at., Nucl.Acids Res., 13.4331 (1986); Zolteref al., Nucl. Acids Res., 10:6487 (1987)), cassette mutagenesis (Wells et al., Gene, 34:315 (1985)), restriction selection mutagenesis (Wells ef a!., Philos. Trans. R. Soc. London SerA, 317:415 (1986)) or other known techniques can be performed on the cloned DNA to produce the 282P1G3 variant DNA.

Scanning amino acid analysis can also be employed to identify one or more amino acids along a contiguous sequence.that is involved in a specific biological activity such as a protein-protein interaction. Among the prefemed scanning 38 amino acids are relatively small, neutral amino acids. Such amino acids include alanine, glycine, serine, and cysteine.

Alanine is typically a preferred scanning amino acid among this group because it eliminates the side-chain beyond the beta-carbon and is less likely to alter the main-chain conformation of the variant Alanine is also typically prefened because it is the most common amino acid. Further, it is frequently found in both buried and exposed positions (Creighton, The Proteins, (W.H. Freeman & Co., N.Y.); Chothia, J. Mol. Biol., 150:1 (1976)). If alanine substitution does not yield adequate amounts of variant, an isosteric amino acid can be used.

As defined herein, 282P1G3 variants, analogs or homologs, have the distinguishing attribute of having at least one epitope that is “cross reactive” with a 282P1G3 protein having an amino acid sequence of Figure 3. As used in this sentence, “cross reactive" means that an antibody or T cell that specifically binds to a 282P1G3 variant also specifically binds to a 282P1G3 protein having an amino acid sequence set forth in Figure 3. A polypeptide ceases to be a variant of a protein shown in Figure 3, when it no longer contains any epitope capable of being recognized by an antibody or T cell that specifically binds to the starting 282P1G3 protein. Those skilled in the art understand that antibodies that recognize proteins bind to epitopes of varying size, and a grouping of the order of about four or five amino acids, contiguous or not, is regarded as a typical number of amino acids in a minimal epitope. See, e.g., Nair et a!., J, Immunol 2000165(12): 6949-6955; Hebbes et at., Mol Immunol (1989) 26(9):865-73; Schwartz ef a/., J Immunol (1985) 135(4):2598-608.

Other classes of 282P1 G3-related protein variants share 70%, 75%, 80%, 85% or 90% or more similarity with an amino acid sequence of Figure 3, or a fragment thereof. Another specific class of 282P1G3 protein variants or analogs comprises one or more of the 282P1G3 biological motifs described herein or presently known in the art. Thus, encompassed by the present invention are analogs of 282P1G3 fragments (nucleic or amino acid) that have altered functional (e.g. immunogenic) properties relative to the starting fragment It is to be appreciated that motifs now or which become part of the art are to be applied to the nucleic or amino acid sequences of Figure 2 or Figure 3.

As discussed herein, embodiments of the claimed invention include polypeptides containing less than the full amino acid sequence of a 282P1G3 protein shown in Figure 2 or Figure 3. For example, representative embodiments of the invention comprise peptides/proteins having any 4, 5, 6, 7,8, 9,10, 11, 12,13,14,15 or more contiguous amino acids of a 282P1G3 protein shown in Figure 2 or Figure 3.

Moreover, representative embodiments of the invention disclosed herein include polypeptides consisting of about amino acid 1 to about amino acid 10 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 10 to about amino acid 20 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 20 to about amino acid 30 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 30 to about amino acid 40 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 40 to about amino acid 50 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 50 to about amino acid 60 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 60 to about amino acid 70 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 70 to about amino acid 80 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 80 to about amino acid 90 of a 282P1G3 protein shown in Figure 2 or Figure 3, polypeptides consisting of about amino acid 90 to about amino acid 100 of a 282P1G3 protein shown in Figure 2 or Figure 3, etc. throughout the entirety of a 282P1G3 amino acid sequence. Moreover, polypeptides consisting of about amino acid 1 (or 20 or 30 or 40 etc.) to about amino acid 20, (or 130, or 140 or 150 etc.) of a 282P1G3 protein shown in Figure 2 or Figure 3 are embodiments of the invention. It is to be appreciated that the starting and stopping positions in this paragraph refer to the specified position as well as that position plus or minus 5 residues. 282P1G3-related proteins are generated using standard peptide synthesis technology or using chemical cleavage methods well known in the art. Alternatively, recombinant methods can be used to generate nucleic add molecules that encode a 39 282P1 G3-related protein, in one embodiment, nucleic acid molecules provide a means to generate defined fragments of a 282P1G3 protein (or variants, homologs or analogs thereof). HLA.) Motif-bearing Protein Embodiments

Additional illustrative embodiments of the invention disclosed herein include 282P1G3 polypeptides comprising the amino acid residues of one or more of the biological motifs contained within a 282P1G3 polypeptide sequence set forth in Figure 2 or Figure 3. Various motifs are known in the art, and a protein can be evaluated for the presence of such motifs by a number of publicly available Internet sites (see, e.g., URL addresses: pfam.wustl.edu/; searchiauncher.bcm.tmc.edu/seq-search/struc-predicLhfrnl; psortims.u-tokyo.ac.jp/; cbs.dtu.dk/; ebi.ac.uk/interpro/scan.html; expasy.ch/tools/scnpsit1.html; Epimatrix™ and Epimer™, Brown University, brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html; and BIMAS, bimas.dcrt.nih.gov/.).

Motif bearing subsequences of all 282P1G3 variant proteins are set forth and identified in Tables VllI-XXl and XXll- XLIX.

Table V sets forth several frequently occurring motifs based on pfam searches (see URL address pfam.wustl.edu/). The columns of Table V list (1) motif name abbreviation, (2) percent identity found amongst the different member of the motif family, (3) motif name or description and (4) most common function; location information is included if the motif is relevant for location.

Polypeptides comprising one or more of the 282P1G3 motifs discussed above are useful in elucidating the specific characteristics of a malignant phenotype in view of the observation that the 282P1G3 motifs discussed above are associated with growth dysregulation and because 282P1G3 is overexpressed in certain cancers (See, e.g., Table I). Casein kinase II, cAMP and camp-dependent protein kinase, and Protein Kinase C, for example, are enzymes known to be associated with the development of the malignant phenotype (see e.g. Chen et a/., Lab Invest., 78(2): 165-174 (1998); Gaiddon et a/., Endocrinology 136(10): 4331-4338 (1995); Hal! et at., Nucleic Acids Research 24(6): 1119-1126 (1996); Peterziel et at., Oncogene 18(46): 6322-6329 (1999) and O'Brian, Oncol. Rep. 5(2): 305-309 (1998)). Moreover, both giycosyiation and myristoylation are protein modifications also associated with cancer and cancer progression (see e.g. Dennis et al., Biochem. Biophys. Acta 1473(1):21-34 (1999); Raju et al., Exp. Cell Res. 235(1): 145-154 (1997)). Amidation is another protein modification also associated with cancer and cancer prdgression (see e.g. Treston et at., J. Natl. Cancer Inst. Monogr. (13): 169-175 (1992)).

In another embodiment, proteins of the invention comprise one or more of the immunoreactive epitopes identified in accordance with art-accepted methods, such as the peptides set forth in Tables VIII-XXI and XXll-XLIX. CTL epitopes can be determined using specific algorithms to identify peptides within a 282P1G3 protein that are capable of optimally binding to specified HLA alleles (e.g., Table IV; Epimatrix™ and Epimer™, Brown University, URL brown.edu/Research/TB-HlV_Lab/epimatrixfepimatrix.html; and BIMAS, URL bimas.dcrtnih.gov/.) Moreover, processes for identifying peptides that have sufficient binding affinity for HLA moiecuies and which are correlated with being immunogenic epitopes, are well known in the art, and are carried out without undue experimentation. In addition, processes for identifying peptides that are immunogenic epitopes, are well known in the art, and are carried out without undue experimentation either in vitro or in vivo.

Also known in the art are principles for creating analogs of such epitopes in order to modulate immunogenicity. For example, one begins with an epitope that bears a CTL or HTL motif (see, e.g., the HLA Class I and HLA Class I! motifs/supermotifs of Table IV). The epitope is anaioged by substituting out an amino acid at one of the specified positions, and replacing it with another amino add specified for that position. For example, on the basis of residues defined in Table IV, one can substitute out a deleterious residue in favor of any other residue, such as a preferred residue; substitute a less-preferred residue with a prefemed residue; or substitute an originally-occurring preferred residue with another preferred residue. Substitutions can occur at primary anchor positions or at other positions in a peptide; see, e.g., Table IV. 40 A variety of references reflect toe art regarding the identification and generation of epitopes in a protein of interest as well as analogs thereof. See, for example, WO 97/33602 to Chesnut ef a/.; Sette, Immunogenetics 1999 50(3-4): 201-212; Sette ef a/, J. Immunol. 2001 166(2): 1389-1397; Sidney ef a/., Hum. Immunol. 1997 58(1): 12-20; Kondo ef al., Immunogenetics 1997 45(4): 249-258; Sidney etal., J. Immunol. 1996 157(8): 3480-90; and Falk ef al., Nature 351: 290-6 (1991); Hunt etal., Science 255:1261-3 (1992); Parker ef al., J. Immunol. 149:3580-7 (1992); Parker etal., J. Immunol. 152:163-75 (1994)); Kast ef a/., 1994 152(8): 3904-12; Borras-Cuesta etal., Hum. Immunol. 2000 61(3): 266-278; Alexander et a/., J. Immunol. 2000 164(3); 164(3): 1625-1633; Alexander ef al., PMID: 7895164, U1:95202582; O’Sullivan ef al., J. Immunol. 1991 147(8): 2663-2669; Alexander etal., Immunity 1994 1(9): 751-761 and Alexander ef al., Immunol. Res. 1998 18(2): 79-92.

Related embodiments of the invention include polypeptides comprising combinations of the different motifs set forth in Table VI, and/or, one or more of the predicted CTL epitopes of Tables Vlil-XXI and XXII-XLiX, and/or, one or more of the predicted HTL epitopes of Tables XLVI-XLIX, and/or, one or more of the T cell binding motifs known in the art Preferred, embodiments contain no insertions, deletions or substitutions either within the motifs or within the intervening sequences of the polypeptides. In addition, embodiments which include a number of either N-terminal and/or C-termina! amino acid residues on either side of these motifs may be desirable (to, for example, include a greater portion of the polypeptide architecture in which the motif is located). Typically, the number of N-terminai and/or C-termina! amino acid residues on either side of a motif is between about 1 to about 100 amino acid residues, preferably 5 to about 50 amino acid residues. 282P1G3-related proteins are embodied in many forms, preferably in isolated form. A purified 282P1G3 protein molecule will be substantially free of other proteins or molecules that impair the binding of 282P1G3 to antibody, T cell or other ligand. The nature and degree of isolation and purification will depend on the intended use. Embodiments of a 282P1G3-related proteins include purified 282P1G3-related proteins and functional, soluble 282P1 G3-reiated proteins. In one embodiment, a functional, soluble 282P1G3 protein or fragment thereof retains the ability to be bound by antibody, T cell or other ligand.

The invention also provides 282P1G3 proteins comprising biologically active fragments of a 282P1G3 amino acid sequence shown in Figure 2 or Figure 3., Such proteins exhibit properties of the starting 282P1G3 protein, such as the ability to elicit the generation of antibodies that specifically bind an epitope associated with the starting 282P1G3 protein; to be bound by such antibodies; to elicit the activation of HTL or CTL; and/or, to be recognized by HTL or CTL that also specifically bind to the starting protein. 282P1G3-related polypeptides that contain particularly interesting structures can be predicted and/or identified using various analytical techniques wel! known in the art, including, for example, the methods of Chou-Fasman, Gamier-Robson, Kyte-Doolittle, Eisenberg, Karplus-Schultz or Jameson-Wolf analysis, or based on immunogenicity. Fragments that contain such structures are particuiariy useful in generating subunit-specific anti-282P1 G3 antibodies or T cells or in identifying cellular factors that bind to 282P1G3. For example, hydrophiiicity profiles can be generated, and immunogenic peptide fragments identified, using the method of Hopp, T.P. and Woods, K.R., 1981, Proc. Nati. Acad. Sci. U.S A 78:3824-3828. Hydropathicity profiles can be generated, and immunogenic peptide fragments identified, using the method of Kyte, J. and Doolittle, R.F., 1982, J. Mol. Biol. 157:105-132. Percent (%) Accessible Residues profiles can be generated, and immunogenic peptide fragments identified, using the method of Janin J., 1979, Nature 277:491-492. Average Flexibility profiles can be generated, and immunogenic peptide fragments identified, using the method of Bhaskaran R., Ponnuswamy P.K., 1988, int. J. PepL Protein Res. 32:242-255. Beta-turn profiles can be generated, and immunogenic peptide fragments identified, using the method of Deleage, G., Roux B., 1987, Protein Engineering 1:289-294. CTL epitopes can be determined using specific algorithms to identify peptides within a 282P1G3 protein that are capable of optimally binding to specified HLA alleles (e.g., by using the SYFPEITHI site at World Wide Web URL syfpeithi.bmi- 41 .heidelberg.com/; the listings in Table IV(A)-(E); Epimatrix™ and Epimer™, Brown University, URL (brown.edu/ResearcWT8-HIV_Labfepimairix/epimatrixhtml); and BIMAS, URL bimas.dcrt.nih.gov/). Illustrating this, peptide epitopes from 282P1G3 that are presented in the context of human MHC Class I molecules, e.g., HLA-A1, A2, A3, A11, A24, B7 and B35 were predicted (see, e.g., Tables Vill-XXl, XXII-XLIX). Specifically, the complete amino acid sequence of the 282P1G3 protein and relevant portions of other variants, i.e., for HLA Class I predictions 9 flanking residues on either side of a point mutation or exon juction, and for HLA Class 11 predictions 14 flanking residues on either side of a point mutation or exon junction corresponding to that variant, were entered into the HLA Peptide Motif Search algorithm found in the Bioinformatics and Molecular Analysis Section (BIMAS) web site listed above; in addition to the site SYFPEITHI, at URL syfpeithi.bmi-heidelberg.com/.

The HLA peptide motif search algorithm was developed by Dr. Ken Parker based on binding of specific peptide sequences in the groove of HLA Class I molecules, in particular HLA-A2 (see, e.g., Falk et al„ Nature 351: 290-6 (1991);

Hunt ef a/., Science 255:1261-3 (1992); Parker et a!., J. Immunol. 149:3580-7 (1992); Parker et al., J. Immunol. 152:163-75 (1994)). This algorithm allows location and ranking of 8-mer, 9-mer, and 10-mer peptides from a complete protein sequence for predicted binding to HLA-A2 as well as numerous other HLA Class I molecules. Many HLA class I binding peptides are 8-, 9-, 10 or 11-mers. For example, for Class IHLA-A2, the epitopes preferably contain a leucine (L) or methionine (M) at position 2 and a valine (V) or leucine (L) at the C-terminus (see, e.g., Parker et a!., J. Immunol. 149:3580-7 (1992)).

Selected results of 282P1G3 predicted binding peptides are shown in Tables Vill-XXl and XXII-XLIX herein. In Tables VIII-XXI and XXII-XLVII, selected candidates, 9-mers and 10-mers, for each family member are shown along with their location, the amino acid sequence of each specific peptide, and an estimated binding score, in Tables XLVI-XLIX, selected candidates, 15-mers, for each family member are shown along with their location, the amino acid sequence of each specific peptide, and an estimated binding score. The binding score corresponds to the estimated halftime of dissociation of complexes containing the peptide at 37°C at pH 6.5. Peptides with the highest binding score are predicted to be the most tightly bound to HLA Class I on the cell surface for the greatest period of time and thus represent the best immunogenic targets for T-cell recognition.

Actual binding of peptides to an HLA allele can be evaluated by stabilization of HLA expression on the antigenprocessing defective cell line T2 (see, e.g., Xue et al., Prostate 30:73-8 (1997) and Peshwa et al., Prostate 36:129-38 (1998)). immunogenicity of specific peptides can be evaluated in vitro by stimulation of CD8+ cytotoxic T lymphocytes (CTL) in the presence of antigen presenting cells such as dendritic cells.

It is to be appreciated that every epitope predicted by the BIMAS site, Epimer™ and Epimatrix™ sites, or specified by the HLA class I or class 11 motifs available in the art or which become part of the art such as set forth in Table IV (or determined using World Wide Web site URL sytpeithi.bmi-heidelberg.com/, or BIMAS, bimas.dcrtnih.gov/) are to be “applied” io a 282P1G3 protein in accordance with the invention. As used in this context “applied" means that a 282P1G3 protein is evaluated, e.g., visually or by computer-based patterns finding methods, as appreciated by those of skill in the relevant art Every subsequence of a 282P1G3 protein of 3,9,10, or 11 amino acid residues that bears an HLA Class I motif, or a subsequence of 9 or more amino acid residues that bear an HLA Class II motif are within the scope of the invention. lll.B.) Expression of 282P1G3-reiated Proteins

In an embodiment described in the examples that follow, 282P1G3 can be conveniently expressed in cells (such as 293T cells) transfected with a commercially available expression vector such as a CMV-driven expression vector encoding 282P1G3 with a C-terminal 6XHis and MYC tag (pcDNA3.1/mycHlS, Invitrogen orTagS, GenHunter Corporation, Nashville TN). The Tag5 vector provides an SgGK secretion signal that can be used to facilitate the production of a secreted 282P1G3 42 protein in transfected cells. The secreted HiS-tagged 282P1G3 in the culture media can be purified, e.g., using a nickel column using standard techniques. ill.C.) Modifications of 282P1G3-related Proteins

Modifications of 282P1 G3-reiated proteins such as covalent modifications are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a 282P1G3 polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C- terminal residues of a 282P1G3 protein. Another type of covalent modification of a 282P1G3 polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of a protein of the invention. Another type of covalent modification of 282P1G3 comprises linking a 282P1G3 polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkyienes, in the manner set forth in U.S. Patent Nos. 4,640,835; 4496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337.

The 282P1 G3-reiated proteins of the present invention can also be modified to form a chimeric molecule comprising 282P1G3 fused to another, heterologous polypeptide or amino acid sequence. Such a chimeric molecule can be synthesized chemically or recombinanily. A chimeric molecule can have a protein of the invention fused to another tumor-associated antigen or fragment thereof. Alternatively, a protein in accordance with the invention can comprise a fusion of fragments of a 282P1G3 sequence (amino or nucleic acid) such that a molecule is created that is not, through its length, directly homologous to the amino or nucleic acid sequences shown in Figure 2 or Figure 3. Such a chimeric molecule can comprise multiples of the same subsequence of 282P1G3. A chimeric molecule can comprise a fusion of a 282P1 G3-related protein with a polyhistidine epitope fag, which provides an epitope to which immobilized nickel can selectively bind, with cytokines or with growth factors. The epitope tag is generally placed at the amino- or carboxyl- terminus of a 282P1G3 protein, in an alternative embodiment, the chimeric molecule can comprise a fusion of a 282P1G3-related protein with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule (also referred to as. an "immunoadhesin"), such a fusion could be to the Fc region of an IgG molecule. The ig fusions preferably include the substitution of a soluble (transmembrane domain deleted or inactivated) form of a 282P1G3 polypeptide in place of at least one variable region within an ig molecule. In a preferred embodiment, the immunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge, CHI, CH2 and CH3 regions of an IgGl molecule. For the production of immunoglobulin fusions see, e.g., U.S. Patent No. 5,428,130 issued June 27,1995. i lil.D.) Uses of 282P1 G3-reiated Proteins

The proteins of the invention have a number of different specific uses. As 282P1G3 is highly expressed in prostate and other cancers, 282P1 G3-related proteins are used in methods that assess the status of 282P1G3 gene products in normal versus cancerous tissues, thereby elucidating the malignant phenotype. Typically, polypeptides from specific regions of a 282P1G3 protein are used to assess the presence of perturbations (such as deletions, insertions, point mutations etc.) in those regions (such as regions containing one or more motifs). Exemplary assays utiiize antibodies or T cells targeting 282P1 G3-related proteins comprising the amino acid residues of one or more of the biological motifs contained within a 282P1G3 polypeptide sequence in order to evaluate the characteristics of this region in normal versus cancerous tissues or to elicit an immune response to the epitope. Alternatively, 282P1G3-related proteins that contain the amino acid residues of one or more of the biological motifs in a 282P1G3 protein are used to screen for factors that interact with that region of 282P1G3. 282P1G3 protein fragments/subsequences are particuiariy useful in generating and characterizing domain-specific antibodies (e.g., antibodies recognizing an extracellular or intracellular epitope of a 282P1G3 protein), for identifying agents or 43 cellular factors that bind to 282P1G3 or a particular structural domain thereof, and in various therapeutic and diagnostic contexts, including but not limited to diagnostic assays, cancer vaccines and methods of preparing such vaccines.

Proteins encoded by the 282P1G3 genes, or by analogs, homologs or fragments thereof, have a variety of uses, including but not limited to generating antibodies and in methods for identifying ligands and other agents and cellular constituents that bind to a 282P1G3 gene product Antibodies raised against a 282P1G3 protein or fragment thereof are useful in diagnostic and prognostic assays, and imaging methodologies in the management of human cancers characterized by expression of 282P1G3 protein, such as those listed in Table I. Such antibodies can be expressed intraceliularly and used in methods of treating patients with such cancers. 282P1 G3-reiated nucleic acids or proteins are also used in generating HTL or CTL responses.

Various immunological assays useful for the detection of 282P1G3 proteins are used, including but not limited to various types of radioimmunoassays, enzyme-linked immunosorbent assays (ELISA), enzyme-linked immunoftuorescent assays (ELIFA), immunocytochemical methods, and the like. Antibodies can be labeled and used as immunological imaging reagents capable of detecting 282P1 G3-expressing cells (e.g., in radioscintigraphic imaging methods). 282P1G3 proteins are also particularly useful in generating cancer vaccines, as further described herein. IV.) 282P1G3 Antibodies .Another aspect of the invention provides antibodies that bind to 282P1G3-related proteins. Preferred antibodies specifically bind to a 282P1G3-related protein and do not bind (or bind weakly) to peptides or proteins that are not 282P1G3-related proteins under physiological conditions. In this context, examples of physiological conditions include: 1) phosphate buffered saline; 2) Tris-buffered saline containing 25mM Tris and 150 mM NaCl; or normal saline (0.9% NaCl); 4) animal serum such as human serum; or, 5) a combination of any of 1) through 4); these reactions preferably taking place at pH 7.5, alternatively in a range of pH 7.0 to 8.0, or alternatively in a range of pH 6.5 to 8.5; also, these reactions faking place at a temperature between 4°C to 37°C. For example, antibodies that bind 282P1G3 can bind 282P1 G3-related proteins such as the homologs or analogs thereof. 282P1G3 antibodies of the invention are particularly useful in cancer (see, e.g., Table I) diagnostic and prognostic assays, and imaging methodologies. Similarly, such antibodies are useful in the treatment, diagnosis, and/or prognosis of other cancers, to the extent 282P1G3 is also expressed or overexpressed in these other cancers. Moreover, intraceliularly expressed antibodies (e-,α. single chain antibodies) are therapeutically useful in treating cancers in which the expression of 282P1G3 is involved, such as advanced or metastatic prostate cancers.

The invention also provides various immunological assays useful for the detection and quantification of 282P1G3 and mutant 282P1 G3-relafed proteins. Such assays can comprise one or more 282P1G3 antibodies capable of recognizing and binding a 282P1G3-related protein, as appropriate. These assays are performed within various immunological assay formats well known in the art, including but not limited to various types of radioimmunoassays, enzyme-linked immunosorbent assays (ELISA), enzyme-linked immunofluorescent assays (ELIFA), and the like.

Immunological non-antibody assays of the invention aiso comprise T cell immunogenicity assays (inhibitory or stimulatory) as well as major histocompatibility complex (MHC) binding assays.

In addition, immunological imaging methods capable of detecting prostate cancer and other cancers expressing 282P1G3 are aiso provided by the invention, including but not limited to radioscintigraphic imaging methods using labeled 282P1G3 antibodies. Such assays are clinically useful in the detection, monitoring,, and prognosis of 282P1G3 expressing cancers such as prostate cancer. 282P1G3 antibodies are also used in methods for purifying a 282P1G3-related protein and for isolating 282P1G3 homologues and related molecules. For example, a method of purifying a 282P1 G3-re!ated protein comprises incubating a 44 282P1G3 antibody, which has been coupled to a solid matrix, wiih a lysate or other solution containing a 282P1 G3-related protein under conditions that permit the 282P1G3 antibody to bind to the 282P1G3-related protein; washing the solid matrix to eliminate impurities; and eluting the 282P1G3-related protein from the coupled antibody. Other uses of 282P1G3 antibodies in accordance with the invention include generating anti-idiotypic antibodies that mimic a 282P1G3 protein.

Various methods for the preparation of antibodies are well known in the art. For example, antibodies can be prepared by immunizing a suitable mammalian host using a 282P1 G3-related protein, peptide, or fragment, in isolated or immunoconjugated form (Antibodies: A Laboratory Manual, CSH Press, Eds., Harlow, and Lane (1988); Harlow, Antibodies, Cold Spring Harbor Press, NY (1989)). In addition, fusion proteins of 282P1G3 can also be used, such as a 282P1G3 GST-tusion protein. In a particular embodiment, a GST fusion protein comprising all or most of the amino acid sequence of Figure 2 or Figure 3 is produced, then used as an immunogen to generate appropriate antibodies. In another embodiment, a 282P1G3-related protein is synthesized and used as an immunogen.

In addition, naked DNA immunization techniques known in the art are used (with or without purified 282P1 G3-re!ated protein or 282P1G3 expressing cells) to generate an immune response to the encoded immunogen (for review, see Donnelly ef a/., 1997, Ann. Rev. Immunol. 15:617-648).

The amino acid sequence of a 282P1G3 protein as shown in Figure 2 or Figure 3 can be analyzed to select specific regions of the 282P1G3 protein for generating antibodies. For example, hydrophobicity and hydrophilicity analyses of a 282P1G3 amino acid sequence are used to identify hydrophiiic regions in the 282P1G3 structure. Regions of a 282P1G3 protein that show immunogenic structure, as well as other regions and domains, can readily be identified using various other methods known in the art, such as Chou-Fasman, Garnier-Robson, Kyte-Doolitfle, Eisenberg, Karplus-Schultz or Jameson-Wolf analysis. Hydrophilicity profiles can be generated using the method of Hopp, T.P. and Woods, K.R., 1981, Proc. Natl. Acad. Sci, U.S.A. 78:3824-3828. Hydropathicity profiles can be generated using the method of Kyte, J. and Doolittle, R.F., 1982, J. Mol. Biol. 157:1 OS-132, Percent (%) Accessible Residues profiles can be generated using the method of Janin J., 1979, Nature 277:491-492. Average Flexibility profiles can be generated using the method of Bhaskaran R., Ponnuswamy P.K., 1988, InL J. PepL Protein Res. 32:242-255. Beta-turn profiles can be generated using the method of Deleage, G., Roux B., 1987, Protein Engineering 1:289-294. Thus, each region identified by any of these programs or methods is within the scope of the present invention. Methods for the generation of 282P1G3 antibodies are further illustrated by way of the examples provided herein. Methods for preparing a protein or polypeptide for use as an immunogen are well known in the art. Also well known in the art are methods for preparing immunogenic conjugates of a protein with a carrier, such as BSA, KLH or other carrier protein. In some circumstances, direct conjugation using, for example, carbodiimide reagents are used; in other instances linking reagents such as. those supplied by Pierce Chemical Co., Rockford, IL, are effective. Administration of a 282P1G3 immunogen is often conducted by injection over a suitable time period and with use of a suitable adjuvant, as is understood in the art During the immunization schedule, titers of antibodies can be taken to determine adequacy of antibody formation. 282P1G3 monoclonal antibodies can be produced by various means well known in the art For example, immortalized cell lines that secrete a desired monoclonal antibody are prepared using the standard hybridoma technology of Kohler and Milstein or modifications that immortalize antibody-producing B cells, as is generally known. Immortalized cell tines that secrete the desired antibodies are screened by immunoassay in which the antigen is a 282P1G3-related protein. When the appropriate immortalized cell culture is identified, the cells can be expanded and antibodies produced either from in vitro cultures or from ascites fluid.

The antibodies or fragments of the invention can also be produced, by recombinant means. Regions that bind specifically to the desired regions of a 282P1G3 protein can also be produced in the context of chimeric or compiementarity-determining region (CDR) grafted antibodies of multiple species origin. Humanized or human 282P1G3 antibodies can also be produced, and are preferred for use in therapeutic contexts. Methods for humanizing murine and other non-human antibodies, by 45 substituting one or more of the non-human antibody CDRs for corresponding human antibody sequences, are well known (see for - example, Jones et at., 1986, Nature 321:522-525; Riechmann eta/., 1988, Nature 332:323-327; Verhoeyen et at., 1988, Science 239:1534-1536). See also, Carter et ai, 1993, Proc. Nat!. Acad. Sci. USA 89:4285 and Sims et at., 1993, J. Immunol. 151: 2296.

Methods for producing fully human monoclonal antibodies include phage display and transgenic methods (for review, see Vaughan et at., 1998, Nature Biotechnology 16:535-539). Fully human 282P1G3 monoclonal antibodies can be generated using cloning technologies employing large human ig gene combinatorial libraries (i.e., phage display) (Griffiths and Hoogenboom, Building an in vitro immune system: human antibodies from phage display libraries. In: Protein Engineering of Antibody Molecules for Prophylactic and Therapeutic Applications in Man, Clark, M. (Ed.), Nottingham Academic, pp 45-64 (1993); Burton and Barbas, Human Antibodies from combinatorial libraries. Id., pp 65-82). Fully human 282P1G3 monoclonal antibodies can also be produced using transgenic mice engineered to contain human immunoglobulin gene loci as described in PCT Patent Application WO98/24893, Kucherlapati and Jakobovits et at., published December 3,1997 (see also, Jakobovits, 1998, Exp. Opin. Invest Drugs 7(4): 607-614;' U.S. patents 6,162,963 issued 19 December 2000; 6,150,584 issued 12 November 2000; and, 6,114598 issued 5 September 2000). This method avoids the in vitro manipulation required with phage display technology and efficiently produces high affinity authentic human antibodies.

Reactivity of 282P1G3 antibodies with a 282P1G3-reiated protein can be established by a number of well known means, including Western blot, immunoprecipitation, ELISA, and FACS analyses using, as appropriate,' 282P1G3-related proteins, 282P1 G3-expressing cells or extracts thereof. A 282P1G3 antibody or fragment thereof can be labeled with a detectable marker or conjugated to a second molecule. Suitable detectable markers include, but are not limited to, a radioisotope, a fluorescent compound, a bioluminescent compound, chemiluminescent compound, a metal chelator or an enzyme. Further, bi-specific antibodies specific for two or more 282P1G3 epitopes are generated using methods generally known in the art Homodimeric antibodies can also be generated by cross-linking techniques known in the art (e.g., Wolff ef a/., Cancer Res. 53:2560-2565). V.) 282P1G3 Cellular Immune Responses

The mechanism by which T cells recognize antigens has been delineated. Efficacious peptide epitope vaccine compositions of the invention induce a therapeutic or prophylactic immune responses in very broad segments of the worldwide population. For an understanding of the value and efficacy of compositions of the invention that induce cellular immune responses, a brief review-of immunology-related technology is provided. A complex of an HLA molecule and a peptidic antigen acts as the ligand recognized by HLA-restricted T cells (Buus, S. ef a/., Cell 47:1071,1986; Babbitt, B. P. ef a/., Nature 317:359,1985; Townsend, A. and Bodmer, H., Annu. Rev, Immunol. 7:601,1989; Germain, R. N., Annu. Rev. Immunol. 11:403,1993). Through the study of single amino acid substituted antigen analogs and the sequencing of endogenously bound, naturally processed peptides, critical residues that correspond to motifs required for specific binding to HLA antigen molecules have been identified and are set forth in Table IV (see also, e.g., Southwood, et al., J. Immunol. 160:3363,1998; Rammensee, ef a/., immunogeneiics 41:178,1995; Rammensee ef a/., SYFPEITHI, access via World Wide Web at URL (134.2.96.221/scripts.hlaserver.dll/home.htm); Sette, A and Sidney, J. Curr. Opin. Immunol. 10:478,1998; Engelhard, V. H„ Curr. Opin. Immunol. 6:13,1994; Sette, A. and Grey, H. M., Curr. Opin. Immunol. 4:79,1992; Sinigaglia, F. and Hammer, J. Curr. Biol. 6:52,1994; Ruppert et at., Cell74:929-937, 1993; Kondo ef al., J. Immunol. 155:4307-4312,1995; Sidney et at., J. Immunol. 157:3480-3490,1996; Sidney ef al., Human Immunol. 45:79-93,1996; Sette, A. and Sidney, J. Immunogeneiics 1999 Nov; 50(3-4):201-12, Review).

Furthermore, x-ray crystallographic analyses of HLA-peptide complexes have revealed pockets within toe peptide binding cieft/groove of HLA molecules which accommodate, in an allele-specific mode, residues borne by peptide ligands; these residues.in turn determine toe HLA binding capacity of toe peptides in which they are present. (See, e.g., Madden, 46 D.R. Annu. Rev. Immunol. 13:587,1995; Smith, et at., Immunity 4:203,1996; Fremont ef a/., Immunity 8:305, 1998; Stern et al., Structure 2:245,1994; Jones, E.Y. Curr. Opin. Immunol. 9:75,1997; Brown, J. H. etal., Nature 364:33, 1993; Guo, H. C. ef at., Proc. Natl. Acad. Sci. USA 90:8053,1993; Guo, H. C. ef a/., Nature 350:364,1992; Silver, M. L. ef al., Nature 360:367, 1992; Matsumura, M. et a!., Science 257:927,1992; Madden et al., Ceii 70:1035,1992; Fremont, D. H. et al., Science 257:919,1992; Saper, M. A./Bjorkman, P. J. and Wiley, D. C., J. Mol. Biol. 219:277,1991.)

Accordingly, the definition of ciass t and class I! allele-specific HLA binding motifs, or class I or class II supermotifs allows identification of regions within a protein that are correlated with binding to particular HLA antigen(s).

Thus, by a process of HLA motif identification, candidates for epitope-based vaccines have been identified; such candidates can be further evaluated by HLA-peptide binding assays to determine binding affinity and/or the time period of association of the epitope and its corresponding HLA molecule. Additional confirmatory work can be performed to select, amongst these vaccine candidates, epitopes with preferred characteristics in terms of population coverage, and/or immunogenicity.

Various strategies can be utilized to evaluate cellular immunogenicity, including: 1) Evaluation of primary T cell cultures from normal individuals (see, e.g., Wentworth, P. A. ef a/., Mol. Immunol. 32:603,1995; Celis, E. et at., Proc. Natl. Acad. Sci. USA 91:2105,1994; Tsai, V. ef al., J. Immunol. 158:1796,1997; Kawashima, I. ef al., Human Immunol. 59:1,1998). This procedure involves the stimulation of peripheral blood lymphocytes (PBL) from normal subjects with a test peptide in the presence of antigen presenting cells in vitro over a period of several weeks. T cells specific for the peptide become activated during this time and are detected using, e.g., a lymphokine- or 51 Cr-release assay involving peptide sensitized target cells. 2) Immunization of HLA transgenic mice (see, e.g., Wentworth, P. A ef al., J. Immunol. 26:97,1996; Wentworth, P. A. ef al., Int. Immunol. 8:651,1996; Alexander, J. ef a/., J. Immunol. 159:4753,1997). For example, in such methods peptides in incomplete Freund's adjuvant are administered subcutaneously to HLA transgenic mice. Several weeks following immunization, splenocytes are removed and cultured in vitro in the presence of test peptide for approximately one week.

Peptide-specific T ceils are detected using, e.g., a Cr-release assay involving peptide sensitized target cells and target cells expressing endogenously generated antigen. · 3) Demonstration of recall T cell responses from immune individuals who have been either effectively vaccinated and/or from chronically ill patients (see, e.g., Rehermann, B. ef a/., J. Exp. Med. 181:1047,. 1995; Doolan, D. L. ef a/., Immunity 7:97,1997; Bertoni, R. et a!., J. Clin. Invest. 100:503,1997; Threlkeld, 8. C. ef a/., J. Immunol. 159:1648,1997; Diepolder, Η. M. ef al., J. Virol. 71:6011,1997). Accordingly, recall responses are detected by culturing PBL from subjects that have been exposed to the antigen due to disease and thus have generated an immune response “naturally”, or from patients who were vaccinated against the antigen. PBL from subjects are cultured in vitro for 1-2 weeks in the presence of test peptide pius antigen presenting ceils (APC) to allow activation of “memory” T ceils, as compared to “naive" T celis. At the end of the culture period, T cell activity is detected using assays including Cr release involving peptide-sensitized targets, T cell proliferation, or lymphokine release. VL) 282P1G3 T ransqenic Animats

Nucleic acids that encode a 282P1 G3-related protein can aiso be used to generate either transgenic animals or "knock out" animals that, in turn, are useful in the development and screening of therapeutically useful reagents. In accordance with established techniques, cDNA encoding 282P1G3 can be used to clone genomic DNA that encodes 282P1G3. The cloned genomic sequences can then be used to generate transgenic animals containing cells that express DNA that encode 282P1G3. Methods for generating transgenic animals, particularly animals such as mice or rats, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 issued 12 April 1988, and 47 4,870,009 issued 26 September 1989. Typically, particular cells would be targeted for 282P1G3 transgene incorporation with tissue-specific enhancers.

Transgenic animals that include a copy of a transgene encoding 282P1G3 can be used to examine the effect of increased expression of DNA that encodes 282P1G3. Such animals can be used as tester animals for reagents thought to confer protection from, for example, pathological conditions associated with its overexpression. In accordance with this aspect of the invention, an animal is treated with a reagent and a reduced incidence of a pathological condition, compared to untreated animals that bear the transgene, would indicate a potential therapeutic intervention for the pathological condition.

Alternatively, non-human homologues of 282P1G3 can be used to construct a 282P1G3 "knock out" animal that has a defective or altered gene encoding 282P1G3 as a result of homologous recombination between the endogenous gene encoding 282P1G3 and altered genomic DNA encoding 282P1G3 introduced into an embryonic cell of the animal. For example, cDNA that encodes 282P1G3 can be used to clone genomic DNA encoding 282P1G3 in accordance with established techniques. A portion of the genomic DNA encoding 282P1G3 can be deleted or replaced with another gene, such as a gene encoding a selectable marker that can be used to monitor integration. Typically, several kiiobases of unaltered flanking DNA (both at the 5' and 3’ ends) are included in the vector (see, e.g., Thomas and Capecchi, Cell, 51_:503 (1987) for a description of homologous recombination vectors). The vector is introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced DNA has homologously recombined with the endogenous DNA are selected (see, e.g., Li ef a/., Cell, 69:915 (1992)). The selected cells are then injected into a blastocyst of an animal (e.g., a mouse or rat) to form aggregation chimeras (see, e.g., Bradley, in Teratocardnomas and Embryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113-152). A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal, and the embryo brought to term to create a "knock out" animal. Progeny harboring the homologously recombined DNA in their germ cells can be identified by standard techniques and used to breed animals in which all cells of the animal contain the homologously recombined DNA. Knock out animals can be characterized, for example, for their ability to defend against certain pathological conditions or for their development of pathological conditions due to absence of a 282P1G3 polypeptide.

Vil.; Methods for the Detection of 282P1G3

Another aspect of the present invention relates to methods for detecting 282P1G3 polynucleotides and 282P1G3-related proteins, as well as methods for identifying a cell that expresses 282P1G3. The expression profile of 282P1G3 makes it a diagnostic marker for metastasized disease. Accordingly, the status of 282P1G3 gene products provides information useful for predicting a variety of factors including susceptibility to advanced stage disease, rate of progression, and/or tumor aggressiveness. As discussed in detail herein, the status of 282P1G3 gene products in patient samples can be analyzed by a variety protocols that are well known in the art including immunohistochemical analysis, the variety of Northern blotting techniques including in situ hybridization, RT-PCR analysis (for example on laser capture miao-dissected samples), Western blot analysis and tissue array analysis.

More particularly, the invention provides assays for the detection of 282P1G3 polynucleotides in a biological sample, such as serum, bone, prostate, and other tissues, urine, semen, cell preparations, and the like. Detectable 282P1G3 polynucleotides include, for example, a 282P1G3 gene or fragment thereof, 282P1G3 mRNA, alternative splice variant 282P1G3 mRNAs, and recombinant DNA or RNA molecules that contain a 282P1G3 polynucleotide. A number of methods for amplifying and/or detecting the presence of 282P1G3 polynucleotides are well known in the art and can be employed in the practice of this aspect of the invention.

In one embodiment, a method for detecting a 282P1G3 mRNA in a biological sample comprises producing cDNA from the sample by reverse transcription using at least one primer; amplifying the cDNA so produced using a 282P1G3 48 polynucleotides as sense and antisense primers to amplify 282P1G3 cDNAs therein; and detecting the presence of the amplified 282P1G3 cDNA. Optionally, the sequence of the amplified 282P1G3 cDNA can be determined.

In another embodiment, a method of detecting a 282P1G3 gene in a biological sample comprises first isolating genomic DNA from the sample; amplifying the isolated genomic DNA using 282P1G3 polynucleotides as sense and antisense primers; and detecting the presence of the amplified 282P1G3 gene. Any number of appropriate sense and antisense probe combinations can be designed from a 282P1G3 nucleotide sequence (see, e.g., Figure 2) and used for this purpose.

The invention also provides assays for detecting the presence of a 282P1G3 protein in a tissue or other biological sample such as serum, semen, bone, prostate, urine, cell preparations, and the like. Methods for detecting a 282P1 G3-related protein are also well known and include, for example, immunoprecipitation, immunohistochemical analysis, Western blot analysis, molecular binding assays, ELISA, ELIFA and the like. For example, a method of detecting the presence of a 282P1G3-related protein in a biological sample comprises first contacting the sample with a 282P1G3 antibody, a 282P1G3-reactive fragment thereof, or a recombinant protein containing an antigen-binding region of a 282P1G3 antibody; and then detecting the binding of 282P1G3-re!ated protein in the sample.

Methods for identifying a cell that expresses 282P1G3 are also within the scope of the invention, in one embodiment an assay for identifying a cell that expresses a 282P1G3 gene comprises detecting the presence of 282P1G3 mRNA in the cell. Methods for the detection of particular mRNAs in cells are well known and include, for example, hybridization assays using complementary DNA probes (such as in situ hybridization using labeled 282P1G3 riboprobes, Northern blot and related techniques) and various nucleic acid amplification assays (such as RT-PCR using complementary primers specific for 282P1G3, and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like). Alternatively, an assay for identifying a cell that expresses a 282P1G3 gene comprises detecting the presence of 282P1G3-related protein in the cell or secreted by the cell. Various methods for the detection of proteins are well known in the art and are employed for the detection of 282P1 G3-related proteins and cells that express 282P1 G3-related proteins. 282P1G3 expression analysis is also useful as a tool for identifying and evaluating agents that modulate 282P1G3 gene expression. For example, 282P1G3 expression is significantly upregulated in prostate cancer, and is expressed in cancers of the tissues listed in Table I. Identification of a molecule or biological agent that inhibits 282P1G3 expression or overexpression in cancer cells is of therapeutic value. For example, such an agent can be identified by using a screen that quantifies 282P1G3 expression by RT-PCR, nucleic acid hybridization or antibody binding. VIII.) Methods for Monitoring the Status of 282P1G3-related Genes and Their Products

Oncogenesis is known to be a multistep process where cellular growth becomes progressively dysregulated and cells progress from a normal physiological state to precancerous and then cancerous states (see, e.g., Alers et al., Lab Invest. 77(5): 437-438 (1997) and Isaacs ef a/., Cancer Surv. 23:19-32 (1995)). In this context, examining a biological sample for evidence of dysregulated ceil growth (such as aberrant 282P1G3 expression in cancers) allows for early detection of such aberrant physiology, before a pathologic state such as cancer has progressed to a stage that therapeutic options are more limited and or the prognosis is worse. In such examinations, the status of 282P1G3 in a biological sample of interest can be compared, for example, to the status of 282P1G3 in a corresponding normal sample (e.g. a sample from that individual or alternatively another individual that is not affected by a pathology). An alteration in the status of 282P1G3 in the biological sample (as compared to the normal sample) provides evidence of dysregulated cellular growth. In addition to using a biological sample that is not affected by a pathology as a normal sample, one can aiso use a predetermined normative value such as a predetermined normal level of mRNA expression (see, e.g., Grever et al., J. Comp. Neurol. 1996. Dec 9; 376(2): 306-14 and U.S. Patent No. 5,837,501) to compare 282P1G3 status in a sample. 49

The term "status" in this context is used according to its art accepted meaning and refers to the condition or state of a gene and its products. Typically, skilled artisans use a number of parameters to evaluate the condition or state of a gene and its products. These include, but are not limited to the location of expressed gene products (including the location of 282P1G3 expressing cells) as well as the level, and biological activity of expressed gene products (such as 282P1G3 mRNA, polynucleotides and polypeptides). Typically, an alteration in the status of 282P1G3 comprises a change in the location of 282P1G3 and/or 282P1G3 expressing cells and/or an increase in 282P1G3 mRNA and/or protein expression. 282P1G3 status in a sample can be analyzed by a number of means well known in the art, including without limitation, immunohistochemical analysis, in situ hybridization, RT-PCR analysis on laser capture micro-dissected samples, Western blot analysis, and tissue array analysis. Typical protocols for evaluating the status of a 282P1G3 gene and gene products are found, for example in Ausubei ef at. eds., 1995, Current Protocols In Molecular Biology, Units 2 (Northern Blotting), 4 (Southern Blotting), 15 (Immunoblotting) and 18 (PCR Analysis). Thus, the status of 282P1G3 in a biological sample is evaluated by various methods utilized by skilled artisans including, but not limited to genomic Southern analysis (to examine, for example perturbations in a 282P1G3 gene), Northern analysis and/or PCR analysis of 282P1G3 mRNA (to examine, for example alterations in the polynucleotide sequences or expression levels of 282P1G3 mRNAs), and, Western and/or immunohistochemical analysis (to examine, for example alterations in polypeptide sequences, alterations in polypeptide localization within a sample, alterations in expression levels of 282P1G3 proteins and/or associations of 282P1G3 proteins with polypeptide binding partners). Detectable 282P1G3 polynucleotides include, for example, a 282P1G3 gene or fragment thereof, 282P1G3 mRNA alternative splice variants, 282P1G3 mRNAs, and recombinant DNA or RNA molecules containing a 282P1G3 polynucleotide.

The expression profile of 282P1G3 makes it a diagnostic marker for local and/or metastasized disease, and provides information on the growth or oncogenic potential of a biological sample. In particular, the status of 282P1G3 provides information useful for predicting susceptibility to particular disease stages, progression, and/or tumor aggressiveness. The invention provides methods and assays for determining 282P1G3 status and diagnosing cancers that express 282P1G3, such as cancers of the tissues listed in Table I. For example, because 282P1G3 mRNA is so highly expressed in prostate and other cancers relative to normal prostate tissue, assays that evaluate the levels of 282P1G3 mRNA transcripts or proteins in a biological sample can be used to diagnose a disease associated with 282P1G3 dysregulation, and can provide prognostic information useful in defining appropriate therapeutic options.

The expression-status of 282P1G3 provides information including the presence, stage and location of dysplastic, precancerous and cancerous cells, predicting susceptibility to various stages of disease, and/or for gauging tumor aggressiveness. Moreover,, the expression profile makes it useful as an imaging reagent for metastasized disease. Consequently, an aspect of the invention is directed to the various molecular prognostic and diagnostic methods for examining the status of 282P1G3 in biological samples such as those from individuals suffering from, or suspected of suffering from a pathology characterized by dysregulated cellular growth, such as cancer.

As described above, the status of 282P1G3 in a biological sample can be examined by a number of well-known procedures in the art. For example, the status of 282P1G3 in a biological sample taken from a specific location in the body can be examined by evaluating the sample for the presence or absence of 282P1G3 expressing cells (e.g. those that express 282P1G3 mRNAs or proteins). This examination can provide evidence of dysregulated cellular growth, for example, when 282P1G3-expressing cells are found in a biological sample that does not normally contain such ceils (such as a lymph node), because such alterations in the status of 282P1G3in a biological sample are often associated with dysregulated cellular growth. Specifically, one indicator of dysregulated cellular growth is the metastases of cancer cells from an organ of origin (such as the prostate) to a different area of the body (such as a lymph node). In this context, evidence of dysregulated cellular growth is important for example because occult lymph node metastases can be detected in a substantial proportion 50 of patients with prostate cancer, and such metastases are associated with known predictors of disease progression (see, e.g., Murphy etal., Prostate 42(4): 315-317 (2000);Su etal., Semin. Surg. Oncol. 18(1): 17-28 (2000) and Freeman ef al., J Urol 1995 Aug 154(2 Pt 1):474-8). in one aspect, the invention provides methods for monitoring 282P1G3 gene products by determining the status of 282P1G3 gene products expressed by cells from an individual suspected of having a disease associated with dysregulated celi growth (such as hyperplasia or cancer) and then comparing the status so determined to the status of 282P1G3 gene products in a corresponding normal sample. The presence of aberrant 282P1G3 gene products in the test sample relative to the normal sample provides an indication of the presence of dysregulated celi growth within the cells of the individual.

In another aspect, the invention provides assays useful in determining the presence of cancer in an individual, comprising detecting a significant increase in 282P1G3 mRNA or protein expression in a test cel! or tissue sample relative to expression levels in the corresponding normal cell or tissue. The presence of 282P1G3 mRNA can, for example, be evaluated in tissues including but not limited to those listed in Table !. The presence of significant 282P1G3 expression in any of these tissues is useful to indicate the emergence, presence and/or severity of a cancer, since the corresponding normal tissues do not express 282P1G3 mRNA or express it at lower levels. in a related embodiment, 282P1G3 status is determined at the protein level rather than at the nucleic acid level. For example, such a method comprises determining the level of 282P1G3 protein expressed by cells in a test tissue sample and comparing the level so determined to the level of 282P1G3 expressed in a corresponding normal sample. In one embodiment, the presence of 282P1G3 protein is evaluated, for example, using immunohistochemical methods. 282P1G3 antibodies or binding partners capable of detecting 282P1G3 protein expression are used in a variety of assay formats well known in the art for this purpose.

In a further embodiment, one can evaluate the status of 282P1G3 nucleotide and amino acid sequences in a biological sample in order to identify perturbations in the structure of these molecules. These perturbations can include insertions, deletions, substitutions and the like. Such evaluations are useful because perturbations in the nucleotide and amino acid sequences are observed in a large number of proteins associated with a growth dysregulated phenotype (see, e.g., Marrogi et at., 1999, J. Cutan. Pathol. 26(8):369-378). For example, a mutation in the sequence of 282P1G3 may be indicative of the presence or promotion of a tumor. Such assays therefore have diagnostic and predictive .value where a mutation in 282P1G3 indicates a potential loss of function or increase in tumor growth. A wide variety of assays for observing perturbations in nucleotide and amino acid sequences are welt known in the art. For example, the size and structure of nucleic acid or amino acid sequences of 282P1G3 gene products are observed by the Northern, Southern, Western, PCR and DNA sequencing protocols discussed herein. In addition, other methods for observing perturbations in nucleotide and amino acid sequences such as single strand conformation polymorphism analysis are well known in the art (see, e.g., U.S. Patent Nos. 5,382,510 issued 7 September 1999, and 5,952,170 issued 17 January 1995).

Additionally, one can examine the methylation status of a 282P1G3 gene in a biological sample. Aberrant demethylation and/or hypermethylation of CpG islands in gene 5’ regulatory regions frequently occurs in immortalized and transformed cells, and can result in altered expression of various genes. For example, promoter hypermethylation of the pi-ciass glutathione S-transferase (a protein expressed in normal prostate but not expressed in >90% of prostate carcinomas) appears to permanently silence transcription of this gene and is the most frequently detected genomic alteration in prostate carcinomas (De Marzo et a!., Am. J. Pathol. 155(6): 1985-1992 (1999)). in addition, this alteration is present in at least 70% of cases of high-grade prostatic intraepithelial neoplasia (PIN) (Brooks ef al., Cancer Epidemiol. Biomarkers Prev., 1998, 7:531-536). in another example, expression of the LAGE-I tumor specific gene (which is not expressed in normal prostate but is expressed in 25-50% of prostate cancers) is induced by deoxy-azacytidine in lymphoblastoid ceils, suggesting that tumoral expression is due to demethylation (Lethe etal., Int. J. Cancer 76(6): 903-908 (1998)). A variety of assays for 51 examining methylation status of a gene are well known in the art For example, one can utilize, in Southern hybridization approaches, methylation-sensitive restriction enzymes that cannot cieave sequences that contain methylated CpG sites to assess the methylation status of CpG islands. In addition, MSP (methylation specific PCR) can rapidly profile the methylation status of all the CpG sites present in a CpG island of a given gene. This procedure involves initial modification of DNA by sodium bisulfite (which will convert all unmethylated cytosines to uracil) followed by amplification using primers specific for methylated versus unmethylated DNA. Protocols involving methylation interference can also be found for example in Current Protocols In Molecular Biology, Unit 12, Frederick M. Ausubel et al. eds., 1995.

Gene amplification is an additional method for assessing the status of 282P1G3. Gene amplification is measured in a sample directly, for example, by conventional Southern blotting or Northern blotting to quantitate the transcription of mRNA (Thomas, 1980, Proc. Natl. Acad. Sci. USA, 77:5201-5205), dot blotting (DNA analysis), or in situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies are employed that recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. The antibodies in turn are labeled and the assay carried out where the duplex is bound to a surface, so that upon the formation of duplex on the surface, the presence of antibody bound to the duplex can be detected.

Biopsied tissue or peripheral blood can be conveniently assayed for the presence of cancer cells using for example, Northern, dot blot or RT-PCR analysis to detect 282P1G3 expression. The presence of RT-PCR amplifiable 282P1G3 mRNA provides an indication of the presence of cancer. RT-PCR assays are well known in the art RT-PCR detection assays for tumor cells in peripheral blood are currently being evaluated for use in the diagnosis and management of a number of human solid tumors. In the prostate cancer field, these include RT-PCR assays for the detection of cells expressing PSA and PSM (Verkaik et a!., 1997, Urol. Res. 25:373-384; Ghossein etal., 1995, J. Clin. Oncol. 13:1195-2000; Heston etai., 1995, Clin. Chem.41:1687-' 1688). A further aspect of the invention is an assessment of the susceptibility that an individual has for developing cancer. In one embodiment, a method for predicting susceptibility to cancer comprises detecting 282P1G3 mRNA or 282P1G3 protein in a tissue sample, its presence indicating susceptibility to cancer, wherein the degree of 282P1G3 mRNA expression correlates to the degree of susceptibility. In a specific embodiment, the presence of 282P1G3 in prostate or other tissue is examined, with the presence of 282P1G3 in the sample providing an indication of prostate cancer susceptibility (or the emergence or existence of a prostate tumor). Similarly, one can evaluate the integrity 282P1G3 nucleotide and amino acid sequences in a biological sample, in order io identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like. The presence of one or more perturbations in 282P1G3 gene products in the sample is an indication of cancer susceptibility (or the emergence or existence of a tumor).

The invention also comprises methods for gauging tumor aggressiveness. In one embodiment, a method for gauging aggressiveness of a tumor comprises determining the level of 282P1G3 mRNA or 282P1G3 protein expressed by tumor cells, comparing the level so determined to the level of 282P1G3 mRNA or 282P1G3 protein expressed in a comesponding normal tissue taken from the same individual or a normal tissue reference sample, wherein the degree of 282P1G3 mRNA or 282P1G3 protein expression in the tumor sample relative to the normal sample indicates the degree of aggressiveness. In a specific embodiment, aggressiveness of a tumor is evaluated by determining the extent to which 282P1G3 is expressed in the tumor ceils, with higher expression levels indicating more aggressive tumors. Another embodiment is the evaluation of the integrity of 282P1G3 nucleotide and amino acid sequences in a biological sample, in order to identify perturbations in the structure of these moiecuies such as insertions, deletions, substitutions and the like. The presence of one or more perturbations indicates more aggressive tumors.

Another embodiment of the invention is directed to methods for observing the progression of a malignancy in an individual over time. In one embodiment, methods for observing the progression of a malignancy in an individual over time 52 comprise determining the level of 282P1G3 mRNA or 282P1G3 protein expressed by ceils in a sample of the tumor, comparing the level so determined to the level of 282P1G3 mRNA or 282P1G3 protein expressed in an equivalent tissue sample taken from the same individual at a different time, wherein the degree of 282P1G3 mRNA or282P1G3 protein expression in the tumor sample over time provides information on the progression of the cancer. In a specific embodiment, the progression of a cancer is evaluated by determining 282P1G3 expression in the tumor cells over time, where increased expression over time indicates a progression of the cancer. Also, one can evaluate the integrity 282P1G3 nucleotide and amino acid sequences in a biological sample in order to identify perturbations in the structure of these molecules such as insertions, deletions, substitutions and the like, where the presence of one or more perturbations indicates a progression of the cancer.

The above diagnostic approaches can be combined with any one of a wide variety of prognostic and diagnostic protocols known in the art. For example, another embodiment of the invention is directed to methods for observing a coincidence between the expression of 282P1G3 gene and 282P1G3 gene products (or perturbations in 282P1G3 gene and 282P1G3gene products) and a factor that is associated with malignancy, as a means for diagnosing and prognosticating the status of a tissue sample. A wide variety of factors associated with malignancy can be utilized, such as the expression of genes associated with malignancy (e.g. PSA, PSCA and PSM expression for prostate cancer etc.) as well as gross cytological observations (see, e.g., Booking et a!., 1984, Anal. Quant. Cytol. 6(2):74-88; Epstein, 1995, Hum. Pathol. 26(2):223-9; Thorson eta/., 1998, Mod. Pathol. 11(6):543-51 pBaisden et al., 1999, Am. J. Surg. Pathol. 23(8):918-24). Methods for observing a coincidence,between the expression of 282P1G3 gene and 282P1G3 gene products (or perturbations in 282P1G3 gene and 282P1G3 gene products) and another factor that is associated with malignancy are useful, for example, because the presence of a set of specific factors that coincide with disease provides information crucial for diagnosing and prognosticating the status of a tissue sample. in one embodiment, methods for observing a coincidence between the expression of 282P1G3 gene and 282P1G3 gene products (or perturbations in 282P1G3 gene and 282P1G3 gene products) and another factor associated with malignancy entails detecting the overexpression of 282P1G3 mRNA or protein in a tissue sample, detecting the overexpression of PSA mRNA. or protein in a tissue sample (or PSCA or PSM expression), and observing a coincidence of 282P1G3 mRNA or protein and PSA mRNA or protein overexpression (or PSCA or PSM expression). In a specific embodiment, the expression of 282P1G3 and PSA mRNA in prostate tissue is examined, where the coincidence of 282P1G3 and PSA mRNA overexpression in the sample indicates the existence of prostate cancer, prostate cancer susceptibility or the emergence or status of a prostate tumor.

Methods for detecting and quantifying the expression of 282P1G3 mRNA or protein are described herein, and standard nucleic acid and protein detection and quantification technologies are well known in the art. Standard methods for the detection and quantification of 282P1G3 mRNA include in situ hybridization using labeled 282P1G3 riboprobes, Northern blot and related techniques using 282P1G3 polynucleotide probes, RT-PCR analysis using primers specific for 282P1G3, and other amplification type detection methods, such as, for example, branched DNA, SISBA, TMA and the like. In a specific embodiment, semi-quantitative RT-PCR is used to detect and quantify 282P1G3 mRNA expression. Any number of primers capable of amplifying 282P1G3 can be used for this purpose, including but not limited to the various primer sets specifically described herein. In a specific embodiment, polyclonal or monoclonal antibodies specifically reactive with the wild-type 282P1G3 protein can be used in an immunohistochemical assay of biopsied tissue. IX.)_Identification of Molecules That interact With 282P1G3

The 282P1G3 protein and nucleic acid sequences disclosed herein allow a skilled artisan to identify proteins, small molecules and other agents that interact with 282P1G3, as well as pathways activated by 282P1G3 via any one of a variety of art accepted protocols. For example, one can utilize one of the so-called interaction trap systems (aiso referred to as the "two-hybrid assay"). In such systems, molecules interact and reconstitute a transcription factor which directs expression of a reporter gene, whereupon the expression of the reporter gene is assayed. Other systems identify protein-protein interactions 53 in-vivo through reconstitution of a eukaryotic transcriptional activator, see, e.g., U.S. Patent Nos. 5,955,280 issued 21 September 1999, 5,925,523 issued 20 July 1999, 5,846,722 issued 8 December 1998 and 6,004,746 issued 21 December 1999. Algorithms are also available in the art for genome-based predictions of protein function (see, e.g., Marcotte, ef al., Nature 402: 4 November 1999, 83-86).

Alternatively one can screen peptide libraries to identify molecules that interact with 282P1G3 protein sequences, in such methods, peptides that bind to 282P1G3 are identified by screening libraries that encode a random or controlled collection of amino acids. Peptides encoded by the libraries are expressed as fusion proteins of bacteriophage coat proteins, the bacteriophage particles are then screened against the 282P1G3 protein(s).

Accordingiy, peptides having a wide variety of uses, such as therapeutic, prognostic or diagnostic reagents, are thus identified without any prior information on the structure of the expected ligand or-receptor molecule. Typical peptide libraries and screening methods that can be used to identify molecules that interact with 282P1G3 protein sequences are disclosed for example in U.S. Patent Nos. 5,723,-286 issued 3 March 1998 and 5,733,731 issued 31 March 1998.

Alternatively, cell fines that express 282P1G3 are used to identify protein-protein interactions mediated by 282P1G3. Such interactions can be examined using immunoprecipitation techniques (see, e.g., Hamilton B.J., ef al.

Biochem. Biophys. Res. Commun. 1999, 261:646-51). 282P1G3 protein can be immunoprecipitated from 282P1G3-expressing cell lines using anti-282P1G3 antibodies. Alternatively, antibodies against His-tag can be used in a cell line engineered to express fusions of 282P1G3 and a His-tag (vectors mentioned above). The immunoprecipitated complex can be examined for protein association by procedures such as Western blotting, 35S-methionine labeling of proteins, protein microsequencing, silver staining and two-dimensional gel electrophoresis.

Small molecules and ligands that interact with 282P1G3 can be identified through related embodiments of such screening assays. For example, small molecules can be identified that interfere with protein* function, including molecules that interfere with 282P1 G3’s ability to mediate phosphorylation and de-phosphorylation, interaction with DNA or RNA molecules as an indication of regulation of cell cycles, second messenger signaling or tumorigenesis. Similarly, small molecules that modulate 282P1 G3-reiated ion channel, protein pump, or ceil communication functions are identified and used to treat patients that have a cancer that expresses 282P1G3 (see, e.g., Hille, B., Ionic Channels of Excitable Membranes 2nd Ed., Sinauer Assoc., Sunderland, MA, 1992). Moreover, ligands that regulate 282P1G3 function can be identified based on their ability to bind 282P1G3 and activate a reporter construct Typical methods are discussed for example in U.S. Patent No. 5,928,868 issued 27 July 1999, and include methods for forming hybrid ligands in which at least one ligand is a small molecule, in an illustrative embodiment, cells engineered to express a fusion protein of 282P1G3 and a DNA-binding protein are used to co-express a fusion protein of a hybrid ligand/smali molecule and a cDNA library transcriptional activator protein. The ceiis further contain a reporter gene, the expression of which is conditioned on the proximity of the first and second fusion proteins to each other, an event that occurs only if the hybrid ligand binds to target sites on both hybrid proteins. Those cells that express the reporter gene are selected and the unknown small molecule or the unknown ligand is identified. This method provides a means of identifying modulators, which activate or inhibit 282P1G3.

An embodiment of this invention comprises a method of screening for a molecule that interacts with a 282P1G3 amino acid sequence shown in Figure 2 or Figure 3, comprising the steps of contacting a population of molecules with a 282P1G3 amino acid sequence, allowing the population of molecules and the 282P1G3 amino acid sequence to interact under conditions that faciiitate an interaction, determining the presence of a molecule that interacts with the 282P1G3 amino acid sequence, and then separating molecules that do not interact with the 282P1G3 amino acid sequence from molecules that do. in a specific embodiment, the method further comprises purifying, characterizing and identifying a molecule that interacts with the 282P1G3 amino acid sequence. The identified molecule can be used to modulate a function performed by 282P1G3. In a preferred embodiment, the 282P1G3 amino acid sequence is contacted with a library of peptides. 54 X.) Therapeutic Methods and Compositions

The identification of 282P1G3 as a protein that is normally expressed in a restricted set of tissues, but which is also expressed in cancers such as those listed in Table i, opens a number of therapeutic approaches to the treatment of such cancers.

Of note, targeted antitumor therapies have been useful even when the targeted protein is expressed on normal tissues, even vital normal organ tissues. A vital organ is one that is necessary to sustain life, such as the heart or colon. A non-vital organ is one that can be removed whereupon the individual is still able to survive. Examples of non-vital organs are ovary, breast, and prostate.

For example, Herceptin® is an FDA approved pharmaceutical that has as its active ingredient an antibody which is immunoreactive with the protein variously known as HER2, HER2/neu, and erb-b-2. It is marketed by Genentech and has been a commercially successful antitumor agent Herceptin sales reached almost $400 million in 2002. Herceptin is a treatment for HER2 positive metastatic breast cancer. However, the expression of HER2 is not limited to such tumors. The same protein is expressed in a number of normal tissues. In particular, it is known that HER2/neu is present in normal kidney and heart, thus these tissues are present in all human recipients of Herceptin. The presence of HER2/neu in normal kidney is also confirmed by Latif, Z., et ai., B.J.U. International (2002) 89:5-9. As shownin this article (which evaluated whether renal cell carcinoma should be a preferred indication for anti-HER2 antibodies such as Herceptin) both protein and mRNA are produced in benign renal tissues. Notably, HER2/neu protein was strongly overexpressed in benign renal tissue. Despite the fact that HER2/neu is expressed in such vital tissues as heart and kidney, Herceptin is a very useful, FDA approved, and commercially successful drug. The effect of Herceptin on cardiac tissue, i.e., “cardiotoxicity,” has merely been a side effect to treatment When patients were treated with Herceptin aione, significant cardiotoxicity occurred in a very low percentage of patients.

Of particular note, although kidney tissue is indicated to exhibit normal expression, possibly even higher expression than cardiac tissue, kidney has no appreciable Herceptin side effect whatsoever. Moreover, of the diverse array of normal tissues in which HER2 is expressed, there is very little occurrence of any side effect Only cardiac tissue has manifested any appreciable side effect at ail. A tissue such as kidney, where HER2/neu expression is especially notable, has not been the basis for any side effect

Furthermore, favorable therapeutic effects have been found for antitumor therapies that target epidermal growth factor receptor (EGFR). EGFR is also expressed in numerous normal tissues. There have been very limited side effects in normal tissues following use of anii-EGFR therapeutics.

Thus, expression of a target protein in normal tissue, even vital normal tissue, does not defeat the utility of a targeting agent for the protein as a therapeutic for certain tumors in which the protein is also overexpressed.

Accordingly, therapeutic approaches that inhibit the activity of a 282P1G3 protein are useful for patients suffering from a cancer that expresses 282P1G3. These therapeutic approaches generally fall into two classes. One class comprises various methods for inhibiting the binding or association of a 282P1G3 protein with its binding partner or with other proteins. Another class comprises a variety of methods for inhibiting the transcription of a 282P1G3 gene or translation of 282P1G3 mRNA. X.A.) Anti-Cancer Vaccines

The invention provides cancer vaccines comprising a 282P1G3-related protein or 282P1G3-related nucleic acid. In view of the expression of 282P1G3, cancer vaccines prevent and/or treat 282P1G3-expressing cancers with minimal or no effects on non-target tissues. The use of a tumor antigen in a vaccine that generates humoral and/or cell-mediated immune responses 55 as anti-cancer therapy is well known in the art and has been employed in prostate cancer using human PSMA and rodent PAP immunogens (Hodge et al., 1995, Int. J. Cancer 63:231-237; Fong ef a!., 1997, J. Immunol. 159:3113-3117).

Such methods can be readily practiced by employing a 282P1 G3-related protein, or a 282P1G3-encoding nucleic acid molecule and recombinant vectors capable of expressing and presenting the 282P1G3 immunogen (which typically comprises a number of antibody or T cell epitopes). Skilled artisans understand that a wide variety of vaccine systems for delivery of immunoreactive epitopes are known in the art (see, e.g., Heryln etal., Ann. Med 1999 Feb 31(1 ):66-78; Maruyama ef al., Cancer Immunol Immunother 2000 Jun 49(3):123-32) Briefly, such methods of generating an immune response (e.g. humoral and/or cell-mediated) in a mammal, comprise the steps of: exposing the mammal’s immune system to an immunoreactive epitope (e.g. an epitope present in a 282P1G3 protein shown in Figure 3 or analog or homolog thereof) so that the mammal generates an immune response that is specific for that epitope (e.g. generates antibodies that specifically recognize that epitope). In a preferred method, a 282P1G3 immunogen contains a biological motif, see e.g., Tables VIII-XXI and XXII-XLIX, or a peptide of a size range from 282P1G3 indicated in Figure 5, Figure 5, Figure 7, Figure 8, and Figure 9.

The entire 282P1G3 protein, immunogenic regions or epitopes thereof can be combined and delivered by various means. Such vaccine compositions can include, for example, lipopeptides (e.g.,Vitiello, A. et al., J. Clin, invest. 95:341, 1995), peptide compositions encapsulated in poly(DL-lactide-co-giycolide) ("PLG”) microspheres (see, e.g., Eldridge, ef al., Molec. Immunol. 28:287-294,1991: Alonso et al, Vaccine 12:299-306,1994; Jones etal, Vaccine 13:675-681,1995), peptide compositions contained in immune stimulating complexes (ISCOMS) (see, e.g., Takahashi et al, Nature 344:873-875,1990; Hu ef al, Clin Exp Immunol. 113:235-243,1998), multiple antigen peptide systems (MAPs) (see e.g., Tam, J. P., Proc. Natl. Acad. Sci. U.S.A. 85:5409-5413,1988; Tam, J.P., J. Immunol. Methods 196:17-32,1996), peptides formulated as multivalent peptides; peptides for use in ballistic delivery systems, typically crystallized peptides, viral delivery' vectors (Perkus, Μ. E. ef al, In: Concepts in vaccine development, Kaufmann, S. H. E„ ed., p. 379,1996; Chakrabarti, S. et al, Nature 320:535,1986; Hu, S. L. ef al, Nature 320:537,1986; Kieny, M.-P. ef al, AIDS Bio/Technology 4:790,1986; Top, F. H. etal, J. Infect. Dis. 124:148,1971; Chanda, P. K. etal, Virology 175:535,1990), particles of viral or synthetic origin (e.g., Kofler, N. ef al, J. Immunol. Methods. 192:25,1996; Eldridge, J. H. et al, Sem. Hematol. 30:16,1993; Falo, L. D„ Jr. ef al, Nature Med. 7:649,1995), adjuvants (Warren, H. S., Vogei, F. R., and Chedid, L. A. Annu. Rev. Immunol. 4:369,1986; Gupta, R. K. etal, Vaccine 11:293,1993), liposomes (Reddy, R. etal, J. Immunol. 148:1585,1992; Rock, K. L, Irnmunol. Today 17:131,1996), or, naked or particle absorbed cDNA (Ulmer, J. B. ef a/., Science 259:1745,1993; Robinson, H. L., Hunt, L A., and Websteh R. G., Vaccine 11:957,1993; Shiver, J. W. et al, in: Concepts in vaccine development, Kaufmann, S. H, E., ed., p. 423,1996; Cease, K. 8., and Berzofsky, J. A., Annu. Rev. Immunol 12:923,1994 and Eldridge, J. H. ef a/., Sem. Hematol. 30:16,1993). Toxin-targeted delivery technologies, also known as receptor mediated targeting, such as those of Avant lmmunotherapeutics, inc. (Needham, Massachusetts) may aiso be used.

In patients with 282P1G3-associated cancer, the vaccine compositions of the invention can also be used in conjunction with other treatments used for cancer, e.g., surgery, chemotherapy, drug therapies, radiation therapies, etc. including use in combination with immune adjuvants such as IL-2, IL-12, GM-CSF, and the like.

Cellular Vaccines: CTL epitopes can be determined using specific algorithms to identify peptides within 282P1G3 protein that bind corresponding HLA alleles (see e.g., Table IV; Epimer™ and Epimatrix™, Brown University (URL brown.edu/Research/TB-HIV_Lab/epimatrix/epimatrix.html); and, BIMAS, (URL bimas.dcrt.nih.gov/; SYFPEITHI at URL syfpeithi.bmi-heidelberg.com/). In a preferred embodiment, a 282P1G3 immunogen contains one or more amino acid sequences identified using techniques well known in the art, such as the sequences shown in-Tabtes Vlli-XXl and XXIl-XLIX or a peptide of 8,9,10 or 11 amino acids specified by an HLA Class I motif/supermotif (e.g., Table IV (A), Table IV (D), or Table IV (E)) and/or a peptide of at least 9 amino acids that comprises an HLA Ciass 11 motif/supermotif (e.g., Table IV (B) or Table IV (C)). As is appreciated in 56 the art, the HLA Class I binding groove is essentially closed ended so that peptides of only a particular size range can fit into the groove and be bound, generally HLA Class I epitopes are 8, 9,10, or 11 amino acids long. In contrast, the HLA Class II binding groove is essentially open ended; therefore a peptide of about 9 or more amino acids can be bound by an HLA Class II molecule. Due to the binding groove differences between HLA Class I and II, HLA Class I motifs are length specific, i.e., position two of a Class I motif is the second amino acid in an amino io carboxyl direction of the peptide. The amino acid positions in a Class il motif are relative only to each other, not the overall peptide, i.e., additional amino adds can be attached to the amino and/or carboxyl termini of a motif-bearing sequence. HLA Class II epitopes are often 9,10,11,12,13, 14,15,16,17,18,19, 20, 21, 22, 23, 24, or 25 amino acids long, or longer than 25 amino acids.

Antibody-based Vaccines A wide variety of methods for generating an immune response in a mammal are known in the art (for example as the first step in the generation of hybridomas). Methods of generating an immune response in a mammal comprise exposing the mammal's immune system to an immunogenic epitope on a protein (e.g. a 282P1G3 protein) so that an immune response is generated. A typical embodiment consists of a method for generating an immune response to 282P1G3 in a host, by contacting the host with a sufficient amount of at least one 282P1G3 B cell or cytotoxic T-cei! epitope or analog thereof; and at least one periodic interval thereafter re-contacting the host with the 282P1G3 B cell or cytotoxic T-cell epitope or analog thereof. Aspecific embodiment consists of a method of generating an immune response against a 282P1G3-related protein or a man-made multiepitopic peptide comprising: administering 282P1G3 immunogen (e.g. a 282P1G3 protein or a peptide fragment thereof, a 282P1G3 fusion protein or analog etc.) in a vaccine preparation to a human or another mammal. Typically, such vaccine preparations further contain a suitable adjuvant (see, e.g., U.S. Patent No. 6,146,635) or a universal helper epitope such as a PADRE™ peptide (Epimmune Inc., San Diego, CA; see, e.g., Alexander etal., J. Immunol. 2000 164(3); 164(3): 1625-1633; Alexander et al., Immunity 1994 1(9):751-761 and Alexander etal., Immunol. Res. 1998 18(2): 79-92). An alternative method comprises generating an immune response in an individual against a 282P1G3 immunogen by: administering in vivo to muscle or skin of the individual’s body a DNA molecule that comprises a DNA sequence that encodes a 282P1G3 immunogen, the DNA sequence operatively linked to regulatory sequences which control the expression of the DNA sequence; wherein the DNA molecule is taken, up by ceils, the DNA sequence is expressed in the ceils and an immune response is generated against the immunogen (see, e.g., U.S. Patent No. 5,962,428). Optionally a genetic vaccine facilitator such as anionic lipids; saponins; lectins; estrogenic compounds; hydroxylated lower alkyls; dimethyl sulfoxide; and urea is also administered, in addition, an antiidiotypic antibody can be administered that mimics 282P1G3, in order to generate a response to the target antigen.

Nucleic Acid Vaccines:

Vaccine compositions of the invention include nucleic acid-mediated modalities. DNA or RNA that encode protein(s) of the invention can be administered to a patienL Genetic immunization methods can be employed to generate prophylactic or therapeutic humoral and cellular immune responses directed against cancer cells expressing 282P1G3. Constructs comprising DNA encoding a 282P1 G3-reiated protein/immunogen and appropriate regulatory sequences can be injected directly into muscle or skin of an individual, such that the cells of the muscle or skin take-up the construct and express the encoded 282P1G3 protein/immunogen. Alternatively, a vaccine comprises a 282P1G3-related protein. Expression of the 282P1G3-related protein immunogen results in the generation of prophylactic or therapeutic humoral and cellular immunity against cells that bear a 282P1G3 protein. Various prophylactic and therapeutic genetic immunization techniques known in the art can be used (for review, see information and references published at Internet address genweb.com). Nucleic acid-based delivery is described, for instance, in Wolff ef. al., Science 247:1465 (1990) as well as U.S. Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98/04720. Examples of DNA- 57 based delivery technologies include “naked DNA”, facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle-mediated (“gene gun”) or pressure-mediated delivery (see, e.g., U.S. Patent No. 5,922,687).

For therapeutic or prophylactic immunization purposes, proteins of the invention can be expressed via viral or bacterial vectors. Various viral gene delivery systems that can be used in the practice of the invention include, but are not limited to, vaccinia, fowlpox, canarypox, adenovirus, influenza, poliovirus, adeno-associated virus, lentivirus, and sindbis virus (see, e.g., Restifo, 1996, Cum Opin. Immunol. 8:658-663; Tsang ef ai. J. Natl. Cancer Inst. 87:982-990 (1995)), Non-viral delivery systems can also be employed by introducing naked DNA encoding a 282P1G3-related protein into the patient (e.g., intramuscularly or intradermally) to induce an anti-tumor response.

Vaccinia virus is used, for example, as a vector to express nucleotide sequences that encode the peptides of the invention. Upon introduction into a host, the recombinant vaccinia virus expresses the protein immunogenic peptide, and thereby elicits a host immune response. Vaccinia vectors and methods useful in immunization protocols are described in, e.g., U.S. Patent No. 4,722,848. Another vector is BCG (Bacille Calmette Guerin). BCG vectors are described in Stover ef al., Nature 351:456-460 (1991). A wide variety of other vectors useful for therapeutic administration or immunization of the peptides of the invention, e.g. adeno and adeno-associated virus vectors, retroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like, will be apparent to those skilled in the art from the description herein.

Thus, gene delivery systems are used to deliver a 282P1G3-related nucleic acid molecule. In one embodiment, the toll· length human 282P1G3 cDNA is employed, in another embodiment, 282P1G3 nucleic acid molecules encoding specific cytotoxic T lymphocyte (CTL) and/or antibody epitopes are employed.

Ex Vivo Vaccines

Various ex vivo strategies can also be employed to generate an immune response. One approach involves the use of antigen presenting cells (APCs) such as dendritic cells (DC) to present 282P1G3 antigen to a patients immune system. Dendritic cells express MHC class I and II molecules, B7 co-stimulator, and IL-12, and are thus highly specialized antigen presenting cells.

In prostate cancer, autologous dendritic cells pulsed with peptides of the prostate-specific membrane antigen (PSMA) are being used in a Phase I clinical trial to stimulate prostate cancer patients’ immune systems (Tjoa ef al., 1996, Prostate 28:65-69; Murphy et at., 1996, Prostate 29:371-380). Thus, dendritic ceils can be used to present 282P1G3 peptides to T ceils in the context of MHC class I or II molecules. In one embodiment, autologous dendritic cells are pulsed with 282P1G3 peptides capable of binding to MHC class I and/or class II molecules. In another embodiment, dendritic ceils are pulsed with the complete 282P1G3 protein. Yet another embodiment involves engineering the overexpression of a 282P1G3 gene in dendritic cells using various implementing vectors known in the art, such as adenovirus (Arthur ef al., 1997, Cancer Gene Trier. 4:17-25), retrovirus (Henderson etal., 1996, CancerRes. 56:3763-3770), lentivirus, adeno-associated virus, DNA transfection (Ribas ef al., 1997, Cancer Res. 57:2865-2869), or tumor-derived RNA transfection (Ashley ef a/., 1997, J. Exp. Med. 186:1177-1182). Ceils that express 282P1G3 can also be engineered to express immune modulators, such as GM-CSF, and used as immunizing agents. X.B.) 282P1G3 as a Target for Antibody-based Therapy 282P1G3 is an attractive target for antibody-based therapeutic strategies. A number of antibody strategies are known in the art for targeting both extraceiiular and intracellular molecules (see, e.g., complement and ADCC mediated killing as well as the use of intrabodies). Because 282P1G3 is expressed by cancer cells of various lineages relative to corresponding normal cells, systemic administration of 282P1G3-immunoreactive compositions are prepared that exhibit excellent sensitivity without toxic, non-specific and/or non-target effects caused by binding of the immunoreactive composition to non-target organs and tissues. Antibodies specifically reactive with domains of 282P1G3 are useful to treat 58 282P1G3-expressing cancers systemically, either as conjugates with a toxin or therapeutic agent, or as naked antibodies capable of inhibiting celi proliferation or function. 282P1G3 antibodies can be introduced into a patient such that the antibody binds to 282P1G3 and modulates a function, such as an interaction with a binding partner, and consequently mediates destruction of the tumor ceiis and/or inhibits the growth of the tumor ceils. Mechanisms by which such antibodies exert a therapeutic effect can include complement-mediated cytolysis, antibody-dependent cellular cytotoxicity, modulation of the physiological function of 282P1G3, inhibition of ligand binding or signal transduction pathways, modulation of tumor cell differentiation, alteration of tumor angiogenesis factor profiles, and/or apoptosis.

Those skilled in the art understand that antibodies can be used to specifically target and bind immunogenic molecules such as an immunogenic region of a 282P1G3 sequence shown in Figure 2 or Figure 3. in addition, skilled artisans understand that it is routine to conjugate antibodies to cytotoxic agents (see, e.g., Sievers ef a!. Blood 93:11 3578-3684 (June 1,1999)). When cytotoxic and/or therapeutic agents are delivered directly to cells, such as.by conjugating them to antibodies specific for a molecule expressed by that ceil (e.g. 282P1G3), the cytotoxic agent will exert its known biological effect (i.e. cytotoxicity) on those ceils. A wide variety of compositions and methods for using antibody-cytotoxic agent conjugates to kill ceils are known in the art. in the context of cancers, typical methods entail administering to an animal having a tumor a biologically effective amount of a conjugate comprising a selected cytotoxic and/or therapeutic agent finked to a targeting agent (e.g. an anti-282P1G3 antibody) that binds to a marker (e.g. 282P1G3) expressed, accessible to binding or localized on (he ceil surfaces. A typical embodiment is a method of delivering a cytotoxic and/or therapeutic agent to a cell expressing 282P1G3, comprising conjugating the cytotoxic agent to an antibody that immunospecifically binds to a 282P1G3 epitope, and, exposing the cell to the antibody-agent conjugate. Another illustrative embodiment is a method of treating an individual suspected of suffering from metastasized cancer, comprising a step of administering pa'renterally to said individual a pharmaceutical composition comprising a therapeutically effective amount of an antibody conjugated to a cytotoxic and/or therapeutic agent

Cancer immunotherapy using anti-282P1G3 antibodies can be done in accordance with various approaches that have been successfully employed in the treatment of other types of cancer, including but not limited to colon cancer (Arlen et al., 1998, Grit Rev. Immunol. 18:133-138), multiple myeloma (Ozaki etal., 1997, Blood 90:3179-3186, Tsunenari etal., 1997, Blood 90:2437-2444), gastric cancer (Kasprzyk et a!., 1992, Cancer Res. 52:2771-2776), B-celi lymphoma (Funakoshi etal., 1996, J. Immunother. Emphasis Tumor Immunol. 19:93-101), leukemia (Zhong ef af., 1996, Leuk. Res. 20:581-589), colorecta! cancer (Moun et al., 1994, Cancer Res. 54:6160-6166; Veiders et al., 1995, Cancer Res. 55:4398-4403), and breast cancer (Shepard ef al., 1991, J. Ciin. Immunol. 11:117-127). Some therapeutic approaches involve conjugation of naked antibody to a toxin or radioisotope, such as the conjugation of Y91 or I131 to anti-CD20 antibodies (e.g., Zevaiin™, IDEC Pharmaceuticals Corp, or Bexxar™, Coulter Pharmaceuticals), while others involve co-administration of antibodies and other therapeutic agents, such as Herceptin™ (trastuzumab) with paclitaxel (Genentech, inc.). The antibodies can be conjugated to a therapeutic agent To treat prostate cancer, for example, 282P1G3 antibodies can be administered in conjunction with radiation, chemotherapy or hormone ablation. Aiso, antibodies can be conjugated to a toxin such as caiicheamicin (e.g., Mylotarg™, Wyeth-Ayerst, Madison, NJ, a recombinant humanized lgG4 kappa antibody conjugated to antitumor antibiotic caiicheamicin) or a maytansinoid (e.g., taxane-based Tumor-Activated Prodrug, TAP, platform, ImmunoGen, Cambridge, MA, also see e.g., US Patent 5,416,064).

Although 282P1G3 antibody therapy is useful for ali stages of cancer, antibody therapy can be particularly appropriate in advanced or metastatic cancers. Treatment with the antibody therapy of the invention is indicated for patients who have received one or more rounds of chemotherapy. Alternatively, antibody therapy of the invention is combined with a 59 chemotherapeutic or radiation regimen for patients who have not received chemotherapeutic treatment Additionally, antibody therapy can enable the use of reduced dosages of concomitant chemotherapy, particularly for patients who do not tolerate the toxicity of the chemotherapeutic agent very well. Fan et al. (Cancer Res. 53:4637-4642,1993), Prewett et al. (international J. of Onco. 9:217-224,1996), and Hancock et al. (Cancer Res. 51:4575-4580,1991) describe the use of various antibodies together with chemotherapeutic agents.

Although 282P1G3 antibody therapy is useful for all stages of cancer, antibody therapy can be particularly appropriate in advanced or metastatic cancers. Treatment with the antibody therapy of the invention is indicated for patients who have received one or more rounds of chemotherapy. Alternatively, antibody therapy of the invention is combined with a chemotherapeutic or radiation regimen for patients who have not received chemotherapeutic treatment. Additionally, antibody therapy can enable the use of reduced dosages of concomitant chemotherapy, particularly for patients who do not tolerate the toxicity of the chemotherapeutic agent very well.

Cancer patients can be evaluated for the presence and level of 282P1G3 expression, preferably using immunohistochemical assessments of tumor tissue, quantitative 282P1G3 imaging, or other techniques that reliably indicate the presence and degree of 282P1G3 expression. Immunohistochemical analysis of tumor biopsies or surgical specimens is preferred for this purpose. Methods for immunohistochemical analysis of tumor tissues are well known in the art

Anti-282P1 G3 monoclonal antibodies that treat prostate and other cancers include those that initiate a potent immune response against the tumor or those that are directly cytotoxic. In this regard, anti-282P1G3 monoclonal antibodies (mAbs) can elicit tumor cell lysis by either complement-mediated or antibody-dependent celt cytotoxicity (ADCC) mechanisms, both of which require an intact Fc portion of the immunoglobulin molecule for interaction with effector cell Fc receptor sites on complement proteins, in addition, anti-282P 1G3 mAbs that exert a direct bioiogicai effect on tumor growth are useful to treat cancers that express 282P1G3. Mechanisms by which directly cytotoxic mAbs act include: inhibition of cell growth, modulation of cellular differentiation, modulation of tumor angiogenesis factor profiles, and the induction of apoptosis. The mechanism(s) by which a particular anB-282P1G3 mAb exerts an anti-tumor effect is evaluated using any number of in vitro assays that evaluate cell death such as ADCC, ADMMC, complement-mediated ceil lysis, and so forth, as is generally known in the art

In some patients, the use of murine or other non-human monoclonal antibodies, or human/mouse chimeric mAbs can induce moderate'to strong immune responses against the non-human antibody. This can result in clearance of the antibody from circulation-§nd reduced efficacy, in the most severe cases, such an immune response can lead to the extensive formation of immune complexes which, potentially, can cause renal failure. Accordingly, preferred monoclonal antibodies used in the therapeutic methods of the invention are those that are either fully human or humanized and that bind specifically to the target 282P1G3 antigen with high affinity but exhibit low or no antigenicity in the patient.

Therapeutic methods of the invention contemplate the administration of single anti-282P1 G3 mAbs as well as combinations, or cocktails, of different mAbs. Such mAb cocktails can have certain advantages inasmuch as they contain mAbs that target different epitopes, exploit different effector mechanisms or combine directly cytotoxic mAbs with mAbs that rely on immune effector functionality. Such mAbs in combination can exhibit synergistic therapeutic effects. In addition, anti-282P1G3 mAbs can be administered concomitantly with other therapeutic modalities, including but not limited to various chemotherapeutic agents, androgen-blockers, immune modulators (e.g., IL-2, GM-CSF), surgery or radiation. The anti-282P1G3 mAbs are administered in their “naked” or unconjugated form, or can have a therapeutic agent(s) conjugated to them.

Ariti-282P1 G3 antibody formulations are administered via any route capable of delivering the antibodies to a tumor celi. Routes of administration include, but are not limited to, intravenous, intraperitoneal, intramuscular, intratumor, intradermal, and the like. Treatment generally involves repeated administration of the anti-282P1G3 antibody preparation, 60 via an acceptable route of administration such as intravenous injection (IV), typically at a dose in the range of about 0.1, .2, .3, .4, .5, .6, .7, .8, .9., 1, 2, 3,4, 5, 6, 7, 8, 9,10,15, 20, or 25 mg/kg body weight. In general, doses in the range of 10-1000 mg mAb per week are effective and well tolerated.

Based on clinical experience with the Herceptin™ mAb in the treatment of metastatic breast cancer, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the anti-282P1G3 mAb preparation represents an acceptable dosing regimen. Preferably, the initial loading dose is administered as .a 90-minute or longer infusion. The periodic maintenance dose is administered as a 30 minute or longer infusion, provided the initial dose was well tolerated. As appreciated by those of skill in the art, various factors can influence the ideal dose regimen in a particular case. Such factors include, for example, the binding affinity and half life of the Ab or mAbs used, the degree of 282P1G3 expression in the patient, the extent of circulating shed 282P1G3 antigen, the desired steady-state antibody concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient

Optionally, patients should be evaluated for the levels of 282P1G3 in a given sample (e.g. the levels of circulating 282P1G3 antigen and/or 282P1G3 expressing cells) in order to assist in the determination of the most effective dosing regimen, etc. Such evaluations are also used for monitoring purposes throughout therapy, and are useful to gauge therapeutic success in combination with the evaluation of other parameters (for example, urine cytology and/or lmmuno,Cyt levels in bladder cancer therapy, or by analogy, serum PSA levels in prostate cancer therapy).

Anti-idiotypic anti-282P1G3 antibodies can aiso be used in anti-cancer therapy as a vaccine for inducing an immune response to cells expressing a 282P1 G3-related protein. In particular, the generation of anti-idiotypic antibodies is well known in the art; this methodology can readily be adapted to generate anti-idiotypic anti-282P1 G3 antibodies that mimic an epitope on a 282P1 G3-related protein (see, for example, Wagner et at., 1997, Hybridoma 16:33-40; Foon et at., 1995, J. Clin, invest 96:334-342; Herlyn ef at., 1996, Cancer Immunol. Immunother. 43:55-76). Such an anti-idiotypic antibody can be used in cancer vaccine strategies. X.C.) 282P1G3 as a Target for Cellular immune Responses

Vaccines and methods of preparing vaccines that contain an immunogenically effective amount of one or more HLA-binding peptides as described herein are further embodiments of the invention. Furthermore, vaccines in accordance with the invention encompass compositions of one or more of the claimed peptides. A peptide can be present in a vaccine individually. Alternatively, the peptide can exist as a homopolymer comprising multiple copies of the same peptide, or as a heteropolymer of various peptides. Polymers have the advantage of increased immunological reaction and, where different peptide epitopes are used to make up the polymer, the additional ability to induce antibodies and/or CTLs that react with different antigenic determinants of the pathogenic organism or tumor-related peptide targeted for an immune response. The composition can be a naturally occurring region of an antigen or can be prepared, e.g., recombinantly or by chemical synthesis.

Carriers that can be used with vaccines of the invention are well known in the art, and include, e.g., thyroglobuiin, albumins such as human serum albumin, tetanus toxoid, polyamino acids such as poly l-lysine, poly L-glutamic acid, influenza, hepatitis B virus core protein, and the like. The vaccines can contain a physiologically tolerable (i.e., acceptable) diluent such as water, or saline, preferably phosphate buffered saline. The vaccines also typically include an adjuvant Adjuvants such as incomplete Freund's adjuvant, aluminum phosphate, aluminum hydroxide, or alum are examples of materials well known in the ait Additionally, as disclosed herein, CTL responses can be primed by conjugating peptides of the invention to lipids, such as tripalmitoyl-S-glycerylcysteinlyseryl- serine (P3CSS). Moreover, an adjuvant such as a 61 synthetic cytosine-phosphorothiolated-guanine-containing (CpG) oligonucleotides has been found to increase CTL responses 10- to 100-fold, (see, e.g. Davila and Celis, J. Immunol. 165:539-547 (2000))

Upon immunization with a peptide composition in accordance with the invention, via injection, aerosol, oral, transdermal, transmucosal, intrapleural, intrathecal, or other suitable routes, the immune system of the host responds to the vaccine by producing large amounts of CTLs and/or HTLs specific for the desired antigen. Consequently, the host becomes at least partially immune to later development of cells that express or overexpress 282P1G3 antigen, or derives at least some therapeutic benefit when the antigen was tumor-associated.

In some embodiments, it may be desirable to combine the class I peptide components with components that induce or facilitate neutralizing antibody and or helper T cell responses directed to the target antigen. A preferred embodiment of such a composition comprises class I and class II epitopes in accordance with the invention. An alternative embodiment of such a composition comprises a class I and/or class I! epitope in accordance with the invention, along with a cross reactive HTL epitope such as PADRE™ (Epimmune, San Diego, CA) molecule (described e.g., in U.S. Patent Number 5,736,142). A vaccine of the invention can also include antigen-presenting cells (APG), such as dendritic cells (DC)/ as a vehicle to present peptides of the invention. Vaccine compositions can be created in vitro, following dendritic cell mobilization and harvesting, whereby loading of.dendritic cells occurs in vitro. For example, dendritic cells are transfected, e.g., with a minigene in accordance with the invention, or are pulsed with peptides. The dendritic cell can then be administered to a patient to elicit immune responses in vivo. Vaccine compositions, either DNA- or peptide-based, can also be administered in vivo in combination with dendritic cell mobilization whereby loading of dendritic cells occurs in vivo.

Preferably, the following principles are utilized when selecting an array of epitopes for inclusion in a polyepitopic composition for use in a vaccine, or for selecting discrete epitopes to be included in a vaccine and/or to be encoded by nucleic acids such as a minigene. It is preferred that each of the following principles be balanced in order to make the selection. The multiple epitopes to be incorporated in a given vaccine composition may be, but need not be, contiguous in sequence in the native antigen from which the epitopes are derived. 1. ) Epitopes are selected which, upon administration, mimic immune responses that have been observed to be correlated with tumor clearance. For HLA Class) this includes 3-4 epitopes that come from at least one tumor associated antigen (TAA). For HLA Class II a similar rationale is employed; again 3-4 epitopes are selected from at least one TAA (see, e.g., Rosenberg ef al., Sgience 278:1447-1450). Epitopes from one TAA may be used in combination with epitopes from one or more additional TAAs to produce a vaccine that targets tumors with varying expression patterns of frequently-expressed TAAs. 2. ) Epitopes are selected that have the requisite binding affinity established to be correlated with immunogenicity: for HLA Class I an ICso of 500 nM or less, often 200 nM or less; and for Class II an IC50 of 1000 nM or less. 3. ) Sufficient supermotif bearing-peptides, or a sufficient array of allele-specific motif-bearing peptides, are selected to give broad population coverage. For example, it is preferable to have at least 80% population coverage. A Monte Carlo analysis, a statistical evaluation known in the art, can be employed to assess the breadth, or redundancy of, population coverage. 4. ) When selecting epitopes from cancer-related antigens it is often useful to select analogs because the patient may have developed tolerance to the native epitope. 5. ) Of particular relevance are epitopes referred to as "nested epitopes.”- Nested epitopes occur where at least two epitopes overlap in a given peptide sequence. A nested peptide sequence can comprise B ceil, HLA class I and/or HLA class II epitopes. When providing nested epitopes, a general objective is to provide the greatest number of epitopes per sequence. Thus, an aspect is fo avoid providing a peptide that is any longer than the amino terminus of the amino terminal 62 epitope and the carboxyl terminus of the carboxyl terminal epitope in the peptide. When providing a multi-epitopic sequence, such as a sequence comprising nested epitopes, it is generally important to screen the sequence in order to insure that it does not have pathological or other deleterious biological properties. 6. ) if a polyepitopic protein is created, or when creating a minigene, an objective is to generate the smallest peptide that encompasses the epitopes of interest. This principle is similar, if not the same as that employed when selecting a peptide comprising nested epitopes. However, with an artificial polyepitopic peptide, the size minimization objective is balanced against the need to integrate any spacer sequences between epitopes in the polyepitopic protein. Spacer amino acid residues can, for example, be introduced to avoid junctional epitopes (an epitope recognized by the immune system, not present in the target antigen, and only created by the man-made juxtaposition of epitopes), or to facilitate cleavage between epitopes and thereby enhance epitope presentation. Junctional epitopes are generally to be avoided because the recipient may generate an immune response to that non-native epitope. Of particular concern is a junctional epitope that is a “dominant epitope." A dominant epitope may lead to such a zealous response that immune responses to other epitopes are diminished or suppressed. 7. ) Where the sequences of multiple variants of the same target protein are present, potential peptide epitopes can also be selected on the basis of their conservancy. For example, a criterion for conservancy may define that the entire sequence of an HLA class I binding peptide or the entire 9-mer core of a class II binding peptide be conserved in a designated percentage of the sequences evaluated for a specific protein antigen. X.G.1. Minigene Vaccines A number of different approaches are available which allow simultaneous delivery of multiple epitopes. Nucleic acids encoding the peptides of the invention are a particularly useful embodiment of the invention. Epitopes for inclusion in a minigene are preferably selected according to the guidelines set forth in the previous section. A preferred means of administering nucleic acids encoding the peptides of the invention uses minigene constructs encoding a peptide comprising one or multiple epitopes of the invention.

The use of multi-epitope minigenes is described below and in, Ishioka et at., J. Immunol. 162:3915-3925,1999; An, L and Whitton, J. L., J. Virol. 71:2292, 1997; Thomson, S. A. ef al., J. Immunol. 157:822,1996; Whitton, J. L ef al., J. Virol. 67:348,1993; Hanke, R. ef a/., Vaccine 16:426,1998. For example, a multi--epitope DNA plasmid encoding supermolif-and/or motif-bearing epitopes derived 282P1G3, the PADRE® universal helper T cell epitope or multiple HTL epitopes from 282P1G3 (see e.g., Tables Vill-XXI and XXII to XLIX), and an endoplasmic reticulum-translocating signal sequence can be engineered. A vaccine may also comprise epitopes that are derived from other TAAs.

The immunogenicity of a multi-epitopic minigene can be confirmed in transgenic mice to evaluate the magnitude of CTL induction responses against the epitopes tested. Further, the immunogenicity of DNA-encoded epitopes in vivo can be conelated with the in vitro responses of specific CTL lines against target cells transfected with the DNA plasmid. Thus, these experiments can show that the minigene serves to both: 1.) generate a CTL response and 2.) that the induced CTLs recognized cells expressing the encoded epitopes.

For example, to create a DNA sequence encoding the selected epitopes (minigene) for expression in human cells, the amino acid sequences of the epitopes may be reverse translated. A human codon usage table can be used to guide the codon choice for each amino acid. These epitope-encoding DNA sequences may be directly adjoined, so that when translated, a continuous polypeptide sequence is created. To optimize expression and/or immunogenicity, additional elements can be incorporated into the minigene design. Examples of amino acid sequences that can be reverse translated and included in the minigene sequence include: HLA class 1 epitopes, HLA class II epitopes, antibody epitopes, a ubiquitination signal sequence, and/or an endoplasmic reticulum targeting signal. In addition, HLA presentation of CTL and 63 HTL epitopes may be improved by including synthetic (e.g. poly-aianine) or naturally-occurring flanking sequences adjacent to the CTL or HTL epitopes; these larger peptides comprising the epitope(s) are within the scope of the invention.

The minigene sequence may be converted to DNA by assembling oligonucleotides that encode the plus and minus strands of the minigene. Overlapping oligonucleotides (30-100 bases long) may be synthesized, phosphoryiated, purified and annealed under appropriate conditions using well known techniques. The ends of the oligonucleotides can be joined, for example, using T4 DNA ligase. This synthetic minigene, encoding the epitope polypeptide, can then be cloned into a desired expression vector.

Standard regulatory sequences well known to those of skill in the art are preferably included in the vector to ensure expression in the target cells. Several vector elements are desirable; a promoter with a down-stream cloning site for minigene insertion; a polyadenylation signal for efficient transcription termination; an £ coli origin of replication; and an E. coli selectable marker (e.g. ampiciliin or kanamycin resistance). Numerous promoters can be used for this purpose, e.g., the human cytomegalovirus (hCMV) promoter. See, e.g., U.S. Patent Nos. 5,580,859 and 5,589,466 for other suitable promoter sequences.

Additional vector modifications may be desired to optimize minigene expression and immunogenicity. in some cases, introns are required for efficient gene expression, and one or more synthetic or naturally-occurring introns could be incorporated into the transcribed region of the minigene. The inclusion of mRNA stabilization sequences and sequences for replication in mammalian cells may also be considered for increasing minigene expression.

Once an expression vector is selected, the minigene is cloned into the poiyiinker region downstream of the promoter. This plasmid is transformed into an appropriate £. coii strain, and DNA is prepared using standard techniques. The orientation and DNA sequence of the minigene, as weii as aii other elements included in the vector, are confirmed using restriction mapping and DNA sequence analysis. Bacteaaf cells harboring the correct plasmid can be stored as a master cell bank and a working cell bank. £

In addition, immunostimulatory sequences (ISSs or CpGs) appear to play a role in the immunogenicity of DNA vaccines. These sequences may be included in the vector, outside the minigene coding sequence, if desired to enhance immunogenicity. tn some embodiments, a bi-cistronic expression vector which allows production of both the minigene-encoded epitopes and a second protein (included to enhance or decrease immunogenicity) can be used. Examples of proteins or polypeptides that could beneficially enhance the immune response if co-expressed include cytokines (e.g., IL-2, IL-12, GM-CSF), cytokine-inducing molecules (e.g., LelF), costimulatory molecules, or for HTL responses, pan-DR binding proteins (PADRE™, Epimmune, San Diego, CA). Helper (HTL) epitopes can be joined to intracellular targeting signals and expressed separately from expressed CTL epitopes; this allows direction of the HTL epitopes to a ceil compartment different than that of the CTL epitopes, if required, this could faciiitate more efficient entry of HTL epitopes into the HLA class II pathway, thereby improving HTL induction. In contrast to HTL or CTL induction, specifically decreasing the immune response by co-expression of immunosuppressive molecules (e.g. TGF-β) may be beneficial in certain diseases.

Therapeutic quantities of plasmid DNA can be produced for example, by fermentation in £. coli, followed by purification. Aliquots from the working cell bank are used to inoculate growth medium, and grown to saturation in shaker flasks or a bioreactor according to well-known techniques. Plasmid DNA can be purified using standard bioseparaiion technologies such as solid phase anion-exchange resins supplied by QiAGEN, Inc. (Valencia, California). If required, supercoiied DNA can be isolated from the open circular and linear forms using ge! electrophoresis or other methods.

Purified plasmid DNA can be prepared for injection using a variety of formulations. The simplest of these is reconstitution of lyophilized DNA in sterile phosphate-buffer saline (PBS). This approach, known as "naked DNA," is currently being used for intramuscular (IM) administration in clinical trials. To maximize the immunotherapeutic effects of 64 minigene DNA vaccines, an alternative method for formulating purified plasmid DNA may be desirable. A variety of methods have been described, and new techniques may become available. Cationic lipids, glycolipids, and fusogenic liposomes can also be used in the formulation (see, e.g., as described by WO 93/24640; Mannino & Gould-Fogerite, BioTechniques 6(7): 682 (1988); U.S. Pat No. 5,279,833; WO 91/06309; and Feigner, et al., Proc. Nat’l Acad. Sci. USA 84:7413 (1987). In addition, peptides and compounds referred to collectively as protective, interactive, non-condensing compounds (PING) couid also be completed to purified plasmid DNA to influence variables such as stability, intramuscular dispersion, or trafficking to specific organs or cell types.

Target ceil sensitization can be used as a functional assay for expression and HLA class I presentation of minigene-encoded CTL epitopes. For example, the plasmid DNA is introduced into a mammalian cell line that is suitable as a target for standard CTL chromium release assays. The transfection method used will be dependent on the final formulation. Electroporation can be used for "naked" DNA, whereas cationic lipids allow direct in vitro transfection. A plasmid expressing green fluorescent protein (GFP) can be co-transfected to allow enrichment of transfected cells using fluorescence activated cel! sorting (FACS). These cells are then chromium-51 (51Cr) labeled and used as target celts for epitope-specific CTL lines; cytolysis, detected by 51Cr release, indicates both production of, and HLA. presentation of, minigene-encoded CTL epitopes. Expression of HTL epitopes may be evaluated in an analogous manner using assays to assess HTL activity.

In vivo immunogenicity is a second approach for functional testing of minigene DNA formulations. Transgenic mice expressing appropriate human HLA proteins are immunized with the DNA product. The dose and route of administration are formulation dependent (e.g., IM for DNA in PBS, intraperitoneal (i.p.) for lipid-complexed DNA). Twenty-one days after immunization, splenocytes are harvested and restimulated for one week in the presence of peptides encoding each epitope being tested. Thereafter, for CTL effector cells, assays are conducted for cytolysis of peptide-loaded, 51Cr-labeled target cells using standard techniques. Lysis of target cells that were sensitized by HLA loaded with peptide epitopes, corresponding to minigene-encoded epitopes, demonstrates DNA vaccine function for in vivo induction of CTLs. Immunogenicity of HTL epitopes is confirmed in transgenic mice in an analogous manner.

Alternatively, the nucleic acids can be administered using ballistic delivery as described, for instance, in U.S.

Patent No. 5,204,253. Using this technique, particles comprised solely of DNA are administered, in a further alternative embodiment, DNA can be adhered to particles, such as gold particles.

Minigenes camglso be delivered using other bacterial or viral delivery systems well known in the art, e.g., an expression construct encoding epitopes of the invention can be incorporated into a viral vector such as vaccinia. X.C.2. Combinations of CTL Peptides with Helper Peptides

Vaccine compositions comprising CTL peptides of the invention can be modified, e.g., analoged, to provide desired attributes, such as improved serum half life, broadened population coverage or enhanced immunogenicity.

For instance, the ability of a peptide to induce CTL activity can be enhanced by linking the peptide to a sequence which contains at least one epitope that is capable of inducing a T helper cell response. Although a CTL peptide can be directly linked to a T helper peptide, often CTL epitope/HTL epitope conjugates are linked by a spacer molecule. The spacer is typically comprised of relatively small, neutral molecules, such as amino acids or amino acid mimetics, which are substantially uncharged under physiological conditions. The spacers are typically selected from, e.g., Ala, Gly, or other neutral spacers of nonpolar amino acids or neutral polar amino acids. It will be understood that the optionally present spacer need not be comprised of the same residues and thus may be a hetero- or homo-oligomer. When present, the spacer will usually be at least one or two residues, more usually three to six residues and sometimes 10 or more residues. The CTL peptide epitope can be linked to the T helper peptide epitope either directly or via a spacer either at the amino or carboxy 65 terminus of the CTL peptide. The amino terminus of either the immunogenic peptide or the T helper peptide may be acylated.

In certain embodiments, the T helper peptide is one that is recognized by T helper cells present in a majority of a genetically diverse population. This can be accomplished by selecting peptides that bind to many, most, or ail of the HLA class Ii molecules. Examples of such amino acid bind many HLA Class II molecules include sequences from antigens such as tetanus toxoid at positions 830-843 (QY1KANSKF1GITE; SEQ ID NO: 37), Plasmodium falciparum circumsporozoite (CS) protein at positions 378-398 (DIEKK1AKMEKASSVFNVVNS; SEQ ID NO:' 38), and Streptococcus 18kD protein at positions 116-131 (GAVDSILGGVATYGAA; SEQ ID NO: 39). Other examples include peptides bearing a DR 1 7 supermotif, or either of the DR3 motifs.

Alternatively, it is possible to prepare synthetic peptides capable of stimulating T helper lymphocytes, in a loosely HLA-restricted fashion, using amino acid sequences not found in nature (see, e.g., PCT publication WO 95107707). These synthetic compounds called Pan-DR-binding epitopes (e.g., PADRE™, Epimmune, Inc., San Diego, CA) are designed, most preferably, to bind most HLA-DR (human HLA class 11) molecules. For instance, a pan-DR-binding epitope peptide having the formula: aKXVAAWTLKAa (SEQ ID NO: 40), where “X" is either cyclohexylalanine, phenylalanine, or tyrosine, and a is either D-alanine on-alanine, has been found to bind to most HLA-DR alleles, and to stimulate the response of T helper lymphocytes from most individuals, regardless of their HLA type. An alternative of a pan-DR binding epitope comprises all “L” natural amino acids and can be provided in the form of nucleic acids that encode the epitope. HTL peptide epitopes can aiso be modified to alter their biological properties. For example, they can be modified to include D-amino acids to increase their resistance to proteases and thus extend their serum half life, or they can be conjugated io other molecules such as lipids, proteins, carbohydrates, and the like to increase their biological activity. For -example, a T helper peptide can be conjugated to one or more palmitic acid chains at either the amino or carboxyl termini. X.C.3. Combinations of CTL Peptides with T Cell Priming Agents in some embodiments it may be desirable to include in the pharmaceutical compositions of the invention at ieast one component which primes B. lymphocytes or T lymphocytes. Lipids have been identified as agents capable of priming CTL in vivo. For example, palmitic acid residues can be attached to the ε-and a- amino groups of a lysine residue and then linked, e.g., via one or more linking residues such as Gty, Giy-Gly-, Ser, Ser-Ser, or the like, to an immunogenic peptide.

The iipidated peptide can then be administered either directly in a micelle or particle, incorporated into a liposome, or emulsified in an adjuvant, e.g., incomplete Freund's adjuvant. In a preferred embodiment, a particularly effective immunogenic composition comprises palmitic acid attached ίο ε- and a- amino groups of Lys, which is attached via linkage, e.g., Ser-Ser, to the amino terminus of the immunogenic peptide.

As another example of lipid priming of CTL responses, E. coli lipoproteins, such as tripalmitoyi-S-glycerylcysteiniyseryl- serine (P3CSS) can be used to prime virus specific CTL when covalently attached to an appropriate peptide (see, e.g., Deres, etal., Nature 342:561,1989). Peptides of the invention can be coupled to P3CSS, for example, and the lipopeptide administered to an individual to prime specifically an immune response to the target antigen. Moreover, because the induction of neutralizing antibodies can also be primed with PaCSS-conjugated epitopes, two such compositions can be combined to more effectively elicit both humoral and cell-mediated responses. X-C.4. Vaccine Compositions Comprising DC Pulsed with CTL and/or HTL Peptides

An embodiment of a vaccine composition in accordance with the invention comprises ex vivo administration of a cocktaii of epitope-bearing peptides to PBMC, or isolated DC therefrom, from the patients blood. A phannaceutical to facilitate harvesting of DC can be used, such as Progenipoietin™ (Pharmacia-Monsanto, St. Louis, MO) or GM-CSF/IL-4. After pulsing the DC with peptides and prior to reinfusion into patients, the DC are washed to remove unbound peptides. In 66 this embodiment, a vaccine comprises peptide-pulsed DCs which present the pulsed peptide epitopes complexed with HLA molecules on their surfaces.

The DC can be pulsed ex vivo with a cocktail of peptides, some of which stimulate CTL responses to 282P1G3. Optionally, a helper T cell (HTL) peptide, such as a natural or artificial loosely restricted HLA Class II peptide, can be included to facilitate the CTL response. Thus, a vaccine in accordance with the invention is used to treat a cancer which expresses or overexpresses 282P1G3. X.D, Adoptive Immunotherapy >

Antigenic 282P1G3-related peptides are used Io elicit a CTL and/or HTL response ex vivo, as well. The resulting CTL or HTL cells, can be used to treat tumors in patients that do not respond to other conventional forms of therapy, or will not respond to a therapeutic vaccine peptide or nucleic acid in accordance with the invention. Ex vivo CTL or HTL responses to a particular antigen are induced by incubating in tissue culture the patient's, or genetically compatible, CTL or HTL precursor cells together with a source of antigen-presenting cells (ARC), such as dendritic cells, and the appropriate immunogenic peptide. After an appropriate incubation time (typically about 7-28 days), in which the precursor cells are activated and expanded into effector cells, the cells are infused back into the patient, where they will destroy (CTL) or facilitate destruction (HTL) of their specific target ceil (e.g., a tumor ceil). Transfected dendritic cells may also be used as antigen presenting cells. X.E. Administration of Vaccines for Therapeutic or Prophylactic Purposes

Pharmaceutical and vaccine compositions of the invention are typically used to treat and/or prevent a cancer that expresses or overexpresses 282P1G3. In therapeutic applications, peptide and/or nucleic acid compositions are administered to a patient in an amount sufficient to elicit an effective B cell, CTL and/or HTL response to the antigen and to cure or at least partially arrest or slow symptoms and/or complications. An amount adequate to accomplish this is defined as "therapeutically effective dose.” Amounts effective for this use will depend on, e.g., the particular composition administered, the manner of administration, the stage and severity of the disease being treated, the weight and general state of health of the patient, and the judgment of the prescribing physician.

For pharmaceutical compositions, the immunogenic peptides of the invention, or DNA encoding them, are generally administered to,an individual already bearing a tumor that expresses 282P1G3. The peptides or DNA encoding them can be administered individually or as fusions of one or more peptide sequences. Patients can be treated with the immunogenic peptides separately or in conjunction with other treatments, such as surgery, as appropriate.

For therapeutic use, administration should generally begin at the first diagnosis of 282P1 G3-associated cancer.

This is followed by boosting doses until at least symptoms are substantially abated and for a period thereafter. The embodiment of the vaccine composition (i.e., including, but not limited to embodiments such as peptide cocktails, polyepitopic polypeptides, minigenes, or TAA-specific CTLs or pulsed dendritic cells) delivered to the patient may vary according to the stage of the disease or the patient's health status. For example, in a patient with a tumor that expresses 282P1G3, a vaccine comprising 282P1G3-specific CTL may be more efficacious in killing tumor celts in patient with advanced disease than alternative embodiments.

It is generally important to provide an amount of the peptide epitope delivered by a mode of administration sufficient to stimulate effectively a cytotoxic T cel! response; compositions which stimulate helper T cell responses can also be given in accordance with this embodiment of the invention,

The dosage for an initial therapeutic immunization generally occurs in a unit dosage range where the lower value is about 1,5, 50,500, or 1,000 pg and the higher value is about 10,000; 20,000; 30,000; or 50,000 pg. Dosage values for a 67 human typically range from about 500 pg to about 50,000 pg per 70 kilogram patient Boosting dosages of between about 1.0 ug to about 50,000 ug of peptide pursuant to a boosting regimen over weeks to months may be administered depending upon the patient’s response and condition as determined by measuring the specific activity of CTL and HTL obtained from the patient’s blood. Administration should continue until at least clinical symptoms or laboratory tests indicate that the neoplasia, has been eliminated or reduced and for a period thereafter. The dosages, routes of administration, and dose schedules are adjusted in accordance with methodologies known in the art. in certain embodiments, the peptides and compositions of the present invention are employed in serious disease states, that is, life-threatening or potentially fife threatening situations. In such cases, as a result of the minimal amounts of extraneous substances and the relative nontoac nature of the peptides in preferred compositions of the invention, it is possible and may be felt desirable by the treating physician to administer substantia! excesses of these peptide compositions relative io these stated dosage amounts.

The vaccine compositions of the invention can also be used purely as prophylactic agents. Generally the dosage for an initial prophylactic immunization generally occurs in a unit dosage range where the lower value is about 1,5,50,500, or 1000 pg and the higher value is about 10,000; 20,000; 30,000; or 50,000 pg. Dosage vaiues for a human typically range from about 500 pg to about 50,000 pg per 70 kilogram patient. This is followed by boosting dosages of between about 1.0 pg to about 50,000 pg of peptide administered at defined intervals from about four weeks to six months after the initial administration of vaccine. The immunogenicity of the vaccine can be assessed by measuring the specific activity of CTL and HTL obtained from a sample of the patient's blood.

The pharmaceutical compositions for therapeutic treatment are intended for parenteral, topical, oral, nasal, intrathecal, or local (e.g. as a cream or topical ointment) administration. Preferably, the pharmaceutical compositions are administered parentally, e.g., intravenously, subcutaneously, intradermally, or intramuscularly. Thus, the invention provides compositions for parenteral administration which comprise a solution of the immunogenic peptides dissolved or suspended in an acceptable carrier, preferably an aqueous carrier. A variety of aqueous carriers may be used, e.g., water, buffered water, 0.8% saline, 0.3% glycine, hyaluronic acid and the like. These compositions may be sterilized by conventional, well-known sterilization techniques, or may be sterile filtered. The resulting aqueous solutions may be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration.

The compositions may contain pharmaceutically acceptabie auxiliary substances as required to approximate physiological conditions, such as pH-adjusfing and buffering agents, tonicity adjusting agents, wetting agents, preservatives, and the like, for example, sodium acetate, sodium lactate, sodium chloride, potassium chloride, calcium chloride, sorbitan monolaurate, triethanolamine oieate, etc.

The concentration of peptides of the invention in the pharmaceutical formulations can vary widely, /.e., from less than about 0.1%, usually at or at least about 2% to as much as 20% to 50% or more by weight, and wit! be selected primarily by fluid volumes, viscosities, etc., in accordance with the particular mode of administration selected. A human unit dose form of a composition is typically included in a pharmaceutical composition that comprises a human unit dose of an acceptabie carrier, in one embodiment an aqueous carrier, and is administered in a volume/quantity that is known by those of skill in the art to be used for administration of such compositions to humans (see, e.g., Remington’s Pharmaceutical Sciences, 17°1 Edition, A. Gennaro, Editor, Mack Publishing Co., Easton, Pennsylvania, 1985). For example a peptide dose for initial immunization can be from about 1 to about 50,000 pg, generally 100-5,000 pg, for a 70 kg patient. For example, for nucleic acids an initial immunization may be performed using an expression vector in the form of naked nucleic acid administered IM (or SC or ID) in the amounts of 0.5-5 mg at multiple sites. The nucieic acid (0.1 to 1000 pg) 68 can also be administered using a gene gun. Following an incubation period of 3-4 weeks, a booster dose is then administered. The booster can be recombinant fowlpox virus administered at a dose of 5-107 to 5x108 pfu.

For antibodies, a treatment generally involves repeated administration'of the anti-282P1G3 antibody preparation, via an acceptable route of administration such as intravenous injection (IV), typically at a dose in the range of about 0.1 to about 10 mg/kg body weight, in general, doses in the range of 10-500 mg mAb per week are effective and welt tolerated. Moreover, an initial loading dose of approximately 4 mg/kg patient body weight IV, followed by weekly doses of about 2 mg/kg IV of the anti- 282P1G3 mAb preparation represents an acceptable dosing regimen. As appreciated by those of skill in the art, various factors can influence the ideal dose in a particular case. Such factors include, for example, half life of a composition, the binding affinity of an Ab, the immunogenicity of a substance, the degree of 282P1G3 expression in the patient, the extent of circulating shed 282P1G3 antigen, the desired steady-state concentration level, frequency of treatment, and the influence of chemotherapeutic or other agents used in combination with the treatment method of the invention, as well as the health status of a particular patient. Non-limiting preferred human unit doses are, for example, 500pg - 1mg, 1mg - 50mg, 50mg - 100mg, 100mg - 200mg, 200mg - 300mg, 400mg - 500mg, 500mg - 600mg, 600mg -7Q0mg, 700mg -800mg, 800mg - 900mg, 900mg - 1g, or 1mg - 700mg. In certain embodiments, the dose is in a range of 2-5 mg/kg body weight, e.g., with follow on weekly doses of 1-3 mg/kg; 0.5mg, 1,2,3,4, 5, 6,7,8, 9,10mg/kg body weight followed, e.g., in two, three or four weeks by weekly doses; 0.5 - 10mg/kg body weight, e.g., followed in two, three or four weeks by weekly doses; 225, 250, 275, 300,325,350,375,400mg m2 of body area weekly; 1-600mg m2 of body area weekly; 225-400mg m2 of body area weekly; these does can be followed by weekly doses for 2,3,4,5,6,7,8,9,19,11,12 or more weeks. in one embodiment, human unit dose forms of polynucleotides comprise a suitable dosage range or effective amount that provides any therapeutic effect As appreciated by one of ordinary ski!! in the art a therapeutic effect depends on a number of factors, including the sequence of the polynucleotide, molecular weight of the polynucleotide and route of administration. Dosages are generally selected by the physician or other health care professional in accordance with a variety of parameters known in the art, such as severity of symptoms, history of the patient and the like. Generally, for a polynucleotide of about 20 bases, a dosage range may be selected from, for example, an independently selected lower limit such as about 0.1, 0.25, 0.5,1, 2, 5,10, 20, 30,40, 50, 60,70, 80, 90,100, 200, 300, 400 or 500 mg/kg up to an independently selected upper limit, greater than the tower limit, of about 60, 80,100, 200,300,400,500, 750,1000,1500, 2000, 3000, 4000,5000,6000,7000, 8000, 9000 or 10,000 mg/kg. For example, a dose may be about any of the following; 0.1 to 100 mg/kg, 0.1 to 50 mg/kg, 0.1 to 25 mg/kg, 0.1 to 10 mg/kg, 1 to 500 mg/kg, 100 to 400 mg/kg, 200 to 300 mg/kg, 1 to 100 mg/kg, 100 to 200 mg/kg, 300 to 400 mg/kg, 400 to 500 mg/kg, 500 to 1000 mg/kg, 500 to 5000 mg/kg, or 500 to 10,000 mg/kg. Generally, parenteral routes of administration may require higher doses of polynucleotide compared to more direct application to the nucleotide to diseased tissue, as do polynucleotides of increasing length.

In one embodiment, human unit dose forms of T-ceiis comprise a suitable dosage range or effective amount that provides any therapeutic effect. As appreciated by one of ordinary skill in the art, a therapeutic effect depends on a number of factors. Dosages are generaliy selected by the physician or other health care professional in accordance with a variety of parameters known in the art, such as severity of symptoms, history of the patient and the like. A dose may be about 104 cells to about 106 cells, about 10® cells to about 108 cells, about 108 to about 1011 cells, or about 108 to about 5 x 1010 cells. A dose may also about 10® cells/m2 to about 1010 cells/m2, or about 106 cells/m2 to about 108 cells/m2.

Proteins(s) of the invention, and/or nucleic acids encoding the protein(s), can also be administered via liposomes, which may aiso serve to: 1) target the proteins(s) to a particular tissue, such as lymphoid tissue; 2) to target selectively to diseases cells; or, 3) to increase the half-life of the peptide composition. Liposomes include emulsions, foams, micelles, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like. In these preparations, the peptide to be delivered is incorporated as part of a liposome, alone or in conjunction with a molecule which binds to a 69 receptor prevalent among lymphoid cells, such as monoclonal antibodies which bind to the CD45 antigen, or with other therapeutic or immunogenic compositions. Thus, liposomes either filled or decorated with a desired peptide of the invention can be directed to the site of lymphoid cells, where the liposomes then deliver the peptide compositions. Liposomes for use in accordance with the invention are formed from standard vesicle-forming iipids, which generally include neutral' and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally guided by consideration of, e.g., liposome size, acid lability and stability of the liposomes in the blood stream. A variety of methods are available for preparing liposomes, as described in, e.g., Szoka, etal., Ann. Rev. Biophys. Bioeng. 9:467 (1980), and U.S. Patent Nos. 4,235,871, 4,501,728, 4,837,028, and 5,019,369.

For targeting cells of the immune system, a ligand to be incorporated into the liposome can include, e.g., antibodies or fragments thereof specific for cell surface determinants of the desired immune system cells. A liposome suspension containing a peptide may be administered intravenously, locally, topically, efc. in a dose which varies according to, inter alia, the manner of administration, the peptide being delivered, and the stage of the disease being treated.

For solid compositions, conventional nontoxic solid carriers may be used which include, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like. For oral administration, a pharmaceutically acceptable nontoxic composition is formed by incorporating any of the normally employed excipients, such as those carriers previously listed, and generally 10-95% of active ingredient, that is, one or more peptides of the invention, and more preferably at a concentration of 25%-75%.

For aerosol administration, immunogenic peptides are preferably supplied in finely divided form along with a surfactant and propellant Typical percentages of peptides are about 0.01 %-20% by weight, preferably about 1 %-10%. The surfactant must, of course, be nontoxic, and preferably soluble in the propellant Representative of such agents are the esters or partial esters of fatty acids containing from about 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, iinolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides may be employed. The surfactant may constitute about 0.1 %-20% by weight of the composition, preferably about 0.25-5%. The balance of the composition is ordinarily propellant. A carrier can also be included, as desired, as with, e.g., lecithin for intranasal delivery.

Xl.) Diagnostic and Prognostic Embodiments of 282P1G3.

As disclosed hgrein, 282P1G3 polynucleotides, polypeptides, reactive cytotoxic T cells (CTL), reactive helper T ceiis (HTL) and anti-polypeptide antibodies are used in well known diagnostic, prognostic and therapeutic assays that examine conditions associated with dysregulated cell growth such as cancer, in particular the cancers listed in Tabie I (see, e.g., both its specific pattern of tissue expression as weil as its overexpression in certain cancers as described for example in the Example entitled “Expression analysis of 282P1G3 in normal tissues, and patient specimens”). 282P1G3 can be analogized to a prostate associated antigen PSA, the archetypal marker that has been used by medical practitioners for years to identify and monitor the presence of prostate cancer (see, e.g., Merrill ef at., J. Urol. 163(2): 503-5120 (2000); Polascik ef al., J. Urol. Aug; 162(2):293-306 (1999) and Fortier ef al., J. Nat Cancer Inst. 91(19): 1635-1640(1999)). A variety of other diagnostic markers are also used in similar contexts including p53 and K-ras (see, e.g.,. Tulchinsky ef al., Int J Mo! Med 1999 Jui 4(1):99-102 and Minimoto ef al., Cancer Detect Prev 2000;24(1 ):1 -12). Therefore, this disclosure of 282P1G3 polynucleotides and polypeptides (as well as 282P1G3 polynucleotide probes and anti-282P1G3 antibodies used to identify the presence of these molecules) and their properties allows skilled artisans to utilize these molecules in methods that are analogous to those used, for example, in a variety of diagnostic assays directed to examining conditions associated with cancer. 70

Typical embodiments of diagnostic methods which utilize the 282P1G3 polynucleotides, polypeptides, reactive T cells and antibodies are analogous to those methods from well-established diagnostic assays, which employ, e.g., PSA polynucleotides, polypeptides, reactive T ceils and antibodies. For example, just as PSA polynucleotides are used as probes (for example in Northern analysis, see, e.g., Sharief et al., Biochem. Mol. Biol. Int. 33(3):567-74(1994)) and primers (for example in PCR analysis, see, e.g., Okegawa et a!., J. Urol. 163(4): 1189-1190 (2000)) to observe the presence and/or the level of PSA mRNAs in methods of monitoring PSA overexpression or the metastasis of prostate cancers, the 282P1G3 polynucleotides described herein can be utilized in the same way to detect 282P1G3 overexpression or the metastasis of prostate and other cancers expressing this gene. Alternatively, just as PSA polypeptides are used to generate antibodies specific for PSA which can then be used to observe the presence and/or the level of PSA proteins in methods to monitor PSA protein overexpression (see, e.g:, Stephan ef a/., Urology 55(4):560-3 (2000)) or the metastasis of prostate cells (see, e.g., Alanen ef a/., Pathol. Res. Pract. 192(3):233-7 (1996)), the 282P1G3 polypeptides described herein can be utilized to generate antibodies for use in detecting 282P1G3 overexpression or the metastasis of prostate cells and cells of other cancers expressing this gene.

Specifically, because metastases involves the movement of cancer cells from an organ of origin (such as the lung or prostate gland etc.) to a different area of the body (such as a lymph node), assays which examine a biological sample for the presence of cells expressing 282P1G3 polynucleotides and/or polypeptides can be used to provide evidence of metastasis. For example, when a biological sample from tissue that does not normally contain 282P1G3-expressing cells (lymph node) is found to contain 282P1 G3-expressing cells such as the 282P1G3 expression seen in LAPC4 and LAPC9, xenografts isolated from lymph node and bone metastasis, respectively, this finding is indicative of metastasis.

Alternatively 282P1G3 polynucleotides and/or polypeptides can be used to provide evidence of cancer, for example, when cells in a biological sample that do not normally express 282P1G3 or express 282P1G3 at a different level are found to express 282P1G3 or have an increased expression of 282P1G3 (see, e.g., the 282P1G3 expression in the cancers listed in Table I and in patient samples etc. shown in the accompanying Figures). In such assays, artisans may further wish to generate supplementary evidence of metastasis by testing the biological sample for the presence of a second tissue restricted marker (in addition to 282P1G3) such as PSA, PSCA etc. (see, e.g., Alanen ef a/., Pathol. Res. Pract. 192(3): 233-237 (1996)).

The use of immunohistochemistry to identify the presence of a 282P1G3 polypeptide within a tissue section can indicate an altered state of certain cells within that tissue. It is well understood in the art that the ability of an antibody to localize to a polypeptide that is expressed in cancer ceils is a way of diagnosing presence of disease, disease stage, progression and/or tumor aggressiveness. Such an antibody can also detect an altered distribution of the polypeptide within the cancer cells, as compared to corresponding non-maiignant tissue.

The 282P1G3 polypeptide and immunogenic compositions are also useful in view of the phenomena of altered subcellular protein localization in disease states. Alteration of cells from normal to diseased state causes changes in cellular morphology and is often associated with changes in subcellular protein localization/distribution. For example, cell membrane proteins that are expressed in a polarized manner in normal cells can be altered in disease, resulting in distribution of the protein in a non-polar manner over the whole cell surface.

The phenomenon of altered subcellular protein localization in a disease state has been demonstrated with MUC1 and Her2 protein expression by use of immunohistochemical means. Normal epithelial cells have a typical apical distribution of MUC1, in addition to some supranuclear localization of the glycoprotein, whereas malignant lesions often demonstrate an apolar staining pattern (Diaz ef al, The Breast Journal, 7; 40-45 (2001); Zhang ef a/, Clinical Cancer Research, 4; 2669-2676 (1998): Cao, ef al, The Journal of Histochemistry and Cytochemistry, 45:1547-1557 (1997)). In addition, normal breast epithelium is either negative for Her2 protein or exhibits only a basoiateral distribution whereas malignant cells can express 71 the protein over the whole cell surface (De Potter, etal, International Journal of Cancer, 44; 969-974 (1989); McCormick, ef al, 117; 935-943 (2002)). Alternatively, distribution of the protein may be altered from a surface only localization to include diffuse cytoplasmic expression in the diseased state. Such an example can be seen with MUC1 (Diaz, ef at, The Breast Journai, 7: 40-45 (2001)).

Alteration in the locatization/distribution of a protein in the celt, as detected by immunohistochemical methods, can also provide valuable information concerning the favorabiiity of certain treatment modalities. This last point is illustrated by a situation where a protein may be intracellular in normal tissue, but cell surface-in malignant cells; the cell surface location makes the ceils favorably amenable to antibody-based diagnostic and treatment regimens. When such an alteration of protein localization occurs for 282P1G3, the 282P1G3 protein and immune responses related thereto are very useful. Accordingly, the ability to determine whether alteration of subcellular protein localization occurred for 24P4C12 make the. 282P1G3 protein and immune responses related thereto very useful. Use of the 282P1G3 compositions allows those skilled in the art to make important diagnostic and therapeutic decisions.

Immunohistochemical reagents specific to 282P1G3 are also useful to detect metastases of tumors expressing 282P1G3 when the polypeptide appears in tissues where 282P1G3 is not normally produced.

Thus, 282P1G3 polypeptides and antibodies resulting from immune responses thereto are useful in a variety of important contexts such as diagnostic, prognostic, preventative and/or therapeutic purposes known to those skilled in the art

Just as PSA polynucleotide fragments and polynucleotide variants are employed by skilled artisans for use in methods of monitoring PSA, 282P1G3 polynucleotide fragments and polynucleotide variants are used in an analogous manner. In particular, typical PSA polynucleotides used in methods of monitoring PSA are probes or primers which consist of fragments of the PSA cDNA sequence. Illustrating this, primers used to PCR amplify a PSA polynucleotide must include less than the whole PSA sequence to function in the polymerase chain reaction. In the context of such PCR reactions, skilled artisans generally create a variety of different polynucleotide fragments that can be used as primers in order to amplify different portions of a polynucleotide of interest or to optimize amplification reactions (see, e.g., Caetano-Anoiles, G. Biotechniques 25(3); 472-475,478-480 (1998); Robertson ef al., Methods Mol. Biot. 98:121-154 (1998)). An additional illustration of the use of such fragments is provided in the Example entitled “Expression analysis of 282P1G3 in norma! tissues, and patient specimens." where a 282P1G3 polynucleotide fragment is used as a probe to show the expression of 282P1G3 RNAs in cancer cells. In addition, variant polynucleotide sequences are typically used as primers and probes for the corresponding mRNAs in PCR and Northern analyses (see, e.g., Sawai et al., Fetal Diagn. Ther. 1996 Nov-Dec 11(6):407-13 and Current Protocols In Molecular Biology, Volume 2, Unit 2, Frederick M. Ausubei ef al. eds., 1995)). Polynucleotide fragments and variants are useful in this context where they are capable of binding to a target polynucleotide sequence (e.g., a 282P1G3 polynucleotide shown in Figure 2 or variant thereof) under conditions of high stringency.

Furthermore, PSA polypeptides which contain an epitope that can be recognized by an antibody or T celt that specifically binds to that epitope are used in methods of monitoring PSA 282P1G3 polypeptide fragments and polypeptide analogs or variants can also be used in an analogous manner. This practice of using polypeptide fragments or polypeptide variants to generate antibodies (such as anti-PSA antibodies or T celis) is typical in the art with a wide variety of systems such as fusion proteins being used by practitioners (see, e.g., Current Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubei ef al. eds., 1995). In this context, each epitope(s) functions to provide the architecture with which an antibody or T ceil is reactive. Typically, skilled artisans create a variety of different polypeptide fragments that can be used in order to generate immune responses specific for different portions of a polypeptide of interest (see, e.g., U.S. Patent No. 5,840,501 and U.S. Patent No. 5,939,533). For example it may be preferable to utilize a polypeptide comprising one of the 282P1G3 biological motifs discussed herein or a motif-bearing subsequence which is readily identified by one of skill in the art based on motifs available in the art. Polypeptide fragments, variants or analogs are typically useful in this context as long 72 as-they comprise an epitope capable of generating an antibody or T cell specific for a target polypeptide sequence (e.g. a 282P1G3 polypeptide shown in Figure 3).

As shown herein, the 282P1G3 polynucleotides and polypeptides (as well as the 282P1G3 polynucleotide probes and anti-282P1 G3 antibodies or T cells used to identity the presence of these molecules) exhibit specific properties that make them useful in diagnosing cancers such as those fisted in Table I. Diagnostic assays that measure the presence of 282P1G3 gene products, in order to evaluate the presence or onset of a disease condition described herein, such as prostate cancer, are used to identify patients for preventive measures or further monitoring, as has been done so successfully with PSA Moreover, these materials satisfy a need in the art for molecules having similar or complementary characteristics to PSA in situations where, for example, a definite diagnosis of metastasis of prostatic origin cannot be made on the basis of a test for PSA alone (see, e.g., Alanen etal., Pathol. Res. PracL 192(3): 233-237 (1996)), and consequently, materials such as 282P1G3 polynucleotides and polypeptides (as well as the 282P1G3 polynucleotide probes and anti-282P1G3 antibodies used to identify the presence of these molecules) need to be employed to confirm a metastases of prostatic origin.

Finally, in addition to their use in diagnostic assays, the 282P1G3 polynucleotides disclosed herein have a number of other utilities such as their use in the identification of oncogenetic associated chromosomal abnormalities in the chromosomal region to which the 282P1G3 gene maps (see the Example entitled “Chromosomal Mapping of 282P1G3” below). Moreover, in addition to their use in diagnostic assays, the 282P1 G3-related proteins and polynucleotides disclosed herein have other utilities such as their use in the forensic analysis of tissues of unknown origin (see, e.g., Takahama K Forensic Sci Int 1996 Jun 28;80(1-2): 63-9).

Additionally, 282P1G3-related proteins or polynucleotides of the invention can be used to treat a pathologic condition characterized by the over-expression of 282P1G3. For example, the amino acid or nucleic acid sequence of Figure 2 or Figure 3, or fragments of either, can be used to generate an immune response to a 282P1G3 antigen. Antibodies or other molecules that react with 282P1G3 can be used to modulate the function of this molecule, and thereby provide a therapeutic benefit. XII.) inhibition of 282P1G3 Protein Function

The invention includes various methods and compositions for inhibiting the binding of 282P1G3 to its binding partner or its associatiorowith other protein(s) as well as methods for inhibiting 282P1G3 function. X11.A.) Inhibition of 282P1G3 With intracellular Antibodies

In one approach, a recombinant vector that encodes single chain antibodies that specifically bind to 282P1G3 are introduced into 282P1G3 expressing cells via gene transfer technologies. Accordingly, the encoded single chain anti-282P1G3 antibody is expressed intracellularly, binds to 282P1G3 protein, and thereby inhibits its function. Methods for engineering such intracellular single chain antibodies are well known. Such intracellular antibodies, also known as “intrabodies", are specifically targeted to a particular compartment within the ceil, providing control over where the inhibitory activity of the treatment is focused. This technology has been successfully applied in the art (for review, see Richardson and Marasco, 1995, TIBTECH vol. 13). Intrabodies have been shown to virtually eliminate the expression of otherwise abundant cell surface receptors (see, e.g., Richardson ef al., 1995, Proc. Natl. Acad. Sci. USA 92: 3137-3141; Beerii ef a/., 1994, J. Biol. Chem. 289:23931-23936; Deshane et al., 1994, Gene Ther. 1:332-337).

Single chain antibodies comprise the variable domains of the heavy and light chain joined by a flexible linker polypeptide, and are expressed as a single polypeptide. Optionally, single chain antibodies are expressed as a single chain variable region fragment joined to the light chain constant region. Well-known intracellular trafficking signals are engineered 73 into recombinant polynucleotide vectors encoding such single chain antibodies in order to target precisely the intrabody to the desired intracellular compartment. For example, intrabodies targeted to the endoplasmic reticulum (ER) are engineered to incorporate a leader peptide and, optionally, a C-terminal ER retention signal, such as the KDEL amino acid motif. Intrabodies intended to exert activity in the nucleus are engineered to include a nuclear localization signal. Lipid moieties are joined to intrabodies in order to tether the intrabody to the cytosolic side of the plasma membrane. Intrabodies can also be targeted to exert function in the cytosol. For example, cytosolic intrabodies are used to sequester factors within toe c'/tosol, thereby preventing them from being transported to their natural cellular destination.

In one embodiment, intrabodies are used to capture 282P1G3 in toe nucleus, thereby preventing its activity within the nucleus. Nuclear targeting signals are engineered into such 282P1G3 intrabodies in order to achieve the desired targeting. Such 282P1G3 intrabodies are designed to bind specifically to a particular 282P1G3 domain. In another embodiment, cytosolic intrabodies that specifically bind to a 282P1G3 protein are used to prevent 282P1G3 from gaining access to the nucleus, thereby preventing it from exerting any biological activity within the nucleus (e.g., preventing 282P1G3 from forming transcription complexes with other factors).

In order to specifically direct the expression of such intrabodies to particular cells, the transcription of the intrabody is placed under the regulatory control of an appropriate tumor-specific promoter and/or enhancer. In order to target intrabody expression specifically to prostate, for example, toe PSA promoter and/or promoter/enhancer can be utilized (See, for example, U.S. Patent No. 5,919,652 issued 6 July 1999).

Xll.B.) Inhibition of 282P1G3 with Recombinant Proteins in another approach, recombinant molecules bind to 282P1G3 and thereby inhibit 282P1G3 function. For example, these recombinant molecules prevent or inhibit 282P1G3 from accessing/binding to its binding partners) or associating with other protein(s). Such recombinant molecules can, for example, contain the reactive part(s) of a 282P1G3 specific antibody molecule. In a particular embodimenf the 282P1G3 binding domain of a 282P1G3 binding partner is engineered into a dimeric fusion protein, whereby the fusion protein comprises two 282P1G3 figand binding domains linked to the Fc portion of a human IgG, such as human lgG1. Such IgG portion can contain, for example, toe Ch2 and Ch3 domains and the hinge region, but not the Ch1 domain. Such dimeric fusion proteins are administered in soluble form fo patients suffering from a cancer associated with toe expression of 282P1G3, whereby the dimeric fusion protein specifically binds to 282P1G3 and blocks 282P1G3 interaction with,a binding partner. Such dimeric fusion proteins are further combined into multimeric proteins using known antibody linking technologies.

Xll.C.) inhibition of 282P1G3 Transcription or Translation

The present invention also comprises various methods and compositions for inhibiting toe transcription of the 282P1G3 gene. Similarly, the invention also provides methods and compositions for inhibiting the translation of 282P1G3 mRNA into protein.

In one approach, a method of inhibiting the transcription of toe 282P1G3 gene comprises contacting toe 282P1G3 gene with a 282P1G3 antisense polynucleotide. In another approach, a method of inhibiting 282P1G3 mRNA translation comprises contacting a 282P1G3 mRNA with an antisense polynucleotide, in another approach, a 282P1G3 specific ribozyme is used to cleave a 282P1G3 message, thereby inhibiting translation. Such antisense and ribozyme based methods can also be directed to the regulatory regions of toe 282P1G3 gene, such as 282P1G3 promoter and/or enhancer elements. Similarly, proteins capable of inhibiting a 282P1G3 gene transcription factor are used to inhibit 282P1G3 mRNA transcription. The various polynucleotides and compositions useful in the aforementioned methods have been described above. The use of antisense and ribozyme molecules to inhibit transcription and translation is well known in the art. 74

Other factors that inhibit the transcription of 282P1G3 by interfering with 282P1G3 transcriptional activation are also useful to treat cancers expressing 282P1G3. Similarly, factors that interfere with 282P1G3 processing are useful to treat cancers that express 282P1G3. Cancer treatment methods utilizing such factors are also within the scope of the invention.

Xll.D.) General Considerations for Therapeutic Strategies

Gene transfer and gene therapy technologies can be used to deliver therapeutic polynucleotide molecules to tumor ceils synthesizing 282P1G3 (i.e., antisense, ribozyme, polynucleotides encoding intrabodies and other 282P1G3 inhibitory molecules). A number of gene therapy approaches are known in the art Recombinant vectors encoding 282P1G3 antisense polynucleotides, ribozymes, factors capable of interfering with 282P1G3 transcription, and so forth, can be delivered to target tumor cells using such gene therapy approaches.

The above therapeutic approaches can be combined with any one of a wide variety of surgical, chemotherapy or radiation therapy regimens. The therapeutic approaches of the invention can enable the use of reduced dosages of chemotherapy (or other therapies) and/or less frequent administration, an advantage for all patients and particuiariy for those that do not tolerate the toxicity of the chemotherapeutic agent well.

The anti-tumor activity of a particular composition (e.g., antisense, ribozyme, intrabody), or a combination of such compositions, can be evaluated using various in vitro and in vivo assay systems, in vitro assays that evaluate therapeutic activity include ceil growth assays, soft agar assays and other assays indicative of tumor promoting activity, binding assays capable of determining the extent to which a therapeutic composition will inhibit the binding of 282P1G3 to a binding partner, etc.

In vivo, the effect of a 282P1G3 therapeutic composition can be evaluated in a suitable animal model. For example, xenogenic prostate cancer models can be used, wherein human prostate cancer explants or passaged xenograft tissues are introduced into immune compromised animals, such as nude or SCID mice (Klein ef al., 1997, Nature Medicine 3:402-408). For example, PCT Patent Application WO98/16628 and U.S. Patent 6,107,540 describe various xenograft models of human prostate cancer capable of recapitulating the development of primary tumors, micrometastasis, and the formation of osteoblastic metastases characteristic of late stage disease. Efficacy can be predicted using assays that measure inhibition of tumor formation, tumor regression or metastasis, and the like. in vivo assays that evaluate the promotion of apoptosis are useful in evaluating therapeutic compositions, in one embodiment, xenografts from tumor bearing mice treated with the therapeutic composition can be examined for the presence of apoptotic foci and compared to untreated controi xenograft-bearing mice. The extent to which apoptotic foci are found in the tumors of the treated mice provides an indication of the therapeutic efficacy of the composition.

The therapeutic compositions used in the practice of the foregoing methods can be formulated into pharmaceutical compositions comprising a carrier suitable for the desired delivery method. Suitable carriers include any material that when combined with the therapeutic composition retains the anti-tumor function of the therapeutic composition and is generally non-reactive with the patient's immune system. Examples include, but are not limited to, any of a number of standard pharmaceutical carriers such as sterile phosphate buffered saline solutions, bacteriostatic water, and the like (see, generally, Remington’s Pharmaceutical Sciences 1681 Edition, A. OsaL, Ed., 1980).

Therapeutic formulations can be solubilized and administered via any route capable of delivering the therapeutic composition to the tumor site. Potentially effective routes of administration include, but are not limited to, intravenous, parenteral, intraperitoneal, intramuscular, intratumor, intradermal, intraorgan, orthotopic, and the like. A preferred formulation for intravenous injection comprises the therapeutic composition in a soiution of preserved bacteriostatic water, sterile unpreserved water, and/or diluted in polyvinylchloride or polyethylene bags containing 0.9% sterile Sodium Chloride for injection, USP. Therapeutic protein preparations can be lyophiiized and stored as sterile powders, preferably under 75 vacuum, and then reconstituted in bacteriostatic water (containing for example, benzyl alcohol preservative) or in sterile water prior to injection.

Dosages and administration protocols for the trealment of cancers using the foregoing methods will vary with the method and the target cancer, and will generally depend on a number of other factors appreciated in the art. XII),) Identification, Characterization and Use of Modulators of 282P1G3

Methods to Identify and Use Modulators

In one embodiment, screening is performed to identify modulators that induce or suppress a particular expression profile, suppress or induce specific pathways, preferably generating the associated phenotype thereby. In another embodiment, having identified differentially expressed genes important in a particular state; screens are performed to identify modulators that alter expression of individual genes, either increase or decrease. In another embodiment, screening is performed to identity modulators that alter a biological function of the expression product of a differentially expressed gene. Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product

In addition, screens are done for genes that are induced in response to a candidate agent. After identifying a modulator (one that suppresses a cancer expression pattern leading to a normal expression pattern, or a modulator of a cancer gene that leads to expression of the gene as in norma! tissue) a screen is performed to identify genes that are specifically modulated in response to the agent Comparing expression profiles between normal tissue and agent-treated cancer tissue reveals genes that are not expressed in normal tissue or cancer tissue, but are expressed in agent treated tissue, and vice versa. These agent-specific sequences are identified and used by methods described herein for cancer genes or proteins, in particular these sequences and the proteins they encode are used in marking or identifying agent-treated cells, in addition, antibodies are raised against the agent-induced proteins and used to target novel therapeutics to the treated cancer tissue sample.

Modulator-related Identification and Screening Assays:

Gene Expression-related Assays

Proteins, nucleic acids, and antibodies of the invention are used in screening assays. The cancer-associated proteins, antibodies, nucjeic acids, modified proteins and cells containing these sequences are used in screening assays, such as evaluating the effect of drug candidates on a "gene expression profile,” expression profile of polypeptides or alteration of biological function. In one embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent (e.g., Davis, GF, et al, J Biol Screen 7:69 (2002); Ziokarnik, et al., Science 279:84-8 (1998); Heid, Genome Res 6:986-94,1996).

The cancer proteins, antibodies, nucleic acids, modified proteins and ceils containing the native or modified cancer proteins or genes are used in screening assays. That is, the present invention comprises methods for screening for compositions which modulate the cancer phenotype or a physiological function of a cancer protein of the invention. This is done on a gene itself or by evaluating the effect of drug candidates on a "gene expression profile" or biologicai function, in one embodiment, expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring after treatment with a candidate agent, see Ziokarnik, supra. A variety of assays are executed directed to the genes and proteins of the invention. Assays are run on an individual nucleic acid or protein level. That is, having identified a particular gene as up regulated in cancer, test compounds are screened for the ability to modulate gene expression or for binding to the cancer protein of the invention. "Modulation" in 76 this context includes an increase or a decrease in gene expression. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tissue undergoing cancer, with changes of at least 10%, preferably 50%, more preferably 100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene exhibits a 4-fold increase in cancer tissue compared to normal tissue, a decrease of about four-fold is often desired; similarly, a 10-fold decrease in cancer tissue compared to normal tissue a target value of a 10-foid increase in expression by the test compound is often desired. Modulators that exacerbate the type of gene expression seen in cancer are also useful, e.g., as an upreguiated target in further analyses.

The amount of gene expression is monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, a gene product itself is monitored, e.g., through the use of antibodies to the cancer protein and standard immunoassays. Proteomics and separation techniques aiso allow for quantification of expression.

Expression Monitoring to Identify Compounds that Modify Gene Expression

In one embodiment, gene expression monitoring, i.e., an expression profile, is monitored simultaneously for a number of entities. Such profiles will typically involve one or more of the genes of Figure 2. in this embodiment, e.g., cancer nucleic acid probes are attached to biochips to detect and quantify cancer sequences in a particular celi. Alternatively, PCR can be used. Thus, a series, e.g., wells of a microtiter plate, can be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well.

Expression monitoring is performed to identify compounds that modify the expression of one or more cancer-associated sequences, e.g., a polynucleotide sequence set out in Figure 2. Generally, a test modulator is added to the celis prior to analysis. Moreover, screens are also provided to identify agents that modulate cancer, modulate cancer proteins of the invention, bind to a cancer protein of the invention, or interfere with the binding of a cancer protein ofthe invention and an.antibody or other binding partner.

In one embodiment, high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such ''combinatorial chemical libraries" are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds," as compounds for screening, or as therapeutics.

In certain embodiments, combinatorial libraries of potential modulators are screened for an ability to bind to a cancer polypeptide or to-ipodulate activity. Conventionally, new chemical entities with useful properties are generated by identifying a chemical compound (called a "lead compound”) with some desirable property or activity, e.g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis.

As noted above, gene expression monitoring is conveniently used to test candidate modulators (e.g., protein, nucleic acid or smaii moiecuie). After the candidate agent has been added and the ceiis allowed to incubate for a period, the sample containing a target sequence to be analyzed is, e.g., added to a biochip. if required, the target sequence is prepared using known techniques. For example, a sample is treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate. For example, an in vitro transcription with labels covalently attached to the nucleotides is performed. Generally, the nucleic acids are labeled with biotin-FITC or PE, or with cy3 or cy5.

The target sequence can be labeled with, e.g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that is detected. Alternatively, the label is a labeled compound or small molecule, such as an enzyme inhibitor, that 77 binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis.

As will be appreciated by those in the art, these assays can be direct hybridization assays or can comprise “sandwich assays", which include the use of multiple probes, as is generally outlined in U.S. Patent Nos. 5,581,702; 5,597,909; 5,545,730; 5,594,117; 5,591,584; 5,571,670; 5,580,731; 5,571,670; 5,591,584; 5,624,802; 5,635,352; 5,594,118; 5,359,100; 5,124,246; and 5,681,697. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex. A variety of hybridization conditions are used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allow formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaoiropic salt concentration pH, organic solvent concentration, etc. These parameters may also be used to control non-specific binding, as is generally outlined in U.S. Patent No. 5,681,697. Thus, it can be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.

The reactions outlined herein can be accomplished in a variety of ways. Components of the reaction can be added simultaneously, or sequentially, in different orders, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g. albumin, detergents, etc. which can be used to facilitate optimal hybridization and detection, and/or reduce nonspecific or background interactions. Reagents that

I otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target The assay data are analyzed to determine the expression levels of individual genes, and changes in expression levels as between states, forming a gene expression profile.

Biological Activity-related Assays

The inventiorrprovides methods identify or screen for a compound that modulates the activity of a cancer-related gene or protein of the invention. The methods comprise adding a test compound, as defined above, to a ceil comprising a cancer protein of the invention. The cells contain a recombinant nucleic acid that encodes a cancer protein of the invention. In another embodiment, a library of candidate agents is tested on a plurality of cells.

In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e.g. hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i.e., cell-cell contacts). In another example, the determinations are made at different stages of the ceil cycle process. In this way, compounds that modulate genes or proteins of the invention are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the cancer protein of the invention. Once identified, similar structures are evaluated to identify critical structural features of the compound.

In one embodiment, a method of modulating (e.g., inhibiting) cancer cell division is provided; the method comprises administration of a cancer modulator. In another embodiment, a method of modulating (e.g., inhibiting) cancer is provided; the method comprises administration of a cancer modulator, in a further embodiment, methods of treating cells or individuals with cancer are provided; the method comprises administration of a cancer modulator. 78

In one embodiment, a method for modulating the status of a cell that expresses a gene of the invention is provided. As used herein status comprises such art-accepted parameters such as growth, proliferation, survival, function, apoptosis, senescence, location, enzymatic activity, signal transduction, etc. of a cell. In one embodiment, a cancer inhibitor is an antibody as discussed above. In another embodiment, the cancer inhibitor is an antisense molecule. A variety of cell growth, proliferation, and metastasis assays are known to those of skill in the art, as described herein.

High Throughput Screening to Identify Modulators

The assays to identify suitable modulators are amenable to high throughput screening. Preferred assays thus detect enhancement or inhibition of cancer gene transcription, inhibition or enhancement of polypeptide expression, and inhibition or enhancement of polypeptide activity. in one embodiment, modulators evaluated in high throughput screening methods are proteins, often naturally occurring proteins or fragments of naturally occurring proteins. Thus, e.g., cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, are used. In this way, libraries of proteins are made for screening in the methods of the invention. Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred. Particularly useful test compound will be directed to the class of proteins to which the target belongs, e.g., substrates for enzymes, or ligands and receptors.

Use of Soft Agar Growth and Colony Formation to Identify and Characterize Modulators

Normal cells require a solid substrate to attach and grow. When cells are transformed, they lose this phenotype and grow detached from the substrate. For example, transformed cells can grow in stirred suspension culture or suspended in semi-solid media, such as semi-solid or soft agar. The transformed cells, when transfected with tumor suppressor genes, can regenerate normal phenotype and once again require a solid substrate to attach io and grow. Soft agar growth or colony formation in assays are used to identify modulators of cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation. A modulator reduces or eliminates the host cells' ability to grow suspended in solid or semisolid media, such as agar.

Techniques for soft agar growlh or colony formation in suspension assays are described in Freshney, Culture of Animal Cells a Manual of Basic Technique (3rd ed., 1994). See also, the methods section of Garkavtsev et al. (1996), supra.

Evaluation of Contact Inhibition and Growth Density Limitation to Identify and Characterize Modulators

Normal cells typically grow in a flat and organized pattern in cel! culture until they touch other cells. When the cells touch one another, they are contact inhibited and stop growing. Transformed cells, however, are not contact inhibited and continue to grow to high densities in disorganized foci. Thus, transformed cells grow to a higher saturation density than corresponding normal cells. This is detected morphologically by the formation of a disoriented monolayer of cells or cells in foci. Alternatively, labeling index with (3H)-thymidine at saturation density is used to measure density limitation of growth, similarly an MTT or Alamar blue assay will reveal proliferation capacity of cells and toe toe ability of modulators to affect same. See Freshney (1994), supra. Transformed cells, when transfected with tumor suppressor genes, can regenerate a normal phenotype and become contact inhibited and would grow to a lower density.

In this assay, labeling index with 3H)-thymidine at saturation density is a preferred method of measuring density limitation of growth. Transformed host celts are transfected with a cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions. The percentage of cells labeling with (3H)-thymidine is determined by incorporated cpm.

Contact independent growth is used to identify modulators of cancer sequences, which had led to abnormal cellular proliferation and transformation. A modulator reduces or eliminates contact independent growth, and returns the cells to a normal phenotype. 79

Evaluation of Growth Factor or Serum Dependence to Identify and Characterize Modulators

Transformed cells have lower serum dependence than their norma! counterparts (see, e.g., Temin, J. Natl. Cancer Inst. 37:167-175 (1966); Eagle et al., J. Exp. Med 131:836-879 (1970)); Freshney, supra. This is in part due to release of various growth factors by the transformed ceils. The degree of growth factor or serum dependence of transformed host celis can be compared with that of control. For example, growth factor or serum dependence of a ceil is monitored in methods to identify and characterize compounds that modulate cancer-associated sequences of the invention.

Use of Tumor-specific Marker Levels to Identify and Characterize Modulators Tumor celis release an increased amount of certain factors (hereinafter "tumor specific markers”) than their normal counterparts. For example, plasminogen activator (PA) is released from human glioma at a higher level than from normat brain cells (see, e.g., Guliino, Angiogenesis, Tumor Vascularization, and Potential Interference with Tumor Growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985)). Similarly, Tumor Angiogenesis Factor (TAF) is released at a higher level in tumor cells than their normal counterparts. See, e.g., Folkman, Angiogenesis and Cancer, Sem Cancer Biol. (1992)), while bFGF is released from endothelial tumors (Ensoli, B et al).

Various techniques which measure the release of these factors are described in Freshney (1994), supra. Also, see, Unkless et al., J. Biol. Chem. 249:4295-4305 (1974); Strickland & Beers, J. Biol. Chem. 251:5694-5702 (1976); Whur et a!., Br. J. Cancer 42:305 312 (1980); Guliino, Angiogenesis, Tumor Vascularization, and Potential Interference with Tumor Growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985); Freshney, Anticancer Res. 5:111-130 (1985).

For example, tumor specific marker levels are monitored in methods to identify and characterize compounds that modulate cancer-associated sequences of the invention. invasiveness into Matriqel to Identify and Characterize Modulators

The degree of invasiveness into Matrigel or an extracellular matrix constituent can be used as an assay to identify and characterize compounds that modulate cancer associated sequences. Tumor cells exhibit a positive correlation between malignancy and invasiveness of ceiis into Matrigel or some other extracellular matrix constituent in this assay, tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells. Techniques described in Cancer Res. 1999; 59:6010; Freshney (1994), supra, can be used. Briefly, the level of invasion of host ceils is measured by using fitters coated with Matrigel or some other extracellular matrix constituent. Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by numbepof cells and distance moved, or by prelabeiing the cells with 1251 and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e.g., Freshney (1984), supra.

Evaluation of Tumor Growth In Vivo io Identify and Characterize Modulators

Effects of cancer-associated sequences on cell growth are tested in transgenic or immune-suppressed organisms. Transgenic organisms are prepared in a variety of art-accepted ways. For example, knock-out transgenic organisms, e.g., mammals such as mice, are made, in which a cancer gene is disrupted or in which a cancer gene is inserted. Knock-out transgenic mice are made by insertion of a marker gene or other heterologous gene into the endogenous cancer gene site in the mouse genome via homologous recombination. Such mice can also be made by substituting the endogenous cancer ί gene with a mutated version of the cancer gene, or by mutating the endogenous cancer gene, e.g., by exposure to carcinogens.

To prepare transgenic chimeric animals, e.g., mice, a DNA construct is introduced into the nuclei of embryonic stem celis. Ceils containing the newly engineered genetic lesion are injected into a host mouse embryo, which is reimplanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells some of which are derived from the mutant ceil line. Therefore, by breeding the chimeric mice it is possible to obtain a new tine of mice containing the introduced genetic lesion (see, e.g., Capecchi et al., Science 244:1288 (1989)). Chimeric mice can be derived 80 according to US Patent 6,365,797, issued 2 April 2002; US Patent 6,107,540 issued 22 August 2000; Hogan et al., Manipulating the Mouse Embryo: A laboratory Manual, Cold Spring Harbor Laboratory (1988) and Teratocarcinomas and Embryonic Stem Ceils: A Practical Approach, Robertson, ed., IRL Press, Washington, D.C., (1987).

Alternatively, various immune-suppressed or immune-deficient host animals can be used. For example, a genetically athymic "nude” mouse (see, e.g., Giovaneiia et a!., J. Natl. Cancer Inst. 52:921 (1974)), a SCID mouse, a thymectornized mouse, or an irradiated mouse (see, e.g., Bradley et al., Br. J. Cancer 38:263 (1978); Selby et a!., Br. J. Cancer 41:52 (1980)) can be used as a host Transplantable tumor celis (typically about 10s cells) injected.into isogenic hosts produce invasive tumors in a high proportion of cases, while normal cells of similar origin will not In hosts which developed invasive tumors, celis expressing cancer-associated sequences are injected subcutaneously or orthotopicaily. Mice are then separated into groups,· including control groups and treated experimental groups) e.g. treated with a modulator). After a suitable length of time, preferably 4-8 weeks, tumor growth is measured (e.g., by volume or by its two largest dimensions, or weight) and compared to the control. Tumors that have statistically significant reduction (using, e.g., Student's T test) are said to have inhibited growth.

In Vitro Assays to Identify and Characterize Modulators

Assays to identify compounds with modulating activity can be performed in vitro. For example, a cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e.g., from 0.5 to 48 hours, in one embodiment, the cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA. The level of protein is measured using immunoassays such as Western blotting, ELISA and the like with an antibody that selectively binds to the cancer polypeptide or a fragment thereof. For measurement of mRNA amplification, e.g., using PCR, LCR, or hybridization assays, e. g., Northern hybridization, RNAse protection, dot blotting, are preferred. The level of protein or mRNA is detected using directly or indirectly labeled detection agents, e.g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein.

Alternatively, a reporter gene system can be devised using a cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or P-gai. The reporter construct is typically transfected into a cell. After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques known to those of skill in the art (Davis GF, supra; Gonzalez, J. & Negulescu, P. Curr. Opin. Biotechnol. 1998: Q:624).

As outlined above, in vitro screens are done on individual genes and gene products. That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself is performed.

In one embodiment, screening for modulators of expression of specific gene(s) is performed. Typically, the expression of only one or a few genes is evaluated. In another embodiment, screens are designed to first find compounds that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity. Moreover, once initial candidate compounds are identified, variants can be further screened to better evaluate structure activity relationships.

Binding Assays to Identify and Characterize Modulators in binding assays in accordance with the invention, a purified or isolated gene product of the invention is generally used. For example, antibodies are generated to a protein of the invention, and immunoassays are run to determine the amount and/or location of protein. Alternatively, ceils comprising the cancer proteins are used in the assays. 81

Thus, the methods comprise combining a cancer protein of the invention and a candidate compound such as a ligand, and determining the binding of the compound to the cancer protein of the invention. Preferred embodiments utilize the human cancer protein; animai models of human disease of can also be developed and used. Also, other analogous mammalian proteins also can be used as appreciated by those of skill in the art. Moreover, in some embodiments variant or derivative cancer proteins are used.

Generally, the cancer protein of the invention, or the ligand, is non-diffusibiy bound to an insoluble support. The support can, e.g., be one having isolated sample receiving areas (a microtiter plate, an array, etc.). The insoluble supports can be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports can be solid or porous and of any convenient shape.

Examples of suitable insoluble supports include microtiter plates, arrays, membranes and beads. These are typically made of glass, plastic {e.g., polystyrene), polysaccharide, nylon, nitrocellulose, or Teflon™, etc. Microtiter plates and arrays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition io the support is not crucial so long as it is-compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable. Preferred methods of binding include the use of antibodies which do not sterically block either the ligand binding site or activation sequence when attaching the protein to the support, direct binding to "sticky” or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding.of the protein or ligand/binding agent to the support, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety. -

Once a cancer protein of toe invention is bound to toe support, and a test compound is added to toe assay. Alternatively, the candidate binding agent is bound to the support and the cancer protein of toe invention is then added. Binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc.

Of particular interest are assays to identify agents that have a low toxicity for human cells. A wide variety of assays can be used for tin's purpose, including proliferation assays, cAMP assays, labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like. A determination of binding of the test compound (ligand, binding agent, modulator, etc.) to a cancer protein of the invention can be done in a number of ways. The test compound can be labeled, and binding determined directly, e.g., by attaching all or a portion of the cancer protein of the invention to a solid support, adding a labeled candidate compound (e.g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps can be utilized as appropriate.

In certain embodiments, only one of the components is labeled, e.g., a protein of the invention or ligands labeled. Alternatively, more than one component is labeled with different labels, e.g., I125, for the proteins and a fluorophor for the compound. Proximity reagents, e.g., quenching or energy transfer reagents are also useful.

Competitive Binding to Identify and Characterize Modulators

In one embodiment, the binding of the “test compound" is determined by competitive binding assay with a “competitor.” The competitor is a binding moiety that binds to the target molecule (e.g., a cancer protein of the invention). Competitors include compounds such as antibodies, peptides, binding partners, ligands, etc. Under certain circumstances, the competitive binding between the test compound and the competitor displaces the test compound. In one embodiment, the test compound is labeled. Either the test compound, the competitor, or both, is added to the protein for a time sufficient 82 to allow binding. Incubations are performed at a temperature that facilitates optimal activity, typically between four and 40°C.

Incubation periods are typically optimized, e.g., to facilitate rapid high throughput screening; typically between zero and one hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.

In one embodiment, the competitor is added first, followed by the test compound. Displacement of the competitor is an indication that the test compound is binding to the cancer protein, and thus is capable of binding to, and potentially modulating, the activity of the cancer protein. In this embodiment, either component can be labeled. Thus, e.g., if the competitor is labeled, the presence of label in the post-test compound wash solution indicates displacement by the test compound. Alternatively, if the test compound is labeled, the presence of the label on the support indicates displacement

In an alternative embodiment, the test compound is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor indicates that the test compound binds to the cancer protein with higher affinity than the competitor. Thus, if the test compound is labeled, the presence of the label on the support, coupled with a lack of competitor binding, indicates that the test compound binds to and thus potentially modulates the cancer protein of the invention.

Accordingly, .the competitive binding methods comprise differential screening to identity agents that are capable of modulating the activity of the cancer proteins of the invention. In this embodiment, the methods comprise combining a cancer protein and a competitor in a first sample. A second sample comprises a test compound, the cancer protein, and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the cancer protein.

Alternatively, differential screening is used to identify drug candidates that bind to the native cancer protein, but cannot bind to modified cancer proteins. For example toe structure of toe cancer protein is modeled and used in rational drug design to synthesize agents that interact with that site, agents which generally do not bind to site-modified proteins. Moreover, such drug candidates that affect the activity of a native cancer protein are also identified by screening drugs for the ability to either enhance or reduce the activity of such proteins.

Positive controls and negative controls can be used in the assays. Preferably control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples occurs for a time sufficient to allow for the binding of toe agent to toe protein. Following incubation, samples are washed free of non-specifically bound. materia! and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples can be counted in a scintillation counter to determine the amount of bound compound. A variety of other reagents can be included in toe screening assays. These include reagents like salts, neutral proteins, e.g. albumin, detergents, etc. which are used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of toe assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., can be used. The mixture of components is added in an order that provides for the requisite binding.

Use of Polynucleotides to Down-requiate or Inhibit a Protein of the Invention.

Polynucleotide modulators of cancer can be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand-binding molecule, as described in WO 91/04753. Suitable ligand-binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with toe ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of toe sense or antisense oligonucleotide 83 or its conjugated version into the cell. Alternatively, a polynucleotide modulator of cancer can be introduced into a ceil containing the target nucleic acid sequence, e.g., by formation of a polynucleotide-lipid complex, as described in WO 90/10448. it is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment

Inhibitory and Antisense Nucleotides in certain embodiments, the activity of a cancer-associated protein is down-regulated, or entirely inhibited, by the use of antisense polynucleotide or inhibitory small nuclear RNA (snRNA), i.e., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a cancer protein of the invention, mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or, stability of the mRNA. in the context of this invention, antisense polynucleotides can comprise naturally occurring nucleotides, or synthetic species formed from naturally occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter-sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species which are known for use in the art. Analogs are comprised by this invention so long as they function effectively to hybridize with nucleotides of the invention. See, e.g., isis Pharmaceuticals, Carlsbad, CA; Sequitor, inc.,

Natick, MA.

Such antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems. The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known to those of skill in the art.

Antisense molecules as used herein include antisense or sense oligonucleotides. Sense oligonucleotides can, e.g., be employed to block transcription by binding to the anti-sense strand. The antisense and sense oligonucleotide comprise a single stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for cancer molecules. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 12 nucleotides, preferably from about 12 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, e.g., Stein SCohen (Cancer Res. 48:2659 (1988 and van der Kroi et ai. (BioTechniques 6:358 (1988)).

Ribozymes ' in addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of cancer-associated nucleotide sequences. A ribozyme is an RNA molecule that catalytically cleaves other RNA molecules. Different kinds of ribozymes have been described, including group I ribozymes, hammerhead ribozymes, hairpin ribozymes, RNase P, and axhead ribozymes (see, e.g., Castanotto et al., Adv. in Pharmacology 25:289-317 (1994) fora genera! review of the properties of different ribozymes).

The general features of hairpin ribozymes are described, e.g., in Hampel etal., Nucl. Acids Res. 18:299-304 (1990); European Patent Publication No. 0360257; U.S. Patent No. 5,254,678. Methods of preparing are well known to those of skill in the art (see, e.g., WO 94/26877; Ojwang et al., Proc. Natl. Acad. Sci. USA 90:6340-6344 (1993); Yamada et al., Human Gene Therapy 1:39-45 (1994); Leavitt et al., Proc. Natl. Acad Sci. USA 92:699- 703 (1995); Leavitt et a!., Human Gene Therapy 5:1151-120 (1994); and Yamada et al., Virology 205:121-126 (1994)).

Use of Modulators in Phenotypic Screening in one embodiment, a test compound is administered to a population of cancer cells, .which have an associated cancer expression profile. By "administration" or "contacting" herein is meant that the modulator is added to the cells in such a manner as to allow the modulator to act upon the ceil, whether by uptake and intracellular action, or by action at the cell surface, in some embodiments, a nucleic acid encoding a proteinaceous agent (i.e., a peptide) is put into a viral construct 84 such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is accomplished, e.g., PCT US97/01019. Reguiatable gene therapy systems can also be used. Once the modulator has been administered to the ceils, the ceils are washed if desired and are allowed to incubate under preferably physiological conditions for some period. The cells are then harvested and a new gene expression profile is generated. Thus, e.g., cancer tissue is screened for agents that modulate, e.g., induce or suppress, the cancer phenotype. A change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on cancer activity. Similarly, altering a biological function or a signaling pathway is indicative of modulator activity. By defining such a signature for the cancer phenotype, screens for new drugs that alter the phenotype are devised. With this approach, the drug target need not be known and need not be represented in the original gene/protein expression screening platform, nor does the level of transcript for the target protein need to change. The modulator inhibiting function will serve as a surrogate marker

As outlined above, screens are done to assess genes or gene products. That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product itself is performed.

Use of Modulators to Affect Peptides of the invention ·. Measurements of cancer polypeptide activity, or of the cancer phenotype are performed using a variety of assays. For example, the effects of modulators upon the function of a cancer polypeptide(s) are measured by examining parameters described above. A physiological change that affects activity is used to assess the influence of a test compound on the polypeptides of this invention. When the functional outcomes are determined using intact cells or animals, a variety of effects can be assesses such as, in the case of a cancer associated with solid tumors, tumor growth, tumor metastasis, neovascularization, hormone release, transcriptional changes to both known and uncharacterized genetic markers (e.g., by Northern blots), changes in cell metabolism such as cel! growth or pH changes, and changes in intracellular second messengers such as cGNIP.

Methods of Identifying Characterizing Cancer-associated Sequences

Expression of various gene sequences is correlated with cancer. Accordingly, disorders based on mutant or variant cancer genes are determined. In one embodiment, the invention provides methods for identifying cells containing variant cancer genes, e.g., determining the presence of, ail or part, the sequence of at least one endogenous cancer gene in a cell. This is accomplished using any number of sequencing techniques. The invention comprises methods of identifying the cancer genotype of an individual, e.g., determining all or part of the sequence of at least one gene of the invention in the individual. This is generaliy done in at least one tissue of the individual, e.g., a tissue set forth in Tabie i, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced gene to a known cancer gene, i.e., a wild-type gene to determine the presence of family members, homologies, mutations or variants. The sequence of all or part of the gene can then be compared to the sequence of a known cancer gene to determine if any differences exist. This is done using any number of known homology programs, such as BLAST, Bestfit, etc. The presence of a difference in the sequence between the cancer gene of the patient and the known cancer gene correlates with a disease state or a propensity for a disease state, as outlined herein.

In a preferred embodiment, the cancer genes are used as probes to determine the number of copies of the cancer gene in the genome. The cancer genes are used as probes to determine the chromosomal localization of the cancer genes. Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as transiocations, and the like are identified in the cancer gene locus. XIV.) KitsfArticles of Manufacture

For use in the laboratory, prognostic, prophylactic, diagnostic and therapeutic applications described herein, kits are within the scope of the invention. Such kits can comprise a carrier, package, or container that is compartmentalized to 85 receive one or more containers such as vials, tubes, and the like, each of the containers) comprising one of the separate elements to be used in the method, along with a label or insert comprising instructions for use, such as a use described herein. For example, the container(s) can comprise a probe that is or can be detectably labeled. Such probe can be an antibody or polynucleotide specific for a protein or a gene or message of the invention, respectively. Where the method utilizes nucleic acid hybridization to detect the target nucleic acid, the kit can also have containers containing nucleotide(s) for amplification of the target nucleic acid sequence. Kits can comprise a container comprising a reporter, such as a biotinbinding protein, such as avidin or streptavidin, bound to a reporter molecule, such as an enzymatic, fluorescent, or radioisotope label; such a reporter can be used with, e.g., a nucleic acid or antibody. The kit can include all or part of the amino acid sequences in Figure 2 or Figure 3 or analogs thereof, or a nucleic acid molecule that encodes such amino acid sequences.

The kit of the invention will typically comprise the container described above and one or more other containers associated therewith that comprise materials desirable from a commercial and user standpoint, including buffers, diluents, filters, needles, syringes; carrier, package, container, vial and/or tube labels listing contents and/or instructions for use, and package inserts with instructions for use. A label can be present on or with the container to indicate that the composition is used for a specific therapy or non-therapeutic application, such as a prognostic, prophylactic, diagnostic or laboratory application, and can also indicate directions for either in vivo or in vitro use, such as those described herein. Directions and or other information can also be included on an inserts) or label(s) which is included with or on the kit The label can be on or associated with the container. A label a can be on a container when letters, numbers or other characters forming the label are molded or etched into the container itself; a label can be associated with a container when it is present within a receptacle or carrier that also holds the container, e.g., as a package insert The label can indicate that the composition is used for diagnosing, treating, prophylaxing or prognosing a condition, such as a neoplasia of a tissue set forth in Table I.

The terms “kit" and “article of manufacture’ can be used as synonyms. in another embodiment of the invention, an articie(s) of manufacture containing compositions, such as amino acid sequence(s), small molecule(s), nucleic acid sequence(s), and/or antibody(s), e.g., materials useful for the diagnosis, prognosis, prophylaxis and/or treatment of neoplasias of tissues such as those set forth in Tabie I is provided. The article of manufacture typically comprises at least one container and at least one label. Suitable containers include, for example, bottles, vials, syringes, and test tubes. The containers can be formed from a variety of materials such as glass, metal or plastic. The container can hold amino acid sequence(s), small molecule(s), nucleic acid sequence(s), cell poputation(s) and/or antibody(s). in one embodiment, the container holds a polynucleotide for use in examining the mRNA expression profile of a ceii, together with reagents used for this purpose, in another embodiment a container comprises an antibody, binding fragment thereof or specific binding protein for use in evaluating protein expression of282P1 G3 in cells and tissues, or for relevant laboratory, prognostic, diagnostic, prophylactic and therapeutic purposes; indications and/or directions for such uses can be included on or with such container, as can reagents and other compositions or toois used for these purposes. In another embodiment, a container comprises materials for eliciting a cellular or humoral immune response, together with associated indications and/or directions. In another embodiment, a container comprises materials for adoptive immunotherapy, such as cytotoxic T cells (CTL) or helper T cells (HTL), together with associated indications and/or directions; reagents and other compositions or toois used for such purpose can also be included.

The container can alternatively hold a composition that is effective for treating, diagnosis, prognosing or prophylaxing a condition and can have a sterile access port (for example the container can be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The active agents in the composition can be an antibody capable of specifically binding 282P1G3 and modulating the function of 282P1G3. 86

The article of manufacture can further comprise a second container comprising a pharmaceutically-acceptable buffer, such as phosphate-buffered saline, Ringer's soiution and/or dextrose solution. It can further include other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, stirrers, needles, syringes, and/or package inserts with indications and/or instructions for use.

With specific reference now to the description in detail, it is stressed that the particulars described are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed fo be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this context, it is to be noted that only subject matter embraced in the scope of the claims appended hereto, whether in the manner defined in the claims or in a manner similar thereto and involving the main features as defined in the claims, is intended to be included in the scope of the present invention, while subject matter of Israel Specification No. 166,531, although described and exemplified to provide background and better understanding of the invention, is not intended for inclusion as part of the present invention. 86a EXAMPLES;

Various aspects of the invention'are further described and illustrated by way of the several examples ihat follow, none of which are intended to limit the scope of the invention.

Example 1: SSH-Generated Isolation of cDNA Fragment ofthe 282P1G3 Gene

To isolate genes that are over-expressed in pancreatic cancer we used the Suppression Subtractive Hybridization (SSH) procedure using cDNA derived from pancreatic cancer tissues. The 282P1G3 SSH cDNA sequence was derived from pancreatic tumor minus cDNAs derived from normal pancreas. The 282P1G3 cDNA was identified as highly expressed in the pancreas cancer.

Materials and Methods

Human Tissues:

The patient cancer and normal tissues were purchased from different sources such as the NDRi (Philadelphia, PA). mRNA for some normal tissues were purchased from Clontech, Palo Alto, CA RNA isolation:

Tissues were homogenized in Trizol reagent (Life Technologies, Gibco BRL) using 10 ml/ g tissue isolate total RNA. Poly A RNA was purified from total RNA using Qiagen’s Oligotex mRNA Mini and Midi kits. Total and mRNA were quantified by spectrophotometric analysis (O.D. 260/280 nm) and analyzed by gel electrophoresis.

Oligonucleotides:

The following HPLC purified oligonucleotides were used: DPNCDN (cDNA synthesis primer): 5TTTTGATCAAGCTT3o3' (SEQ ID NO: 41)

Adaptor 1: 5’CTAAT4CGACTCACTATAGGGCTCGAGCGGCCGCCCGGGCAG3’ (SEQ ID NO: 42) 3OGCCCGTCCTAG5’ (SEQ ID NO: 43)

Adaptor 2: 5’GTAATACGACTCACTATAGGGCAGCGTGGTCGCGGCCGAG3' (SEQ ID NO: 44) 3OGGCTCCTAG5' (SEQ ID NO: 45) PCR primer 1: 5’CTAATACGACTCACTATAGGGC3’ (SEQ ID NO: 46)

Nested primer (NP)1: 5’TCGAGCGGCCGCCCGGGCAGGA3’ (SEQ ID NO: 47)

Nested primer (NP)2: 5'AGCGTGGTCGCGGCCGAGGA3' (SEQ ID NO: 48)

Suppression Subtractive Hybridization:

Suppression Subtractive Hybridization (SSH) was used to identify cDNAs corresponding to genes that may be differentially expressed in pancreas cancer. The SSH reaction utilized cDNA from pancreas cancer and normal tissues. 87

The gene 282P1G3 sequence was derived from pancreas cancer minus normal pancreas cDNA subtraction. The SSH DNA sequence (Figure 1) was identified.

The cDNA derived from normal pancreas mixed with a pool of 9 normal tissues was used as the source of the “driver’ cDNA, while the cDNA from pancreas cancer was used as the source of the “tester” cDNA. Double stranded cDNAs corresponding to tester and driver cDNAs were synthesized from 2 pg of poly(A)* RNA isolated from the relevant xenograft tissue, as described above, using CLONTECH's PCR-Select cDNA Subtraction Kit and 1 ng of oligonucleotide DPNCDN as primer. First-and second-strand synthesis were carried out as described in the Kit’s user manual protocol (CLONTECH Protocol No. PT1117-1, Catalog No. K1804-1). The resulting cDNA was digested with Dpn II for 3 hrs at 37°C. Digested cDNA was extracted with phenol/chloroform (1:1) and ethanol precipitated.

Driver cDNA was generated by combining in a 1:1 ratio Dpn I! digested cDNA from normal pancreas with a mix of digested cDNAs derived from the nine normal tissues: stomach, skeletal muscle, lung, brain, liver, kidney, pancreas, small intestine, and heart.

Tester cDNA was generated by diluting 1 pi of Dpn IS digested cDNA from the relevant tissue source (see above) (400 ng) in 5 pi of water. The diluted cDNA (2 pi, 160 ng) was then ligated to 2 μ! of Adaptor 1 and Adaptor 2 (10 pM), in separate ligation reactions, in a total volume of 10 pi at 16°C overnight, using 400 u of T4 DNA ligase (CLONTECH). Ligation was terminated with 1 pl,of 0.2 M EDTA and heating at 72°C for 5 min.

The first hybridization was performed by adding 1.5 pi (600 ng) of driver cDNA to each of two tubes containing 1.5 μ! (20 ng) Adaptor 1- and Adaptor 2- ligated tester cDNA In a final volume of 4 pi, the samples were overlaid with mineral oil, denatured in an MJ Research thermal cycler at 98°C for 1.5 minutes, and then were allowed to hybridize for 8 hrs at S8°C. The two hybridizations were then mixed together with an additional 1 pi of fresh denatured driver cDNA and were aiiowed to hybridize overnight at 68°C. The second hybridization was then diluted in 200 pi of 20 mM Hepes, pH 8.3, 50 mM NaCl, 0.2 mM EDTA heated at 70°C for 7 min. and stored at -20°C. PCR Amplification, Cloning and Sequencing of Gene Fragments Generated from SSH:

To amplify gene fragments resulting from SSH reactions, two PCR amplifications were performed. In the primary PCR reaction 1 pi of the diluted final hybridization mix was added to 1 pi of PCR primer 1 (10 pM), 0.5 pi dNTP mix (10 μΜ), 2.5 pi 10 x reaction buffer (CLONTECH) and 0.5 pi 50 x Advantage cDNA polymerase Mix (CLONTECH) in a final volume of 25 pi. PCR 1 was conducted using the following conditions: 75°C for 5 min., 94°C for 25 sec., then 27 cycles of 94°C for 10 sec, 66°C for 30 sec, 72°C for 1.5 min. Five separate primary PCR reactions were performed for each experimenL The products were pooled and diluted 1:10 with water. For the secondary PCR reaction, 1 pi from the pooled and diluted primary PCR reaction was added to the same reaction mix as used for PCR 1, except that primers NP1 and NP2 (10 pM) were used instead of PCR primer 1. PCR 2 was performed using 10-12 cycles of 94°C for 10 sec, 68°C for 30 sec, and 72°C for 1.5 minutes. The PCR products were analyzed using 2% agarose gel electrophoresis.

The PCR products were inserted into pCR2.1 using the T/A vector cloning kit (invitrogen). Transformed E. coli were subjected to blue/white and ampicillin selection. White colonies were picked and arrayed into 96 well plates and were grown in liquid culture overnight. To identify inserts, PCR amplification was performed on 1 μΙ of bacterial culture using the conditions of PCR1 and NP1 and NP2 as primers. PCR products were analyzed using 2% agarose gel electrophoresis.

Bacterial clones were stored in 20% glycerol in a 96 well formaL Plasmid DNA was prepared, sequenced, and subjected to nucleic acid homology searches of the GenBank, dBest, and NCI-CGAP databases. RT-PCR Expression Analysis:

First strand cDNAs can be generated from 1 pg of mRNA with oligo (dT)12-18 priming using the Gibco-BRL Superscript Preampiification system. The manufacturer's protocol was used which included an incubation for 50 min at 42°C with reverse 88 transcriptase followed by RNAse H treatment at 37°C for 20 min. After completing the reaction, the volume can be increased to 200 pi with water prior to normalization. First strand cDNAs from 16 different normal human tissues can be obtained from

Cion tech.

Normalization of the first strand cDNAs from multiple tissues was performed by using the primers 5'atatcgccgcgctcgtcgtcgacaa3' (SEQ ID NO: 49) and 5'agccacacgcagctcattgtagaagg 3’ (SEQ ID NO: 50) to amplify β-actin. First strand cDNA (5 pi) were amplified in a total volume of 50 pi containing 0.4 pM primers, 0.2 pM each dNTPs, 1XPCR buffer (Clontech, 10 mM Tris-HCL, 1.5 mM MgCb, 50 mM KOI, pH8.3) and 1X Klentaq DNA polymerase (Clontech). Five pi of the PCR reaction can be removed at 18, 20, and 22 cycles and used for agarose gel electrophoresis. PCR was performed using an MJ Research thermal cycler under the following conditions: Initial denaturafion can be at 94°C for 15 sec, followed by a 18, 20, and 22 cycles of 94°C for 15, 65°C for 2 min, 72°C for 5 sec. A final extension at 72°C was carried out for 2 min. After agarose gel electrophoresis, the band intensities of the 283 bp β-actin bands from multiple tissues were compared by visual inspection.

Dilution factors for the first strand cDNAs were calculated to result in equal β-actin band intensities in all tissues after 22 cycles of PCR. Three rounds of normalization can be required to achieve equal band intensities in all tissues after 22 cycles of PCR.

To determine expression levels of the 282P1G3 gene, 5 pi of normalized first strand cDNA were analyzed by PCR using 26, and 30 cycles of amplification. Semi-quantitative expression analysis can be achieved by comparing the PCR products at cycle numbers that give light band intensities. The primers used for RT-PCR were designed using the 282P1G3 SSH sequence and are listed below: 282P1G3.1 5’- TAAGGTCTCAGCTGTAAACCAAAAG - 3’ (SEQ ID NO: 51) 282P1G3.2 5’- CTGTTTTAAGATTGTTGGAACCTGT- 3’ (SEQ ID NO: 52) A typical RT-PCR expression analysis is shown in Figure 14. First strand cDNA was prepared from vital pool 1 (liver, lung and kidney), vital pool 2 (pancreas, colon and stomach), normal pancreas, ovary cancer pool, and pancreas cancer pod. Normalization was performed by PCR using primers to actin and GAPDH. Semi-quantitative PCR, using primers to 282P1G3, was performed at 26 and 30 cycles of amplification. Expression of 282P1G3 was detected in ovary cancer pool, pancreas cancer pool vital pool 1, but not in vital pool 2 nor in normal pancreas.

Example 2: Isolation of Full Length 282P1G3 Encoding cDNA

The 282P1G3 SSH cDNA sequence was derived from a substraction consisting of pancreas cancer minus a normal pancreas. The SSH cDNA sequence of 321 bp (Figure 1) was designated 282P1G3. 282P1G3 v.2 of 3464 bp was cloned from a pool of normal tissue cDNA library, revealing an ORF of 1171 amino acids (Figure 2 and Figure 3). Other variants of 282P1G3 were also identified and these are listed in Figure 2 and Figure 3. 282P1G3 v.1, v.9, v.10, v.11, v.24 and v.25 proteins are 1224 amino acids in length and differ from each other by one amino acid as shown in Figure 11. 282P1G3 v.12 through v.23, v.26 and v.27 are SNP variants and code for the same protein as 282P1G3 v.1. 282P1G3 v.2, v.3, v.4, v.5, v.6, v.7, and v.8 are splice variants of 282P1G3 v.1 and code·for proteins of 1171) 893, 1117,1208,1183,1236, and 1195 amino acids, respectively. 282P1G3 v.28 is a splice variant identified by the 282P1G3 SSH, and deletes the second exon of v. 1. 282P1G3 v.1 shows 99% identity over 7650 nucleotides to cell adhesion molecule with homology, to L1CAM (close homolog of L1) (CHL1), accession number NM_006614. It is a neural recognition molecule that may be involved in signal transduction pathways. 282P1G3 v.2 is a novel splice variant of 282P1G3 and has not been previously described. 89

Example 3: Chromosomal Mapping of 282P1G3

Chromosomal localization can implicate genes in disease pathogenesis. Several chromosome mapping approaches are available including fluorescent in situ hybridization (FISH), human/hamster radiation hybrid (RH) panels (Walter et at, 1994;

Nature Genetics 7:22; Research Genetics, Huntsville Al), human-rodent somatic cell hybrid pane's such as is available from the Cornell institute (Camden, New Jersey), and genomic viewers utilizing BLAST homologies to sequenced and mapped genomic clones (NCBI, Bethesda, Maryland). 282P1G3 maps to chromosome 3p26.1 using 282P1G3 sequence and the NCBI BLAST tool located on the World Wide Web at: (.ncbi.nlm.nih.gov/genome/seq/page.cgi?F=HsBlast.html&&ORG=Hs).

Example 4: Expression Analysis of 282P1G3 in Normal Tissues and Patient Specimens

Expression analysis by RT-PCR demonstrated that 282P1G3 is strongly expressed in pancreas cancer and ovary cancer patient specimens (Figure 14). First strand cDNA was prepared from (A) vital pool 1 (liver, lung and kidney), vital pool 2 (pancreas, colon and stomach), normal pancreas, ovary cancer pool, and pancreas cancer pool; (B) normal stomach, normal brain, normal heart, normal liver, normal skeletal muscle, normal testis, normal prostate, norma! bladder, normal kidney, normal colon, normal lung, normal pancreas, and a pool of cancer specimens from pancreas cancer patients, ovary cancer patients, and cancer metastasis specimens. Normalization was performed by PCR using primers to actin. Semi-quantitative PCR, using primers to 282P1G3, was performed at 26 and 30 cycles of amplification. (A) Expression of 282P1G3 was detected in ovary cancer pool, pancreas cancer pool vital pool 1, but not in vital pool 2 nor in normal pancreas. (B) Samples were run on an agarose gei, and PCR products were quantitated using the Alphalmager software.

Results show strong expression in pancreas cancer, ovary cancer, cancer metastasis, and normal brain compared to al! other normal tissues tested.

Extensive expression of 282P1G3 in normal tissues is shown in Figure 15. Two multiple tissue northern blots (Clontech) both with 2 pg of mRNA/iane were probed with the 282P1G3 sequence. Size standards in kilobases (kb) are indicated on the side. Results show expression of an approximately 9-1 Okb transcript in normal but not in any other norma! tissue tested.

Expression of 282P1G3 in pancreas cancer patient specimens is shown in Figure 16. RNA was extracted from pancreas cancer cell lines (CL), normal pancreas (N), and pancreas cancer patient tumor (T). Northern blots with 10pg of total RNA were probed with the 282P1G3 SSH fragment. Size standards in kilobases are on the side. Results show expression of 282P1G3 in pancreas cancer patient tumor specimen but not in the cell lines nor in the normal pancreas.

Expression of 282P1G3 was also detected in ovary cancer patient specimens (Figure 17). RNA was extracted from ovary cancer cell lines (CL), normal ovary (N), and ovary cancer patient tumor (T). Northern blots with 1Opg of total RNA were probed with the 282P1G3 DNA probe. Size standards in kilobases are on the side. Results show expression of 282P1G3 in ovary cancer patient tumor specimen but not in the cell lines nor in the norma! ovary.

Figure 18 shows expression of 282P1G3 in lymphoma cancer patient specimens. RNA was extracted from peripheral blood lymphocytes, cord blood isolated from normal individuals, and from lymphoma patient canc'er specimens. Northern blots with 10pg of total RNA were probed with the 282P1G3 sequence. Size standards in kilobases are on the side. Results show expression of 282P1G3 in lymphoma patient specimens but not in the norma! blood cells tested.

The restricted expression of 282P1G3 in normal tissues and the expression detected in cancer patient specimens suggest that 282P1G3 is a potential therapeutic target and a diagnostic marker for human cancers. 90

Example 5: Transcript Variants of 282P1G3

Transcript variants are variants of mature mRNA from the same gene which arise by alternative transcription or alternative splicing. Alternative transcripts are transcripts from the same gene but start transcription at different points.

Splice variants are mRNA variants spliced differently from the same transcript in eukaryotes, when a multi-exon gene is transcribed from genomic DNA, the initial RNA is spliced to produce functional mRNA, which has only exons and is used for translation into an amino acid sequence. Accordingly, a given gene can have zero to many alternative transcripts and each.transcript can have zero to many splice variants. Each transcript variant has a unique exon makeup, and can have different coding and/or non-coding (5’ or 3’ end) portions, from the original transcript Transcript variants can code for similar or different proteins with the same or a similar function or can encode proteins with different functions, and can be expressed in the same tissue at the same time, or in different tissues at the same time, or in the same tissue at different times, or in different tissues at different times. Proteins encoded by transcript variants can have similar or different cellular or extracellular localizations, e.g., secreted versus intracellular.

Transcript variants are identified by a variety of art-accepted methods. For example, alternative transcripts and splice variants are identified by full-length cloning experiment, or by use of full-length transcript and EST sequences. First, all human ESTs were grouped into clusters which show direct or indirect identity with each other. Second, ESTs in the same cluster were further grouped into sub-clusters and assembled into a consensus sequence. The original gene sequence is compared to the consensus sequence(s) or other full-length sequences. Each consensus sequence is a potential splice variant for that gene. Even when a variant is identified that is not a full-length clone, that portion of the variant is very useful for antigen generation and for further cloning of the full-length splice variant, using techniques known in the art.

Moreover, computer programs are available in the art that identify transcript variants based on genomic sequences. Genomic-based transcript variant identification programs include FgenesH (A. Salamov and V. Solovyev, “Ab initio gene finding in Drosophila genomic DNA," Genome Research. 2000 Aprii;10(4):516-22); Grail (URL compbio.ornl.gov/Grail-bin/EmptyGrailForm) and GenScan (URL genes.mit.edu/GENSCAN.htmi). For a general discussion of splice variant identification protocols see., e.g., Southan, C., A genomic perspective on human proteases, FEBS Lett. 2001 Jun 8; 498(2-3):214-8; de Souza, S.J., ef al., Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags, Proc. Natl Acad Sci U S A. 2000 Nov 7; 97(23):12690-3.

To further confirm the parameters of a transcript variant a variety of techniques are available in the art, such as full-length cloning, proteopiic validation, PCR-based validation, and 5' RACE validation, etc. (see e.g., Proteomic Validation: Brennan, S.O., et at, Albumin banks peninsula: a new termination variant characterized by electrospray mass spectrometry, Biochem Biophys Acta. 1999 Aug 17;1433(1-2):321-6; Ferranti P, et al., Differential splicing of pre-messenger RNA produces multiple forms of mature caprine alpha(s1 )-casein, Eur J Biochem. 1997 Oct 1;249(1 ):1-7. For PCR-based Validation: Wellmann S, ef al., Specific reverse transcription-PCR quantification of vascular endothelial growth factor (VEGF) splice variants by LightCycier technology, Clin Chem. 2001 Apr;47(4):654-60; Jia,· H.P., ef al., Discovery of new human beta-defensins using a genomics-based approach, Gene. 2001 Jan 24; 263(1-2):211-8. For PCR-based and 5’ RACE Validation: Brigle, K.E., ef al., Organization of the murine reduced folate earner gene and identification of variant splice forms, Biochem Biophys Acta. 1997 Aug 7; 1353(2): 191 -8).

St is known in the art that genomic regions are modulated in cancers. When the genomic region to which a gene maps is modulated in a particular cancer, the alternative transcripts or splice variants of toe gene are modulated as well. Disclosed herein is that 282P1G03 has a particular expression profile related to cancer. Alternative transcripts and splice variants of 282P1G03 may also be involved in cancers in the same or different tissues, thus serving as tumor-associated markers/antigens. 91

Using the full-length gene and EST sequences, eight additional transcript variants were identified, designated as 282P1G03 v.2, v.3, v.4, v.5, v.6, v.7, v.8 and v.28. The boundaries of exons in the original transcript, 282P1G03 v,1 were shown in Table LI. Figure 12 shows the structures of the transcript variants. Theoretically, each different combination of exons in spatiai order (aligned on the genomic sequence), e.g. exons 2,3,5,7, and 9-28 of v.1, is a potential splice variant Tables Lli(a) - (h) through LV(a) - (h) are set forth on a variant-by-variant bases. Tables Lll(a) - (h) show the nucleotide sequence of the transcript variant. Tables Llli(a) - (h) show the alignment of the transcript variant with nucleic acid sequence of 282P1G03 v.l. Tables UV(a) - (h) show the amino acid translation of the transcript variant for the identified reading frame orientation. Tables LV(a) - (h) display alignments of the amino acid sequence encoded by the splice variant with that of 282P1G03 v, 1.

Example 6: Single Nucleotide Polymorphisms of 282P1G3 A Single Nucleotide Polymorphism (SNP) is a single base pair variation in a nucleotide sequence at a specific location. At any given point of the genome, there are four possible nucleotide base pairs: A/T, C/G, G/C and T/A. Genotype refers to the specific base pair sequence of one or more locations in the genome of an individual. Haplotype refers to the base pair sequence of more than one location on the same DNA molecule (or the same chromosome in higher organisms), often in the context of one gene or in the context of several tightly linked genes. SNP that occurs on a cDNA is called cSNP. This cSNP may change amino acids of the protein encoded by the gene and thus change the functions of the protein. Some SNP cause inherited diseases; others contribute to quantitative variations in phenotype and reactions to environmental factors including diet and drugs among individuals. Therefore, SNP and/or combinations of alleles (called haplotypes) have many applications, including diagnosis of inherited diseases, determination of drug reactions and dosage, identification of genes responsible for diseases, and analysis of the genetic relationship between individuals (P. Nowotny, J. M. Kwon and A. M. Goate, “ SNP analysis to dissect human traits,” Curr. Opin. Neurobio!. 2001 Oct; 11 (5):637-641; M. Pirmohamed and B. K. Park, “Genetic susceptibility to adverse drug reactions,” Trends Pharmacol. Sci. 2001 Jun; 22(6):298-305: J.,H. Riiey, C. J. Allan, E. Lai and A. Roses, “The use of single nucleotide polymorphisms in the isolation of common disease genes,” Pharmacogenomics. 2000 Feb; 1 (1 );39-47; R. Judson, J. C. Stephens and A. Windemuth, "The predictive power of haplotypes in ciinical response,” Pharmacogenomics. 2000 Feb; 1(1):15-26). SNP are identified by a variety of art-accepted methods (P. Bean, “The promising voyage of SNP target discovery," Am. Clin. Lab. 2001 OcfcNov; 20(9): 18-20; K. M. Weiss, “In search of human variation," Genome Res. 1998 Jul; 8(7):691-697; Μ. M. She, "Enabling large-scale pharmacogenetic studies by high-throughput mutation detection and genotyping technologies,” Clin. Chem. 2001 Feb; 47(2):164-172). For example, SNP can be identified by sequencing DNA fragments that show polymorphism by gel-based methods such as restriction fragment length polymorphism (RFLP) and denaturing gradient gel electrophoresis (DGGE). They can aiso be discovered by direct sequencing of DNA samples pooled from different individuals or by comparing sequences from different DNA samples. With the rapid accumulation of sequence data in public and private databases, one can discover SNP by comparing sequences using computer programs (Z. Gu, L Hillier and P. Y. Kwok, “Single nucleotide polymorphism hunting in cyberspace,” Hum. Mutat 1998; 12(4):221-225). SNP can be verified and genotype or haplotype of an individual can be determined by a variety of methods including direct sequencing and high throughput microarrays (P. Y. Kwok, “Methods for genotyping single nucleotide polymorphisms," Annu. Rev. Genomics Hum. Genet 2001; 2:235-258; M. Kokoris, K. Dix, K. Moynihan, J. Mathis, B. Erain, P. Grass, B; Hines and A. Duesterhoeft, “High-throughput SNP genotyping with the Masscode system," Mol. Diagn, 2000 Dec; 5(4):329-340).

Using the methods described above, 19 SNP were identified in the original transcript, 282P1G03 v.1, at positions 320 (c/t), 668 (c/t), 1178 (a/g), 3484 (c/t), 4615 (g/a), 4636 (-/t), 5078 (c/t), 5530 (t/a), 5812 (c/t), 6114 (a/g), 6229 (c/t), 6383 (g/a), 6626 (c/t), 6942 (c/t), 7085 (c/t), 2684 (a/g), 3864 (Vc), 5768 (Vc) and 6125 (c/t). The transcripts or proteins with 92 alternative allele were designated as variant 282P1G03 v.9 through v.25, as shown in Figure 10. Figure 11 shows the schematic alignment of protein variants, corresponding to nucleotide variants. Nucleotide variants that code for the same amino acid sequence as v.1 are not shown in Figure 11. These alleles of the SNP, though shown separately here, can occur in different combinations (haplotypes) and in any one of the transcript variants (such as 282P1G03 v.2) that contains the site of the SNP.

Example 7: Production of Recombinant 282P1G3 in Prokaryotic Systems

To express recombinant 282P1G3 and 282P1G3 variants in prokaryotic cells, the full or partial length 282P1G3 and 282P1G3 variant cDNA sequences are cloned into any one of a variety of expression vectors known in the art. One or more of the following regions of 282P1G3 variants are expressed: the full length sequence presented in Figures 2 and 3, or any 8, 9, 10, 11, 12,13,14,15, 16,17,18,19,20, 21, 22, 23, 24, 25, 26, 27,28, 23, 30 or more contiguous amino acids from 282P1G3, variants, or analogs thereof. A. in vitro transcription and translation constructs: pCRIl: To generate 282P1G3 sense and anti-sense RNA probes for RNA in situ investigations, pCRIl constructs (Invitrogen,Carlsbad CA) are generated encoding either all or fragments of the 282P1G3 cDNA. The pCRIl vector has Sp6 and T7 promoters flanking the insert to drive the transcription of 282P1G3 RNA for use as probes in RNA in situ hybridization experiments. These probes are used to analyze the cell and tissue expression of 282P1G3 at the RNA level. Transcribed 282P1G3 RNA representing the cDNA amino acid coding region of the 282P1G3 gene is used in in vitro translation systems such as the TnT™ Coupled Reticulolysate System (Promega, Corp., Madison, Wl) to synthesize 282P1G3 protein. B. Bacterial Constructs: pGEX Constructs: To generate recombinant 282P1G3 proteins in bacteria that are fused to the Glutathione S-transferase (GST) protein, all or parts of the 282P1G3 cDNA protein coding sequence are cloned into the pGEX family of GST-fusion vectors (Amersham Pharmacia Biotech, Piscataway, NJ). These constructs allow controlled expression of recombinant 282P1G3 protein sequences with GST fused at the amino-terminus and a six histidine epitope (6X His) at the carboxyl-terminus. The GST and 6X His tags permit purification of the recombinant fusion protein from induced bacteria with the appropriate affinity matrix and allow recognition of the fusion protein with anti-GST and anti-His antibodies. The 6X His tag is generated by adding 6 histidine codons to the cloning primer at the 3’ end, e.g., of the open reading frame (ORF). A proteolytic cleavage site, quch as the PreScission™ recognition site in pGEX-6P-1, may be employed such that it permits cleavage of the GST fag from 282P1 G3-related protein. The ampicillin resistance gene and pBR322 origin permits selection and maintenance of the pGEX plasmids in E. coli. pMAL Constructs: To generate, in bacteria, recombinant 282P1G3 proteins that are fused to maltose-binding protein (MBP), all or parts of the 282P1G3 cDNA protein coding sequence are fused to the MBP gene by cloning into the pMAL-c2X and pMAL-p2X vectors (New England Biolabs, Beverly, MA). These constructs allow controlled expression of recombinant 282P1G3 protein sequences with MBP fused at the amino-terminus and a 6X His epitope tag at the carboxyl-terminus. The MBP and 6X His tags permit purification of the recombinant protein from induced bacteria with the appropriate affinity matrix and allow recognition of the fusion protein with anti-MBP and anti-His antibodies. The 6X His epitope tag is generated by adding 6 histidine codons to the 3' cloning primer. A Factor Xa recognition site permits cleavage of the pMAL tag from 282P1G3. The pMAL-c2X and pMAL-p2X vectors are optimized to express the recombinant protein in the cytoplasm or periplasm respectively. Periplasm expression enhances folding of proteins with disulfide bonds. pET Constructs: To express 282P1G3 in bacterial ceils, ail or parts of the 282P1G3 cDNA protein coding sequence are cloned into the pET family of vectors (Novagen, Madison, Wl). These vectors allow tightly controlled expression of recombinant 282P1G3 protein in bacteria with and without fusion to proteins that enhance solubility, such as 93

NusA and thioredoxin (Trx), and epitope tags, such as 6X His and S-Tag ™ that aid purification and detection of the recombinant protein. For example, constructs are made utilizing pET NusA fusion system 43.1 such that regions of the 282P1G3 protein are expressed as amino-terminal fusions to NusA. C. Yeast Constructs: □ESC Constructs: To express 282P1G3 in the yeast species Saccharomyces cerevisiae for generation of recombinant protein and functional studies, al! or parts of the 282P1G3 cDNA protein coding sequence are cloned into the pESC family of vectors each of which contain 1 of 4 selectable markers, HIS3, TRP1, LEU2, and URA3 (Stratagene, La Jolla, CA). These vectors allow controlled expression from the same plasmid of up to 2 different genes or cloned sequences containing either Flag™ or Myc epitope tags in the same yeast cell. This system is useful to confirm protein-protein interactions of 282P1G3. in addition, expression in yeast yields similar post-translational modifications, such as giycosylations and phosphorylations that are found when expressed in eukaryotic cells. pESP Constructs: To express 282P1G3 in the yeast species Saccharomyces pombe, all or parts of the 282P1G3 cDNA protein coding sequence are cloned into the pESP family of vectors. These vectors allow controlled high level of expression of a 282P1G3 protein sequence that is fused at either the amino terminus or at the carboxyl terminus to GST which aids purification of the recombinant protein. A Flag™ epitope tag allows detection of the recombinant protein with anti-Flag™ antibody.

Example 8: Production of Recombinant 282P1G3 in Higher Eukaryotic Systems A. Mammalian Constructs:

To express recombinant 282P1G3 in eukaryotic cells, the full or partial length 282P1G3 cDNA sequences were cloned into any one of a variety of expression vectors known in the art. One or more of the following regions of 282P1G3 were expressed in these constructs, amino acids 1 to 1224, or any 8, 9,10,11,12,13,14,15,16,17,18,19,20,21, 22,23, 24,25, 26, 27,28, 29,30 or more contiguous amino acids from 282P1G3 v.1, and v.9 through v.25; amino acids 1 to 1171,1 to 893,1 to 1117,1 to 1208,1 to 1183,1 to 1236,1 to 1195 of v.2, v.3, v.4, v.5, v.6, v.7, and v.8 respectively; or any 8, 9,10, 11,12, 13, 14,15,16,17,18,19, 20, 21,22, 23,24, 25, 26, 27, 28, 29, 30 or more contiguous amino acids from 282P1G3 variants, or analogs thereof.

The constructs can be transfected into any one of a wide variety of mammalian celis such as 293T celis. Transfected 293T cell lysates can be probed with the anti-282P1 G3 polyciona! serum, described herein. pcDNA4/HisiVlax Constructs: To express 282P1G3 in mammalian cells, a 282P1G3 ORF, or portions thereof, of 282P1G3 are cloned into pcDNA4/HisMax Version A (Invitrogen, Carlsbad, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter and the SP16 translational enhancer. The recombinant protein has Xpress™ and six histidine (6X His) epitopes fused to the amino-terminus. The pcDNA4/HisMax vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability along with the SV40 origin for episoma! replication and simple vector rescue in ceil lines expressing the large T antigen. The Zeocin resistance gene allows for selection of mammalian cells expressing the protein and the ampiciliin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in £. coli. pcDNA3,1/MycHis Constructs: To express 282P1G3 in mammalian cells, a 282P1G3 ORF, or portions thereof, of 282P1G3 with a consensus Kozak translation initiation site is cloned into pcDNA3.1/MycHis Version A (Invitrogen, Carlsbad, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter. The recombinant proteins have the myc epitope and 6X His epitope fused to the carboxyl-terminus. The pcDNA3.1/MycHis vector aiso contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability, along with the SV40 origin for episomai replication and simple vector rescue in cell lines expressing the large T antigen. The Neomycin 94 resistance gene can be used, as it allows for selection of mammalian cells expressing the protein and the ampicillin resistance gene and ColEf origin permits selection and maintenance of the plasmid in £ co/f.

The complete ORF of 282P1G3 v.2 was cloned into the pcDNA3.1/MycHis construct to generate 282P1 G3.pcDNA3.1/MycHis. Figure 19 shows expression of 282P1 G3.pcDNA3.1/MycHis following transfection into 293T ceils. 293T cells were transfected with either 282P1G3.pcDNA3.1/MycHis or pcDNA3.1/MycHis vector control. Forty hours later, cel! lysates were collected. Samples were run on an SDS-PAGE acrylamide get, blotted and stained with anti-his antibody. The blot was developed using the ECL chemiluminescence kit and visualized by autoradiography. Results show expression of 282P1G3 from the 282P1G3.pcDNA3.1/MycHis construct in the lysates of transfected cells. pcDNA3.1fCT-GFP-TOPO Construct: To express 282P1G3 in mammalian cells and to allow detection of the recombinant proteins using fluorescence, a 282P1G3 ORF, or portions thereof, with a consensus Kozak translation initiation site are cloned into pcDNA3.1/CT-GFP-TOPO (Invitrogen, CA). Protein expression is driven from the cytomegalovirus (CMV) promoter. The recombinant proteins have the Green Fluorescent Protein (GFP) fused to the carboxyt-ierminus facilitating non-invasive, in vivo detection and cell biology studies. The pcDNA3.1 CT-GFP-TOPO vector also contains the bovine growth hormone (BGH) polyadenylation signal and transcription termination sequence to enhance mRNA stability along with the SV40 origin for episomal replication and simple vector rescue in cel! lines expressing the large T antigen. The Neomycin resistance gene allows for selection of mammalian cells that express the protein, and the ampicillin resistance gene and ColE1 origin permits selection and maintenance of the plasmid in £. coli. Additional constructs with an amino-terminal GFP fusion are made in pcDNA3.1/NT-GFP-TOPO spanning the entire length of a 282P1G3 protein. PAPtag: A 282P1G3 ORF, or portions thereof, is cloned into pAPtag-5 (GenHunter Corp. Nashville, TN). This construct generates an alkaline phosphalase fusion at the carboxyl-terminus of a 282P1G3 protein while fusing the igGx signal sequence to the amino-terminus. Constructs are also generated in which alkaline phosphatase with an amino-terminal IgGK signal sequence is fused to the amino-terminus of a 282P1G3 protein. The resulting recombinant 282P1G3 proteins are optimized for secretion into the media of transfected mammalian cells and can be used to identify proteins such as ligands or receptors that interact with 282P1G3 proteins. Protein expression is driven from the CMV promoter and the recombinant proteins also contain myc and 6X His epitopes fused at the carboxyl-terminus that facilitates detection and purification. The Zeocin resistance gene present in the vector allows for selection of mammalian cells expressing the recombinant protein and the ampicillin resistance gene permits selection of the plasmid in £. coli. pTag5: A 282P1G3 ORF, or portions thereof, were cloned into pTag-5. This vector is similar to pAPtag but without the alkaline phosphatase fusion. This construct generates 282P1G3 protein with an amino-terminal IgGK signal sequence and myc and 6X His epitope tags at the carboxyl-terminus that facilitate detection and affinity purification. The resulting recombinant 282P1G3 protein is optimized for secretion into the media of transfected mammalian cells, and is used as immunogen or ligand to identify proteins such as ligands or receptors that interact with the 282P1G3 proteins. Protein expression is driven from the CMV promoter. The Zeocin resistance gene present in the vector allows for selection of mammalian cells expressing the protein, and the ampicillin resistance gene permits selection of the plasmid in £. coli.

The extracellular domain, amino acids 26-1043, of 282P1G3 v.2 was cloned into the pTag5 construct to generate 282P1G3.pTag5. Figure 20 shows expression and secretion of the extracellular domain of-282P1G3 following 282P1G3.pTag5 vector transfection into 293T cells. 293T cells were transfected with 282P1G3.pTag5 construct Forty, hours later, supernatant as well as ceil lysates were collected. Samples were run on an SDS-PAGE acrylamide gel, blotted and stained with anti-his antibody. The blot was developed using the ECL chemiluminescence kit -and visualized by autoradiography. Results show expression and secretion of 282P1G3 from the 282P1G3.pTag5 transfected cells.

PsecFc: A 282P1G3 ORF, or portions thereof, is also cloned into psecFc. The psecFc vector was assembled by cloning the human immunoglobulin G1 (IgG) Fc (hinge, CH2, CH3 regions) into pSecTag2 (invitrogen, California). This 95 construct generates an lgG1 Fc fusion at the carboxyl-terminus of the 282P1G3 proteins, while fusing the lgGK signal sequence to N-terminus. 282P1G3 fusions utilizing tbe murine lgG1 Fc region are also used. The resulting recombinant 282P1G3 proteins are optimized for secretion into the media of transfected mammalian cells, and can be used as immunogens or to identify proteins such as ligands or receptors that interact with 282P1G3 protein. Protein expression is driven from the CMV promoter. The hygromycin resistance gene present in the vector allows for selection of mammalian ceiis that express the recombinant protein, and the ampiciliin resistance gene permits selection of the plasmid in E co//. pSRa Constructs: To generate mammalian ceil tines that express 282P1G3 constitutiveiy, 282P1G3 ORF, or portions thereof, of 282P1G3 were cloned into pSRa. constructs. Amphotropic and ecotropic retroviruses were generated by transfection of pSRa constructs into the 293T-10A1 packaging line or co-transfection of pSRa and a helper plasmid (containing deleted packaging sequences) into the 293 cells, respectively. The retrovirus is used to infect a variety of mammalian cell lines, resulting in the integration of the cloned gene, 282P1G3, into the host cell-lines. Protein expression is driven’from a long terminal repeat (LTR). The Neomycin resistance gene present in1 the vector allows for selection of mammalian cells that express the protein, and the ampiciliin resistance gene and ColE1 origin permit selection and maintenance of the plasmid in E. coli. The retroviral vectors can thereafter be used for infection and generation of various cell lines using, for example, PC3, NIH 3T3, TsuPrl, 293 or rat-1 ceils.

AdditionakpSRa constructs are made that fuse an epitope tag such as the FLAG™ tag to the carboxyl-terminus of 282P1G3 sequences to allow detection using anti-Flag antibodies. For example, the FLAG™ sequence 5' gat tac aag gat· gac gac gat aag 3’ (SEQ ID NO: 53) is added to cloning primer at the 3' end of the ORF. Additional pSRa constructs are made to produce both amino-terminal and carboxyl-terminal GFP and myc/6X His fusion proteins of the full-length 282P1G3 proteins.

Additional Viral Vectors: Additional constructs are made for viral-mediated delivery and expression of 282P1G3. High virus titer leading io high level expression of 282P1G3 is achieved in viral delivery systems such as adenoviral vectors and herpes ampiicon vectors. A 282P1G3 coding sequences or fragments thereof are amplified by PCR and subcloned into the AdEasy shuttle vector (Stratagene). Recombination and virus packaging are performed according to the manufacturer’s instructions to generate adenoviral vectors. Alternatively, 282P1G3 coding sequences or fragments thereof are cloned into the HSV-1 vector (Imgenex) to generate herpes viral vectors. The viral vectors are thereafter used for infection of various ceil lines such as PC3, NIH 3T3, 293 or rat-1 ceils.

Regulated Expression Systems-. To control expression of 282P1G3 in mammalian cells, coding sequences of 282P1G3, or portions thereof, are cloned into regulated mammalian expression systems such as the T-Rex System (Invitrogen), the GeneSwitch System (Invitrogen) and the tightly-regulated Ecdysone System (Sratagene). These systems allow the study of the temporal and concentration dependent effects of recombinant 282P1G3. These vectors are thereafter used to control expression of 282P1G3 in various cell lines such as PC3, NIH 3T3,293 or rat-1 ceiis. B. Baculovirus Expression Systems

To generate recombinant 282P1G3 proteins in a baculovirus expression system, 282P1G3 ORF, or portions thereof, are cloned into the baculovirus transfer vector pBlueBac 4.5 (Invitrogen), which provides a His-tag at the N-terminus. Specifically, pBlueBac-282P1G3 is co-transfected with helper plasmid pBac-N-8lue (invitrogen) into SF9 (Spodoptera frugiperda} insect ceils to generate recombinant baculovirus (see invitrogen instruction manual for details). Baculovirus is then collected from celt supernatant and purified by plaque assay.

Recombinant 282P1G3 protein is then generated by infection of HighFive insect cells (invitrogen) with purified baculovirus. Recombinant 282P1G3 protein can be detected using anti-282P1 G3 or anti-His-tag antibody. 282P1G3 protein can be purified and used in various cell-based assays or as immunogen to generate polyclonal and monoclonal antibodies specific for 282P1G3. 96

Example 9: Antigenicity Profiles and Secondary Structure

Figure 5(A-C), Figure 6(A-C), Figure 7(A-C), Figure 8(A-C), and Figure 9(A-C) depict graphically five amino acid profiles of 282P1G3 variants 1, 3, and 7, each assessment available by accessing the ProtScaie website located on the World Wide Web at (.expasy.ch/cgi-bin/protscaie.pi) on the ExPasy moiecuiar biology server.

These profiles: Figure 5(A-C), Hydrophilicity, (Hopp T.P., Woods K.R., 1981. Proc. Mati. Acad. Sci. U.S.A. 78:3824-3828); Figure 6(A-C), Hydropathicity, (Kyte J., Doolittle R.F., 1982. J. Mol. Biol. 157:105-132); Figure 7(A-C), Percentage Accessible Residues (Janin J., 1979 Nature 277:491-492); Figure 8(A-C), Average Flexibility, (Bhaskaran R., and Ponnuswamy P.K., 1988. Int J. Pept Protein Res. 32:242-255); Figure 9(A-C), Beta-turn (Deleage, G., Roux B. 1987 Protein Engineering 1:289-294); and optionally others available in the art, such as on the ProtScaie website, were used to identify antigenic regions of each of the 282P1G3 variant proteins. Each of the above amino acid profiles of 282P1G3 variants were generated using the following ProtScaie parameters for analysis: 1) A window size of 9; 2) 100% weight of the window edges compared to the window center; and, 3) amino acid profile values normalized to lie between 0 and 1.

Hydrophilicity (Figure 5), Hydropathicity (Figure 6) and Percentage Accessible Residues (Figure 7) profiles were used to determine stretches of hydrophilic amino acids (i.e., values greater than 0.5 on the Hydrophilicity and Percentage Accessible Residues profile, and values less than 0.5 on the Hydropathicity profile). Such regions are likely to be exposed to the aqueous environment, be present on the surface of the protein, and thus available for immune recognition, such as by antibodies.

Average Flexibility (Figure 8) and Beta-turn (Figure 9) profiles determine stretches of amino acids (i.e., values greater than 0.5 on the Beta-tum profile and the Average Flexibility profile) that are not constrained in secondary structures such as beta sheets and alpha helices. Such regions are also more iikely to be exposed on the protein and thus accessible to immune recognition, such as by antibodies.

Antigenic sequences ofthe 282P1G3 variant proteins indicated, e.g., by the profiles set forth in Figure 5(A-C), Figure 6(A-C), Figure 7(A-C), Figure 8(A-C), and/or Figure 9(A-C) are used to prepare immunogens, either peptides or nucleic acids that encode them, to generate therapeutic and diagnostic anti-282P1G3 antibodies. The immunogen can be any 5,6, 7, 8, 9,10,11,12,13,14,15,16,17,18,19, 20, 21, 22, 23, 24, 25, 30, 35,40,45, 50 or more than 50 contiguous amino acids, or the corresponding nucleic acids that encode them, from the 282P1G3 protein variants listed in Figures'2 and 3, In particular, peptide immunogens of the invention can comprise, a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Hydrophilicity profiles of Figure 5; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value less than 0.5 in the Hydropathicity profile of Figures 6; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Percent Accessible Residues profiles of Figure 7; a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Average Flexibility profiles on Figure 8; and, a peptide region of at least 5 amino acids of Figures 2 and 3 in any whole number increment that includes an amino acid position having a value greater than 0.5 in the Beta-tum profile of Figures 9. Peptide immunogens of the invention can also comprise nucleic acids that encode any of the forgoing.

Al! immunogens ofthe invention, peptide or nucleic acid, can be embodied in human unit dose form, or comprised by a composition that includes a pharmaceutical excipient compatible with human physiology.

The secondary structure of 282P1G3 protein variants 1 through 8, namely the predicted presence and location of alpha helices, extended strands, and random coils, is predicted from the primary amino acid sequence using the HNN -

Hierarchical Neurai Network method (Guermeur, 1997, http://pbii.ibcp.fr/cgi-bin/npsa_automat.pl7page=npsa_nn.htmi), 97 accessed from the ExPasy molecular biology server located on the World Wide Web at (.expasy.ch/tools/). The analysis indicates that 282P1G3 variant 1 is composed of 15.77% alpha helix, 26.14% extended strand, and 58.09% random coil (Figure 13A). Variant 2 is composed of 14.86% alpha helix, 26.39% extended strand, and 58.75% random coil (Figure 13B). Variant 3 is composed of 14.00% alpha helix, 29.34% extended strand, and 56.66% random coil (Figure 13C). Variant 4 is composed of 15.94% alpha helix, 26.14% extended strand, and 57.92% random coil (Figure 13D). Variant 5 is composed of 15.73% alpha helix, 26.32% extended strand, and 57.95% random coil (Figure 13E). Variant 6 is composed of 16.99% alpha helix, 25.36% extended strand, and 57.65% random coil (Figure 13F). Variant 7 is composed of 15.78% alpha helix, 26.13% extended strand, and 58.09% random coil (Figure 13G). Variant 8 is composed of 16.99% alpha helix, 25.36% extended strand, and 57.66% random coil (Figure 13H).

Analysis for the potential presence of transmembrane domains in the 282P1G3 variant proteins was carried out using a variety of transmembrane prediction algorithms accessed from the ExPasy molecular biology server located on the World Wide Web at (.expasy.ch/tools/). Shown graphically in figure 131 and 13J are the results of analysis of variant 1 depicting the presence and location of 1 transmembrane domain using the TMpred program (Figure 131) and 1 transmembrane domain using the TMHMM program (Figure 13J). Shown graphically in figure 13K and 13L are the results of analysis of variant 2 depicting the presence and location of 1 transmembrane domains using the TMpred program (Figure 13K) and 1 transmembrane domain using the TMHMM program (Figure 13L). Shown graphically in figure 13M and 13N are the results of analysis of variant 3 depicting no transmembrane domain using both the TMpred program (Figure 13M) and TMHMM program (Figure 13N). Shown graphically in figure 130 and 13P are the results of analysis of variant 4 depicting the presence and location of 1 transmembrane domain using the TMpred program (Figure 130) and 1 transmembrane domain using the TMHMM program (Figure 13P). Shown graphically in figure 13Q and 13R are the results of analysis of variant 5 depicting the presence and location of 1 transmembrane domain using the TMpred program (Figure 13Q) and 1 transmembrane domain using the TMHMM program (Figure 13R). Shown graphically in figure 13S and 13T are the results of analysis of variant 6 depicting the presence and location of 1 transmembrane domain using the TMpred program (Figure 13S) and 1 transmembrane domain using the TMHMM program (Figure 13T). Shown graphically in figure 13U and 13V are the results of analysis of variant 7 depicting the presence and location of 1 transmembrane domain using the TMpred program (Figure 13U) and 1 transmembrane domain using the TMHMM program (Figure 13V). Shown graphically in figure 13W and 13X are the results of analysis of variant 8 depicting the presence and location of 1 transmembrane domain using the TMpred program (Figure 13W) and 1 transmembrane domain using the TMHMM program (Figure 13X), The results of each program, namely the amino acids, encoding the transmembrane domains are summarized in Table VL

Example 10: Generation of 282P1G3 Polyclonal Antibodies

Polyclonal antibodies can be raised in a mamma!, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections, in addition to immunizing with a full length 282P1G3 protein variant, computer algorithms are employed in design of immunogens that, based on amino acid sequence analysis contain characteristics of being antigenic and available for recognition by the immune system of the immunized host (see the Example entitled “Antigenicity Profiles and Secondary Structure"). Such regions would be predicted to be hydrophilic, flexible, in beta-turn conformations, and be exposed on the surface of the protein (see, e.g., Figure 5(A-C), Figure 6(A & G), Figure 7(A-C), Figure 8(A -C), or Figure 9(A-C) for amino acid profiles that indicate such regions of 282P1G3 protein variants).

For example, recombinant bacterial fusion proteins or peptides containing hydrophilic, flexible, beta-tum regions of 282P1G3 protein variants are used as antigens to generate polyclonal antibodies in New Zealand White rabbits or monoclonal antibodies as described in Example 11. For example, in 282P1G3 variant 1, such regions include, but are not 98 limited to, amino acids 57-75, amino acids 131-135, amino acids 210-265, amino acids 550-588, and amino acids 662-688. in sequence unique to variant 3, such regions include, but are not limited to, amino acids 855-872 and amino acids 856-886.

In sequence specific for variant 7, such regions include, but are not limited to, amino acids 345-356. It is useful to conjugate the immunizing agent to a protein known to be immunogenic in the mamma! being immunized. Examples of such immunogenic proteins include, but are not limited to, keyhole limpet hemocyanin (KLH), serum albumin, bovine thyroglobuiin, and soybean trypsin inhibitor. In one embodiment, a peptide encoding amino acids 57-75 of 282P1G3 variant 1 was conjugated to KLH and used to immunize a rabbit. Alternatively the immunizing agent may include aii or portions of the 282P1G3 variant proteins, analogs or fusion proteins thereof. For example, the 282P1G3 variant 1 amino acid sequence can be fused using recombinant DNA techniques to any one of a variety of fusion protein partners that are well known in the art, such as glutalhione-S-transferase (GST) and HIS tagged fusion proteins, in another embodiment, amino acids 26-265'of 282P1G3 variant 1 was fused to GST using recombinant techniques and the pGEX expression vector, expressed, purified and used to immunize a rabbit. Such fusion proteins are purified from induced bacteria using the appropriate affinity matrix.

Other recombinant bacterial fusion proteins that may be employed include maltose binding protein, LacZ, thioredoxin, NusA, or an immunoglobulin constant region (see the section entitled “Production of 282P1G3 in Prokaryotic Systems” and Current Protocols In Molecular Biology, Volume 2, Unit 16, Frederick M. Ausubul et al. eds., 1995; Linsley, P.S., Brady, W., Urnps, M., Grosmaire, L, Damie, N., and Ledbetter, L.(1991) J.Exp. Med. 174, 561-566).

In addition to bacterial derived fusion proteins, mammalian expressed protein antigens are aiso used. These antigens are expressed from mammalian expression vectors such as theTag5 and Fc-fusion vectors (see the section entitled “Production of Recombinant 282P1G3 in Eukaryotic Systems”), and retains post-translational modifications such as gtycosyiations found in native protein. In one embodiment, amino acids 26-1,043 of variant 2, encoding the extracellular domain, was cloned into the Tag5 mammalian secretion vector, and expressed in 293T cells. The recombinant protein is purified by metal chelate chromatography from tissue culture supernatants of 293T cells stably expressing the recombinant vector. The purified Tag5 282P1G3 protein is then used as immunogen.

During the immunization protocol, it is useful to mix or emulsify the antigen in adjuvants that enhance the immune response of the host animal. Examples of adjuvants include, but are not limited to, complete Freund's adjuvant (CFA) and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).

In a typical protocol, rabbits are initially immunized subcutaneously with up to 200 pg, typically 100-200 pg, of fusion protein or peptidd-conjugated to KLH mixed in complete Freund's adjuvant (CFA). Rabbits are then injected subcutaneously every two weeks with up to 200 pg, typically 100-200 pg, of the immunogen in incomplete Freund's adjuvant (IFA). Test bleeds are taken approximately 7-10 days following each immunization and used to monitor the titer of the antiserum by ELISA.

To test reactivity and specificity of immune serum, such as the rabbit serum derived from immunization with the Tag5-282P1G3 variant 2 protein, the full-length 282P1G3 variant 1 cDNA is cloned into pCDNA 3.1 myc-his expression vector (Invitrogen, see the Example entitled “Production of Recombinant 282P1G3 in Eukaryotic Systems”). After transfection of the constructs into 293T cells, cell lysates are probed with the anti-282P1 G3 serum and with anfi-His antibody (See Figure 19; Santa Cruz Biotechnologies, Santa Cruz, CA) to determine specific reactivity to denatured 282P1G3 protein using the Western blot technique. In addition, the immune serum is tested by fluorescence microscopy, flow cytometry and immunoprecipitation against 293T and other recombinant 282P1 G3-expressing cells to determine specific recognition of native protein. Western blot, immunoprecipitation, fluorescent microscopy, and flow cytometric techniques using cells that ' endogenously express 282P1G3 are aiso carried out to test reactivity and specificity.

Anti-serum from rabbits immunized with 282P1G3 variant fusion proteins, such as GST and MBP fusion proteins, are purified by depletion of antibodies reactive to the fusion partner sequence by passage over an affinity column containing 99 the fusion partner either aione or in the context of an irrelevant fusion protein. For example, antiserum derived from a GST-282P1G3 variant 1 fusion protein is first purified by passage over a column of GST protein covalently coupled to AffiGel matrix (BioRad, Hercules, Calif.). The antiserum is then affinity purified by passage over a column composed of a MBP-282P1G3 fusion protein covalently coupled to Affigel matrix. The serum is then further purified by protein G affinity chromatography to isolate the IgG fraction. Sera from other His-tagged antigens and peptide immunized rabbits as well as fusion partner depleted sera are affinity purified by passage over a column matrix composed of the original protein immunogen or free peptide.

Example 11: Generation of 282P1G3 Monoclonal Antibodies (mAbs)

In one embodiment, therapeutic mAbs to 282P1G3 variants comprise those that react with epitopes specific for each variant protein or specific to sequences in common between the variants that would disrupt or modulate the biological function of the 282P1G3 variants, for example those that would disrupt the interaction with ligands and binding partners. Immunogens for generation of such mAbs include those designed to encode or contain the entire 282P1G3 protein variant sequence, regions of the 282P1G3 protein variants predicted to be antigenic from computer analysis of the amino acid sequence (see, e.g., Figure 5(A-C), Figure 6(A-C), Figure 7(A-C), Figure 8(A-C), or Figure 9(A-C), and the Example entitled “Antigenicity Profiles and Secondary Structure"). Immunogens include peptides, recombinant bacterial proteins, and mammalian expressed Tag 5 proteins and human and murine IgG FC fusion- proteins, in addition, ceils engineered to express high levels of a respective 282P1G3 variant, such as 293T-282P1G3 variant 1 orbo0.19-282P1G3 variant Imurine Pre-B cells, are used to immunize mice.

To generate mAbs to a 282P1G3 variant, mice are first immunized intraperitoneaily (IP) with, typically, 10-50 pg of protein immunogen or 107 282P1 G3-expressing ceils mixed in complete Freund’s adjuvant. Mice are then subsequently immunized IP every 2-4 weeks with, typically, 10-50 pg of protein immunogen or 107 cells mixed in incomplete Freund’s adjuvant. Alternatively, MPL-TDM adjuvant is used in immunizations. In addition to the above protein and cell-based immunization strategies, a DNA-based immunization protocol is employed in which a mammalian expression vector encoding a 282P1G3 variant sequence is used to immunize mice by direct injection ofthe plasmid DNA. For example, amino acids 26-1,043 of variant 2 was cloned into the Tdg5 mammalian secretion vector and the recombinant vector wiii then be used as immunogen, in another example the same amino acids are cioned into an Fc-fosion secretion vector in which the 282P1G3 variant 2'sequence is fused at the amino-terminus to an IgK leader sequence and at the carboxyl-terminus to the coding sequence of the human or murine IgG Fc region. This recombinant vector is then used as immunogen. The plasmid immunization protocols are used in combination with purified proteins expressed from the same vector and with celis expressing the respective 282P1G3 variant.

During the immunization protocol, test bleeds are taken 7-10 days following an injection to monitor titer and specificity of the immune response. Once appropriate reactivity and specificity is obtained as determined by ELISA, Western blotting, immunoprecipitation, fluorescence microscopy, and flow cytometric analyses, fusion and hybridoma generation is then carried out with established procedures well known in the art (see, e.g., Harlow and Lane, 1988). in one embodiment for generating 282P1G3 monoclonal antibodies, a Tag5-282P1 G3 variant 2 antigen encoding amino acids 26-1,043, was expressed (Figure 20) and then purified from stably transfected 293T celis. Baib C mice are initially immunized intraperitoneaily with 25 pg of the Tag5-282P1G3 variant 2 protein mixed in complete Freund's adjuvant Mice are subsequently immunized every two weeks with 25 ug ofthe antigen mixed in incomplete Freund's adjuvant for a total of three immunizations. ELISA using the Tag5 antigen determines the titer of serum from immunized mice. Reactivity and specificity of serum to full length 282P1G3 variant 2 protein is monitored by Western blotting, immunoprecipitation and flow cytometry using 293T cells transfected with an expression vector encoding the 282P1G3 variant 2 cDNA (see e.g., the 100

Example entitled "Production of Recombinant 282P1G3 in Eukaryotic Systems" and Figure 19). Other recombinant 282P1G3 variant 2-expressing cells or cells endogenously expressing 282P1G3 variant 2 are also used. Mice showing the strongest reactivity are rested and given a final injection of Tag5 antigen in PBS and then sacrificed four days later. The spleens of the sacrificed mice are harvested and fused to SPO/2 myeloma cells using standard procedures (Harlow and Lane, 1988). Supernatants from HAT selected growth wells are screened by ELISA, Western blot, immunoprecipitation, fluorescent microscopy, and flow cytometry to identify 282P1G3 specific antibody-producing clones.

To generate monoclonal antibodies that are specific for each 282P1G3 variant protein, immunogens are designed to encode sequences unique for each variant For example, peptides or recombinant protein antigens (i.e. Tag5 fusion proteins) encompassing the unique sequence derived from alternate exon usage in splice variants 2, 3, 4, 5, 6, and 7 are used as immunogens, in one embodiment, a Tag5 protein encoding amino acids 838-893 unique to 282P1G3 variant 3 is produced, purified, and used as immunogen to derive monoclonal antibodies specific to 282P1G3 variant 3. In another embodiment, an antigenic peptide composed of amino acids 1025-1037 of 282P1G3 variant 2 is coupled to KLH and used as immunogen. In another embodiment, an antigenic peptide composed of amino acids 817-829 of 282P1G3 variant 4 is coupled to KLH and used as immunogen, in another embodiment, an antigenic peptide composed of amino acids 220-232 of 282P1G3 variant 5 is coupled to KLH and used as immunogen. In another embodiment, an antigenic peptide composed of amino acids 122-134 of 282P1G3 variant 6 is coupled to KLH and used as immunogen. In another embodiment, an antigenic peptide composed of amino acids 339-362 of 282P1G3 variant 7 is coupled to KLH and used as immunogen. Hybridoma supernatants are then screened on the respective antigen and then further screened on cells expressing the specific variant and cross-screened on cells expressing the other variants to derive variant-specific monoclonal antibodies.

The binding affinity of a 282P1G3 variant monoclonal antibody is determined using standard technologies. Affinity measurements quantify the strength of antibody to epitope binding and are used to help define which 282P1G3 variant monoclonal antibodies preferred for diagnostic or therapeutic use, as appreciated by one of skill in the art. The BIAcore system (Uppsala, Sweden) is a preferred method for determining binding affinity. The BIAcore system uses surface piasmon resonance (SPR, Welford K. 1991, Opt. Quant. Elect. 23:1; Morton and Myszka, 1998, Methods in Enzymology 295: 268) to monitor biomolecular interactions in real time. BIAcore analysis conveniently generates association rate constants, dissociation rate constants, equilibrium dissociation constants, and affinity constants.

Example 12: HLA Class I and Class li Binding Assays HLA class I and class II binding'assays using purified HLA molecules are performed in accordance with disclosed protocols (e.g., PCT publications WO 94/20127 and WO 94/03205; Sidney et al., Current Protocols in Immunology 18.3.1 (1998); Sidney, et at, J. Immunol. 154:247 (1995); Sette, ef a/., Mol. Immunol. 31:813 (1994)). Briefly, purified MHO molecules (5 to 500 nM) are incubated with various unlabeled peptide inhibitors and 1-10 nM 125I-radio!abe!ed probe peptides as described. Following incubation, MHC-peptide complexes are separated from free peptide by gel filtration and the fraction of peptide bound is determined. Typically, in preliminary experiments, each MHC preparation is titered in the presence of fixed amounts of radiolabeled peptides to determine the concentration of HLA molecules necessary to bind 10-20% of the total radioactivity. All subsequent inhibition and direct binding assays are performed using these HLA concentrations.

Since under these conditions pabel]<[HLA] and ICso>[HLA], the measured ICso values are reasonable approximations of the true Ko values. Peptide inhibitors are typically tested at concentrations ranging from 120 gg/ml to 1.2 ng/ml, and are tested in two to four completely independent experiments. To allow comparison of the data obtained in different experiments, a relative binding figure is calculated for each peptide by dividing the IC50 of a positive control for inhibition by the ICso for each tested peptide (typically unlabeled versions of the radiolabeled probe peptide). For database 101 purposes, and inter-experiment comparisons, relative binding values are compiled. These values can subsequently be converted back into ICso nM values by dividing the ICso nM of the positive controls for inhibition by the relative binding of the peptide of interest. This method of data compilation is accurate and consistent for comparing peptides that have been tested on different days, or with different lots of purified MHC.

Binding assays as outlined above may be used to analyze HLA, supermotif and/or HLA motif-bearing peptides (see

Table IV).

Example 13: Identification of HLA Supermotif- and Motif-Bearing CTL Candidate Epitopes HLA vaccine compositions of the invention can include multiple epitopes. The multiple epitopes can comprise multiple HLA supermotifs or motifs to achieve broad population coverage. This example illustrates the identification and confirmation of supermotif- and motif-bearing epitopes for the inclusion in such a vaccine composition. Calculation of population coverage is performed using the strategy described below.

Computer searches and algorithms for identification of supermotif and/or motif-bearing epitopes

The searches performed to identify the motif-bearing peptide sequences in the Example entitled “Antigenicity Profiles” and Tables VIll-XXl and XXI l-XLIX employ the protein sequence data from the gene product of 282P1G3 set forth in Figures 2 and 3, the specific search peptides used to generate the tables are listed in Table VII.

Computer searches for epitopes bearing HLA Class I or Class I! supermotifs or motifs are performed as follows. All translated 282P1G3 protein sequences are analyzed using a text string search software program to identity potential peptide sequences containing appropriate HLA binding motifs; such programs are readily produced in accordance with information in the art in view of known motif/supermotif disclosures. Furthermore, such calculations can be made mentally.

Identified A2-, A3-, and DR-supermotif sequences are scored using polynomial algorithms to predict their capacity to bind to specific HLA-Class I or Class II molecules. These polynomial algorithms account for the impact of different amino acids at different positions, and are essentially based on the premise that the overall affinity (or AG) of peptide-HLA molecule interactions can be approximated as a linear polynomial function of the type: “AG“ = ai,-xaaxa3i.xara· where a; is a coefficient which represents the effect of the presence of a given amino acid (/)'at a given position (/) along the sequence of a peptide of n amino acids. The crucial assumption of this method is that the effects at each position are essentially independent of each other (i.e., independent binding of individual side-chains). When residue j occurs at position i in the peptide, it is assumed to contribute a constant amount j,· to the free energy of binding of the peptide irrespective of the sequence of the rest of the peptide.

The method of derivation of specific algorithm coefficients has been described in Gulukota et at., J. Mol. Biol. 257:1258-126,1997; (see also Sidney ef at., Human Immunol. 45:79-93,1996; and Southwood et at., J. Immunol. 160:3363-3373, 1998). Briefly, for all i positions, anchor and non-anchor alike, the geometric mean of the average relative binding (ARB) of all peptides carrying j is calculated relative to the remainder of the group, and used as the estimate of j;. For Class II peptides, if multiple alignments are possible, only the highest scoring alignment is utiiized, following an iterative procedure. To calculate an algorithm score of a given peptide in a test set, the ARB values corresponding to the sequence of the peptide are multiplied. If this product exceeds a chosen' threshold, the peptide is predicted to bind. Appropriate thresholds are chosen as a function of the degree of stringency of prediction desired.

Selection of HLA-A2 supertype cross-reactive peptides f

Protein sequences from 282P1G3 are scanned utilizing motif identification software, to identify 8-, 9 and 1 rimer sequences containing the HLA-A2-supermotif main anchor specificity. Typically, these sequences are then scored using 102 the protocol described above and the peptides corresponding to the positive-scoring sequences are synthesized and tested for their capacity to bind purified HLA-A*0201 molecules in vitro (HLA-A*0201 is considered a prototype A2 supertype molecule).

These peptides are then tested for the capacity to bind to additional A2-supertype molecules (A*0202/A*0203, A*0206, and A*6802). Peptides that bind to at least three of the five A2-supertype aileles tested are typically deemed A2-supertype cross-reactive binders. Preferred peptides bind at an affinity equal to or less than 500 nM to three or more HLA-A2 supertype molecules.

Selection of HLA-A3 supermotif-bearinq epitopes

The 282P1G3 protein sequence(s) scanned above is also examined for the presence of peptides with the HLA-A3-supermotif primary anchors. Peptides corresponding to the HLA A3 supermotif-bearing sequences are then synthesized and tested for binding to HLA-AO301 and HLA-A*1101 molecules, the molecules encoded by the two most prevalent A3-supertype alleles. The peptides that bind at least one of the two alleles with binding affinities of &lt;500 nM, often &lt; 200 nM, are then tested for binding cross-reactivity to the other common A3-supertype alleles (e.g., A*3101, A*3301, and A*6801) to identify those that can bind at least three of the five HLA-A3-supertype molecules tested.

Selection of HLA-B7 supermotif bearing epitopes

The 282P1G3 protein(s) scanned above is also analyzed for the presence of 8-, 9 , or 1.1-mer peptides with the HLA-B7-supermotif. Corresponding peptides are synthesized and tested for binding to HLA-B’0702, the molecule encoded by the most common B7-supertype allele (i.e., the prototype B7 supertype allele). Peptides binding B‘0702 with !Cso of &lt;500 nM are identified using standard methods. These peptides are then tested for binding to other common B7-supertype molecules (e.g., B*3501, B*5101, B*5301, and B*5401). Peptides capable of binding to three or more of the five B7-supertype alleles tested are thereby identified.

Selection of A1 and A24 motif-bearing epitopes ' To further increase population coverage, HLA-A1 and -A24 epitopes can also be incorporated into vaccine compositions. An analysis of the 282P1G3 protein can also be performed to identify HLA-A1- and A24-motif-containing sequences.

High affinity and/or cross-reactive binding epitopes that bear other motif and/or supermotifs are identified using analogous methodology.

Example 14: Confirmation of Immunoqenicity

Cross-reactive candidate CTL A2-supermotif-bearing peptides that are identified as described herein are selected to confirm in vitro immunogenicity. Confirmation is performed using the following methodology:

Target Cell Lines for Cellular Screening:

The .221A2.1 cell line, produced by transferring the HLA-A2.1 gene into the HLA-A, -B, -C null mutant human B-lymphobiastoid cell line 721.221, is used as the peptide-loaded target to measure activity of HLA-A2.1-restricted CTL. This ceil line is grown in RPMI-1640 medium supplemented with antibiotics, sodium pyruvate, nonessential amino acids and 10% (v/v) heat inactivated FCS. Ceils that express an antigen of interest, or transfectants comprising the gene encoding the antigen of interest, can be used as target cells to confirm the ability of peptide-specific CTLs to recognize endogenous antigen.

Primary CTL Induction Cultures: 103

Generation of Dendritic Celis (DC): PBMCs are thawed in RPMI with 30 pg/ml DNAse, washed twice and resuspended in complete medium (RPM1-1640 plus 5% AB human serum, non-essential amino acids, sodium pyruvate, L-glutamine and penicillin/streptomycin). The monocytes are purified by plating 10x10® PBMC/well in a 6-well plate. After 2 hours at 37“C, the non-adherent cells are removed by gently shaking the plates and aspirating the supernatants. The wells are washed a total of three times with 3 ml RPMI to remove most of the non-adherent and loosely adherent cells. Three ml of complete medium containing 50 ng/ml of GM-CSF and 1,000 U/ml of IL-4 are then added to each well. TNFa is added to the DCs on day 6 at 75 ng/ml and the celis are used for CTL induction cultures on day 7. induction of CTL with DC and Peptide: CD8+ T-cells are isolated by positive selection with Dynal immunomagnetic beads (Dynabeads® M-450) and the detacha-bead® reagent. Typically about 200-250x106 PBMC are processed to obtain 24x10s CD8+ T-cells (enough for a 48-well plate culture). Briefly, the PBMCs are thawed in RPMI with 30pg/mt DNAse, washed once with PBS containing 1% human AB serum and resuspended in PBS/1% AB serum at a concentration of 20x10®cells/ml. The magnetic beads are washed 3 times with PBS/AB serum, added to the cells (140μΙ beads/20x10® celis) and incubated for 1 hour at 4°C with continuous mixing. The beads and cells are washed 4x with PBS/AB serum to remove the nonadherent cells and resuspended at 100x10® cells/ml (based on the original cell number) in PBS/AB serum containing ΙΟΟμΙ/mLdetacfia-bead® reagent and 30 pg/ml DNAse. The mixture is incubated for 1 hour at room temperature with continuous mixing. The beads are washed again with PBS/AB/DNAse to collect the CD8+ T-cells. The DC are collected and centrifuged at 1300 rpm for 5-7 minutes, washed once with PBS with 1 % BSA, counted and pulsed with 40pg/ml of peptide at a cell concentration of 1-2x10®/ml in the presence of 3pg/ml 82- microglobulin for 4 hours at 20°C. The DC are then irradiated (4,200 rads), washed 1 time with medium and counted again.

Setting up induction cultures: 0.25 ml cytokine-generated DC (at 1x105 cells/ml) are co-cultured with 0.25ml of CD8+ T-cells (at 2x10® cell/ml) in each well of a 48-well plate in the presence of 10 ng/ml of IL-7. Recombinant human IL-10 is added the next day at a final concentration of 10 ng/ml and rhuman IL-2 is added 48 hours later at 10 lU/ml.

Restimulation of the induction cultures with peptide-pulsed adherent celis: Seven and fourteen days after the primary induction, the cells are restimulated with peptide-puised adherent cells. The PBMCs are thawed and washed twice with RPMI and DNAse. The cells are resuspended at 5x10® cells/ml and irradiated at -4200 rads. The PBMCs are plated at 2x10s in 0.5 rnl complete medium per well and incubated for 2 hours at 37°C. The plates are washed twice with RPMI by tapping the plate gently to remove the nonadherent cells and the adherent cells pulsed with ,10pg/ml of peptide in the presence of 3 pg/ml (Ly-microglobulin in 0.25ml RPMI/5%AB per well for 2 hours at 37°C. Peptide solution from each well is aspirated and the wells are washed once with RPMI. Most of the media is aspirated from the induction cultures (CD8+ cells) and brought to 0.5 ml with fresh media. The cells are then transferred to the wells containing the peptide-pulsed adherent cells. Twenty four hours later recombinant human IL-10 is added at a final concentration of 10 ng/ml and recombinant human 1L2 is added the next day and again 2-3 days later at 50IU/ml (Tsai ef al., Critical Reviews in immunology 18(1-2):65-75, 1998). Seven days later, the cultures are assayed for CTL activity in a 51Cr release assay. In some experiments the cultures are assayed for peptide-specific recognition in the in situ IFNy ELISA at the time of the second restimulation followed by assay of endogenous recognition 7 days later. After expansion, activity is measured in both assays for a side-by-side comparison.

Measurement of CTL lytic activity by 51Cr release.

Seven days after the second restimulation, cytotoxicity is determined in a standard (5 hr) s1Cr release assay by assaying Individual wells at a single E:T. Peptide-pulsed targets are prepared by incubating the cells with 10pg/ml peptide overnight at 37°C.

Adherent target cells are removed from culture flasks with trypsin-EDTA. Targe! cells are labeled with 200pCi of 51Cr sodium chromate (Dupont, Wilmington, DE) for 1 hour at 37°C. Labeled target cells are resuspended at 10® per mi and 104 i diluted 1:10 with K562 cells at a concentration of 3.3x106/ml (an NK-sensitive erythrobiastoma ceii line used to reduce nonspecific lysis). Target cells (100 μ!) and effectors (1 OOpl) are plated in 96 well round-bottom plates and incubated for 5 hours at 37°C. At that time, 100 pi of supernatant are collected from each well and percent lysis is determined according to the formula: [(cpm of the test sample- cpm of the spontaneous 51Cr release sampie)/(cpm of the maximal 5!Cr release sampie-cpm of the spontaneous 51Cr release sample)] x 100.

Maximum and spontaneous release are determined by incubating the labeled targets with 1% Triton X-100 and media aione, respectively. A positive culture is defined as one in whictvthe specific lysis (sample- background) is 10% or higher in the case of individual wells and is 15% or more at the two highest E:T ratios when expanded cultures are assayed. in situ Measurement of Human IFNy Production as an indicator of Peptide-specific and Endogenous Recognition

Immuion 2 plates are coated with mouse anti-human IFNy monoclonal antibody (4 pg/ml 0.1 M NaHCCh, pH8.2) overnight at 4°C. The plates are washed with Ca2+, Mg2+-free PBS/0.05% Tween 20 and blocked with PBS/10% FCS for two hours, after which the CTLs (10Q μΙ/well) and targets (10Q μΙ/well) are added to each weii, leaving empty weiis for the standards and blanks (which received media only). The target cells, either peptide-pulsed or endogenous targets, are used at a concentration of 1x106 cells/ml. The plates are incubated for 48 hours at 37°C with 5% CO2.

Recombinant human IFN-gamma is added to the standard wells starting at 400 pg or 1200pg/100 microliter/weli and the plate incubated for two hours at 37°C. The plates are washed and 100 μΙ of biotinylated mouse anti-human IFN-gamma monoclonal antibody (2 microgram/ml in PBS/3%FCS/0.05% Tween 20) are added and incubated for 2 hours at room temperature. After washing again, 100 microliter HRP-streptavidin (1:4000) are added and the plates incubated for one hour at room temperature. The plates are then washed 6x with wash buffer, 100 microiiter/weii developing solution (TMB 1:1) are added, and the plates allowed to develop for 5-15 minutes. The reaction is stopped with 50 microiiter/weii 1M H3PQ4 and read at OD450. A culture is considered positive if it measured at least 50 pg of IFN-gamma/welt above background and is twice the background level of expression. CTL Expansion.

Those cultures that demonstrate specific iytic activity against peptide-pulsed targets and/or tumor targets are expanded over a two week period with anti-CD3. Briefly, 5x104 CD8+ ceiis are added to a T25 flask containing the following: 1x106 irradiated (4,200 rad) PBMC (autologous or allogeneic) per ml, 2x105 irradiated (8,000 rad) EBV- transformed cells per mi, and OKT3 (anti-CD3)' at 30ng per ml in RPMI-1640 containing 10% (v/v) human AB serum, non-essential amino acids, sodium pyruvate, 25pM 2-mercaptoethanoi, L-glutamine and peniciiiin/streptomycin. Recombinant human IL2 is added 24 hours iater at a final concentration of 200IU/ml and every three days thereafter with fresh media at 50IU/ml. The cells are split if the ceii concentration exceeds 1 x106/ml and the cultures are assayed between days 13 and 15 at E:T ratios of 30,10, 3 and 1:1 in the 51Cr release assay or at 1x105/ml in the in situ IFNy assay using the same targets as before the expansion.

Cultures are expanded in the absence of anti-CD3+ as follows. Those cultures that demonstrate specific lytic activity against peptide and endogenous targets are selected .and 5x104 CD8* cells are added to a T25 flask containing the following: 1X106 autologous PBMC per ml which have been peptide-pulsed with 10 p.g/m! peptide for two hours at 37° C and irradiated (4,200 rad); 2x10s irradiated (8,000 rad) EBV-transformed cells per ml RPMI-1640 containing 10%(v/v) human AB serum, non-essential AA, sodium pyruvate, 25mM 2-ME, L-glutamine and gentamicin.

Immunogenicity of A2 supermotif-bearinq peptides A2-supermotif cross-reactive binding peptides are tested in the cellular assay for the ability to Induce peptide-specific CTL in normal individuals. ' In this analysis, a peptide is typically considered io be an epitope if it induces peptide-specific CTLs in at least individuals, and preferably, also recognizes the endogenously expressed peptide. 105

Immunogenicity can also be confirmed using PBMCs isolated from patients bearing a tumor that expresses 282P1G3. Briefly, PBMCs are isolated from patients, re-stimulated with peptide-pulsed monocytes and assayed for the ability to recognize peptide-pulsed target cells as well as transfected cells endogenously expressing the antigen.

Evaluation of A*03/At 1 immunogenicity HLA-A3 supermotif-bearing cross-reactive binding peptides are also evaluated for immunogenicity using methodology analogous for that used to evaluate the immunogenicity of the HLA-A2 supermotif peptides.

Evaluation of B7 immunogenicity immunogenicity screening of the B7-supertype cross-reactive binding peptides identified as set forth herein are confirmed in a manner analogous to the confirmation of A2-and A3-supermotif-bearing peptides.

Peptides bearing other supermotifs/motifs, e.g., HLA-A1, HLA-A24 efc. are also confirmed using similar methodology

Example 15: Implementation of the Extended Supermotif to improve the Binding Capacity of Native Epitopes by

Creating Analogs HLA motifs and supermotifs (comprising primary and/or secondary residues) are useful in the identification and preparation of highly cross-reactive native peptides, as demonstrated herein. Moreover, the definition of HLA motifs and supermotifs also allows one to engineer highly cross-reactive epitopes by identifying residues within a native peptide sequence which can be analoged to confer upon the peptide certain characteristics, e.g. greater cross-reactivity within the group of HLA molecules that comprise a supertype, and/or greater binding affinity for some or all of those HLA molecules. Examples of anaioging peptides to exhibit modulated binding affinity are set forth in this example.

Analoqinq at Primary Anchor Residues

Peptide engineering strategies are implemented to further increase the cross-reactivity of the epitopes. For example, the main anchors of A2-supermotif-bearing peptides are altered, for example, to introduce a preferred L, I, V, or M at position 2, and i or V at the C-terminus.

To analyze the cross-reactivity of the analog peptides, each engineered analog is initially tested for binding to the prototype A2 supertype allele A*Q201, then, if A*0201 binding capacity is maintained, for A2-supertype cross-reactivity.

Alternatively, a peptide is confirmed as binding one or all supertype members and then analoged to modulate binding affinity to any one (or more) of the supertype members to add population coverage.

The selection of analogs for immunogenicity in a cellular screening analysis is typically further restricted by the capacity of the parent wild type (WT) peptide to bind at least weakly, i.e., bind at an ICso of 5000nM or less, to three of more A2 supertype alleles. The rationale for this requirement is that the WT peptides must be present endogenously in sufficient quantity to be biologically relevant. Analoged peptides have been shown to have increased immunogenicity and crossreactivity by T cells specific for the parent epitope (see, e.g., Parkhurst ef al., J. Immunol. 157:2539,1996; and Pogue ef al., Proc. Natl. Acad. Sci. USA 92:8166,1995).

In the cellular screening of these peptide analogs, it is important to confirm that analog-specific CTLs are also able to recognize the wild-type peptide and, when possible, target cells that endogenously express the epitope.

Analoqinq of HLA-A3 and B7-superm0tif-bearinq peptides

Analogs of HLA-A3 supermotif-bearing epitopes are generated using strategies similar to those employed in anaioging HLA-A2 supermotif-bearing peptides. For example, peptides binding to 3/5 of the A3-supertype molecules are engineered at primary anchor residues to possess a preferred residue (V, S, M, or A) at position 2. 106

The analog peptides are then tested for the ability to bind A*03 and A*11 (prototype A3 supertype alleles). Those peptides that demonstrate &lt; 500 nM binding capacity are then confirmed as having A3-supertype cross-reactivity.

Similarly to the A2- and A3- motif bearing peptides, peptides binding 3 or more B7-supertype alleles can be improved, where possible, to achieve increased cross-reactive binding or greater binding affinity or binding naif life. B7 supermotif-bearing peptides are, for example, engineered to possess a preferred residue (V, I, L, or F) at the C-terminal primary anchor position, as demonstrated by Sidney ef al. (J. Immunol. 157:3480-3490,1996).

Analoging at primary anchor residues of other motif and/or supermotif-bearing epitopes is performed in a like manner.

The analog peptides are then be confirmed for immunogenicity, typically in a cellular screening assay. Again, it is generally important to demonstrate that analog-specific CTLs are also able to recognize the wild-type peptide and, when possible, targets that endogenously express the epitope.

Analoging at Secondary Anchor Residues

Moreover, HLA supermotifs are of value in engineering highly cross-reactive peptides and/or peptides that bind HLA molecules with.increased affinity by identifying particular residues at secondary anchor positions that are associated with such properties. For example, the binding capacity of a B7 supermotif-bearing peptide with an F residue at position 1 is analyzed. The peptide is then analoged to, for example, substitute L for F at position 1. The analoged peptide is evaluated for increased binding affinity, binding half life and/or increased cross-reactivity. Such a procedure identifies analoged peptides with enhanced properties.

Engineered analogs with sufficiently improved binding capacity or cross-reactivity can also be tested for immunogenicity in HLA-B7-transgenic mice, following for example, IFA immunization or lipopeptide immunization. Analoged peptides are additionally tested for the ability to stimulate a recall response using PBMC from patients with 282P1G3-expressing tumors.

Other analoging strategies

Another form of peptide analoging, unrelated to anchor positions, involves the substitution of a cysteine with a-amino butyric acid. Due to its chemical nature, cysteine has the propensity to form disulfide bridges and sufficiently aiter the peptide structurally so as to reduce binding capacity. Substitution of α-amino butyric acid for cysteine not only alleviates this problem, but has been shown to improve binding and crossbinding capabilities in some instances (see, e.g., the review by Sette ef a/., In: Persistent Viral infections, Eds. R. Ahmed and i. Chen, John Wiley &amp;amp; Sons, England, 1999).

Thus, by the use of single amino acid substitutions, the binding properties and/or cross-reactivity of peptide ligands for HLA supertype molecules can be modulated.

Example 16: Identification and confirmation of 282P1G3-derived sequences with HLA-DR binding motifs

Peptide epitopes bearing an HLA class II supermofif or motif are identified and confirmed as outlined below using methodology similar to that described for HLA Class I peptides.

Selection of HLA-DR-supermotif-bearinq epitopes.

To identity 282P1G3-derived, HLA class II HTL epitopes, a 282P1G3 antigen is analyzed for the presence of sequences bearing an HLA-DR-motif or supermotif. Specifically, 15-mer sequences are selected comprising a DR-supermotif, comprising a 9-mer core, and three-residue N- and C-terminal flanking regions (15 amino' acids total).

Protocols for predicting peptide binding to DR molecules have been developed (Southwood etal., J. Immunol. 160:3363-3373,1998). These protocols, specific for individual DR molecules, allow the scoring, and ranking, of 9-mer core regions. Each protocol not only scores peptide sequences for the presence of DR-supermotif primary anchors (i.e., at 107 position 1 and position 6) within a 9-mer core, but additionally evaluates sequences for the presence of secondary anchors. Using alleie-specific selection tables (see, e.g., Southwood et a!., ibid.}, it has been found that these protocols efficiently select peptide sequences with a high probability of binding a particular DR molecule. Additionally, it has been found that performing these protocots in tandem, specifically those for DR1, DR4w4, and DR7, can efficiently select DR cross-reactive peptides.

The 282P1 G3-derived peptides identified above are tested for their binding capacity for various common HLA-DR molecules. All peptides are initially tested for binding to the DR molecules in the primary panel: DR1, DR4w4, and DR7. Peptides binding at least two of these three DR molecules are then tested for binding to DR2w2 β1, DR2w2 β2, DR6w19, and DR9 molecules in secondary assays. Finally, peptides binding at least two of the four secondary panel DR molecules, and thus cumulatively at least four of seven different DR molecules, are screened for binding to DR4w15, DR5w11, and DR8w2 molecules in tertiary assays. Peptides binding at least seven of the ten DR molecules comprising the primary, secondary, and tertiary screening assays are considered cross-reactive DR binders. 282P1G3-derived peptides found to bind common HLA-DR alleles are of particular interest.

Selection of DR3 motif peptides

Because HLA-DR3 is an allele that is prevalent in Caucasian, Black, and Hispanic populations, DR3 binding capacity is a relevant criterion in the selection of HTL epitopes. Thus, peptides shown to be candidates may also be assayed for their DR3 binding capacity. However, in view of the binding specificity of the DR3 motif, peptides binding only to DR3 can also be considered as candidates for inclusion in a vaccine formulation.

To efficiently identify peptides that bind DR3, target 282P1G3 antigens are analyzed for sequences carrying one of the two DR3-specific binding motifs reported by Geluk et al. (J. Immunol. 152:5742-5748,1994). The corresponding peptides are then synthesized and confirmed as having the ability to bind DR3 with an affinity of 1 μΜ or better, i.e., less than 1 μΜ. Peptides are found that meet this binding criterion and qualify as HLA class II high affinity binders. DR3 binding epitopes identified in this manner are included in vaccine compositions with DR supermotif-bearing peptide epitopes.

Similarly to the case of HLA class 1 motif-bearing peptides, the class II motif-bearing peptides are analoged to improve affinity or cross-reactivity. For example, aspartic acid at position 4 of the 9-mer core sequence is an optimal residue for DR3 binding, and substitution for that residue often improves DR 3 binding. v

Example 17: immunogenicity of 282P1G3-derived HTL epitopes

This example determines immunogenic DR supermotif- and DR3 motif-bearing epitopes among those identified using the methodology set forth herein.

Immunogenicity of HTL epitopes are confirmed in a manner analogous to the determination of immunogenicity of CTL epitopes, by assessing the ability to stimulate HTL responses and/or by using appropriate transgenic mouse models. Immunogenicity is determined by screening for: 1.) in vitro primary induction using normal PBMC or 2.) recall responses from patients who have 282P1 G3-expressing tumors.

Example 18: Calculation of phenotypic frequencies of HLA-supertypes in various ethnic backgrounds to determine breadth of population coverage

This example illustrates the assessment of the breadth of population coverage of a vaccine composition comprised of multiple epitopes comprising multiple supermotifs and/or motifs.

In order to analyze population coverage, gene frequencies of HLA alleles are determined. Gene frequencies for each HLA allele are calculated from antigen or ailele frequencies utilizing the binomial distribution formulae gf=1-(SGRT(1- 108 at)) (see, e.g., Sidney et al., Human Immunol. 45:79-93,1996). To obtain overall phenotypic frequencies, cumulative gene frequencies are calculated, and the cumulative antigen frequencies derived by the use of the inverse formula [af=1 -(1-Cgf)2].

Where frequency data is not available at the level of DNA typing, correspondence to the serologically defined antigen frequencies is assumed. To obtain total potential supertype population coverage no linkage disequilibrium is assumed, and only alleles confirmed to belong to each of the supertypes are included (minimal estimates). Estimates of total potential coverage achieved by inter-ioci combinations are made by adding to the A coverage the proportion of the non-A covered population that could be expected to be covered by the B alleles considered (e.g., total=A+B*(1-A)). Confirmed members of the A3-like supertype are A3, A11, A31, A*3301, and A*6801. Although the A3-like supertype may also include A34, A66, and A*7401, these alleles were not included in overall frequency calculations. Likewise, confirmed members of the A2-like supertype family are A*0201, A*0202, A*0203, A*02Q4, Α&amp;#908;205, A*0206, A*0207, A*6802, and A*6901. Finally, the B7-!ike supertype-confirmed alleles are: B7, B*3501-03, B51, B*5301, B*5401, B*5501-2, B*5601, B*6701, and B*7801 (potentially also Β&amp;#906;401, B*35Q4-06, B*4201, and B‘56Q2).

Population coverage achieved by combining the A2-, A3- and B7-supertypes is approximately 86% in five major ethnic groups. Coverage may be extended by including peptides bearing the A1 and A24 motifs. On average, A1 is present in 12% and A24 in 29% of the population across five different major ethnic groups (Caucasian, North American Black, Chinese, Japanese, and Hispanic). Together, these alleles are represented with an average frequency of 39% in these same ethnic populations. The total coverage across the major ethnicities when A1 and A24 are combined with the coverage of the A2-, A3- and B7-supertype alleles is >95%, see, e.g., Table IV (G). An analogous approach can be used to estimate population coverage achieved with combinations of class II motif-bearing epitopes.

Immunogenicity studies in humans (e.g., Bertoni et at., J. Clin. Invest. 100:503,1997; Doolan eta/., Immunity7:97, 1997; and Threlkeid ef a/., J. Immunol. 159:1648,1997) have shown that highly cross-reactive binding peptides are almost always recognized as epitopes. The use of highly cross-reactive binding peptides is an important selection criterion in identifying candidate epitopes for inclusion in a vaccine that is immunogenic in a diverse population.

With a sufficient number of epitopes (as disclosed herein and from the art), an average population coverage is predicted to be greater than 95% in each of five major ethnic populations. The game theory Monte Carlo simulation analysis, which is known in the art (see e.g., Osborne, M.J. and Rubinstein, A. "A course in game theory” MIT Press, 1994), can be used to estimate what percentage of the individuals in a population comprised of the Caucasian, North American Black, Japanese, Chinese, and,.Hispanic ethnic groups would recognize the vaccine epitopes described herein. A preferred percentage is 90%. A more preferred percentage is 95%. -

Example 19: CTL Recognition Of Endogenously Processed Antigens After Priming

I

This example confirms that CTL induced by native or analoged peptide epitopes identified and selected as described herein recognize endogenously synthesized, i.e., native antigens.

Effector cells isolated from transgenic mice that are immunized with peptide epitopes, for example HLA-A2 supermotif-bearing epitopes, are re-stimulated in vitro using peptide-coated stimulator cells. Six days later, effector cells are assayed for cytotoxicity and the ceil lines that contain peptide-specific cytotoxic activity are further re-stimulated. An additional six days later, these cell lines are tested for cytotoxic activity on51 Cr labeled Jurkat-A2.1/Kb target cells in the absence or presence of peptide, and also tested on 51Cr labeled target ceils bearing the endogenously synthesized antigen, i.e. cells that are stably transfected with 282P1G3 expression vectors.

The results demonstrate that CTL lines obtained from animals primed with peptide epitope recognize endogenously synthesized 282P1G3 antigen. The choice of transgenic mouse model to be used for such an analysis depends upon the epitope(s) that are being evaluated. In addition to HLA-A*0201/Kb transgenic mice, several other 109 transgenic mouse models including mice with human A11, which may also be used to evaluate A3 epitopes, and B7 alleles have been characterized and others (e.g., transgenic mice for HLA-A1 and A24) are being developed. HLA-DR1 and HLA- DR3 mouse models have also been developed, which may be used to evaluate HTL epitopes.

Example 20: Activity Of CTL-HTL Conjugated Epitopes in Transgenic Mice

This example illustrates the induction of CTLs and HTLs in transgenic mice, by use of a 282P1G3-derived CTL and HTL peptide vaccine compositions. The vaccine composition used herein comprise peptides to be administered to a patient with a 282P1G3-expressing tumor. The peptide composition can comprise multiple CTL and/or HTL epitopes. The epitopes are identified using methodology as described herein. This example also illustrates that enhanced immunogenicity, can be achieved by inclusion of one or more HTL epitopes in a CTL vaccine composition; such a peptide composition can comprise an HTL epitope conjugated to a CTL epitope. The CTL epitope can be one that binds to multiple HLA family members at an affinity of 500 nM or less, or analogs of that epitope. The peptides may be lipidated, if desired. immunization procedures: Immunization of transgenic mice is performed as described (Alexander et al., J.

Immunol. 159:4753-4761,1997). For example, A2/Kb mice, which are transgenic for the human HLA A2.1 allele and are used to confirm the immunogenicity of HLA-A*0201 motif- or HLA-A2 supermotif-bearing epitopes, and are primed subcutaneously (base of the tail) with a 0.1 ml of peptide in incomplete Freund’s Adjuvant or if the peptide composition is a ' lipidated CTL/HTL conjugate, in DMSO/saline, or if the peptide composition is a polypeptide, in PBS or Incomplete Freund's AdjuvanL Seven days after priming, splenocytes obtained from these animals are restimulated with syngenic irradiated LPS-activated lymphoblasts coated with peptide.

Ce// lines: Target cells for peptide-specific cytotoxicity assays are Jurkat cells transfected with the Η&amp;#943;Α-Α2.1/Κ» chimeric gene (e.g., Vitiello ef al., J. Exp. Med. 173:1007,1991)

In vitro CTL activation: One week after priming, spleen cells (30x105. cells/flask) are co-cultured at 37° C with syngeneic, irradiated (3000 rads), peptide coated lymphoblasts {10x106 cells/flask) in 10 ml of culture medium/T25 flask.

After six days, effector cells are harvested and assayed for cytotoxic activity.

Assay for cytotoxic activity: Target ceils (1.0 to 1.5x10s) are incubated at 37°C in the presence of 200 μΙ of 51Cr. After 60 minutes, cells are washed three times and resuspended in R10 medium. Peptide is added where required at a concentration of 1 pg/ml. For the assay, 104 51Cr-labeled target cells are added to different concentrations of effector cells (final volume of 200 μ!) in U-bottom 96-well plates. After a six hour incubation period at 37°C, a 0.1 ml aliquot of supernatant is removed from each well and radioactivity is determined in a Micromedic automatic gamma counter. The percent specific lysis is determined by the formula: percent specific release = 100 x (experimental release - spontaneous release)/(maximum release - spontaneous release). To facilitate comparison between separate CTL assays run under the same conditions, % 51Cr release data is expressed as lytic units/106 cells. One lytic unit is arbitrarily defined as the number of effector cells required to achieve 30% lysis of TO,000 target cells in a six hour 51Cr release assay. To obtain specific lytic units/10s, the lytic units/106 obtained in the absence of peptide is subtracted from the lytic units/106 obtained in the presence of peptide. For example, if 30% 51Cr release is obtained at the effector (E): target (T) ratio of 50:1 (i.e., 5x105 effector cells for 10,000 targets) in the absence of peptide and 5:1 (i.e., 5x1ο4 effector cells for 10,000 targets) in the presence of peptide, the specific lytic units would be: [(1/50,000)-(1/500,000)] x 106 = 18 LU.

The results are analyzed to assess the magnitude of the CTL responses of animals injected with the immunogenic CTL/HTL conjugate vaccine preparation and are compared to the magnitude of the CTL response achieved using, for example, CTL epitopes as outlined above in the Example entitled “Confirmation of immunogenicity.’ Analyses similar to this may be performed to confirm the immunogenicity of peptide conjugates containing multiple CTL epitopes and/or multiple HTL 110 epitopes, in accordance with these procedures, it is found that a CTL response is induced, and concomitantly that an HTL response is induced upon administration of such compositions.

Example 21: Selection of CTL and HTL epitopes for inclusion in a 232P1G3-specific vaccine.

This example illustrates a procedure for selecting peptide epitopes for vaccine compositions of the invention. The peptides in the composition can be in the form of a nucleic acid sequence, either single or one or more sequences (i.e., minigene) that encodes peptide(s), or can be singie and/or poiyepitopic peptides.

The following principles are utilized when selecting a plurality of epitopes for inclusion in a vaccine composition. Each of the following principles is balanced in order to make the selection.

Epitopes are selected which, upon administration, mimic immune responses that are correlated with 282P1G3 clearance. The number of epitopes used depends on observations of patients who spontaneously clear 282P1G3. For example, if it has been observed that patients who spontaneously clear 282P1 G3-expressing cells generate an immune response to at least three (3) epitopes from 282P1G3 antigen, then at least three epitopes should be included for HLA class I. A similar rationale is used to determine HLA class II epitopes.

Epitopes are often selected that have a binding affinity of an ICso of 500 nM or less for an HLA class i moiecuie, or for class ii, an ICso of 1000 nM or less; or HLA Class I peptides with high binding scores from the BIMAS web site, at URL bimas.dcrt.nih.gov/. in order to achieve broad coverage of the vaccine through out a diverse population, sufficient supermotif bearing peptides, or a sufficient array of allele-specific motif bearing peptides, are selected to give broad population coverage. In one embodiment, epitopes are selected to provide at least 80% population coverage. A Monte Carlo analysis, a statistical evaluation known in the art, can be employed to assess breadth, or redundancy, of population coverage.

When creating poiyepitopic compositions, or a minigene that encodes same, it is typically desirable to generate the smallest peptide possible that encompasses the epitopes of interest. The principles employed are similar, if not the same, as those employed when selecting a peptide comprising nested epitopes. For example, a protein sequence for the vaccine composition is selected because it has maximal number of epitopes contained within the sequence, i.e., it has a high concentration of epitopes. Epitopes rnay be nested or overlapping (i.e., frame shifted relative to one another). For example, with overlapping epitopes, two 9-mer epitopes and one 10-mer epitope can be present in a 10 amino acid peptide. Each epitope can be exposed end bound by an HLA molecule upon administration of such a peptide. A multi-epitopic, peptide can be generated synthetically, recombinanily, or via cleavage from the native source. Alternatively, an analog can be made of this native sequence, whereby one or more of the epitopes comprise substitutions that alter the cross-reactivity and/or · binding affinity properties of the poiyepitopic peptide. Such a vaccine composition is administered for therapeutic or prophylactic purposes. This embodiment provides for the possibility that an as yet undiscovered aspect of immune system processing will apply to the native nested sequence and thereby facilitate the production of therapeutic or prophylactic immune response-inducing vaccine compositions. Additionally such an embodiment provides for the possibility of motifbearing epitopes for an HLA makeup that is presently unknown. Furthermore, this embodiment (absent the creating of any analogs) directs the immune response to multiple peptide sequences that are actually present in 282P1G3, thus avoiding the need to evaluate any junctional epitopes. Lastly, the embodiment provides an economy of scale when producing nucleic acid vaccine compositions. Related to this embodiment, computer programs can be derived in accordance with principles in the art, which identify in a target sequence, the greatest number of epitopes per sequence length. A vaccine composition comprised of selected peptides, when administered, is safe, efficacious, and elicits an immune response similar in magnitude to an immune response that controls or clears ceils that bear or overexpress 282P1G3.

Ill

Example 22: Construction of “Minigene" Multi-Epitope DNA Plasmids

This example discusses the construction of a minigene expression plasmid. Minigene plasmids may, of course, contain various configurations of B ceil, CTL and/or HTL epitopes or epitope analogs as described herein. A minigene expression plasmid typically includes multiple CTL and HTL peptide epitopes. In the present example, HLA-A2, -A3, -B7 supermotif-bearing peptide epitopes and HLA-A1 and -A24 motif-bearing peptide epitopes are used in conjunction with DR supermotif-bearing epitopes and/or DR3 epitopes. HLA class I supermotif or motif-bearing peptide epitopes derived 282P1G3, are selected such that multiple supermotifs/motifs are represented to ensure broad population coverage. Similarly, HLA class II epitopes are selected from 282P1G3 to provide broad population coverage, i.e. both HLA DR 4-7 supermotif-bearing epitopes and HLA DR-3 motif-bearing epitopes are selected for inclusion in the minigene construct. The selected CTL and HTL epitopes are then incorporated into a minigene for expression in an expression vector.

Such a construct may additionally include sequences that direct the HTL epitopes to the endoplasmic reticulum.

For example, the li protein may be fused to one or more HTL epitopes as described in toe art, wherein the CLIP sequence of the li protein is removed and replaced with an HLA class li epitope sequence so that HLA class li epitope is directed to the endoplasmic reticulum, where the epitope binds to an HLA class 11 molecules.

This example illustrates the methods to be used for construction of a minigene-bearing expression plasmid. Other expression vectors that may be used for minigene compositions are available and known to those of skill in the art.

The minigene DNA plasmid of this example contains a consensu? Kozak sequence and a consensus murine kappa Ig-light chain signal sequence followed by CTL and/or HTL epitopes selected in accordance with principles disclosed herein. The sequence encodes an open reading frame fused to the Myc and His antibody epitope tag coded for by the pcDNA 3.1 Myc-His vector.

Overlapping oligonucleotides that can, for example, average about 70 nucleotides in length with 15 nucleotide overlaps, are synthesized and HPLC-puriiied. The oligonucleotides encode the selected peptide epitopes as well as appropriate linker nucleotides, Kozak sequence, and signal sequence. The final multiepitope minigene is assembled by extending the overlapping oligonucleotides in three sets of reactions using PCR. A Perkin/Elmer 9600 PCR machine is used and a total of 30 cycles are performed using the foiiowing conditions: 95°C for 15 sec, annealing temperature (5° below the lowest calculated Tm of each primer pair) for 30 sec, and 72°C for 1 min.

For example, a minigene is prepared as follows. For a first PCR reaction, 5 μρ of each of two oligonucleotides are annealed and extended: in an example using eight oligonucleotides, i.e., four pairs of primers, oligonucleotides 1+2,3+4, 5+6, and 7+8 are combined in 100 μ&amp;#912; reactions containing Pfu polymerase buffer (1x= 10 mM KGL, 10 mM (NH4)zSO4,20 mM Tris-chloride, pH 8.75, 2 mM MgSO, 0.1% Triton X-100,100 pg/ml BSA), 0.25 mM each dNTP, and 2.5 U of Pfu polymerase. The full-length dimer products are gel-purified, and two reactions containing the product of 1+2 and 3+4, and the product of 5+6 and 7+8 are mixed, annealed, and extended for 10 cycles. Half of the two reactions are then mixed, and 5 cycles of annealing and extension carried out before flanking primers are added to amplify the full length product. The full-length product is gel-purified and cloned into pCR-blunt (Invitrogen) and individual clones are screened by sequencing.

Example 23: The Plasmid Construct and the Degree to Which It Induces Immunogenicity.

The degree to which a plasmid construct, for example a plasmid constructed in accordance with the previous Example, is able to induce immunogenicity is confirmed in vitro by determining epitope presentation by APC following transduction or transfection of the APC with an epitope-expressing nucleic acid construct Such a study determines "antigenicity” and allows the use of human APC. The assay determines the ability of the epitope to be presented by the APC in a context that is recognized by a T ceil by quantifying the density of epitope-HLA class I complexes on the cell surface. 112

Quantitation can be performed by directly measuring the amount of peptide eluted from the APC (see, e.g., Sijts ef a!., J. Immunol. 156:683-692,1996; Demote ef al., Nature 342:682-684,1989); or the number of peptide-HLA class I complexes can be estimated by measuring the amount of lysis or lymphokine release induced by diseased or transfected target cells, and then determining the concentration of peptide necessary to obtain equivalent levels of lysis or lymphokine release (see, e.g., Kageyama etal., J. Immunol. 154:567-576,1995).

Alternatively, immunogenicity is confirmed through in vivo injections into mice and subsequent in vitro assessment of CTL and HTL activity, which are analyzed using cytotoxicity and proliferation assays, respectively, as detailed e.g., in Alexander etal., Immunity 1:751-761,1994.

For example, to confirm the capacity of a DNA minigene construct containing at least one HLA-A2 supermofif peptide to induce CTLs in vivo, HLA-A2.1/Kb transgenic mice, for example, are immunized intramuscularly with 100 pg of naked cDNA. As a means of comparing the level of CTLs induced by cDNA immunization, a control group of animals is also immunized with an actual peptide composition that comprises multiple epitopes synthesized as a single polypeptide as they would be encoded by the minigene.

Splenocytes from immunized animals are stimulated twice with each of the respective compositions (peptide epitopes encoded in the minigene or the polyepitopic peptide), then assayed for peptide-specific cytotoxic activity in a 51Cr release assay. The results indicate the magnitude of the CTL response directed against the A2-restricted epitope, thus indicating the in vivo immunogenicity of the minigene vaccine and poiyepitopic vaccine.

It is, therefore, found that the minigene elicits immune responses directed toward the HLA-A2 supermotif peptide epitopes as does the poiyepitopic peptide vaccine. A similar analysis is also performed using other HLA-A3 and HLA-B7 transgenic mouse models to assess CTL induction by HLA-A3 and HLA-B7 motif or supermotif epitopes, whereby it is also found that the minigene elicits appropriate immune responses directed toward the provided epitopes.

To confirm the capacity of a class ii epitope-encoding minigene to induce HTLs in vivo, DR transgenic mice, or for those epitopes that cross react with the appropriate mouse MHC molecule, l-Ab-restricted mice, for example, are immunized intramuscularly with 100 pg of plasmid DNA. As a means of comparing the level of HTLs induced by DNA immunization, a group of control animals is also immunized with an actual peptide composition emulsified in complete Freund's adjuvant CD4+ T cells, i.e. HTLs, are purified from splenocytes of immunized animals and stimulated with each of the respective compositions (peptides encoded in the minigene). The HTL response is measured using a 3H-thymidine incorporation proliferation assay, (see. ^.g., Alexander ef al. immunity 1:751-761,1994). The results indicate the magnitude of the HTL response, thus demonstrating the in vivo immunogenicity of the minigene. DNA minigenes, constructed as described in the previous Example, can also be confirmed as a vaccine in combination with a boosting agent using a prime boost protocol. The boosting agent can consist of recombinant protein (e.g., Barnett ef al., Aids Res. and Human Retroviruses 14, Supplement 3:S299-S309,1998) or recombinant vaccinia, for example, expressing a mtnigene or DNA encoding the complete protein of interest (see, e.g., Hanke ef ai., Vaccine 16:439-445,1998; Sedegah et a!., Proc. Natl. Acad. Sci USA 95:7648-53,1998; Hanke and McMichael, Immunol. Letters 66:177-181,1999; and Robinson ef al., Nature Med. 5:526-34,1999).

For example, the efficacy of the DNA minigene used in a prime boost protocol is initially evaluated in transgenic mice. In this example, A2.1/K11 transgenic mice are immunized IM with 100 pg of a DNA minigene encoding the immunogenic peptides including at least one HLA-A2 supermotif-bearing peptide. After an incubation period (ranging from 3-9 weeks), the mice are boosted IP with 107 pfufmouse of a recombinant vaccinia virus expressing the same sequence encoded by the DNA minigene. Control mice are immunized with 100 pg of DNA or recombinant vaccinia without the minigene sequence, or with DNA encoding the minigene, but without the vaccinia boost After an additional incubation period of two weeks, splenocytes from the mice are immediately assayed for peptide-specific activity in an ELISPOT assay. 113 Τ ,. Additionally, splenocytes are stimulated in vitro with the A2-restricted peptide epitopes encoded in the minigene and recombinant vaccinia, then assayed for peptide-specific activity in an alpha, beta and/or gamma 1FN ELISA.

It is found that the minigene utilized in a prime-boost protocol elicits greater immune responses toward the HLA-A2 supermotif peptides than with DNA alone. Such an analysis can also be performed using HLA-A11 or HLA-87 transgenic mouse models to assess CTL induction by HLA-A3 or HLA-87 motif or supermotif epitopes. The use of prime boost protocols in humans is described below in the Example entitled “Induction of CTL Responses Using a Prime Boost Protocol.”

Example 24: Peptide Compositions for Prophylactic Uses

Vaccine compositions of the present invention can be used to prevent 282P1G3 expression in persons who are at risk for tumors that bear this antigen. For example, a polyepitopic peptide epitope composition (or a nucleic acid comprising the same) containing multiple CTL and HTL epitopes such as those selected in the above Examples, which are aiso selected to target greater than 80% of the population, is administered to individuals at risk for a 282P1 G3-associated tumor.

For example, a peptide-based composition is provided as a single polypeptide that encompasses multiple epitopes. The vaccine is typically administered in a physiological solution that comprises an adjuvant, such as Incomplete Freunds Adjuvant. The dose of peptide for the initial immunization is from about 1 to about 50,000 pg, generally 100-5,000 pg, for a 70 kg patient. The initial administration of vaccine is followed by booster dosages at 4 weeks followed by evaluation of the magnitude of the immune response in the patient, by techniques that determine the presence of epitope-specific CTL populations in a PBMC sample. Additional booster doses are administered as required. The composition is found to be both safe and efficacious as a prophylaxis against 282P1G3-associated disease.

Alternatively, a composition typicaiiy comprising transfecting agents is used for the administration of a nucleic acid-based vaccine in accordance with methodologies known in the art and disclosed herein.

Example 25: Polyepitopic Vaccine Compositions Derived from Native 282P1G3 Sequences A native 282P1G3 polyprotein sequence is analyzed, preferably using computer algorithms defined for each class I and/or class II supermotif or motif, to identify “relatively short” regions of the polyprotein that comprise multiple epitopes. The "relatively short" regions are preferably less in length than an entire native antigen. This relatively short sequence that contains multiple distinct or overlapping, “nested" epitopes can be used to generate a minigene construct The construct is engineered to express the peptide, which corresponds to the native protein sequence. The “relatively short” peptide is generally less than 250 amino acids in length, often less than 100 amino acids in length, preferably less than 75 amino acids in length, and more preferably less than 50 amino acids in length. The protein sequence of the vaccine composition is selected because it has maximal number of epitopes contained within the sequence, i.e., it has a high concentration of epitopes. As noted herein, epitope motifs may be nested or overlapping (i.e., frame shifted relative to one another). For example, with overlapping epitopes, two 9-mer epitopes and one 10-mer epitope can be present in a 10 amino acid peptide. Such a vaccine composition is administered for therapeutic or prophylactic purposes.

The vaccine composition will include, for example, multiple CTL epitopes from 282P1G3 antigen and at least one HTL epitope. This polyepitopic native sequence is administered either as a peptide or as a nucieic acid sequence which encodes the peptide. Alternatively, an analog can be made of this native sequence, whereby one or more of the epitopes comprise substitutions that alter the cross-reactivity and/or binding affinity properties of the polyepitopic peptide.

The embodiment of this example provides for the possibility that an as yet undiscovered aspect of immune system processing will appiy to the native nested sequence and thereby facilitate the production of therapeutic or prophylactic immune response-inducing vaccine compositions. Additionally, such an embodiment provides for the possibility of motif-' bearing epitopes for an HLA makeup(s) that is presently unknown. Furthermore, this embodiment (excluding an analoged 114 embodiment) directs the immune response to multiple peptide sequences that are actually present in native 282P1G3, thus avoiding the need to evaluate any junctional epitopes. Lastly, the embodiment provides an economy of scale when producing peptide or nucleic acid vaccine compositions.

Related to this embodiment, computer programs are available in the art which can be used to identify in a target sequence, the greatest number of epitopes per sequence length.

Example 26: Polyepitopic Vaccine Compositions from Multiple Antigens

The 282P1G3 peptide epitopes of the present invention are used in conjunction with epitopes from other target tumor-associated antigens, to create a vaccine composition that is useful for the prevention or treatment of cancer that expresses 282P1G3 and such other antigens. For example, a vaccine composition can be provided as a single polypeptide that incorporates multiple epitopes from 282P1G3 as well as tumor-associated antigens that are often expressed with a target cancer associated with 282P1G3 expression, or can be administered as a composition comprising a cocktail of one or more discrete epitopes. Alternatively, the vaccine can be administered as a minigene construct or as dendritic cells which have been loaded with the peptide epitopes in vitro.

Example 27: Use of peptides to evaluate an immune response

Peptides of toe invention may be used to analyze an immune response for the presence of specific antibodies, CTL or HTL directed to 282P1G3. Such an analysis can be performed in a manner described by Ogg ef al., Science 279:2103-2106,1998. In this Example, peptides in accordance wito the invention are used as a reagent for diagnostic or prognostic purposes, not as an immunogen.

In this example highly sensitive human leukocyte antigen teframeric complexes (“teiramers") are used for a cross-sectional analysis of, for example, 282P1G3 HLA-A*0201-specific CTL frequencies from HLA A*0201-positive individuals at different stages of disease or following immunization comprising a 282P1G3 peptide containing an A*0201 motif. Teframeric complexes are synthesized as described (Musey ef al., N. Engl. J. Med. 337:1267,1997). Briefly, purified HLA heavy chain (A*0201 in this example) and p2-microglobuiin are synthesized by means of a prokaryotic expression system. The heavy chain is modified by deletion of the transmembrane-cytosolic tail and COOH-terminal addition of a sequence containing a BirA enzymatic biotinylation site. The heavy chain, p2-microglobulin, and peptide are refolded by dilution. The 45-kD refolded product is isolated by fast protein liquid chromatography and then biotinylated by BirA in toe presence of biotin (Sigma, St. Louis, Missouri), adenosine 5’ triphosphate and magnesium. Streptavidin-phycoerythrin conjugate is added in a 1:4 molar ratio, and toe teframeric product is concentrated to 1 mg/ml. The resulting product is referred to as tetramer-phycoerythrin.

For toe analysis of patient blood samples, approximately one million PBMCs are centrifuged at 300g for 5 minutes and resuspended in 50 μΙ of cold phosphate-buffered saline. Tri-color analysis is performed with toe tetramer-phycoerythrin, along wito anti-CD8-Tricolor, and anti-CD38. The PBMCs are incubated with tetramer and antibodies on ice for 30 to 60 min and then washed twice before formaldehyde fixation. Gates are applied to contain >99.98% of control samples. Controls for toe tetramers include both A*0201-negative individuals and A*0201-positive non-diseased donors. The percentage of cells stained wito toe tetramer is then determined by flow cytometry. The results indicate toe number of ceils in the PBMC sample that contain epitope-restricted CTLs, thereby readily indicating the extent of immune response to the 282P1G3 epitope, and thus the status of exposure to 282P1G3, or exposure to a vaccine that elicits a protective or therapeutic response.

Example 28: Use of Peptide Epitopes to Evaluate Recall Responses 115

The peptide epitopes of the invention are used as reagents to evaluate T cell responses, such as acute or recall responses, in patients. Such an analysis may be performed on patients who have recovered from 282P1G3-associated disease or who have been vaccinated with a 282P1G3 vaccine.

For example, the class I restricted CTL response of persons who have been vaccinated may be analyzed. The vaccine may be any 282P1G3 vaccine. PBMC are collected from vaccinated individuals and HLA typed. Appropriate peptide epitopes of the invention that, optimally, bear supermotifs to provide cross-reactivity with multiple HLA supertype family members, are then used for analysis of samples derived from individuals who bear that HLA type. PBMC from vaccinated individuals are separated on Ficoll-Histopaque density gradients (Sigma Chemical Co., St. Louis, MO), washed three times in BBSS (GIBCO Laboratories), resuspended in RPMH640 (GIBCO Laboratories) supplemented with L-glutamine (2mM), penicillin (50U/ml), streptomycin (50 pg/ml), and Hepes (10mM) containing 10% ' heat-inactivated human AB serum (complete RPMl) and plated using microculture formats. A synthetic peptide comprising an epitope of the invention is added at .10 pg/ml to each well and HBV core 128-140 epitope is added at 1 pg/ml to each well as a source of T cell help during the first week of stimulation.

In the microculture format, 4 χ 105 PBMC are stimulated with peptide in 8 replicate cultures in 96-well round bottom plate in 100 μΙ/well of complete RPML On days 3 and 10,100 μΙ of complete RPMl and 20 U/ml final concentration of rlL-2 are added to each well. On day 7 the cultures are transferred into a 96-well flat-bottom plate and restimulated with peptide, rlL-2 and 105 irradiated (3,000 rad) autologous feeder cells. The cultures are tested for cytotoxic activity on day 14. A positive CTL response requires two or more of the eight replicate cultures to display greater than 10% specific 51Cr release, based on comparison with non-diseased control subjects as previously described (Rehermann, ef a/., Nature Med. 2:1104,1108,1996; Rehermann et al., J. Clin. Invest. 97:1655-1665,1996; and Rehermann et ai. J. Ciin. invest, 98:1432-1440,1996).

Target cell lines are autologous and allogeneic EBV-transformed B-LCL that are either purchased from the American Society for Histocompatibility and lmmunogenetics (ASHI, Boston, MA) or established from the pool of patients as described (Guilhot, etal. J. Virol. 66:2670-2678,1992).

Cytotoxicity assays are performed in the following manner. Target cells consist of either allogeneic HLA-matched or autologous EBV-transformed B lymphoblastoid cell line that are incubated overnight with the synthetic peptide epitope of the invention at 10 μΜ, and labeled with 100 pCi of 51Cr (Amersham Corp., Arlington Heights, IL) for 1 hour after which they are washed four times with HBSS.

Cytolytic activity is determined in a standard 4-h, split well 51Cr release assay using U-bottomed 96 well plates containing 3,000 targets/well. Stimulated PBMC are tested at effector/target (E/T) ratios of 20-50:1 on day 14. Percent cytotoxicity is determined from the formula: 100 x [(experimental release-spontaneous release)/maximum release-spontaneous release)]. Maximum release is determined by lysis of targets by detergent (2% Triton X-100; Sigma Chemical Co., St. Louis, MO). Spontaneous release is &lt;25% of maximum release for all experiments.

The results of such an analysis indicate the extent to which HLA-restricted CTL populations have been stimulated by previous exposure to 282P1G3 or a 282P1G3 vaccine.

Similarly, Class IS restricted HTL responses may also be analyzed. Purified PBMC are cultured in a 96-well flat bottom plate at a density of 1,5x10s cells/well and are stimulated with 10 μα/ml synthetic peptide of the invention, whole 282P1G3 antigen, or PHA. Cells are routinely plated in repiicates of 4-6 wells for each condition. After seven days of culture, the medium is removed and replaced with fresh medium containing 10U/ml IL-2. Two days later, 1 pCi 3H-thymidine is added to each well and incubation is continued for an additional 18 hours. Cellular DNA is then harvested on glass fiber mats and analyzed for 3H-thymidine incorporation. Antigen-specific T celi proliferation is calculated as the ratio of 3H-thymidine incorporation in the presence of antigen divided by the 3H-thymidine incorporation in the absence of antigen. 116

Example 29: Induction Of Specific CTL Response In Humans A human clinical trial for an immunogenic composition comprising CTL and HTL epitopes of the invention is set up as an IND Phase I, dose escalation study and carried out as a randomized, double-blind, placebo-controlled trial. Such a trial is designed, for example, as follows: A total of about 27 individuals are enrolled and divided into 3 groups:

Group I: 3 subjects are injected with placebo and 6 subjects are injected with 5 pg of peptide composition·,

Group II: 3 subjects are injected with placebo and 6 subjects are injected with 50 pg peptide composition;

Group III: 3 subjects are injected with placebo and 6 subjects are injected with 500 pg of peptide composition.

After 4 weeks following the first injection, all subjects receive a booster inoculation at the same dosage.

The endpoints measured in this study relate to the safety and tolerability of the peptide composition as well as its immunogenicity. Cellular immune responses to the peptide composition are an index of the intrinsic activity of this the peptide composition, and can therefore be viewed as a measure of biological efficacy. The following summarize the clinical and laboratory data that relate to safety and efficacy endpoints.

Safety: The incidence of adverse events is monitored in the placebo and drug treatment group and assessed in terms of degree and reversibility. ,

Evaluation of Vaccine Efficacy: For evaluation of vaccine efficacy, subjects are bled before and after injection. Peripheral blood mononuclear cells are isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation, aliquoied in freezing media and stored frozen. Samples are assayed for CTL and HTL activity.

The vaccine is found to be both safe and efficacious.

Example 30: Phase II Trials In Patients Expressing 282P1G3

Phase II trials are performed to study the effect of administering the CTL-HTL peptide compositions to patients having cancer that expresses 282P1G3. The main objectives of the trial are to determine an effective dose and regimen for inducing CTLs in cancer patients that express 282P1G3, to establish the safety of inducing a CTL and HTL response in these patients, and to see to what extent activation of CTLs improves the clinical picture of these patients, as manifested, e.g., by the reduction and/or shrinking of lesions. Such a study is designed, for example, as follows:

The studies are-performed in multiple centers. The trial design is an open-label, uncontrolled, dose escalation protocol wherein the peptide composition is administered-as a single dose followed six weeks later by a single booster shot of the same dose. The dosages are 50, 500 and 5,000 micrograms per injection. Drug-associated adverse effects (severity and reversibility) are recorded.

There are three patient groupings. The first group is injected with 50 micrograms of the peptide composition and the second and third groups with 500 and 5,000 micrograms of peptide composition, respectively. The patients within each group range in age from 21-65 and represent diverse ethnic backgrounds. All of them have a tumor that expresses 282P1G3.

Clinical manifestations or antigen-specific T-cell responses are monitored to assess the effects of administering the peptide compositions. The vaccine composition is found to be both safe and efficacious in the treatment of 282P1G3-associated disease.

Example 31: induction of CTL Responses Using a Prime Boost Protocol A prime boost protocol similar in its underlying principle to that used to confirm the efficacy of a DNA vaccine in transgenic mice, such as described above in the Example entitled 'The Plasmid Construct and the Degree to Which It 117

Induces Immunogenicity," can aiso be used for the administration of the vaccine to humans. Such a vaccine regimen can include an initial administration of, for example, naked DNA followed by a boost using recombinant virus encoding the vaccine, or recombinant protein/polypeptide or a peptide mixture administered in an adjuvant

For example, the initial immunization may be performed using an expression vector, such as that constructed in the Example entitled “Construction of “Minigene” Multi-Epitope DNA Plasmids” in the form of naked nucleic acid administered IM (or SC or ID) in the amounts of 0.5-5 mg at multiple sites. The nucleic acid (0.1 to 1000 pg) can also be administered using a gene gun. Following an incubation period of 3-4 weeks, a booster dose is then administered. The booster can be recombinant fowlpox virus administered at a dose of 5-107 to 5x109 pfu. An alternative recombinant virus, such as an MVA, canarypox, adenovirus, or adeno-associated virus, can also be used for the booster, or the polyepitopic protein or a mixture of the peptides can be administered. For evaluation of vaccine efficacy, patient blood samples are obtained before immunization as well as at intervals following administration of the initial vaccine .and booster doses of the vaccine.

Peripheral blood mononuclear cells are isolated from fresh heparinized blood by Ficoll-Hypague density gradient centrifugation, aliquoted in freezing media and stored frozen. Samples are assayed for CTL and HTL activity.

Analysis of the results indicates that a magnitude of response sufficient to achieve a therapeutic or protective immunity against 282P1G3 is generated.

Example 32: Administration of Vaccine Compositions Using Dendritic Cells (DC)

Vaccines comprising peptide epitopes of the invention can be administered using APCs, or “professional” APCs such as DC. In this example, peptide-pulsed DC are administered to a patient to stimulate a CTL. response in vivo. In this method, dendritic ceiis are isolated, expanded, and pulsed with a vaccine comprising peptide CTL and HTL epitopes of the invention. The dendritic cells are infused hack into the patient to elicit CTL and HTL responses in vivo. The induced CTL and HTL then destroy or facilitate destruction, respectively, of the target cells that bear the 282P1G3 protein from which the epitopes in the vaccine are derived.

For example, a cocktail of epitope-comprising peptides is administered ex vivo to PBMC, or isolated DC therefrom. A pharmaceutical to facilitate harvesting of DC can be used, such as Progenipoietin™ (Monsanto, St. Louis, MO) or GM-CSF/IL-4. After pulsing the DC with peptides, and prior to reinfusion into patients, the DC are washed to remove unbound peptides.

As appreciatectclinically, and readily determined by one of skill based on clinical outcomes, the number of DC reinfused into the patient can vary (see, e.g:, Nature Med. 4:328,1998; Nature Med. 2:52,1996 and Prostate 32:272,1997). Although 2-50 x 106 DC per patient are typically administered, larger number of DC, such as 107 or 108 can also be provided. Such cell populations typically contain between 50-90% DC.

In some embodiments, peptide-loaded PBMC are injected into patients without purification of the DC. For example, PBMC generated after treatment with an agent such as Progenipoietin™ are injected into patients without purification of the DC. The total number of PBMC that are administered often ranges from 108 to 1010. Generally, the cel! doses injected into patients is based on the percentage of DC in the blood of each patient, as determined, for example, by immunofluorescence analysis with specific anti-DC antibodies. Thus, for example, if Progenipoietin™ mobilizes 2% DC in the peripheral blood of a given patient, and that patient is to receive 5 χ 106 DC, then the patient will be injected with a total of 2.5 χ 108 peptide-loaded PBMC. The percent DC mobilized by an agent such as Progenipoietin™ is typically estimated to be between 2-10%, but can vary as appreciated by one of skill in the art.

Ex vivo activation of CTL/HTL responses

Alternatively, ex vivo CTL or HTL responses to 282P1G3 antigens can be induced by incubating, in tissue culture, the patient's, or genetically compatible, CTL or HTL precursor cells together with a source of APC, such as DC, and 118 immunogenic peptides. After an appropriate incubation time (typically about 7-28 days), in which the precursor cells are activated and expanded into effector cells, the cells are infused into the patient, where they will destroy (CTL) or facilitate destruction (HTL) of their specific target celis, i.e., tumor ceils.

Example 33: An Alternative Method of Identifying and Confirming Motif-Bearing Peptides .

Another method of identifying and confirming motif-bearing peptides is to elute them from ceiis bearing defined MHC molecules. For example, EBV transformed B cell lines used for tissue typing have been extensively characterized to determine which HLA molecules they express. In certain cases these ceils express only a singie type of HLA molecule. These ceils can be transfected with nucleic acids that express the antigen of interest, e.g. 282P1G3. Peptides produced by endogenous antigen processing of peptides produced as a result of transfection wiii then bind to HLA molecules within the ceil and be transported and displayed on the cell’s surface. Peptides are then eluted from the HLA molecules by exposure to mild acid conditions and their amino acid sequence determined, e.g., by mass spectral analysis (e.g., Kubo et a!., J.

Immunol. 152:3913,1994). Because the majority of peptides that bind a particular HLA molecule are motif-bearing, this is an alternative modality for obtaining the motif-bearing peptides correlated with the particular HLA moiecuie expressed on the cell.

Alternatively, cell lines that do not express endogenous HLA molecules can be transfected with an expression construct encoding a single HLA allele. These celis can then be used as described, i.e., they can then be transfected with nucieic acids ihat encode 282P1G3 to isolate peptides corresponding to 282P1G3 that have been presented on the celi surface. Peptides obtained from such an analysis will bear motif(s) that correspond to binding to the singie HLA aileie that is expressed in the celi.

As appreciated by one in the art, one can perform a similar analysis on a cell bearing more than one HLA allele and subsequently determine peptides specific for each HLA aliele expressed. Moreover, one of skill would also recognize that means other than transfection, such as loading with a protein antigen, can be used to provide a source of antigen to the cell.

Example 34: Complementary Polynucleotides

Sequences complementary to the 282P1G3-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring 282P1G3. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentialiy the same procedure is used with smaller or with larger sequence fragments. Appropriate oligonucleotides are designed using, e.g., OLIGO 4.06 software (National Biosciences) and the coding sequence of 282P1G3. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5' sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to a 282P1 G3-encoding transcript

Example 35: Purification of Naturally-occurring or Recombinant 282P1G3 Using 282P1G3-Specific Antibodies

Naturally occurring or recombinant 282P1G3 is substantially purified by immunoaffinity chromatography using antibodies specific for 282P1G3. An immunoaffinity column is constructed by covalently coupling anti-282P1G3 antibody to amactivated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupling, the resin is blocked and washed according to the manufacturer’s instructions.

Media containing 282P1G3 are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of 282P1G3 (e.g., high ionic strength buffers in the presence of detergent). 119 5 The column is eluted under conditions that disrupt antibody/282P1 G3 binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and GCR.P is collected. - -w o.

Example 36: Identification of Moiecuies Which interact with 282P1G3 282P1G3, or biologically active fragments thereof, are labeled with 121 1 Bolton-Hunter reagent (See, e.g., Bolton ef al. (1973) Biochem. J. 133:529.) Candidate molecules previously arrayed in the weils of a multi-well piate are incubated with the labeled 282P1G3, washed, and any wells with labeled 282P1G3 complex are assayed. Data obtained using wA-different concentrations of 282P1G3 are used to calculate values for the number, affinity, and association of 282PTG3wvith the candidate molecules. “ i

Example 37: In Vivo Assay for 282P1G3 Tumor Growth Promotion

The effect of the 282P1G3 protein on tumor cell growth is evaluated in vivo by evaluating tumor development and growth of ceils expressing or lacking 282P1G3. For example, SCID mice are injected subcutaneously on each flank with 1 x 10s of either 3T3, ovarian (e.g. PA-1 cells), pancreatic (e.g. Panc-1 cells) or lymphoma (e.g. Daudi cells) cancer cell fines containing tkNeo empty vector or 282P1G3. At least two strategies may be used: (1) Constitutive 282P1G3 expression under regulation of a promoter such as a constitutive promoter obtained from the genomes of viruses such as polyoma virus, fowlpox virus (UK 2,211,504 published 5 July 1989), adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40), or from heterologous mammalian promoters, e.g., the actin promoter or an immunoglobulin promoter, provided such promoters are compatible with the host ceil systems, and (2) Regulated expression under control of an inducible vector system, such as ecdysone, tetracycline, etc., provided such promoters are compatible with the host cell systems. Tumor volume is then monitored by caliper measurement at the appearance of palpable tumors and followed over time to determine if 282P1 G3-expressing cells grow at a faster rate and whether tumors produced by 282P1 G3-expressing cells demonstrate characteristics of altered aggressiveness (e.g. enhanced metastasis, vascularization, reduced responsiveness to chemotherapeutic drugs).

Additionally, mice can be implanted with 1 x 10s of the same ceils orthotopically to determine if 282P1G3 has an effect on local growth in the pancreas, and whether 282P1G3 affects the ability of the cells to metastasize, specifically to lymph nodes, and bone (Miki, T etal, Oncol Res. 2001;12:209; Fu Xetal, lnt J Cancer. 1991,49:938). The effect of 282P1G3 on bone tumor formation and growth may be assessed by injecting tumor cells intratibially.

The assay is aiso useful to determine the 282P1G3 inhibitory effect of candidate therapeutic compositions, such as, 282P1G3 intrabodies, 282P1G3 antisense molecules and ribozymes.

Example 38: 282P1G3 Monoclonal Antibody-mediated Inhibition of Tumors in Vivo

The significant expression of 282P1G3 in cancer tissues and surface localization, together with its restrictive expression in normal tissues makes 282P1G3 a good target for antibody therapy. Similarly, 282P1G3 is a target for T cell-based immunotherapy. Thus, the therapeutic efficacy of anti-282P1 G3 mAbs in human cancer xenograft mouse models, including ovarian, pancreatic or lymphoma and other -282P1G3cancers listed in Table l, is evaluated by using recombinant cell lines such as Pa 282P1G3, Panc1-282P1G3, Daudi-282P1G3, and 3T3-282P1G3 (see, e.g., Kaighn, M.E., etal., Invest Urol, 1979.17(1): 16-23), as well as human xenograft models (Saffran et al PNAS1999,10:1073-1078).

Antibody efficacy on tumor growth and metastasis formation is studied, e.g., in a mouse orthotopic ovary, pancreas, or blood cancer xenograft models. The antibodies can be unconjugated, as discussed in this Example, or can be conjugated to a therapeutic modality, as appreciated in the art. Anti-282P1 G3 mAbs inhibit formation of tumors in mouse xenografts. Anti-282P1G3 mAbs also retard the growth of established orthotopic tumors and prolonged survival of tumor- 120 bearing mice. These results indicate the utility of anti-282P1 G3 mAbs in the treatment of local and advanced stages several solid tumors. (See, e.g., Saffran, D., etal., PNAS 10:1073-1078 or world wide web URL pn as.org/cgi/doiZ10.1073/pnas .051624698).

Administration of the anti-282P1 G3 mAbs led to retardation of established orthotopic tumor growth and inhibition of metastasis to distant sites, resulting in a significant prolongation in the survival of tumor-bearing mice. These studies indicate that 282P1G3 as an attractive target for immunotherapy and demonstrate the therapeutic potential of anti-282P1G3 mAbs for the treatment of local and metastatic cancer. This example indicates that unconjugated 282P1G3 monoclonal antibodies are effective to inhibit the growth of human pancreatic, ovarian and lymphomas tumor xenografts grown in SCID mice; accordingly a combination of such efficacious monoclonal antibodies is aiso effective.

Tumor inhibition using multiple unconjugated 282P1G3 mAbs

Materials and Methods: 282P1G3 Monoclonal Antibodies:

Monoclonal antibodies are raised against 282P1G3 as described in the Example entitled “Generation of 282P1G3 MonoclonaLAntibodies (mAbs).” The antibodies are characterized by ELISA, Western blot, FACS, and immunoprecipitation for their capacity to bind 282P1G3. Epitope mapping data for the anti-282P1G3 mAbs, as determined by ELISA and Western analysis, recognize epitopes on the 282P1G3 protein. Immunohistochemical analysis of cancer tissues and cells with these antibodies is performed.

The monoclonal antibodies are purified from ascites or hybridoma tissue culture supernatants by Protein-G Sepharose chromatography, diaiyzed against PBS, filter sterilized, and stored at -20°C. Protein determinations are performed by a Bradford assay (Bio-Rad, Hercules, CA). A therapeutic monoclonal antibody or a cocktail comprising a mixture of individual monoclonal antibodies is prepared and used for the treatment of mice receiving subcutaneous or orthotopic injections of PC3, UM-UC3, CaKi and A427 tumor xenografts.

Cell Lines and Xenografts

The cancer cel! lines PA-1, Panel, Daudi cell lines, as well as the fibroblast line NIH 3T3 (American Type Culture Collection) are maintained in DMEM supplemented with L-glutamine and 10% FBS. PA1-282P1G3, Panc1-282P1G3, Daudi-282P1 G3 and 3T3-282P1G3 ceil populations are generated by retroviral gene transfer as described in Hubert, R.S., et ai., Proc Natl Acad Sci USA, 1999. 96(25): 14523.

Human patient-derived xenografts are passaged in 6- to 8-week-old male ICR-severe combined immunodeficient (SCID) mice (Taconic Farms) by s.c. trocar implant (Craft, N., et ai., Nat Med. 1999, 5:280). Single-cell suspensions of tumor cells are prepared as described in Craft, et al.

Xenograft Mouse Models.

Subcutaneous (s.c.) tumors are generated by injection of 2 x 106 cancer cells mixed at a 1:1 dilution with Matrigel (Collaborative Research) in the right flank of male SCID mice. To test antibody efficacy on tumor formation, i.e. antibody injections are started on the same day as tumor-cell injections. As a control, mice are injected with either purified mouse IgG (ICN) or PBS; or a purified monoclonal antibody that recognizes an irrelevant antigen not expressed in human cells. In preliminary studies, no difference is found between mouse IgG or PBS on tumor growth. Tumor sizes are determined by caliper measurements, and the tumor volume is calculated as length x width x height. Mice with Subcutaneous tumors greater than 1.5 cm in diameter are sacrificed. 121 Λυντ/ν _iv , Orthotopic injections are performed under anesthesia by using ketamine/xylazine. Following tumor implantation, the mice are segregated into groups for the-appropriate treatments, with anti-282P1G3 or control mAbs being injected i.p.

To monitor tumor growth, mice are palpated and blood is collected on a weekly basis to measure hCG levels.

Anti-282P1G3 mAbs Inhibit Growth of 282P1G3-Expressinq Xenograft-Cancer Tumors

The effect of anti-282P 1G3 mAbs on tumor formation is tested by using cel! line (e.g. PA-1, Panel, Daudi and 3T3) and patient-derived tumor orthotopic models. As compared with the s.c. tumor model, the orthotopic model, which requires injection of tumor ceils directly in the mouse organ results in a local tumor growth, development of metastasis in distal sites, deterioration of mouse health, and subsequent death (Saffran, D., et al., PNAS supra). The features make the orthotopic mode! more representative of human disease progression and allowed us to follow the therapeutic effect of mAbs on clinically relevant end points. A major advantage of the orthotopic cancer models is the ability to study the development of metastases. Formation of metastasis in mice bearing established orthotopic tumors is studies by 1HC analysis on iung sections using an antibody against a tumor-specific cell-surface protein such as anti-CK20 for prostate cancer (Lin S et al, Cancer Detect Prev. 2001;25:202).

Another advantage of xenograft cancer models is the ability to study neovascularization and angiogenesis. Tumor growth is partly dependent on new blood vessel development Although the capillary system and developing blood network is of host origin, the initiation and architecture of the neovasculature is regulated by the xenograft tumor (Davidoff AM et al, Clin Cancer Res. 2001 ;7:2870; Solesvik 0 et al„ Eur J Cancer Clin Oncol. 1984, 20:1295).' The effect of antibody and small molecule on neovascularization is studied in accordance with procedures known in the art, such as by !HC analysis of tumor tissues and their surrounding microenvironment.

Mice bearing established orthotopic tumors are administered 1000pg injections of either anti-282P1G3 mAb or PBS over a 4-week period. Mice in both groups are allowed to establish a high tumor burden, to ensure a high frequency of metastasis formation in mouse lungs. Mice then are killed and their bladders, livers, bone and lungs are analyzed for the presence of tumor ceils by IHC analysis. These studies demonstrate a broad anti-tumor efficacy of anti-282P1G3 antibodies on initiation and progression of prostate cancer in xenograft mouse models. Anti-282P1 G3 antibodies inhibit tumor formation of tumors as well as retarding the growth of already established tumors and prolong the survival of treated mice. Moreover, anti-282P1 G3 mAbs demonstrate a dramatic inhibitory effect on the spread of local prostate tumor to distal sites, even in the presence of a large tumor burden. Thus, anti-282P1 G3 mAbs are efficacious on major ciinicaliy relevant end points (tumor growth), prolongation of survival, and health.

Example 39: Therapeutic and Diagnostic use of Anti-282P1G3 Antibodies in Humans.

Anti-282P1G3 monoclonal antibodies are safely and effectively used for diagnostic, prophylactic, prognostic and/or therapeutic purposes in humans. Western blot and immunohistochemical analysis of cancer tissues and cancer xenografts with anti-282P1 G3 mAb show strong extensive staining in carcinoma but significantly lower or undetectable levels in normal tissues. Detection of 282P1G3 in carcinoma and in metastatic disease demonstrates the usefulness of the mAb as a diagnostic and/or prognostic indicator. Anti-282P1G3 antibodies are therefore used in diagnostic applications such as immunohistochemistry of kidney biopsy specimens to detect cancer from suspect patients.

As determined by flow cytometry, anti-282P1G3 mAb specifically binds to carcinoma ceils. Thus, anti-282P1G3 antibodies are used in diagnostic whole body imaging applications, such as radioimmunoscintigraphy and radioimmunotherapy, (see, e.g., Potamianos S., et. al. Anticancer Res 20(2A);925-948 (2000)) for the detection of localized and metastatic cancers that exhibit expression of 282P1G3. Shedding or release of an extracellular domain of 282P1G3 into 122 .the extracellular milieu, such as that seen for alkaiine phosphodiesterase B10 (Meerson, N. Ft, Hepatology 27:563-568 (1998)), allows diagnostic detection of 282P1G3 by an0-282P1G3 antibodies in serum and/or urine samples from suspect patients.

Anti-282P1G3 antibodies that specifically bind 282P1G3 are used in therapeutic applications for the treatment of cancers that express 282P1G3. Anti-282P1G3 antibodies are used as an unconjugated modality and as conjugated form in which the antibodies are attached to one of various therapeutic or imaging modalities weii known in the art, such as a prodrugs, enzymes or radioisotopes. In preciinical studies, unconjugated and conjugated anti-282P1 G3 antibodies are tested for efficacy of tumor prevention and growth inhibition in the SCID mouse cancer xenograft models, e.g., kidney cancer models AGS-K3 and AGS-K6, (see, e.g., the Example entitled “282P1G3 Monoclonal Antibody-mediated Inhibition of Bladder and Lung Tumors In Vivo”}. Either conjugated and unconjugated anti-282P1G3 antibodies are used as a therapeutic modality in human clinical trials either atone or in combination with other treatments as described in following Examples.

Example 40: Human Clinical Trials for the Treatment and Diagnosis of Human Carcinomas through use of Human

Anti-282P1 G3 Antibodies in vivo

Antibodies are used in accordance with the present invention which recognize an epitope on 282P1G3, and are used in the treatment of certain tumors such as those listed in Table I. Based upon a number of factors, including 282P1G3 expression levels, tumors such as those listed in Table I are presently preferred indications. In connection with each of these indications, three clinical approaches are successfully pursued. I. ) Adjunctive therapy: in adjunctive therapy, patients are treated with anti-282P1 G3 antibodies in combination with a chemotherapeutic or antineopiasiic agent and/or radiation therapy. Primary cancer targets, such as those listed in Table I, are treated under standard protocols by the addition anti-282P1G3 antibodies to standard first and second line therapy. Protocol designs address effectiveness as assessed by reduction in tumor mass as well as the ability to reduce usual doses of standard chemotherapy. These dosage reductions allow additional and/or prolonged therapy by reducing dose-related toxicity of the chemotherapeutic agent. Anti-282P1G3 antibodies are utilized in several adjunctive clinicai trials in combination with the chemotherapeutic or anfineoplastic agents adriamycin (advanced prostrate carcinoma), cisplatin (advanced head and neck and lung carcinomas), taxoi (breast cancer), and doxorubicin (preciinical). II. ) Monotherapy: In connection with the use of the anti-282P1 G3 antibodies in monotherapy of tumors, the antibodies are administered to patients without a chemotherapeutic or anfineoplastic agent. In one embodiment, monotherapy is conducted clinically in end stage cancer patients with extensive metastatic disease. Patients show some disease stabilization. Trials demonstrate an effect in refractory patients with cancerous tumors. III. ) Imaging Agent Through binding a radionuclide (e.g., iodine or yttrium (I131, Y90) to anti-282P1G3 antibodies, the radiolabeled antibodies are utilized as a diagnostic and/or imaging agent In such a rote, the labeled antibodies localize to both solid tumors, as well as, metastatic lesions of cells expressing 282P1G3. in connection with the use of the anti-282P 1G3 antibodies as imaging agents, the antibodies are used as an adjunct to surgical treatment of solid tumors, as both a pre-surgical screen as well as a post-operative follow-up to determine what tumor remains and/or returns, in one embodiment, a (111 ln)-282P1G3 antibody is used as an imaging agent in a Phase I human clinical trial in patients having a carcinoma that expresses 282P1G3 (by analogy see, e.g., Divgi etai. J. Natl. Cancer Inst. 83:97-104 (1991)). Patients are followed with standard anterior and posterior gamma camera. The results indicate that primary lesions and metastatic lesions are identified.

Dose and Route of Administration

As appreciated by those of ordinary skill in the art, dosing considerations can be determined through comparison with the analogous products that are in the clinic. Thus, anti-282P1 G3 antibodies can be administered with doses in the 123 range of 5 to400 mg/m2, with the tower doses used, e.g., in connection with safety studies. The affinity of anti-282P1G3 antibodies relative to the affinity of a known antibody for its target is one parameter used by those of skill in the art for determining analogous dose regimens. Further, anti-282P1G3 antibodies that are fully human antibodies, as compared to the chimeric antibody, have slower clearance; accordingly, dosing in patients with such fully human anfi-282P1G3 antibodies can be lower, perhaps in the range of 50 to 300 mg/m2, and stiii remain efficacious. Dosing in mg/m2, as opposed to the conventional measurement of dose in mg/kg, is a measurement based on surface area and is a convenient dosing measurement that is designed to include patients of all sizes from infants to adults.

Three distinct delivery approaches are useful for delivery of anti-282P1 G3 antibodies. Conventional intravenous delivery is one standard delivery technique for many tumors. However, in connection with tumors in the peritoneal cavity, such as tumors of the ovaries, biliary duct, other ducts, and the like, intraperitoneal administration may prove favorable for obtaining high dose of antibody at the tumor and to also minimize antibody clearance. In a similar manner, certain solid tumors possess vasculature that is appropriate for regional perfusion. Regional perfusion allows for a high dose of antibody at the site of a tumor and minimizes short term clearance of the antibody.

Clinical Development Plan (CDP)

Overview: The CDP follows and develops treatments of anti-282P1G3 antibodies in connection with adjunctive therapy, monotherapy, and as an imaging agent. Trials initially demonstrate safety and thereafter confirm efficacy in repeat doses. Trails are open label comparing standard chemotherapy with standard therapy plus anti-282P1G3 antibodies. As will be appreciated, one criteria that can be utilized in connection with enrollment of patients is 282P1G3 expression levels in their tumors as determined by biopsy.

As with any protein or antibody infusion-based therapeutic, safety concerns are related primarily to (i) cytokine release syndrome, i.e., hypotension, fever, shaking, chills; (ii) the development of an immunogenic response to the material (i.e., development of human antibodies by the patient to the antibody therapeutic, or HAHA response); and, (iii) toxicity to normal cells that express 282P1G3. Standard tests and follow-up are utilized to monitor each of these safety concerns. Anti-282P1G3 antibodies are found to be safe upon human administration.

Example 41: Human Clinical Trial Adjunctive Therapy with Human Anti-282P1G3 Antibody and Chemotherapeutic

Agent A phase i human clinical trial is initiated to assess the safety of six intravenous doses of a human anti-282P1 G3 antibody in connection with the treatment of a solid tumor, e.g., a cancer of a tissue listed in Table 1. in the study, the safety of single doses of anti-282P1G3 antibodies when utilized as an adjunctive therapy to an antineoplastic or chemotherapeutic agent as defined herein, such as, without limitation: cisplatin, topotecan, doxorubicin, adriamycin, taxol, or the like, is assessed. The trial design includes delivery of six single doses of an anti-282P1 G3 antibody with dosage of antibody escalating from approximately about 25 mg/m2 to about 275 mg/m2 over the course of the treatment in accordance with the following schedule:

Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 mAb Dose 25 75 125 175 225 275 mg/m2 mg/m2 mg/m2 mg/m2 mg/m2 mg/m2 Chemotherapy (standard dose) + + + + + + 124

Patients are closely followed for one-week following each administration of antibody and chemotherapy. In particular, patients are assessed for the safety concerns mentioned above; (i) cytokine release syndrome, i.e., hypotension, fever, shaking, chills; (ii) the development of an immunogenic response to the material (i.e., development of human antibodies by the patient to the human antibody therapeutic, or HAHA response); and, (iii) toxicity to normal cells that express 282P1G3. Standard tests and follow-up are utilized to monitor each of these safety concerns. Patients are also assessed for clinical outcome, and particularly reduction in tumor mass as evidenced by MR! or other imaging.

The anti-282P1 G3 antibodies are demonstrated to be safe and efficacious, Phase II trials confirm the efficacy and refine optimum dosing.

Example 42: Human Clinical Trial: Monotherapy with Human Anti-282P1G3 Antibody

Anti-282P1G3 antibodies are safe in connection with the above-discussed adjunctive trial, a Phase II human clinical trial confirms the efficacy and optimum dosing for monotherapy. Such trial is accomplished, and entails the same safety and outcome analyses, to the above-described adjunctive trial with the exception being that patients do not receive chemotherapy concurrently with the receipt of doses of anti-282P1 G3 antibodies.

Example 43: Human Clinical Trial: Diagnostic imaging with Anti-282P1G3 Antibody

Once again, as the adjunctive therapy discussed above is safe within the safety criteria discussed above, a human clinical trial is conducted concerning the use of anti-282P 1G3 antibodies as a diagnostic imaging agent. The protocol is designed in a substantially similar manner to those described in the art, such as in Divgi et al. J. Natl. Cancer Inst. 83:97-104 (1991). The antibodies are found to be both safe and efficacious when used as a diagnostic modality.

Example 44 Homology Comparison of 282P1G3 to Known Seguences:

The human 282P1G3 protein exhibit a high degree of homology to a known human protein, cell adhesion molecule with homology to L1CAM precursor (gi 27894376), also known Close Homolog of 11 (CHL1) or CALL. Human CHL1 shows 99% identity to 282P1G3 at the protein level (Figure 4A). The mouse homolog of 282P1G3 has been identified as murine CHL1 (gi 6680936), and shows 82% identity and 89% homology to 282P1G3 (Figure 4B). CHL1 has been reported to regulate neuronal development by altering cell adhesion and axonal projections (Montag-Sallaz M et al, Mol. Ceil. Bioi. 2002, 22:7967). In addition, CHL1 was found to play a role in neurite growth and survival (Dong L et al, J. Neurosci. Res, 2002; Chaisuksunt V et al, J. Comp. Neurol 2000,425:382). Mutations in CHL1 have been associated with schizophrenia and metal disorders (Sakurai et al, Mol Psychiatry 2002,7:412; We H et ai, Hum Genet 1998,103:355).

The prototype member of the 282P1G3 family, 282P1G3v.1, is a 1224 amino acids protein. Initial bioinformatics analysis using topology prediction programs suggested that 191P2D14 may contain 2 transmembranes based on hydrophobicity profile. However, the first hydrophobic domain was identified as a signal sequence, rendering 191P2D12 a single transmembrane protein.

The 282P1G3 gene has several variants, including 5 SNP represented by 282P1G3 v.9, v.10, v.11, v.24 and v,25. In addition, several splice variants have been identified, including deletion variants such as 282P1G3 v.2, v.4, v.5 and v.6, as weil as insertion mutants such as 282P1G3 v.7 and v.8, and a splice variant at aa 838 of 282P1G3 v.1, namely 282P1G3 v.3.

Motif analysis revealed the presence of several protein functional motifs in the 282P1G3 protein (Table L). Six immunoglobulin domains have been identified in addition to four fibronectin type 111 repeats. Immunoglobulin domains are found in numerous proteins and participate in protein-protein such including protein-ligand interactions (Weismann et al, J Mol Med 2000,78:247). In addition, Ig-domains function in cell adhesion, allowing the interaction of leukocytes and blood-born cells with the endothelium (Wang and Springer, Immunol Rev 1998,163:197). Fibronectin type III repeals are 100 125 amino acid domains with binding sites for various molecules, including DNA, heparin, basement membrane and cell surface proteins (Kimizuka etal, J Biol Chem, 1991, 266:3045; Yokosaki et al, J Biol Chem. 1998, 273:11423). The majority for proteins containing fibronectin 111 motifs participate in cell surface binding, binding to specific substrates including heparin, collagen, DNA, actin and fibrin, or are involved in binding to fibronectin receptors. Fibronectins have been reported to function in wound healing; ceil adhesion, cell differentiation, ceii migration and tumour metastasis (Bloom et al, Moi Biol Ceil. 1998,10:1521; Brodt P. Cancer Met Rev 1991,10:23). The motifs found in 282P1G3 as well as its similarity to CHL1 indicate that 282P1G3 can participate in tumor growth and progression by enhancing the initial stages of tumorigenesis, including tumor establishment and tumor growth, by allowing adhesion to basement membranes and surrounding cells, by mediating cell migration and metastasis.

Accordingly, when 282P1G3 functions as a regulator of tumor establishment, tumor formation, tumor growth, survival or cell signaling, 282P1G3 is used for therapeutic, diagnostic, prognostic and/or preventative purposes. In addition, when a molecule, such as a splice variant or SNP of 282P1G3 is expressed in cancerous tissues, such as those listed in Table I, they are used for therapeutic, diagnostic, prognostic and/or preventative purposes.

Example 45 Regulation of Transcription:

The cell surface localization of 282P1G3 coupled to the presence of lg-domains within its sequence indicate that 282P1G3 modulates signal transduction and the transcriptional regulation of eukaryotic genes. Regulation of gene expression is confirmed, e.g., by studying gene expression in celis expressing or lacking 282P1G3. For this purpose, two types of experiments are performed. in toe first set of experiments, RNA from parental and 282P1G3-expressing cells are extracted and hybridized to commercially available gene arrays (Clontech) (Smid-Koopman E et al. Br J Cancer. 2000. 83:246). Resting cells as well as cells treated with FBS, androgen or growth factors are compared. Differentially expressed genes are identified in accordance with procedures known in the art. The differentially expressed genes are then mapped to biological pathways . (Chen Ketal. Thyroid. 2001.11:41.).

In the second set of experiments, specific transcriptional pathway activation is evaluated using commercially available (Stratagene) luciferase reporter constructs including: NFkB-luc, SRE-luc, ELKI-iuc, ARE-iuc, p53-luc, and CRE-luc. These transcriptional reporters contain consensus binding sites for known transcription factors that lie downstream of well-characterized signal transduction pathways, and represent a good tool to ascertain pathway activation and screen for positive and negative modulators of pathway activation.

Thus, 282P1G3 plays a role in gene regulation, and it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes.

Example 46 identification and Confirmation of Potential Signal Transduction Pathways:

Many mammalian proteins have been reported to interact with signaling molecules and to participate in regulating signaling pathways. (J Neurochem. 2001;76:217-223). Immunoglobulin-like molecules in particular has been associated with several tyrpsine kinases including Lyc, Blk, syk (Tamir and Gambier, Oncogene. 1998,17:1353), the MAPK signaling cascade that control ceil mitogenesis and calcium flux (Vilen J et al, J Immunol 1997,159:231; Jiang F, Jia Y, Cohen I.

Blood. 2002, 99:3579). In addition, the 282P1G3 protein contains several phosphorylation sites (see Table Vi) indicating an association with specific signaling cascades. Using immunoprecipitation and Western blotting techniques, proteins are identified that associate with 282P1G3 and mediate signaling events. Several pathways known to play a role in cancer biology can be regulated by 282P1G3, including phospholipid pathways such as PI3K, AKT, etc, adhesion and migration pathways, including FAK, Rho, Rac-1, catenin, etc, as well as mitogenic/survival cascades such as ERK, p38, etc (Ceii 126

Growth Differ. 2000,11:279; J Biol Chem. 1999,274:801; Oncogene. 2000,19:3003, J. Cell Biol. 1997,138:913.). ). In order to determine whether expression of 282P1G3 is sufficient to regulate specific signaling pathways not otherwise active in resting cancer ceils, the effect of 282P1G3 on the activation of the signaling cascade is investigated in the cancer cell lines PA-1, Panel and Daudi. Cancer cells stably expressing 282P1G3 or neo are stimulated with growth factor, FBS or other activating molecules. Whole cell lysates are analyzed by western blotting.

To confirm that 282P1G3 directly or indirectly activates known signal transduction pathways in cells, luciferase (luc)based transcriptional reporter assays are carried out in cells expressing individual genes. These transcriptional reporters contain consensus-binding sites for known transcription factors that lie downstream of well-characterized signal transduction pathways. The reporters and examples of these associated transcription factors, signal transduction pathways, and activation stimuli are listed below. 1. NFkB-luc, NFkB/Rel; Ik-kinase/SAPK; growth/apoptosis/stress 2. SRE-luc, SRF/TCF/ELK1; MAPK/SAPK; growth/differeniiation 3. AP luc, FOS/JUN; MAPK/SAPK/PKC; growth/apoptosis/stress 4. ARE-luc, androgen receptor; steroids/MAPK; growth/differentiation/apoptosis 5. p53-luc, p53; SAPK; growth/differentiation/apoptosis 6. CRE-luc, CREB/ATF2; PKA/p38; growth/apoptosis/stress 7. TCF-luc, TCF/Lef; -catenin, Adhesion/invasion t,

Gene-mediated effects can be assayed in cells showing mRNA expression. Luciferase reporter plasmids can be introduced by lipid-mediated transfection (TFX-50, Promega). Luciferase activity, an indicator of relative transcriptional activity, is measured by incubation of cell extracts with luciferin substrate and luminescence of the reaction is monitored in a luminometer.

Signaling pathways activated by 282P1G3 are mapped and used for the identification and validation of therapeutic targets. When 282P1G3 is involved in ceil signaling, it is used as target for diagnostic, prognostic, preventative and/or therapeutic purposes.

Example 47 Involvement in Tumor Progression:

Based on the role of ig-domains and fibronectin motifs in cell growth and signal transduction, the 282P1G3 gene can contribute to the growth, invasion and transformation of cancer cells. The role of 282P1G3 in tumor growth is confirmed in a variety of primary an'd transfected cell lines including prostate ceii lines, as weli as NiH 3T3 ceiis engineered to stabiy express 282P1G3. Parental cells lacking 282P1G3 and cells expressing 282P1G3 are evaluated for cell growth using a well-documented proliferation assay (Fraser SP, Grimes JA, Djamgoz MB. Prostate. 2000;44:61, Johnson DE, Ochieng J,

Evans SL Anticancer Drugs. 1996,7:288).

To confirm the roie of 282P1G3 in the transformation process, its effect in colony forming assays is investigated. Parental NIH-3T3 cells lacking 282P1G3 are compared to N1H-3T3 cells expressing 282P1G3, using a soft agar assay under stringent and more permissive conditions (Song Z. et al. Cancer Res. 2000;60:6730).

To confirm the role of 282P1G3 in invasion and metastasis of cancer ceils, a well-established assay is used, e.g., a Transweil Insert System assay (Becton Dickinson) (Cancer Res. 1999; 59:6010). Control cells, including prostate, breast and kidney cell lines lacking 282P1G3 are compared to cells expressing 282P1G3. Ceiis are loaded with the fluorescent dye, calcein, and plated in the top well of the Transwell insert coated with a basement membrane analog. Invasion is determined by fluorescence of cells in the lower chamber relative to the fluorescence of the entire ceil population. 282P1G3 can also play a roie in cel! cycle and apoptosis. Parental cells and cells expressing 282P1G3 are compared for differences in ceil cycle regulation using a well-established BrdU assay (Abdel-Malek ZA. J Cell Physiol. 127 1988,136:247). in short, cells are grown under both optimal (full serum) and limiting (low serum) conditions are labeled with BrdU and stained with anii-BrdU Ab and propidium iodide. Cells are analyzed for entry into the G1, S, and G2M phases of the cell cycle. Alternatively, the effect of stress on apoptosis is evaluated in control parental cells and ceils expressing 282P1G3, including normal and tumor prostate ceils. Engineered and parental cells are treated with various chemotherapeutic agents, such as etoposide, taxoi, etc, and protein synthesis inhibitors, such as cycioheximide. Cells are stained with annexin V-FITC and cell death is measured by FACS analysis. The modulation of cell death by 282P1G3 can play a critical role in regulating tumor progression and tumor load.

When 282P1G3 plays a role in cell growth, transformation, invasion or apoptosis, it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes.

Example 48 Involvement in Angiogenesis:.

Angiogenesis or new capillary blood vessel formation is necessary for tumor growth (Hanahan D, Folkman J. Ceil. 1996,86:353; Folkman J. Endocrinology. 1998 139:441). Based on the effect of fibronectins on tumor cell adhesion and their interaction with endothelial cells, 282P1G3 plays a role in angiogenesis (Mareel and Leroy: Physiol Rev, 83:337; DeFouw L et al, Microvasc Res 2001,62:263). Several assays have been developed to measure angiogenesis in vitro and in vivo, such as the tissue culture assays endothelial cell tube formation and endothelial cel] proliferation. Using these assays as well as in vitro neo-vascularization, the rote of 282P1G3 in angiogenesis, enhancement or inhibition, is confirmed.

For example, endothelial cells engineered to express 282P1G3 are evaluated using tube formation and proliferation assays. The effect of 282P1G3 is also confirmed in animal models in vivo. For example, cells either expressing or lacking 282P1G3 are implanted subcutaneously in immunocompromised .mice. Endothelial cel! migration and angiogenesis are evaluated 5-15 days later using immunohistochemistry techniques. 282P1G3 affects angiogenesis, and it is used as a target for diagnostic, prognostic, preventative and/or therapeutic purposes.

Example 49 Involvement in Protein-Protein Interactions: ig-domains and fibronectin motifs have been shown to mediate interaction with other.proteins, including cell surface protein. Using immunoprecipitation techniques as well as two yeast hybrid systems, proteins are identified that associate with 282P1G3. Immunoprecipitates from cells expressing 282P1G3 and cells lacking 282P1G3 are compared for specific protein-protein associations.

Studies are performed to confirm the extent of association of 282P163 with effector molecules, such as nuclear proteins, transcription factors, kinases, phosphates etc. Studies comparing 282P1G3 positive and 282P1G3 negative cells as well as studies comparing unstimulated/resting cells and cells treated with epithelial cell activators, such as cytokines, growth factors, androgen and anti-integrin Ab reveal unique interactions.

In addition, protein-protein interactions are confirmed using two yeast hybrid methodology (Cum. Opin. Chem. Biol. 1999, 3:64). A vector carrying a library of proteins fused to the activation domain of a transcription factor is introduced into yeast expressing a 282P1G3-DNA-binding domain fusion protein and a reporter construct. Protein-protein interaction is detected by colorimetric reporter activity. Specific association with effector molecules and transcription factors directs one of skill to the mode of action of 282P1G3, and thus identifies therapeutic, prognostic, preventative and/or diagnostic targets for cancer. This and similar assays are aiso used to identify and screen for small molecules that interact with 282P1G3.

Thus, it is found that282P1G3 associates with proteins and smalt molecules. Accordingly, 282P1G3 and these proteins and small molecules are used for diagnostic, prognostic, preventative and/or therapeutic purposes.

Example 50 Involvement of 282P1G3 in cell-cell communication.: 128

Cell-cell communication is essential in maintaining organ integrity and homeostasis, both of which become deregulated during tumor formation and progression. Based on the presence of a fibronectin motif in 282P1G3, a motif known to be involved in celi interaction and cell-cell adhesion, 282P1G3 can regulate cell communication. Intercellular communications can be measured using two types of assays (J. Biol. Chem. 2000, 275:25207). in the first assay, ceiis loaded with a fluorescent dye are incubated in the presence of unlabeled recipient ceiis and the celi populations are examined under fluorescent microscopy. This qualitative assay measures the exchange of dye between adjacent ceils, in the second assay system, donor and recipient ceil populations are treated as above and quantitative measurements of the recipient ceil population are performed by FACS analysis. Using these two assay systems, ceils expressing 282P1G3 are compared to controls that do not express 282P1G3, and it is found that 282P1G3 enhances cell communications. Small molecules and/or antibodies that modulate cell-cell communication mediated by 282P1G3 are used as therapeutics for cancers that express 282P1G3. When 282P1G3 functions in cell-cell communication and small molecule transport, it is used as a target or marker for diagnostic, prognostic, preventative and/or therapeutic purposes.

Throughout this application, various website data content, publications, patent applications and patents are referenced. (Websites are referenced by their Uniform Resource Locator, or URL, addresses on the World Wide Web.)

The present invention is not to be limited in scope by the embodiments disclosed herein, which are intended as single illustrations of individual aspects of the invention, and any that are functionally equivalent are within the scope of the invention. Various modifications to the models and methods of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and teachings, and are similarly intended to fall within the scope of the invention. Such modifications or other embodiments can be practiced without departing from the time scope and spirit of the invention. i 129.TABLES: TABLE I: Tissues that Express 282P1G3: a. Malignant Tissues Pancreas Ovary'

Lymph node TABLE !!: Amino Acid Abbreviations SINGLE LETTER THREE LETTER FULL NAME F Phe phenylalanine L Leu leucine S Ser serine Y Tyr tyrosine c. cys. cysteine w Trp tryptophan P Pro proline H His histidine Q Gin glutamine R Arg arginine 1 lie isoleucine M Met methionine T 1 TL. I Hi threonine N Asn asparagine K Lys lysine V Val valine A Ala alanine D Asp aspartic acid E Glu glutamic acid G Gly glycine 130 TABLE III: Amino Acid Substitution Matrix

Adapted from the GCG Software 9.0 BLOSUM62 amino acid substitution matrix (block substitution matrix). The higher the value, the more likely a substitution is found in related, natural proteins. (See world wide web URL ikp.unibe.ch/manuai/biosum62.html) Ξ 1 F -9 G 0 H -2 I -1 K L M N p -1 Q -1 R s 1 T 0 V 0 W -3 y -2 A •4 -2 -3 -3 -1 -3 -1 -1 -3 -3 -3 -3 -1 -1 -1 -2 -2 C 2 -3 -1 -1 -3 -1 -4 -3 1 -1 0 -2 0 -1 -3 -4 -3 D 5 -3 -2 0 -3 1 -3 -2 0 -1 2 0 0 -1 -2 -3 -2 Ξ 6 -3 -1 0 -3 0 0 -3 -4 -3 -3 "2 -2 -1 1 3 F 6 -2 -4 -2 -4 -3 0 -2 -2 -2 0 -2 -3 -2 -3 G 8 -3 -1 -3 -2 1 -2 0 0 -1 -2 -3 -2 2 H 4 -3 2 1 -3 -3 -3 -3 -2 -1 3 -3 -1 I 5 -2 -1 0 -1 1 2 0 -1 -2 -3 -2 K 4 2 "3 , -3 -2 -9 -2 -1 1 -2 -1 L 5 -2 -2 0 -1 -1 -1 1 -1 -1 M 6 -2 0 0 1 0 -3 -4 -2 N 7 -1 -2 -1 -1 -2 -4 -3 P 5 1 0 -1 -2 -2 -1 Q 5 -1 -1 -3 -3 -2 R 4 1 -2 -3 -2 S 5 0 -2 -2 T 4 -3 -1 V 11 2 w

7 Y 131 TABLE IV: HLA Class l/ll Motifs/Supermotifs TABLt IV (A): HLA Class &amp;#943; Supermotifs/Motifs

SUPERMOTIF POSITION POSITION POSITION 2 (Primary Anchor) 3 (Primary Anchor) C Terminus (Primary Anchor) A1 TILVMS FWY A2 LIVMATQ IVMATL A3 VSMATL/ RK A24 YFWIVLMT FtYWL/W B7 P ViLFMVm B27 RHK ' FYLWM/VA B44 ED FWYLIMVA B58 ATS FWYL/VMA B62 QLIVMP FWYM/VLA MOTIFS A1 TSM Y A1 DEAS Y A2.1 UAVQIAT VLi MAT A3 LMVISATFCGD KYRHFA A11 VTMLISAGN CDF KRYH A24 YFWM FL1W A*3101 MVTALIS RK A*3301 MVALF/ST RK A*6801 AVTMSL/ RK B*0702 P LMF WYA/V B*3501 P LMFWY/VA B51 P LIVFWYAM B*5301 P IMFWYALV B*5401 P ATIVLMFWY

Bolded residues are prefemed, italicized residues are less preferred: A peptide is considered motif-bearing if if has primary anchors at each primary anchor position for a motif or supermotif as specified in the above table. TABLE IV (B): HLA Class II Supermotif

1 6 9 W, F.Y, V, ,I,L A, V, I, L, P, C, S, T A, V,!, 1, C, S, T, Μ, Y 132 TABLE IV (C): HLA Class 1! Motifs

MOTIFS 1’ anchor 1 2 3 4 5 1° anchor 6 7 8 9 DR4 preferred FMYLiVW M T 1 VSTCPAL/M MH MH deleterious W R VVDE DR1 preferred MFL/VWY PAMQ VMATSPLJC M AVM deleterious C CH FD CWD GDE D DR7 preferred MFL/VWY M W A iVMSACTPL M IV deleterious C G GRD N G DR3 MOTIFS Γ anchor 1 2 3 Γ anchor 4 5 1° anchor 6 Motif a preferred LIVMFY D Motif b preferred LiVMFAY DNQEST KRH DR Supermotif MFL/VWY VMSTACPU

Italicized residues indicate less preferred or “tolerated” residues TABLE IV (D): HLA Class! Supermotifs SUPER- MOTIFS . POSITION: 1 2 3 4 5 6 7 8 C-terminus A1 Γ Anchor Γ Anchor TILVAiS FWY A2 Γ Anchor Γ Anchor LIVMATQ LiVMAT A3 Preferred 1° Anchor YFW YFW YFW P Γ Anchor VSMATLI (4/5) (3/5) (4/5) (4/5) RK deleterious DE (3/5); DE P (5/5) (4/5) A24 Γ Anchor Γ Anchor YFW/VLMT FIYWLM B7 Preferred FWY (5/5) 1° Anchor FWY FWY 1’Anchor LiVM (3/5) P (4/5) (3/5) VILF/WWYA deleterious DE (3/5); DE G QN DE P(5/5); (3/5) (4/5) (4/5) (4/5) G(4/5); A(3/5); QN(3/5)

B27 Γ Anchor RHK 1’Anchor FYLWWA B44 Γ Anchor 1°Anchor ED FWYUMVA B58 1 ° Anchor Γ Anchor ATS FWLIVMA B62 Γ Anchor Γ Anchor QUVMP . FWYM/VLA italicized residues indicate less preferred or “tolerated'’ residues 133 TABLE IV (E): HLA Class I Motifs

POSITION 1 2 3 4 5 6 7 8 9 C- ierminus or C-terminus A1 , preferred GFYW TAnchor DEA YFW P DEQN YFW 1“Anchor 9-mer STM Y deleterious DE RHKLIVMP A G A A1 preferred GRHK ASTCL1VM TAnchor GSTC ASTC LIVM DE 1 “Anchor 9-mer DEAS Y deleterious A RHKDEPYFW DE PQN RHK PG GP A1 preferred YFW 1 “Anchor DEAQN A YFWQN PASTC GDE P TAnchor 10- STM Y mer deleterious GP RHKGLIVM DE RHK QNA RHKYFWRHK A Al preferred YFW STCLIVM 1 “Anchor A YFW PG G YFW TAnchor 10- DEAS Y mer deleterious RHK RHKDEPYFW P G PRHK QN A2.1 preferred YFW 1 “Anchor YFW STC YFW A P 1 “Anchor 9-mer L.MIVQAT VLIMAT deleterious DEP DERKH RKH DERKH POSITION: 1 2 3 4 5 6 7 8 9 C- Terminus A2.1 preferred AYFW 1 “Anchor LVIM G G FYWL TAnchor 10- IMIVQAT VIM VLIMAT mer deleterious DEP DE RKHA P RKH DERKHRKH A3 preferred RHK 1 “Anchor YFW PRHKYF A YFW P TAnchor LMVISATFCGD W KYRHFA deleterious DEP DE A11 preferred A 1 “Anchor YFW YFW A YFW YFW P TAnchor VTLMISAGNCD c KRYH deleterious DEP A G A24 preferred YFWRHK ΓAnchor STC YFW YFW TAnchor 9-mer YFWM FLIW deleterious DEG DE G QNP DERHKG AQN A24 Preferred 1 “Anchor P YFWP P 1 “Anchor 10- YFWM FLIW mer Deleterious GDE.QN RHK DE A QN DEA A3101 Preferred RHK Γ Anchor YFW P YFW YFW AP TAnchor MVTAUS RK Deleterious DEP DE ADE DE DE DE A3301 Preferred . T Anchor YFW AYFW TAnchor MVALF/ST RK Deleterious GP DE. A6801 Preferred YFWSTC 1’Anchor YFWLIV YFW P 1 “Anchor AVTMSU M RK deleterious GP DEG RHK A B0702Preferred RHKFWY TAnchor RHK RHK RHK RHK. PA TAnchor P LMFWYA/ deleterious DEQNP DEP DE DE GDE QN 'DE V B3501 Preferred FWYLI VM 1 “Anchor FWY FWY TAnchor P LMFWY/V

A 134

POSITION 1 2 3 4 5 6 7 8 9 C~ terminus or C-terminus A1 preferred GFYW 1“Anchor DEA YFW P DEQN YFW 1’Anchor 9-mer STM Y deleterious DE RHKLIVMP A G A Al preferred GRHK ASTCLIVM 1 “Anchor GSTC ASTC LIVM DE 1 “Anchor 9-mer DEAS Y deleterious A RHKDEPYFW DE PQN RHK PG GP deleterious AGP G G B51 Preferred LIVMFWY 1 "Anchor FWY STC FWY G FWY 1“Anchor P LIVFWYA M deleterious AGPDER DE G DEQN GDE HKSTC B5301 preferred LIVMFWY 1 “Anchor FWY STC FWY LIVMFWYFWY 1 “Anchor P IMFWYAt deleterious AGPQN G RHKQN DE V B5401 preferred FWY 1"Anchor FWYLIVM LIVM ALIVM FWYA 1°Anchor P P ATIVLMF wy deleterious GPQNDE GDESTC RHKDE DE QNDGE DE 135 TABLE iV (F):

Summary of HLA-supertypes Overall phenotypic frequencies of HLA-supertypes in different ethnic populations Specificity Phenotypic frequency Supertype 3osition 2 C-Terminus Caucasian N.A. Black Japanese Chinese Hispanic Average B7 P AILMVFWY 43.2 55.1 57.1 43.0 49.3 49.5 A3 AILMVST RK 37.5 42.1 45.8 52.7 43.1 44.2 A2 AILMVT AILMVT 45.8 39.0 42.4 45.9 43.0 42.2 . A24 YF (WIVLMT) FI (YWLM) 23.9 . 38.9 58.6 40.1 38.3 40.0 B44 ,E(D) FWYLIMVA 43.0 121.2 42.9 39.1 39.0 37.0 A1 T! (LVMS) FWY 47.1 16.1 21.8 14.7 26.3 25.2 B27 RHK FYL(WMI) 28.4 26.1 13.3 13.9 35.3 23.4 B62 OL (IVMP) FWY (MIV) 12.6 4.8 36.5 25.4 11.1 18.1 B58 ATS FWY (LIV) 10.0 25.1 1.6 9.0 5.9 10.3 TABLE IV (G):

Calculated population coverage afforded by different HLA-supertype combinations HLA-supertypes Phenotypic frequency A2, A3 and B7 A2, A3, B7, A24, B44 and A1 A2, A3, B7, A24, B44, A1,B27, B62, and B 58 Caucasian M.A Blacks Japanese Chinese Hispanic Average 83.0 86.1 87.5 88.4 86.3 86.2 99.5 98.1 100.0 99.5 99.4 99.3 99.9 99.6 100.0 99.8 99.9 99.8

Motifs indicate the residues defining supertype specificites. The motifs incorporate residues determined on the basis of published data to be recognized by multiple alleles within the supertype. Residues within brackets are additional residues also predicted to be tolerated by multiple alleles within the supertype.

Table V: Frequently Occurring Motifs Name • avrg. % dentity Description Potential Function zf-C2H2 34% Zinc finger, C2H2 type Nucleic acid-binding protein functions as transcription factor, nuclear location probable cytochrome b N 68% Cytochrome b(N-terminal)/b6/petB membrane bound oxidase, generate superoxide ig 19% Immunoglobulin domain domains are one hundred amino acids long and include a conserved intradomain disulfide bond. WD40 18% WD domain, G-beta repeat tandem repeats of about 40 residues, each containing a Trp-Asp motif. Function in signal transduction and protein interaction PDZ 23% PDZ domain may function in targeting signaling molecules to sub-membranous sites LRR 28% Leucine Rich Repeat short sequence motifs involved in protein-protein interactions Pkinase 23% Protein kinase domain conserved catalytic core common to both serine/threonine and tyrosine protein kinases containing an ATP binding site and a catalytic site 136 PH 16% PH domain pleckstrin homology involved in intracellular signaling or as constituents of the cytoskeleton EGF 34% EGF-like domain 30-40 amino-acid long found in the extracellular domain of membrane-bound proteins or in secreted proteins Rvt 49% Reverse transcriptase RNA-dependent DNA polymerase) - 25% Ank repeat Cytoplasmic protein, associates integral membrane proteins to the cytoskeleton Oxidored q1 32% NADH- Ubiquinone/plastoquinone (complex 1), various chains membrane associated. Involved in proton translocation across the membrane Efhand 24% EF hand calcium-binding domain, consists of a12 residue loop flanked on both sides by a 12 residue alpha-helical domain Rvp 79% Retroviral aspartyl protease Aspartyl or acid proteases, centered on a catalytic aspartyl residue Collagen 42% Collagen triple helix repeat (20 copies) extracellular structural proteins involved in formation of connective tissue. The sequence consists of the G-X-Y and the polypeptide chains forms a triple helix. Fn3 20% Fibronectin type iii domain Located in the extracellular ligandbinding region of receptors and is about 200 amino acid residues tong with two pairs of cysteines involved in disulfide bonds 7tm 1 19% 7 transmembrane receptor (rhodopsin family) seven hydrophobic transmembrane regions, with the N-terminus located extracellularly while, the C-terminus is cytoplasmic. Signal through G proteins

Table Vl: Motifs and Post-transiational Modifications of 282P1G3 N-giycosylation site ~ 87-90 NNSG (SEQ ID NO: 54) 231 -234 NDSS (SEQ ID NO: 55) 315-318 NVSY (SEQ ID NO: 56) 410-413 NHTA (SEQ ID NO: 57) 492 - 495 NGTL (SEQ ID NO: 58) 498 - 501 NRTT (SEQ ID NO: 59) 529 - 532 NATK (SEQ ID NO: 60) 578-581 NGTE (SEQ ID NO: 61) 591 - 594 NLTl (SEQ ID NO: 62) 596-599 NVTL (SEQ ID NO: 63) 641 - 644 NRSV (SEQ ID NO: 64) 657 - 660 NISE (SEQ ID NO: 65) 783 - 786 NHTL (SEQ ID NO: 66) 838 - 841 NSTL (SEQ ID NO: 67) 961 -964 NLTG (SEQ ID NO: 68) 973 - 976 NDTY (SEQ ID NO: 69) 985 - 988 NITT (SEQ SD NO: 70) 1000- 1003 NATT (SEQ ID NO: 71) 1042-1045 NLTQ (SEQ ID NO: 72) 1071 -1074 NDSI (SEQ ID NO: 73) 1213-1216 NGSS (SEQ ID NO: 74)

Tyrosine sulfation site 817-831 TLYSGEDYPDTAPVI (SEQ ID NO: 75) 137 -.1083-1097 GREYAGLYDDISTQG (SEQ ID NO: 76) 1145- 1159 KDETFGEYSDSDEKP (SEQ ID NO: 77) 1176-1190 SADSLVEYGEGDHGL (SEQ ID NO: 78) cAMP- and cGMP-dependent protein kinase phosphorylation site 684-687 KKTT (SEQ ID NO: 79)

Pkinase C phosphorylation site 91 - 93 TFR

112-114 SNK 183- 185 SQK 226 - 228 SLK 245-247 SIK 310-312 TLK 350-352 TKK 377 - 379 TIK 536-538 SPK 563-565 SLK 637 - 639 SER 643 - 645 SVR 766 - 768 TWK 785-787 TLR 1002-1004 TTK 1044-1046 TQK v 1128- 1130 SVK 1143-1145 SVK 1163-1165 SLR

Casein kinase II phosphorylation site 198-201 SRND (SEQiDNO: 80) 235 - 238 SSTE (SEQIDNO: 81) 260-263 SGSE (SEQIDNO: 82) 317-320 SYQD (SEQIDNO: 83) 385 - 388 SPVD (SEQ ID NO: 84) 500 - 503 TTEE (SEQ ID NO: 85) 501 - 504 TEED (SEQ ID NO: 86) 554 - 557 SKCD (SEQ ID NO: 87) 598 - 601 TLED (SEQ ID NO: 88) 611-614 TALD (SEQIDNO: 89) 615-618 SAAD (SEQIDNO: 90) 623 - 626 TVLD (SEQ ID NO: 91) 809-812 SGPD (SEQIDNO: 92) 820-823 SGED (SEQIDNO: 93} 870 - 873 SLLD (SEQ ID NO: 94) 1027-1030 TLGE (SEQIDNO: 951 1128-1131 SVKE (SEQIDNO: 96) 1143-1146 SVKD (SEQIDNO: 97) 1148-1151 TFGE (SEQIDNO: 98) 1153-1156 SDSD (SEQIDNO: 99) 1179-1182 SLVE (SEQIDNO: 100)

Tyrosine kinase phosphorylation site 480 - 487 KPL.EGRRY (SEQIDNO: 101) N-myristoylation site . 116-121 GiAMSE (SEQ ID NO: 102) 240 - 245 GSKANS (SEQIDNO; 103) 261 - 266 GSESS! (SEQ ID NO: 104) 322-327 GNYRCT (SEQ ID NO: 105) 364-369 GILLCE (SEQIDNO: 106) 424 - 429 GTILAN (SEQIDNO: 107) 506 - 511 GSYSCW (SEQIDNO: 108) 579 - 584 GTEDGR (SEQIDNO: 109) 138 589-594 GANLTI (SEQ ID NO: 110) 603 - 608 GIYCCS (SEQ ID NO: 111) 651 -656 GADHNS (SEQ ID NO: 112) 888-893 GQRNSG (SEQ ID NO: 113) 893 - 898 GMVPSL (SEQ ID NO: 114) 960-965 GNLTGY (SEQ ID NO: 115) 1040-1045 GVNLTQ (SEQ ID NO: 116) 1101-1106 GLMCAI (SEQIDNO: 117) 1124- 1129 GGKYSV (SEQIDNO: 118) 1162-1167 GSLRSL (SEQIDNO: 119) 1195-1200 GSFIGA (SEQIDNO: 120) 1199-1204 GAYAGS (SEQIDNO: 121) 1208-1213 GSVESN (SEQIDNO: 122) 1214-1219 GSSTAT (SEQIDNO: 123)

Amidation site 483 - 486 EGRR (SEQIDNO: 124) 682- 685 QGKK (SEQIDNO: 125)

Table Vii:

Search Peptides v.l ORF: 272-3946 9-mers, 10-mers and 15-mers (SEQ ID NO: 126)

MEPLLDGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYR.CF EEIEFIVPSV PKLPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSLKHA SKANSIKQRK PKLLLPPTES GSESSITILK GEILLLECFA EGLPTPQVDW RETKENYGKT LKIENVSYQD KGNYRCTASN FLGTATHDFH VIVEEPPRWT GSNGILLCEA EGEPQPTIKW RVNGSPVDNH PFAGDWFPR EISFTNLQPN NVHGTILANA NIDWDVRPL IQTKDGENYA TWGYSAFLH CEFFASPEAV PLEGRRYHIY ENGTLQINRT TEEDAGSYSC WVENAIGKTA VTANLDIRNA RIPKLHMLEL HCESKCDSHL KHSLKLSWSK DGEAFEINGT EDGRIIIDGA DQGIYCCSAH TALDSAADIT QVTVLDVPDP PENLHLSERQ NRSVRLTWEA YIVEFEGNKE EPGRWEELTR VQGKKTTVIL PLAPFVRYQF RVIAVNEVGR etppaapdrn pqnirvqasq pkemiikwep lksmeqngpg leyrvtwkpq VTNHTLRVMT PAVYAPYDVK VQAINQLGSG PDPQSVTLYS GEDYPDTAPV LVKVTWSTVP KDRVHGRLEG YQINWWKTKS LLDGRTHPKE . VNILRFSGQR FSEFHLTVLA YNSKGAGPES EPYIFQTPEG VPEQPTFLKV IKVDKDTATL NLTGYLLQYQ iindtyeige lndinittps kpswhlsnln attkykfylr ITEESSTLGE GSKGIGKISG VNLTQKTHPI EVFEPGAEHI VRLMTKNWGD TRGREYAGLY ddistqgwfi glmcaiallt lllltvcfvk RNRGGKYSVK IQSVKDETFG EYSDSDEKPL KGSLRSLNRD MQPTESADSL VEYGEGDHGL YAGSKEKGSV ESNGSSTATF PLRA

EYFQIECEAK

ASNKLGIAMS

LEHIEQDERV

NDSSSSTEIG

NKIGGDLPKG

KKPQSAVYST

HTAVYQCEAS

VSWQKVEEVK

TKLR.VSPKNP

NLTISNVTLE

GADHNSNISE

SQPSQPSDHH

GAPVEWEEET

IHGVDVINST

NSGMVPSLDA

SWGLPKKLNG

ACTSQGCGKP

NDSIFQDVIE

EKEDLHPDPE

FSEDGSFIGA 50 120 180 240 3Q0 350 42 0 480 540 600 650 720 730 840 SOO 950 1020 1080 1140 1200 1224 v.2 ORF- 3787 9-mers aa 125-141 FIVPSVPKFPKEKIDPL (SEQ ID NO: 127) aa 295-311 GDLPKGREAKENYGKTL (SEQ ID NO: . 128) aa 1024-1040 ESSTLGEGKYAGLYDDI (SEQ ID NO: 129) 10-mers aa 124-142 aa 294-312 aa 1023-1041 EFIVPSVPKFPKEKIDPLE GGDLPKGREAKENYGKTLK EES STLGEGKYAGLYDDIS (SEQ ID NO: 130) (SEQ ID NO: 131) (SEQ ID NO: 132) 15-mers aa 119-147 MSEEIEFIVPSVPKFPKEKIDPLEVEEGD (SEQ ID NO aa 289-317 DWNKIGGDLPKGREAKENYGKTLKIENVS (SEQ ID NO aa 1018-1046 GKPITEESSTLGEGKYAGLYDDISTQGWF (SEQ ID NO v.3 ORF:272.2953 Frame +2 9-mers 133) 134) 135) 139 —“’•YT’vz'TsvrVTrv'A'vr^®*· ’ _.-.-

Aa 830-848 VIHGVDVINTTYVSN TTYVSNATGSPQ PSIFICSKEQ ELSYRNRNML· AEDFIQKSTS CNYVEKSSTF FKI (SEQ ID NO: 136) 10-raers

aa 825-849 PVIHGVDVINTTYVSN TTYVSNATGSPQ PSIFICSKEQ ELSYRNRNML AEDFIQKSTS CNYVEKSSTF FKI (SEQ ID NO: 13 7) 15-mers aa 824-854 YPDTAPVIHGVDVINTTYVSN TTYVSNATGSPQ PSIFICSKEQ ELSYRNRNML AEDFIQKSTS CNYVEKSSTF FKI (SEQ ID NO: 13 8) v.4 ORF:272.3625 Frame +2 9- mers aa 816-832 VTLYSGEDLPEQPTFLK (SEQ ID NO: 139) 10- mers aa 815-833 SVTLYSGEDLPEQPTFLKV (SEQ ID NO: 140) 15-mers aa 810-838 GPDPQSVTLYSGEDLPEQPTFLKVIKVDK (SEQ ID NO: 141) v.5 ORF: 272.3898 Frame +2 9- mers aa 219-235 PMKLTVNSSNSIKQRKP (SEQ ID NO: 142) 10- mers aa 218-236 MPMKLTVNSSNSIKQRKPK (SEQ ID NO: 143) 15-mers aa 213-241 TIVQKMPMKLTVNSSNSIKQRKPKLLLPP (SEQ ID NO: 144) v.6 ORF: 272.3823 Frame +2 9- mers aa 121-137 EEIEFIVPKLEHIEQDE (SEQ ID NO: 145) 10- mers aa 122-139 SEEIEFIVPKLEHIEQDER (SEQ ID NO: 146) 15-mers aa 115-143 LGIAMSEEIEFIVPKLEHIEQDERVYMSQ (SEQ ID NO: 147) v.7 ORF:272.3982 Frame +2 9-mers aa 337-364 HDFHVIVEDNISHELFTLHPEPPRWTKK (SEQ ID NO: 148) lOmers :aa 336-365 THDFHVIVEDNISHELFTLHPEPPRWTKKP (SEQ ID NO: 149) 15-mers aa 331-370 FLGTATHDFHVIVEDNISHELFTLHPEPPR.WTKKPQSAVY (SEQ ID NO: 150) 140

Tables VII!-XXI:

Table VIII-V1-HLA-A1- 9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 3 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence | Score 500 TTEEDAGSY 112.5 00 919 ESEPYiFQT 67.50 0 173 HIEQDERVY' 45.00 0 1078 VIETRGREY 45.00 0 371 egepqptik' 45.00 0 931 VPEQPTFLK 22.50 0 524 NLDIRNATK 20.00 0 760 GLEYRVTWK 18.00 0 547 MLELHCESK... 18.00 0 579 GTEDGRIII 11.25 0 871 LLDGRTHPK 10.00 0 343 VEEPPRWTK 9.000 1191 FSEDGSFIG 6.750 119 MSEEJEFIV 6.750 78 FTDHRIIPS 6.250 145 EGDPIVLPC 6.250 721 ETPPAAPDR 5.000 915 GAGPESEPY 5.000 396 WFPREISF 5.000 168 NIELEHIEQ 4.500 598 TLEDQGIYC 4.500 917 GPESEPYIF 4.500 149 IVLPCNPPK 4.000 1154 DSDEKPLKG 3.750 434 VVDVRPLIQ 2.500 948 ATLSWGLPK 2.500 961 NLTGYLLQY [ΣδΟΟ

Table VIII-V1-HLA-A1-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score| 287 QVDWNKIGG 2.500] 789 MTPAVYAPY 2.5001 586 IIDGANLT1 2.5001 810 | GPDPQSVTL 2.500] 236) STEIGSKAN 2.250] 1021 ITEESSTLG 2.250] 1183 YGEGDHGLF 2.250] 62 NPEPTFSWT 2.2501 416 QCEASNVHG 1.8001 142 EVEEGDPIV ] 1.800] 122 EIEFIVPSV 1.8θθ| 1175 ESADSLVEY 1.500] 261 GSESSITIL 1.350( 901 FSEFHLTVL 1.350 627 VPDPPENLH 1.250 1144 VKDETFGEY 1.250 1136 HPDPEIQSV 1.250 816 VTLYSGEDY 1.250 70 TKDGNPFYF] 1.250 597 VTLEDQGIY 1.250 157 KGLPPLHIY 1.250 571 DGEAFEING 1.125 270 KGEILLLEC 1.125 978 IGELNDINI 1.125 1112 LLLTVCFVK 1.000 137 KIDPLEVEE 1.000 616 AADITQVTV 1.000 45 VAFPFDEYF 1.000 835 DVINSTLVK 1.000 279 FAEGLPTPQ 0.900 369 EAEGEPQPT 0.900 54 Q1ECEAKGN 0.900 342 IVEEPPRWT 0.900] 192 NVEEKDSRN 0.900 753 SMEQNGPGL 0.900

Table V1I1-V1-HLA-A1-9mers-282P1G3 Each peptide is a portion of SEQ ID MO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 511 WVENAIGKT 0.900 1056 GAEHIVRLM 0.900 551 HCESKCDSH 0.900 367 LCEAEGEPQ 0.900 1180 LVEYGEGDH 0.900 275 LLECFAEGL 0.900 24 .AIEIPSSVQ 0.900 1209 SVESNGSST 0.900 738 ASQPKEMil 0.750 316 VSYQDKGNY 0.750 1152 YSDSDEKPL 0.750 199 RNDYCCFAA 0.625 1068 WGDNDSIFQ 0.625 44 QVAFPFDEY 0.500 99 HISHFQGKY 0.500 1000 NATTKYKFY 0.500 158 GLPPLHIYW 0.500 117 lAMSEEiEF 0.500 392 FAGDWFPR 0.500 1176 SADSLVEYG 0.500 612 ALDSAADIT 0.500 651 GADHNSNIS 0.500 875 RTHPKEVNI 0.500 833 GVDVINSTL 0.500 202 YCCFAAFPR 0.500 897 SLDAFSEFH 0.500 906 LTVLAYNSK 0.500 986 ITTPSKPSW 0.500 555 KCDSHLKHS 0.500 893 GMVPSLDAF 0.500 957 KLNGNLTGY 0.500 689 ILPLAPFVR 0.500 853 RVHGRLKGY 0.500 13 YLMFLLLKF 0.500 929 EGVPEQPTF (0.500 141 - Table VIII-V1-HLA-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start, position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Sqore 1052 VFEPGAEHI 0.450 213 TIVQKMPMK ! 0.400 949 TLSWGLPKK 0.400

Table VII1-V2-HLA-A1 -9mers-(SET 1)- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 1 FIVPSVPKF 2.000 3 I VPSVPKFPK 0.250 5 SVPKFPKEK 0.020 4 PSVPKFPKE 0.003 2 IVPSVPKFP 0.001 6 VPKFPKEKI 0.000 9 FPKEKIDPL 0.000 7 PKFPKEKID 0.000 8 KFPKEKIDP 0.000

Table V1II-V2-HLA-A1-9mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 9 AKENYGKTL 0.045 δ GREAKENYG 0.045 2 DLPKGREAK 0.020 5 KGREAKENY 0.013 1 GDLPKGREA 0.005 7 REAKENYGK 0.002 8 EAKENYGKT 0.001

Table VIII-V2-HLA-A1- 9mers-(SET 2)-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide Is 9 amino acids, and the end position for each peptide is the start position plus eight

Start Subsequence Score 3 LPKGREAKE‘ 0.000 4 PKGREAKEN 0.000 Table VIII-V2-HLA-A1-9mers-(SET 3)- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 2 SSTLGEGKY 0.750 5 LGEGKYAGL 0.450 1 ESSTLGEGK 0.300 3 STLGEGKYA 0.025 4 TLGEGKYAG 0.020 6 GEGKYAGLY 0.003 9 KYAGLYDD! 0.001 7 EGKYAGLYD 0.000 8 GKYAGLYDD j 0.000

Table VII1-V3-HLA-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 4 GVDV1NTTY 25.00 . o 36 EQELSYRNR 1.350 10 TTYVSNTTY 1.250 55 STSCNYVEK 1.000 46 MLAEDFIQK 1.000 47 LAEDFiQKS 0.900 60 YVEKSSTFF 0.900

Table VIII-V3-HLA-A1-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start' Subsequence Score 34 SKEQELSYR 0.450 33 CSKEQELSY 0.375 23 TGSPQPSIF 0.250 25 SPQPSIFIC 0.125 24 GSPQPSIFI 0.075 22 ATGSPQPS! 0.050 27 QPSIFICSK 0.050 16 TTYVSNATG 0.050 13 VSNTTYVSN 0.030 15 NTTYVSNAT 0.025 48 AEDFIQKST 0.025 45 NMLAEDFIQ 0.025 9 NTTYVSNTT 0.025 1 VIHGVDVIN 0.020 7 VINTTYVSN 0.020 12 YVSNTTYVS 0.020 6 DVINTTYVS 0.020 19 VSNATGSPQ 0.015 56 TSCNYVEKS 0.015 29 SIFICSKEQ 0.010 21 NATGSPQPS 0.010 57 SCNYVEKSS 0.010 38 ELSYRNRNM 0.010 31 FICSKEQEL 0.010 52 IQKSTSCNY 0.007 61 VEKSSTFFK 0.005 . 59 NYVEKSSTF 0.005 43 NRNMLAEDF 0.005 54 KSTSCNYVE 0.003 3 HGVDVINTT 0.003 44 RNMLAEDF! 0.003 8 INTTYVSNT 0.003 58 CNYVEKSST 0.003 14 SNTTYVSNA 0.003 62 EKSSTFFKl 0.003 2 IHGVDVINT 0.003 39 LSYRNRNML 0.002 142

Table V1II-V3-HLA-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence j Score 51 FIGKSTSCN 0.001 18 YVSNATGSP 0.001 32 ICSKEQELS 0.001 35 KEQELSYRN 0.001 26 PQPSIFICS 0.001 37 QELSYRNRN 0.001 20 SNATGSPQP 0.001 5 VDVINTTYV 0.001 49 EDFIQKSTS 0.001 11 TYVSNTTYV 0.001 50 DFIQKSTSC 0.001 53 QKSTSCNYV 0.001 17 TYVSNATGS 0.001 40 SYRNRNMLA 0.000 28 PSIFICSKE 0.000 42 RNRNMLAED 0.000 30 IFiCSKEQE 0.000 41 YRNRNMLAE 0.000

Table VIIPVT-HLA.-AI-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 9 LPEQPTFLK 22.50 0 7 EDLPEQPTF 0.100 4 YSGEDLPEQ 0.030 6 GEDLPEQPT 0.025 1 VTLYSGEDL 0.025 5 SGEDLPEQP 0.022 8 DLPEQPTFL 0.010 2 TLYSGEDLP 0.001 3 LYSGEDLPE 0.000

Table VIII-V5-HLA-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 8 SSNSIKQRK 0.300 5 TVNSSNSIK 0.200 7 NSSNSIKQR 0.150 4 LTVNSSNSI 0.025 6 VNSSNSIKQ 0.013 3 KLTVNSSNS 0.010 I 2 MKLTVNSSN 0.001 | 9 SNSIKQRKP 0.000 1 PMKLTVNSS 0.000

Table VIII-V6-HLA-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 2 EIEFIVPKL 1.800 5.1 FIVPKLEH! 0.100 i 9 KLEHIEQDE 0.090 1 EEIEFIVPK 0.020 4 EFIVPKLEH 0.003 7 VPKLEHIEQ 0.001 6 IVPKLEHIE 0.000 3 IEFIVPKLE 0.000 8 PKLEHIEQD 0.000

Table VII1-V7-HLA-A1-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence j Score

Table V1II-V7-HLA-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 19 HPEPPRWTK 45.000 16 FTLHPEPPR 0.500 17 TLHPEPPRW 0.200 6 IVEDNISHE 0.090 5 VIVEDNISH 0.050 10 NISHELFTL 0.050 7 VEDNISHEL 0.025 12 SHELFTLHP 0.022 11 ISHELFTLH 0.015 9 DNISHELFT 0.013 20 PEPPRWTKK 0.010 4 HVIVEDNIS 0.010 8 EDNISHELF 0.005 14 ELFTLHPEP 0.002 2 DFHVIVEDN 0.001 18 LHPEPPRWT 0.001 3 FHVIVEDNI 0.001 1 HDFHVIVED 0.000 15 LFTLHPEPP 0.000 13 HELFTLHPE 0.000

Table IX-V1-HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 261 GSESSITILK 135.000 810 GPDPQSVTL Y 62.500 62 NPEPTFSWT K 45.000 1152 YSDSDEKPLK 30.000 1136 HPDPEIQSVK . 25.000 1028 LGEGSKGIGK 22.500 143

Table IX-V1-HLA-A1-10mers-282P1G3 I able !X-V1-HLA-A1-10mers-282P1G3 Table !X-V1-HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score Start Subsequence Score Start Subsequence Score 312 KIENVSYQDK 18.000 279 FAEGLPTPQV 1.800 L j 342 1VEEPPRWTK 18.000 ( 460 HCEFFASPEA 1.800 . 303 TKENYGKTLK| 0.900 738 ASQPKEMIIK 15.000 173 HIEQDERVYM 1.800 675 WEELTRVQG K 0.900 371 EGEPQPTIKW 11.250 24 AIEIPSSVQQ 1.800 406 NLQPNHTAV Y 10.000 300 GRETKENYG K 1.800 1209 SVESNGSST A 0.900 343 VEEPPRWTK K 9.000 598 TLEDQGIYCC 1.800 996 LSNLNATTKY 0.750 919 ESEPYIFQTP 1.350 1154 DSDEKPLKG S 0.750 170 ELEH1EQDER 9.000 636 LSERQNRSV R 1.350 1075 FQDVIETRGR 0.750 658 ISEYIVEFEG 6.750 1191 FSEDGSF1GA 6.750 1192 SEDGSFIGAY 1.250 119 MSEEIEFIVP 0.675 627 VPDPPENLHL 6.250 499 RTTEEDAGS Y 1.250 824 YPDTAPVIHG 0.625 960 GNLTGYLLQY 0.625 788 VMTPAVYAP Y 5.000 917 GPESEPYIFQ 1.125 431 NIDWDVRPL 0.500 688 VILPLAPFVR 5.000 1021 ITEESSTLGE 1.125 616 AADITQVTVL 0.500 137 KIDPLEVEEG 5.000 1183 YGEGDHGLF S 1.125 586 IIDGANLTIS 0.500 1056 GAEHiVRLMT 4.500 847 STVPKDRVH G 0.500 481 PLEGRRYHIY 4.500 579 GTEDGRIIID 1.125 236 i STEIGSKANS 4.500 931 VPEQPTFLKV 1.125 395 DWFPRE1SF 0.500 1149 FGEYSDSDE K 4.500 930 GVPEQPTFLK 1.000 524 NLDIRNATKL 0.500 948 ATLSWGLPK K 1.000 555 KCDSHLKHSL 0.500 466 SPEAWSWQ K 4.500 833 GVDViNSTLV 0.500 1111 LLLLTVCFVK 1.000 686 TTVILPLAPF j 0.500 ( 475 KVEEVKPLEG 4.500 212 RTIVQKMPMK 1.000 596 NVTLEDQGIY i 0.500 142 EVEEGDPIVL 4.500 11 IVYLMFLLLK 1.000 14 LMFLLLKFSK 0.500 901 FSEFHLTVLA 2.700 126 IVPSVPKLPK 1.000 315 NVSYQDKGN Y 0.500 434 WDVRPUQT 2.500 689 ILPLAPFVRY 1.000 897 SLDAFSEFHL 2.500 30 SVQQVPTIIK 1.000 815 SVTLYSGEDY 0.500 78 FTDHRIIPSN 2.500 624 VLDVPDPPEN 1.000 478 EVKPLEGRR Y 0.500 145 EGDPIVLPCN 2.500 947 TATLSWGLPK 1.000 . 4 LLLGRGLIVY 2.500 1078 VIETRGREYA 0.900 440 L1QTKDGENY 0.500 | 199 rndyccfaa F 2.500 511 WVENAIGKTA 0.900 283 LPTPQVDWN K 0.500 1180 LVEYGEGDH G 0.900 [612* aldsaaditq 2.500 116 GIAMSEEIEF 0.500 j 500 {tteedagsys 2.250 416 QCEASNVHG T 0.900 1077 DVIETPGREY 0.500 1109 LTLLLLTVCF 0.500 747 KWEPLKSME Q 2.250 547 MLELHCESK C 0.900 1134 DLHPDP0QS 0.500 270 KGE1LLLECF 2.250 445 DGENYATW G 0.450 551 HCESKCDSH 0.900 [369 eaegepqpti 1.800 144 : Table iX-V1-HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence || Score 669 i KEEPGRWEEj θ45θ

Table IX-V2-HLA-A1-10mers-(SET1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score | 3 IVPSVPKFPK 1.000) 5 PSVPKFPKEK 0.300 1 EFIVPSVPKF 0.010 2 FIVPSVPKFP 0.010 6 SVPKFPKEKI 0.001 4 VPSVPKFPKE 0.001 8 PKFPKEKIDP 0.000 10 FPKEKIDPLE 0.000 9 KFPKEKIDPL 0.000 7 VPKFPKEKID 0.000

Table IX-V2-HLA-A1-" 10mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 5 LGEGKYAGLY 11.25 0 -I ESSTLGEGKY 0.750 3 STLGEGKYAG^ 0.050 4 TLGEGKYAGL 0.020 2 SSTLGEGKYA 0.015 8 gkyaglyddi 0.001

Table IX-V2-HLA-A1-10mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 7 EGKYAGLYDD 0.000 6 GEGKYAGLY D 0.000

Table IX-V2-HLA-A1-10mers- (SET 3)-282P1 G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 6 LGEGKYAGLY 11.250 2 ESSTLGEGKY 0.750 4 STLGEGKYAG 0.050 5 TLGEGKYAGL 0.020 3 SSTLGEGKYA 0.015 1 EESSTLGEGK 0.010 10 KYAGLYDDIS 0.001 9 GKYAGLYDDI 0.001 8 EGKYAGLYDD 0.000 ) 7 GEGKYAGLYD 0.000

Table iX-V3-HLA-A1-10mers- I 282P1G3 I Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 61 YVEKSSTFFK 9.000 . 10 NTTYVSNTTY 1.250 ) 48 LAEDFIQKST 0.900 55 KSTSCNYVEK 0.600 46 NMLAEDFIQK 0.500 5 GVDVINTTYV 0.500

Table IX-V3-HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 33 ICSKEQELSY 0.250 23 ATGSPQPSIF 0.250 ) 37 EQELSYRNRN 0.135 26 SPQPSIFICS 0.125 4 HGVDVINTTY 0.125 24 TGSPQPSIFl 0.125 35 SKEQELSYRN 0.090 25 GSPQPSIFIC 0.075 ' 52 | FIQKSTSCNY ) 0.050 16 | NTTYVSNATG 0.050 2 VIHGVDV1NT 0.050 49 AEDFIQKSTS 0.025 56 STSCNYVEKS 0.025 dd 1 i TTYVSNTTYV π noc u.uZu 17 TTYVSNATGS 0.025 59 CNYVEKSSTF 0.025 13 YVSNTTYVSN 0.020' 22 NATGSPQPSI 0.020 7 DVINTTYVSN 0.020 34 CSKEQELSYR 0.015 14 VSNTTYVSNA 0.015 57 TSCNYVEKSS 0.015 [45 RNMLAtDFIQ 0.013 47 MLAEDFIQKS 0.010 32 FICSKEQELS 0.010 58 SCNYVEKSST 0.010 8 j VINTTYVSNT 0.010 19 YVSNATGSPQ 0.0101 39 ELSYRNRNML 0.010) 40 LSYRNRNMLA 0.008 60 NYVEKSSTFF 0.005 36 KEQELSYRNR 0.005 20 VSNATGSPQP 0.003 27 PQPSIFICSK 0.003 15 SNTTYVSNAT 0.003 43 RNRNMLAEDF 0.003 9 INTTYVSNTT 0,003 145

Table IX-V3-HLA-A1-10mers-' 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start | Subsequence j Score 21 I I SNATGSPQPS 0.003 1 I PVIHGVDVIN 0.002 29 PSIFICSKEQ 0.002 12 TYVSNTTYVS 0.001 30 SIFICSKEQE 0.001 6 VDVINTTYVS 0.001 31 IFICSKEQEL 0.001 38 QELSYRNRNM 0.001 3 IHGVDVINTT 0.001 51 j DFIQKSTSCN 0.001 50 EDFIQKSTSC 0.001 44 NRNMLAEDFI 0.001 62 VEKSSTFFKI 0.000 ADQICIPei/C μγοιγ iVQfxc; Z.0 U'.UUU 53 IQKSTSCNYV 0.000 54 QKSTSCNYVE 0.000 18 TYVSNATGSP 0.000 41 SYRNRNMLAE 0.000 42 l-1 YRNRNMLAED 0.000

Table lX-V4-HLA-A1-10mers- I 282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 10 LPEQPTFLKV 1.125 9 DLPEQPTFLK 1.000 7 GEDLPEQPTF 0.500 6 SGEDLPEQPTj 0.225 1 SVTLYSGEDL 0.010 8 EDLPEQPTFL 0.005 3 TLYSGEDLPE 0.005 2 VTLYSGEDLP 0.003 |5 YSGEDLPEQP 0.002

Table IX-V4-HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start) Subsequence | Score 4 LYSGEDLPEQj 0.001

Table IX-V5-HLA-A1-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 5 LTVNSSNSIK 0.500 8 NSSNSIKQRK 0.300 10 SNSIKQRKPK 0.050 6 TVNSSNSIKQ n ! - i 7 VNSSNSIKQR 0.025 | 4 KLTVNSSNSI 0.010 | 9 SSNSIKQRKP 0.002 I 3 MKLTVNSSNS 0.001 I 1 MPMKLTVNSS 0.000 2 PMKLTVNSSN 0.000

Tabie Xl-V6-HLA-A1-1Gmers- 282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start | Subsequence Score 10 KLEHIEQDER 9.000 1 SEEIEF1VPK 1.800 3 ElEFiVPKLE 0.090 6 FiVPKLEHIE 0.010 7 1VPKLEHIEQ 0.005 4 1EFIVPKLEH 0.003 2 EEIEFIVPKL 0.001 5 EFIVPKLEHI 0.001

Tabie Xl-V6-HLA-Al-Wmers-_282P1G3_

Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 8 VPKLEHIEQD 0.000 9 PKLEHIEQDE 0.000

Tabie Xl-V7-HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each . peptide is the start position plus nine. Start Subsequence Score 20 HPEPPRWTKK 45.000 7 IVEDNISHEL 0.900 8 VEDNISHELF CL25CL. 18 TLHPEPPRWT 0.100 5 HVIVEDNISH 0.050 17 FTLHPEPPRW 0.050 10 ) DNISHELFTL 0.013 19 LHPEPPRWTK 0.010 16 {PTJ HPFPPR 0,010 11 NISHELFTLH 0.010 12 ISHELFTLHP 0.007 . 1 THDFHVIVED 0.005 13 SHELFTLHPE 0.005 ) 9 1 EDNISHELFT 0.003' 15 ELFTLHPEPP 0.001 6 VIVEDNISHE 0.001 - 2 HDFHVIVEDN 0.001 4 FHVIVEDNIS 0.001 3 DFHVIVEDNI 0.001 14 HELFTLHPEP 0.000 21 PEPPRWTKKP 0.000

Table X-V1-HLA-A0201-' 9mers-282P1G3 146 , Each peptide is a portion of SEQ ID NO: 3; each start Table X-V1-HLA-A0201-9mers-282P1 G3 Table X-V1-HLA-A0201-9mers-282P1G3 position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each . peptide is the start position Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position Start Subsequence Score — 1111 LLLLTVCFV 5534.14 plus eight. plus eight 8 Start Subsequence Score Start Subsequence Score 688 VILPLAPFV 330.846 585 lllDGANLT 7.142 - 819 YSGEDYPDT 1.376 1108 LLTLLLLTV 271.948 335 ATHDFHVIV 6.171 280 AEGLPTPQV 1.352 9 GLIVYLMFL 270.234 680 RVQGKKTTV 6.086 1099 FIGLMCAIA 1.288 17 LLLKFSKA! 249.365 780 TVTNHTLRV 6.086 185 KGDLYFANV 1.208 118 AMSEEIEFI 191.488 333 GTATHDFHV 5.603 374 PQPTIKWRV 1.164 1101 GLMCAIALL 181.794 785 TLRVMTPAV 5.286 991 KPSWHLSNL 1.123 4 ι LLLGRGLIV 179.368 1092 DISTQGWFI 4.438 988 TPSKPSWHL 1.046 16 FLLLKFSKA 160.655 275 LLECFAEGL 4.328 272 EILLLECFA 1.043 426 ILANANSDV 118.238 1106 IALLTLLLL 4.292 846 WSTVPKDRV 1.023 923 YIFQTPEGV 79.757 14 LMFLLLKFS 4.282 753 SMEQNGPGL 0.987 406 NLQPNHTAV 69.552 458 FLHCEFFAS 3.778 203 CCFAAFPRL 0.980 10 LIVYLMFLL 66.613 619 ITQVTVLDV 3.777 586 IIDGANLTI 0.975 1107 ALLTLLLLT 63.417 174 IEQDERVYM 3.703 1066 KNWGDNDSl 0.969 840 TLVKVTWST 55.890 1033 KGIGKISGV 3.655 252 KLLLPPTES 0.965 1027 TLGEGSKG1 42.774 274 LLLECFAEG 3.651 743 EMIIKWEPL 0.964 930 GVPEQPTFL 42.151 774 VEWEEETVT 3.437 318 YQDKGNYRC 0.927 47 FPFDEYFQ1 41.346 603 GIYCCSAHT 3.279 746 IKWEPLKSM 0.918 166 WMNIELEH1 i 39.062 214 IVQKMPMKL 3.178 534 RVSPKNPR! 0.913 | 836 VINSTLVKV 37.393 1105 AIALLTLLL 2.937 596 NVTLEDQGI 0.913 125 F1VPSVPKL 31.077 584 RIIIDGANL 2.937 1100 IGLMCAIAL 0.877 591 NLTISNVTL 21.362 268 ILKGEILLL 2.923 210 RLRTIVQKM 0.868 11 IVYLMFLLL 4.9.320 13 YLMFLLLKF 2.917 736 VQASQPKEM 0.856 544 KLHMLELHC 17.388 942 KVDKDTATL 2.617 370 AEGEPQPTl 0.832 1166 SLNRDMQPT 17.140 1053 FEPGAEHIV 2.551 1214 GSSTATFPL 0.809 23 KAIEIPSSV 13.862 980 ELNDINITT 2.291 427 LANANIDW 0.759 103 FQGKYRCFA 12.744 939 KVIKVDKDT 2.282 267 TILKGEILL 10.868 429 NANIDWDV 2.222 Table X-V2-HLA-A201-9mers- 1042 NLTQKTHPI 10.433 589 GANLTISNV 2.222 451 TWGYSAFL 10.281 611 TALDSAAD! 2.198 Each peptide is a portion of SEQ ID NO: 5; each start position Is specified, the length 1001 ATTKYKFYL 9.465 976 YElGELNDt 2.146 967 LQYQIINDT 9.453 444 KDGENYATV 2.079 of peptide is 9 amino acids, and the end position for each oeDtide is the start position 1102 LMCAIALLT 9.149 863 INWWKTKSL 1.968 787 RVMTPAVYA 8.846 950 LSWGLPKKL L968 plus eight 1073 SIFQDVIET 8.720 83 IIPSNNSGT 1.742 Start Subsequence Score 908 VLAYNSKGA 8.446 26 EIPSSVQQV 1,650 1 FIVPSVPKF 2.000 ‘471 VSWQKVEEV 7.220 1 916 | AGP’eSEPYI 1.536 3 VPSVPKFPK 0.250 598 TLEDQGIYC 7.170 970 QIINDTYEI pL435~ 5 I- SVPKFPKEK 0.020 147 /

Table X-V2-HLA-A201-9mers-1 (SET 1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start) Subsequence Score 4 PSVPKFPKE 0.003 2 IVPSVPKFP 0.001 6 VPKFPKEKI 0.000 9 FPKEKIDPL 0.000 7 PKFPKEKID 0.000 8 KFPKEKIDP 0.000

Table X-V2-HLA-A201-9mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 1 GDLPKGREA 0.005 9 AKENYGKTL 0.002 2 DLPKGREAK 0.001 7 | REAKENYGK 0.000 5 &amp;#943; KGREAKENY 0.000 8 EAKENYGKT 0.000 3 LPKGREAKE 0.000 L 6 GREAKENYG 0.000 I 4 PKGREAKEN 0.000

Table X-V2-HLA-A201-9mers-(SET 3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start . position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Start Subsequence Score 3 STLGEGKYA 1.404 4 TLGEGKYAG 0.306 5 LGEGKYAGL 0.023 9 KYAGLYDD! 10.004

Table X-V2-HLA-A201-9mers-(SET 3)-282P1 G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 6 GEGKYAGLY| 0.000 8 GKYAGLYDD 0.000 2 SSTLGEGKY 0.000 1 ESSTLGEGK 0.000 7 EGKYAGLYD 0.000

Table X-V3-HLA-A201-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 7; each start . position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 31 FICSKEQEL 13.51 2 5 VDVINTTYV 0.903 | 39 LSYRNRNML 0.759) I 44 RNMLAEDFI 0.679) I 53 QKSTSCNYV 0.531 24 GSPQPSIFI 0.375 I 46 MLAEDF1QK 0.197 ! θ INTTYVSNT | 0.190 25 SPQPSIFIC j 0.177 ).58 CNYVEKSST 0.156 22 ATGSPQPSI 0.145 9 NTTYVSNTT 0.104 15 NTTYVSNAT 0.104 45 NMLAEDFIQ 0.095 14 SNTTYVSNA 0.075 38 | ELSYRNRNM 0.075 48 AEDFIQKST 0.058 11 TYVSNTTYV 0.053 51 FIQKSTSCN 0.047 7 V1NTTYVSN 0.026 35 KEQELSYRN 0.021 I 2 iHGVDVINT 0.020 1-i

Table X-V3-HLA-A201-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 3 HGVDVINTT 0.016 12 YVSNTTYVS 0.012 62 EKSSTFFKI 0.012 60 YVEKSSTFF 0.011 29 SIFICSKEQ 0.008 1 VIHGVDVIN 0.007 37 QELSYRNRN 0.005 47 LAEDFIQKS 0.004 10 TTYVSNTTY 0.003 16 - TTYVSNATG 0.003 4 GVDVINTTY 0.003 13 VSNTTYVSN 0.001 21 NATGSPQPS| 0.001 27 QRSIFICSK 0.001 18 YVSNATGSP 0.001 61 VEKSSTFFK 0.001 56 TSCNYVEKS 0.001] 57 SCNYVEKSS 0.000 52 IQKSTSCNY 0.000 32 ICSKEQELS 0.000 I 26 PQPSIFICS 0.000 [ 55 STSCNYVEK 0.000 50 DFIQKSTSC 0.000 6 DVINTTYVS 0.000 23 TGSPQPSIF 0.000 19 VSNATGSPQ 0.000 54 KSTSCNYVE o.ooo] 20 SNATGSPQP 0.000 33 CSKEQELSY o.QOO ( 40 SYRNRNMLA &amp;#943; 0.000 59 NYVEKSSTF | o.ooo 49 EDFIQKSTS 0.000 41 YRNRNMLAE 0.000 42 . RNRNMLAED | o.ooo 34 SKEQELSYR [ 0.000 17 TYVSNATGS 0.000 30 IFICSKEQE 0.000 148

Table X-V3-HLA-A201- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 43 NRNMLAEDF 0.000 36 EQELSYRNR 0.000 28 PSIFICSKE 0.000

Table X-V4-HLA-A0201-9mers-282P1 G3 Each peptide is a portion of , SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 8 DLPEQPTFL 36.12 9 1 VTLYSGEDL 0.914 6 GEDLPEQPT 0.058 2 TLYSGEDLP 0.023 4 YSGEDLPEQ 0.004 9 LPEQPTFLK 0.000 7 EDLPEQPTF 0.000 5 SGEDLPEQP 0.000 3 LYSGEDLPE 0.000

Table X-V5-HLA-A0201-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 3 KLTVNSSNSj 0.261 4 LTVNSSNSI ) 0.246 2 MKLTVNSSN) 0.001 5 TVNSSNSIK) 0.001 7 NSSNSIKQR 0.000 6 VNSSNSIKQ 0.000

Table X-V5-HLA-A0201- 9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight Start Subsequence Score 8 SSNSIKQRK 0.000 1 PMKLTVNSS 0.000 9 SNSIKGRKP 0.000

Table X-V6-HLA-A0201-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 5 FIVPKLEHI 7.437 2 EIEFIVPKL 0.032 9 KLEH1EQDE 0.003 3 IEFIVPKLE 0.002 6 IVPKLEH1E 0.001 1 EEIEFIVPK 0.001 8 PKLEHIEQD 0.000 7 1 VPKLEHIEQ 0.000 4 1 EFiVPKLEH 0.000 . Table X-V7-HLA-A0201- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 10 NISHELFTL 39.184 7 VEDNISHEL 0.282 17 TLHPEPPRW 0.075 5 VIVEDNISH 0.071 18 LHPEPPRWT 0.040 .9 DNISHELFT 0.020 3 FHVIVEDNI 0.016

Table X-V7-HLA-AQ201-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 11 ISHELFTLH 0.006 14 ELFTLHPEP 0.004 16 FTLHPEPPR 0.004 6 IVEDNISHE 0.001 4 HVIVEDNIS 0.000 13 ) I. ( HELFTLHPE 0.000 20 PEPPRWTKK 0.000 15 LFTLHPEPP 0.000 1 HDFHVIVED 0.000 2 DFHVIVEDN 0.000 8 EDNISHELF 0.000 12 SHELFTLHP 0.000 | 19 HPEPPRWTK 0.000

Table XI-V1-HLA-A0201-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score | 1110 TLLLLTVCFV 3255.38 1 274 LLLECFAEGL 1025.80 4 16 I FLLLKFSKAI 674.752) 1107 ALLTLLLLTV j 591.388 118 AMSEEIEFIV 489.752 5 LLGRGLIVYL 459.398 9 GLIVYLMFLL 284.974 1189 GLFSEDGSFI 212.307 840 TLVKVTWSTV 118.238 132 KLPKEKIDPL 84.264 158 GLPPLHIYWM 62.845 1102 LMCAIALLTL 60.325 426 ILANANIDW 54.634 149 ' Table XI-V1-HLA-A0201- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence) Score 957 KLNGNLTGYL 53.459 396 WFPREiSFT 51.883 ) 897 SLDAFSEFHL 49.561 221 KLTVNSLKHA 39.992 150 VLPCNPPKGL 36.316 425 TILANANIDV 35,385 687 TVILPLAPFV 33.472 966 LLQYQIINDT 29.137 1101 GLMCAIALLJ 27.572 267 TILKGEILLL 24.997 949 TLSWGLPKKL 21.362 792 AVYAPYDVK V 19.475 413 AVYQGEASN V 19.475 114 KLGIAMSEEI 17.892 13 YLMFLLLKFS 16.044 765 VTWKPQGAP v 13.630 1099 FiGLMCAIAL 13.512 j 470 WSWQKVEE V 11.660 585 IIIDGANLTI »3.999 597 VTLEDQGIYC 9.787 ] 693 APFVRYQFR V 9.743 36 TIIKQSKVQV &amp;#906;&amp;#912;δκΓ1 10 LIVYLMFLLL 9.488 1000 NATTKYKFYL 9.465 524 NLDIRNATKL 8.545 456 SAFLHCEFFA 8.144 1108 LLTLLLLTVC 7.964 341 VIVEEPPRWT &amp;#910;δδΠ 752 - - KSMEQNGPG L 7.404 859 KGYQINWWK T 6.947 541 RIPKLHMLEL 5.756 1105 AiALLTLLLL 6.756

Table XI-V1-HLA-AQ201-10mers-282P1G3 Each peptide is a portion of SEQ ID NO; 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 8 RGLIVYLMFL 6.527 | 117 IAMSEEIEFI 5.649 25 IEIPSSVQQV 5.288 969 YQIINDTYEI 4.866 441 IQTKDGENYA 4.710 742 KEMIIKWEPL 4.481 332 LGTATHDFHV 4.477 615 SAADITQVTV 3.961 141 LEVEEGDPIV 3.865 480 KPLEGRRYHI 3.616 598 TLEDQGIYCC 2.998 1034 GIGK1SGVNL 2.937 213 TIVQKMPMKL 2.937 862 QINWWKTKS L 2.937 356 AVYSTGSNGI 2.921 839 STLVKVTWST 2.872 953 GLPKKLNGNL 2.777 214 IVQKMPMKLT 2.550 461 CEFFASPEAV 2.452 833 GVDVINSTLV 2.434 3 PLLLGRGLIV 2.321 512 VENAIGKTAV 2.299 565 KLSWSKDGE A 2.260 1181 VEYGEGDHG L 2.260 987 TTPSKPSWH L 2225 603 GIYCCSAHTA 2.186 61 GNPEPTFSW T 2.084 795 APYDVKVQAI 2.055 1100 IGLMCAIALL 2.017 218 MPMKLTVNS L 2.017 863 INWWKTKSLL 1.968 635 HLSERQNRS V 1.939

Table X1-V1-HLA-A0201-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius nine. Start Subsequence Score 1172 QPTESADSLV 1.861. 1171 MQPTESADS L 1.804 1008 YLRACTSQG C 1.737 405 TNLQPNHTA V 1.680 618 DITQVTVLDV 1.650 836 VINSTLVKVT 1.643 1043 LTQKTHPIEV 1.642 450 ATWGYSAFL 1.632 907 TVLAYNSKGA 1.608 681 VQGKKTTVIL 1.510 334 TATHDFHVi'v 1.505 1106 IALLTLLLLT 1.497 206 AAFPRLRTIV 1.465 452 WGYSAFLH C 1.404 378 IKWRVNGSP V 1.363 181 YMSQKGDLY F 1.362 202 YCCFAAFPRL 1.219 171 LEH1EQDE.RV 1.12? 1113 LLTVCFVKRN 1.107 835 DV1NSTLVKV 1.050 934 QPTFLKVIKV 1.044 428 ANAN1DWDV 1.044 82 RIIPSNNSGT 1.025

Table XI-V2-HLA-A0201-10mers-(SET 1)-282P1G3 Each peptide is a portion of I SEQ ID NO: 5; each start position is specified, the length of peptide is 10 aminoj acids, and the end position j for each peptide Is the start position plus nine. | Start Subsequence Score| ' 6 SVPKFPKEKI 0.4471 150

Table X1-V2-HLA-A0201-10mers-(SET 1)-282P1G3 I t Table X1-V2-HLA-A0201 -10mers-(SET 3)-282P1G3 Table XI-V3-HLA-A0201-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start | Subsequence Score Start Subsequence Score Start Subsequence Score 9 KFPKEK1DPL 0.059 79 52 FIQKSTSCNY 0.047 2 FIVPSVPKFP 0.052 3 SSTLGEGKYA 0.178 48 LAEDFIQKST 0.046 3 IVPSVPKFPK 0.013 9 GKYAGLYDDI 0.034 13 YVSNTTYVSN 0.045 4 VPSVPKFPKE 0.000 4 STLGEGKYAG 0.004 31 IFICSKEQEL 0.025 10 FPKEKIDPLE 0.000 7 GEGKYAGLYD 0.002 32 FICSKEQELS 0.023 1 EFIVPSVPKF 0.000 1 EESSTLGEGK 0.000 3 IHGVDVINTT 0.020 5 PSVPKFPKEK 0.000 10 KYAGLYDDIS 0.000 61 YVEKSSTFFK 0.012 7 VPKFPKEKID 0.000 6 LGEGKYAGLY 0.000 19 YVSNATGSPQ 0.006 8 PKFPKEKIDP j 0.000 2 ESSTLGEGKY 0.0001 44 NRNMLAEDFl 0.004 8 EGKYAGLYDD 0.000 30 SIFICSKEQE 0.004 : Table XI-V2-HLA-A0201- 17 TTYVSNATGS 0.003 10mers-(SET 2)-282P1 G3 Tahle XI-V8-HI Α-ΑΠ2Π1- I 50 EDFIQKSTSC 0.002 Each peptide is a portion of 10mers-282P1G3 I 59 CNYVEKSSTF 0.002 V, uw V» l uiui I position is specified, the length rxrtrthrlrt tf* «&amp;#943; »-»ζ·»»4&amp;#943;&lt;·μ·» «-it i l_CJOI 1 U&amp;amp;^UUt SO a JJUI tiut » Ul I SEQ ID NO: 7; each start position is specified, the length 36 KEQELSYRNR 0.001 of peptide is 10 amino acids, and the end position for each peptide is the start position 56 STSCNYVEKS 0.001 of peptide is 10 amino acids, and the end position for each peptide is the start position 10 NTTYVSNTTY 0.001 plus nine. 16 NTTYVSNATG 0.001 Start Subsequence Score plus nine. 26 SPQPSIFICS 0.001 4 TLGEGKYAGL 131.37 Start Subsequence Score 45 RNMLAEDFIQ 0.001 y 11 TTYVSNTTYV 17.002 33 ICSKEQELSY 0.001 2 SSTLGEGKYA . 0.178 5 GVDVINTTYV 13.389 7 DVINTTYVSN 0.001 8 GKYAGLYDDI — U.Uo4 47 MLAEDFIQKS 4.540 49 AEDFIQKSTS 10.001 3 STLGEGKYAG 0.004 8 VINTTYVSNT 4.006 55 KSTSCNYVEK 0.001 b GEGKYAGLYD 0.002 2 VIHGVDVINT 4.006 57 TSCNYVEKSS 0.00Q 5 LGEGKYAGLY 0.000 53 IQKSTSCNYV 2.308 21 SNATGSPQPS 0.000 1 ESSTLGEGKY 0.000 39 ELSYRNRNML 1.602 23 ATGSPQPSIF | o.ooo 7 EGKYAGLYDD 0.000 24 TGSPQPSIFl 0.375 27 PQPSIFICSK . | o.ooo 25 GSPQPSIFIC 0.177 60 NYVEKSSTFF 0.000 I aDie AI-VZ-rlLA-AUZUl-10mers-(SET 3T282P1G3 40 LSYRNRNMLA 0.176 34 CSKEQELSYR 0.000 22 NATGSPQPSI 0.145 VSNATGSPQP 0.000 Each Deotide is a Dortion of 20 SEQ ID NO: 5; each start 62 VEKSSTFFK! 0.133 28 QPSIFICSKE 0.000 position is specified, the length of peptide is 10 amino acids, and the end position for each 14 VSNTTYVSNA 0.127 6 VDVINTTYVS 0.000 9 INTTYVSNTT 0.083 4 HGVDVINTTY 0.000 peptide is the start position 46 NMLAEDFIQK 0.076 1 PVIHGVDVIN 0.000 pius nine. 38 QELSYRNRNM 0.071 37 EQELSYRNRN 0.000 Start bUDsequence bcore 15 SNTTYVSNAT 0.049 42 YRNRNMLAED 0.000 5 TLGEGKYAGL 131.3 58 SCNYVEKSST 0.049 43 RNRNMLAEDF 0.000 151 &lt; Table XI-V3-HLA-A0201- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 54 QKSTSCNYVE 0.000 35 SKEQELSYRN 0.000 12 TYVSNTTYVS 0.000 51 DFIQKSTSCN 0.000 29 PSIFICSKEQ 0.000 41 SYRNRNMLAE 0.000 18 11-1 TYVSNATGSP 0.000 j

Table XI-V4-HLA 10mers-282P1GS Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence j Score 1 SVTLYSGEDL) 0.916 10 LPEQPTFLKV! 0.094 | 3 TLYSGEDLPE 0.048 | _ EDLPEQPTFL 0.045 [9 DLPEQPTFLK 0.027 6 SGEDLPEQPT -0.013 5 YSGEDLPEQP 0.001 2 VTLYSGEDLP 0.001 7 GEDLPEQPTF 0.001 4 LYSGEDLPEQ 0.000

Table Xl-V5-HLA 10mers-l 282P1G3 | Each peptide is a portion of I SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end posiiion for each peptide is the start position plus nine. ) Start] Subsequence | Score | 4 KLTVNSSNSI 36.515 ] 1 MPMKLTVNSS 0.007 |

Table XI-V5-HLA 10mers-] 282P1G3 j Each peptide is a portion of I SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. j Start Subsequence Score | 6 TVNSSNSIKQ 0.001 | 3 MKLTVNSSNS 0.001 | '7 VNSSNSIKQR 0.000 5 LTVNSSNSIK 0.000 .10 SNSIKQRKPK 0.000 8 NSSNSIKQRK 0.000 2 PMKLTVNSSN 0.000 9 SSNSIKQRKP o.ooo I

Table XI-V6-HLA I 10mers-282P1G3 j Each peptide is a portion of j SEQ ID NO: 13; each start position is specified, the length j of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. | Start Subsequence Score | 2 EEIEFIVPKL 0.294 I Li IEFIVPKLEH 0.009 6 FIVPKLEHIE 0.004 7 IVPKLEHIEQ 0.002 10 KLEHIEQDER 0.002 5 EFIVPKLEHI 0.001 1 SEEIEFIVPK 0.000 3 ElEFiVPKLE 0.000 9 PKLEHIEQDE 0.000 8 VPKLEHIEQD 0.000

Table XI-V7-HLA 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end posiiion for each peptide is the start position plus nine. Start Subsequence | Score 18 TLHPEPPRWT | 8.197

Table XI-V7-HLA 10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 7 IVEDNISHEL 0.834 10 DNISHELFTL 0.140 6 VIVEDNISHE 0.033 11 NISHELFTLH 0.019 17 FTLHPEPPRW 0.018 9 EDNISHELFT 0.004 12 ISHELFTLHP 0.003 15 ELFTLHPEPP 0.002 19 LHPEPPRWTK 0.001 8 VEDNISHELF 0.000 3 DFHVIVEDNI 0.000 5 HVIVEDNISH 0.000 4 FHVIVEDNIS 0.000 14 HELFTLHPEP 0.000 16 LFTLHPEPPR 0.000 2 HDFHVIVEDN 0.000 1 THDFHVIVED 0.000 21 PEPPRWTKKP 0.000 13 SHELFTLHPE 0.000 20 [HPEPPRWTKK 0.000

Table X!l-V1-HLA-A3-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score (760 GLEYRVTWK 180.000 |1112 LLLTVCFVK 135.000 | 961 NLTGYLLQY 54.000 I 937 FLKVIKVDK 30.000 | 949 TLSWGLPKK 30.000 I 871 LLDGRTHPK 30.000 I 957 KLNGNLTGY 27.000 9 GLIVYLMFL 24.300 152 .Table XII-V1 -HLA-A3-9mers- 282P1G3

Each pepiide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start] Subsequence Score 893 GMVPSLDAF 20.250 524 NLDIRNATK 20.000 547 MLELHCESK 20.000 792 AVYAPYDVK 15.000 5 LLGRGLIVY 12.000 1113 LLTVCFVKR 12.000 689 ILPLAPFVR 12.000 998 NLNATTKYK 10.000 744 MIIKWEPLK, 91000 1189 GLFSEDGSF 9.000 13 YLMFLLLKF 9.000 948 ATLSWGLPK 9.000 843 KVTWSTVPK 6.000 296 DLPKGRETK 6.000 213 TIVQKMPMK 4.500 149 IVLPCNPPK 4.500 661 YIVEFEGNK 4.050 1101 GLMCAIALL 4.050 181 YMSQKGDLY 4.000 310 TLKIENVSY 4.000 396 WFPREISF 3.000 1110 TLLLLTVCF | 3.000 530 ATKLRVSPK 3.000 268 ILKGEILLL 2.700 [677 ELTRVQGKK 2.700 331 FLGTATHDF 2.000 11 IVYLMFLLL 1.800 275 LLECFAEGL 1.800 857 RLKGYQINW 1.800 739 SQPKEMIIK 1.800 44 QVAFPFDEY 1.800 835 DVINSTLVK 1.800 31 VQQVPTIIK 1.800 158 glpplhiyw 1.800 1197 figayagsk 1.800 1002 TTKYKFYLR 1.800 906 LTVLAYNSK 1.500

Table XII-V1-HLA-A3-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of pepiide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 1199 GAYAGSKEK 1.500 859 KGYQINWWK 1.350 ) 118 AMSEEIEFI 1.350 17 LLLKFSKAI 1.350 436 | DVRPLIQTK 1.350 657 NtSEYIVEF 1.350 861 YQINWWKTKj 1.350 221. KLTVNSLKH 1.200 544 KLHMLELHC 1.200 129 SVPKLPKEK 1.000 166 WMNIELEHI 0.900' 931 VPEQPTFLK 6.900 4 LLLGRGLIV 0.900 1111 LLLLTVCFV 0.900 1150 GEYSDSDEK 0.900 867 KTKSLLDGR 0.900 282 GLPTPQVDW 0.900 210 RLRTIVQKM 0.900 242 KANSIKQRK 0.900 16 FLLLKFSKA j 0.900 1094 ] STQGWFIGL ! j 0.810 840 TLVKVTWST ___———.. j 0.675 687 TVILPLAPF ] 0.675 520 AVTANLDIR 0.600 163 HIYWMNIEL 0.600 591 NLTISNVTL 0.600 983 DINITTPSK 0.600 j 1108 LLTLLLLTV 0.600 j 1042 NLTQKTHPI 0.600 127 VPSVPKLPK 0.600 897 SLDAFSEFH 0.600 1118 FVKRNRGGK 0.600 74 NPFYFTDHR 0.600 340 HVIVEEPPR 0.600 536 SPKNPRIPK 0.600 i 753 SMEQNGPGL 0.600 j 882 NILRFSGQR 0.540 }

Table Xll-V1-HLA-A3-9mers-_282P1G3

Each peptide is a portion of SEQ ID WO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each 'peptide is the start position plus eight,

Start Subsequence j Score 392 FAGDWFPR | 0.540 562 HSLKLSWSK 0.450 284 PTPQVDWNK 0.450 853 RVHGRLKGY 0.450 45 VAFPFDEYF 0.450 1027 TLGEGSKGI 0.450 1088 GLYDDISTQ 0.450 1107 ALLTLLLLT 0.450 125 F1VPSVPKL 0.405 10 LIVYLMFLL 0.405 451 TWGYSAFL 0.405 343 VEEPPRWTK 0.405 702 VIAVNEVGR 0.400 426 1LANAN1DV 0.400 598 TLEDQGIYC 0.400 161 PLHIYWMNi 0.360 99 HISHFQGKY 0.360 458 FLHCEFFAS 0.360 |

Table XII-V2-HLA-A3-9mers- ( 3ET1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each ' peptide is the start position plus eight Start Subsequence Score 5 SVPKFPKEK 3.000 1 FIVPSVPKF 1.350 3 VPSVPKFPK 0.900 9 FPKEK1DPL 0.013 6 VPKFPKEKI 0.009 2 IVPSVPKFP 0.002 8 KFPKEKIDP 0.000 4 PSVPKFPKE 0.000 7 PKFPKEKID 0.000 153 "Table Xil-V2-HLA-A3-9mers-(SET 2)-282P1G3 Table Xl!-V3-A3-9mers-282P1G3 Table XII-V3-A3-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5: each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start | Subsequence Score Start Subsequence Score Start Subsequence Score | 2 DLPKGREAK 6.000 00 58 CNYVEKSST 0.0011 7 REAKENYGK 0.180 4 GVDVINTTY 1.800 54 KSTSCNYVE 0.001 5 KGREAKENY 0.018 10 TTYVSNTTY 1.000 35 KEQELSYRN 0.001 9 AKENYGKTL 0.001 55 STSCNYVEK 1.000} 21 NATGSPQPS 0.001 3 LPKGREAKE 0.000 27 QPSIFICSK 0.9001. t 18 YVSNATGSP 0.001 1 GDLPKGREA 0.000 60 YVEKSSTFF 0.200 2 IHGVDVINT 0.001 8 EAKENYGKT 0.000 61 VEKSSTFFK 0.180 32 ICSKEQELS 0.000 6 GREAKENYG 0.000 52 IQKSTSCNY 0.120 40 SYRNRNMLA ] 0.000 4 PKGREAKEN 0.000 i 45 NMLAEDFIQ 0.090 3 HGVDViNTT | 0.000 33 CSKEQELSY 0.060 5 VDVINTTYV 0.000 Table XI1-V2-HLA-A3-9mers-(SET 3)-282P1G3 31 FICSKEQEL 0.060 11 TYVSNTTYV 0.000 22 ATGSPQPSI 0.045 57 SCNYVEKSS 0.000 Each peptide is a portion of ιγ&amp;#940; r.___u —i t ocu iu nu. o, eaun stall position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. 24 GSPQPSIFI 0.027 37 QELSYRNRN 0.000 39 LSYRNRNML 0.015 48 AEDFIQKST 0.000 25 SPQPSIFIC 0.013 53 QKSTSCNYV 0.000 12 YVSNTTYVS 0.012 19 VSNATGSPQ 0.000 15 NTTYVSNAT 0.007 13 VSNTTYVSN 0.000 Start Subsequence] Score 9 | NTTYVSNTT 0.007 j 50 DFIQKSTSC 0.000 4 TLGEGKYAG] 0.090 34 SKEQELSYR 0.006 | 42 RNRNMLAED 0.000 6 GEGKYAGLY 0.032 38 ELSYRNRNM 0.006 j 17 TYVSNATGS 0.000 1 ESSTLGEGK 0.030 6 DViNTTYVS 0.005 I 41 YRNRNMLAE 0.000 3 STLGEGKYA 0.011 29 SIFICSKEQ 0.005 I 49 1 EDFIQKSTS 0.000 2 SSTLGEGKY 0.006 16 TTYVSNATG 0.005 1 20 SNATGSPQP 0.000 9 KYAGLYDDI 0.003 59 NYVEKSSTF 0.005 1 30 IFICSKEQE 0.000 8 GKYAGLYDD 0.001 VIHGVDVIN 0.005 28 | PSIFICSKE 0.000 5 LGEGKYAGL 0.001 14 SNTTYVSNA 0.004 7 EGKYAGLYD 0.000 36 EQELSYRNR 0.004 Table XII-V4-HLA-A3-9mers-282P1 G3 23 TGSPQPSIF 0.003 Table X!l-V3-A3-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. 43 NRNMLAEDF 0.002 51 FIQKSTSCN 0.002 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. 7 VINTTYVSN 0.002 44 RNMLAEDFi 0.002 8 INTTYVSNT 0.002 56 TSCNYVEKS 0.002 Start Subsequence Score 47 laedfiqks 0.002 9 LPEQPTFLK1 0.900 Start Subsequence Score 62 eksstffki 0.002 8 DLPEQPTFL 0.270 46 | MLAEDFiQK 180OJ I 26 Γ PQPSIFICS 0.001 2 TLYSGEDLP 0.100 154 . liable XII-V4-HLA-A3- 9mers-282P1G3 Each peplide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence,1 Score) 1 VTLYSGEDL 0.045 7 EDLPEQPTF 0.001 6 GEDLPEQPT) 0.001 4 YSGEDLPEQ) 0.000 3 LYSGEDLPE) 0.000 5 SGEDLPEQP) 0.000

Table XH-V5-HLA-A3- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 5 TVNSSNSIK 2.000 8 SSNSIKQRK 0.150 3 KLTVNSSNS 0.120 4 LTVNSSNSI 0.045 7 NSSNSIKQR 0.015 1 PMKLTVNSS 0.012 6 VNSSNSIKQ 0.000 ) 2 1 MKLTVNSSN 0.000 ) 9 SNSIKQRKP 0.000

Table XII-V6-HLA-A3- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, toe length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start (Subsequence) Score 5 FIVPKLEHI 0.203 1 EEIEFIVPK ) 0.182 9 KLEHIEQDE 0.090 2 I EIEFIVPKL 0.081

Table XII-V6-HLA-A3- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence) Score 6 IVPKLEHIE 0.002 7 VPKLEHIEQ 0.000 4 EFIVPKLEH 0.000 3 IEFIVPKLE I 0.000 j 8 PKLEHIEQD | o.ooo

Table XII-V7-HLA-A3- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start) Subsequence Score 19 HPEPPRWTK 1.350 16 ) FTLHPEPPR 0.450 17 TLHPEPPRW 0.300 10 NISHELFTL 0.270 5 VIVEDNISH 0.090 14 ELFTLHPEP 0.030 20 PEPPRWTKK 0.009 4 HVIVEDNIS 0.006 ) 11 ISHELFTLH 0.005) I θ IVEDNISHE 0.003) 7 VEDNISHEL 0.003 ) 3 FHVIVEDNI 0.001 8 EDNISHELF 0.001 1 HDFHVIVED 0.000 9 DNISHELFT 0.000 13 HELFTLHPE 0.000 12 SHELFTLHP 0.000 2 DFHVIVEDN 0.000 18 LHPEPPRWT 0.000 15 LFTLHPEPP 0.000

Table Xlll-V1-HLA-A3-10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 14 LMFLLLKFSK 300.000 1111 LLLLTVCFVK 135.000 11 IVYLMFLLLK 90.000 187 DLYFANVEEK 90.000 546 HMLELHCES K 45.000 930 GVPEQPTFLK 40.500 870 SLLDGRTHPK 30.000 743 EMHKWEPLK 27:000 | 4 LLLGRGLIVY 27.000 995 HLSNLNATTK 20.000 905 HLTVLAYNSK 20.000 532 KLRVSPKNPR 18.000 1112 LLLTVCFVKR 18.000 689 ILPLAPFVRY 18.000 342 IVEEPPRWTK 13.500 1037 KISGVNLTQK 13.500 9 GLIVYLMFLL 12.150 788 VMTPAVYAP Y 9.000 1189 | GLFSEDGSFl 9.000 312 [KIENVSYQDK 6.000 30 | SVQQVPTIIK 6.000 406 |NLQPNHTAV I Y 6.000 126 | IVPSVPKLPK 6.000 998 [nLNATTKYKF 6.000 1073 I SIFQDVIETR 4.500 274 (lllecfaegl 4.050 158 (GLPPLHIYWM 4.050 633 j NLHLSERQN I R 4.000 181 jYMSQKGDLY I F 4.000 785 (TLRVMTPAVY 4.000 33 QVPTIIKOSK 3.000 219 PMKLTVNSLK 3.000 62 NPEPTFSWT K 2.700 132 KLPKEKIDPL 2.700 155

Table XII!-V1-HLA-A3-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 688 VILPLAPFVR 2.700 212 RTiVQKMPMK 2.250 948 ATLSWGLPK K 2.250.&amp;#943; 509 SCWVENAIG K 2.000 733 NIRVQASQPK 2.000 1102 LMCAIALLTL 1.800 1001 ATTKYKFYLR 1.800. 897 SLDAFSEFHL 1.800 114 KLGIAMSEEI 1.800 1101 GLMCAIALLT 1.350 118 AMSEEIEFIV 1.350 691 PLAPFVRYQF 1.350 16 FLLLKFSKAI 1.350 283 LPTPQVDWN K 1.350 18 LLKFSKAIEl 1.200 170 ELEHlEQDER| 1.200 848 TVPKDRVHG R 1.200 116 GIAMSEEIEF 1.200 947 TATLSWGLPK (-1.200 105 GKYRCFASN K 0.900 967 LQYQIiNDTY 0.900 5 LLGRGUVYL 0.900 488 HIYENGTLQI 0.900 466 SPEAWSWQ K 0.900 598 TLEDQGIYCC 0.900 261 GSESSITILK 0.900 1107 ALLTLLLLTV 0.900 292 KIGGDLPKGR 0.900 1110 TLLLLTVCFV 0.900 309 KTLKIENVSY 0.900 957 KLNGNLTGYL 0.810 43 VQVAFPFDEY 0.810

Table Xlll-V1-HLA-A3-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 471 VSWQKVEEV K 0.750 844 VTWSTVPKD R 0.750 481 | PLEGRRYHIY 0.600 524 NLDIRNATKL 0.600 44 QVAFPFDEYF 0.600 529 NATKLRVSPK 0.600 701 RVIAVNEVGR 0.600 238 EIGSKANSIK 0.600 810 GPDPQSVTL Y 0.540- 10 LIVYLMFLLL 0.540 953 GLPKKLNGNL 0.540 738 ASQPKEMIIK 0.450 857 RLKGYQINW W 0.450 221 KLTVNSLKHA 0.450 123 IEFIVPSVPK 0.450 1088 GLYDDISTQG 0.450 i Iso" jVLPCNPPKGL 0.450 1136 |HPDPElQSVK 0.450 440 LIQTKDGENY 0.400 815 SVTLYSGEDY 0.400 ] 559 HLKHSLKLSW 0.400 j 902 SEFHLTVLAY 0.360 1143 SVKDETFGEY 0.360 886· TTVILPLAPF 0.338 960 GNLTGYLLQY 0.324 148 PIVLPCNPPK | 0.300 1108 LLTLLLLTVC 0.300 356 AVYSTGSNGl 0.300 426 ILANANIDVV 0.300 817 TLYSGEDYPD 0.300 535 VSPKNPRIPK 0.300 69 WTKDGNPFY F 0.300 840 TLVKVTWSTV ] 0.300

Tabie XllI-V1-HLA-A3-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 603 GIYCCSAHTA 0.300 |

Start Subsequence Score 603 GIYCCSAHTA 0.300 Table XH1-V2-HLA-A3-10mers-(SET 1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 3 IVPSVPKFPK 9.000 6 SVPKFPKEKl 0.090 5 PSVPKFPKEK 0.034 2 FIVPSVPKFP 0.003 9 KFPKEKIDPL 0.003 1 EFIVPSVPKF 0.003 4 VPSVPKFPKE 0.001 10 FPKEKIDPLE 0.000 7 VPKFPKEKID 0.000 8 PKFPKEKIDP 0.000 [ Table XIII-V2-HLA-A3- 10mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 4 TLGEGKYAG L 0.900 8 gkyaglyddF 0.009 3 STLGEGKYA G 0.007 5 ' LGEGKYAGL y 0,005 1 ESSTLGEGK Y 0.002 156 (./.Table XIII-V2-HLA-A3- 10mers-(SET2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence | Score 2 SSTLGEGKY A 0.001 6 GEGKYAGLY D 0.000 7 EGKYAGLYD D 0.000

Table XI1I-V2-HLA-A3-1 Omers-(SET3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 5 TLGEGKYAGL 0.900 1 EESSTLGEGK 0.018 9 GKYAGLYDDI 0.009 4 STLGEGKYAG 0.007 6 LGEGKYAGLY 0.005 2 ESSTLGEG.KY 0.002 10 KYAGLYDDIS 0.001 3 SSTLGEGKYA "0.001 7 GEGKYAGLYD 0.000 8 EGKYAGLYDD 0.000

Table X!ll-V3-HLA-A3-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 46 NMLAEDFIQK 180.00 0 61 YVEKSSTFFK 6.000 52 FIQKSTSCNY 0.400

Table XIII-V3-HLA-A3-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 55 KSTSCNYVEK 0.300 47 MLAEDFIQKS 0.270 27 PQPSIFICSK 0.270 10 NTTYVSNTTY 0.200 39 ELSYRNRNML 0.180 23 ATGSPQPStF 0.100 8 VINTTYVSNT ! 0.090 2 VIHGVDVINT 0.090 33 ICSKEQELSY 0.080 5 GVDVINTTYV 0.060 11 TTYVSNTTYV 0.050 34 CSKEQELSYR 0.045 59 CNYVEKSSTF 0.020 56 STSCNYVEKS 0.018 62 VEKSSTFFKI 0.016 25 GSPQPSIFIC 0.013 22 NATGSPQPSI 0.013 30 SIFICSKEQE 0.010 17 TTYVSNATGS 0.010 | 40 LSYRNRNMLA 0.010 4 HGVDViNTTY 0.009 14 VSNTTYVSNA 0.009 53 IQKSTSCNYV 0.006 26 SPQPSIFICS 0.005 36 KEQELSYRNR 0.005 60 NYVEKSSTFF 0.005 ( 32 FICSKEQELS 0.004 43 RNRNMLAEDF 0.004 24 TGSPQPSIFi 0.003 19 YVSNATGSPQ 0.002 13 YVSNTTYVSN 0.002 16 NTTYVSNATG 0.001 58 SCNYVEKSST 0.001 31 IFICSKEQEL 0.001 7 DVINTTYVSN 0.001 48 LAEDFIQKST 0.001 j 44 | NRNMLAEDFl 0.001

Table Xlll-V3-HLA-A3-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 37 EQELSYRNRN 0.001 1 PVIHGVDVIN 0.000 28 QPSIFICSKE 0.000 15 SNTTYVSNAT 0.000 9 INTTYVSNTT 0.000 50 EDFIQKSTSC 0.000 3 IHGVDVINTT 0.000 45 RNMLAEDFIQ 0.000 . 12 TYVSNTTYVS 0.000 6 VDVINTTYVS 0.000 57 TSCNYVEKSS 0.000 49 AEDFIQKSTS 0.000 20 VSNATGSPQP 0.000 38 QELSYRNRNM 0.000 21 SNATGSPQPS 0.000 ( 35 SKEQELSYRN 0.000 54 QKSTSCNYVE 0.000 41 SYRNRNMLAE o.ooo | 42 YRNRNMLAED 0.000 18 TYVSNATGSP 0.000 51 DFIQKSTSCN 0.000 29 PSIFICSKEQ 0.000

Table Xlll-V4-HLA-A3-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 9 DLPEQPTFLK 40.500 3 TLYSGEDLPE 0.200 1 ! iSVTLYSGEDL 0.060 7 GEDLPEQPTF 0.018 10 LPEQPTFLKV 0.012 2 VTLYSGEDLP 0.002 157

Table Xll!-V4-HLA-A3-10mers-282P1G3 Table XIII-V6-HLA-A3-10mers-282P1G3 Table XIV-V1-HLA-A1101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score Start Subsequence Score Start Subsequence Score 8 EDLPEQPTFL 0.000 7 IVPKLEHIEQ 0.004 843 j KVTWSTVPK 6.000 6 SGEDLPEQPT 0.000 3 ElEFIVPKLE '0.000 792 | AVYAPYDVK 4.000 5 YSGEDLPEQP 0.000 5 EFIVPKLEH! 0.000 149 IVLPCNPPK 3.000 4 LYSGEDLPEQ 0.000 8 VPKLEHIEQD 0.000 948 ATLSWGLPK 3.000 9 PKLEHIEQDE 0.000 1118 FVKRNRGGK 2.000 Table X!li-V5-HLA-A3-10mers-1 282P1G3 j 835 DVINSTLVK 1.800 Table Xlll-V7-HLA-A3-10mers-282P1G3 1112 LLLTVCFVK 1.800 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 906 LTVLAYNSK 1.500 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 739 SQPKEMIIK 1.200 760 GLEYRVTWK 1.200 12 VYLMFLLLK 1.200 106 KYRCFASNK 1.200 Start) Subsequence I Score 31 VQQVPT1IK 1.200 4 KLTVNSSNSI 1.800 Start Subsequence | Score 129 SVPKLPKEK 1.000 5 LTVNSSNSIK 1.500. 20 HPEPPRWTKK 0.300 530 ATKLRVSPK 1.000 "&amp;#906;Γ NSSNSIKQRK 0.150 19 LHPEPPRWTK 0.135 15 MFLLLKFSK 0.900 10 SNSIKQRKPK 0.020 7 IVEDNISHEL 0.090 188 LYFANVEEK 0.800 7 VNSSNSIKQR 0.006 11 NISHELFTLH 0.060 1199 GAYAGSKEK 0.600 j 6 TVNSSNSIKQ 0.004 5 HVIVEDNISH 0.060 436 DVRPLIQTK 0.600 2 PMKLTVNSSN 0.003 15 ELFTLHPEPP 0.030 340 HVIVEEPPR 0.600 1 MPMKLTVNSS 0.002 18 TLHPEPPRWT 0.022 744 MIIKWEPLK 0.600 3 MKLTVNSSNS 0.000 17 FTLHPEPPRW 0.015 931 VPEQPTFLK 0.600 9 SSNSIKQRKP 0.000 6 VIVEDNISHE 0.007 242 KANSIKQRK 0.600 16 LFTLHPEPPR 0.006 661 YIVEFEGNK 0.600 Table X!ll-V6-HLA-A3-10mers-282P1G3 8 VEDNISHELF 0.006 ] 867 KTKSLLDGR 0.600 10 DNISHELFTL 0.002 213 TIVQKMPMK 0.600 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 12 ISHELFTLHP 0.001 i J 861 YQINWWKTK 0.450 2 HDFHVIVEDN 0.000 ] 127 VPSVPKLPK 0.400 3 DFHVIVEDNI 0.000 I J 536 SPKNPRIPK 0.400 14 HELFTLHPEP 0.000 1 871 LLDGRTHPK 0.400 4 FHVIVEDNIS 0.000 937 FLKVIKVDK 0.400 Start Subsequence Score 9 EDNISHELFT L0.000 547 MLELHCESK 0.400 10 KLEHIEQDER 12.000 1 THDFHVtVED 0.000 524 NLDIRNATK 0.400 1 FsEEIEFtVPK 0.270 13 SHELFTLHPE 0.000 520· AVTANLDIR 0.400 4 IEFIVPKLEH 0.009 21 pepprwtkkp 0.000 1002 TTKYKFYLR 0.400 2 EEIEFIVPKL 0,005 949 TLSWGLPKK 0.400 6 fivpklehie 0.005 1197 FIGAYAGSK 0.400 158 '--Table XIV-V1-HLA-A1101-9mers-282P1G3 Table XIV-V1-HLA-A1101- &amp;#906; 9mers-282P1G3 Table XIV-V2-HLA-A1101-9mers-(SET1)-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start j Subsequence Score Start Subsequence Score Start Subsequence Score 1150 GEYSDSDEK 0.360 510 CWVENAIGK j 0.060 | 1 FIVPSVPKF 0.006 301 RETKENYGK 0.360 680 RVQGKKTTV 0.060 I I 6 VPKFPKEKI 0.002 1029 GEGSKGIGK 0.360 I i I 1 i • [ 764 RVTWKPQGA 0,060 | 9 FPKEKIDPL 0.002 859 KGYQINWWK 0.240 942 | KVDKDTATL 0.060 8 KFPKEKIDP 0.001 689 ILPLAPFVR 0.240 721 ETPPAAPDR 0.060 2 IVPSVPKFP 0.001 34 VPTIIKQSK [ 0.200 534 RVSPKNPR! 0.060 4 PSVPKFPKE 0.000 52 YFQIECEAK 0.200 930 GVPEQPTFL 0.060 7 PKFPKEKID 0.000 934 QPTFLKVIK 0.200 833 GVDVINSTL 0.060 1011 ACTSQGCGK 0.200 313 lENVSYQDK 0.060 Table XIV-V2-HLA-A1101-9mers-(SET 2)-282P1G3 998 NLNATTKYK 0.200 452 WGYSAFLH 0.060 284 PTPQVDWNK 0.200 579 GTEDGRIII 0.060 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL 304 KENYGKTLK 0.180 424 GTILANANI 0.045 787 RVMTPAVYA 0.120 1115 TVCFVKRNR 0.040 983 DINITTPSK 0.120 780 TVTNHTLRV 0.040 262 SESSITILK 0.120 214 IVQKMPMKL 0.040 j 478 EVKPLEGRR 0.120 849 VPKDRVHGR 0.040 Start | Subsequence Score 392 FAGDWFPR 0.120 1074 IFQDVIETR 0.040 7 REAKENYGK 0.360 343 VEEPPRWTK 0.120 9 GLIVYLMFL 0.036 2 DLPKGREAK 0.120 296 DLPKGRETK 0.120 247 KQRKPKLLL 0.036 5 KGREAKENY 0.001 882 NILRFSGQR 0.120 734 IRVQASQPK 0.030 Q u LPKGREAKE 0.000 202 YCCFAAFPR 0.120 220 MKLTVNSLK 0.030 9 AKENYGKTL 0.000 677 ELTRVQGKK vO.120 1124 GGKYSVKEK 0.030 1 GDLPKGREA 0.000 98 GHISHFQGK 0.090 685 KTTVILPLA 0.030 6 GREAKENYG 0.000 333 GTATHDFHV 0.090 687 TVILPLAPF 0.030 8 EAKENYGKT 0.000 212 RTIVQKMPM 0.090 1001 ATTKYKFYL 0.030 4 PKGREAKEN 0.000 779 ETVTNHTLR 0.090 875 RTHPKEVNI 0.030 124 EFIVPSVPK 0.090 Table XIV-V2-HLA-A1101- I 9mers-(SET3)-282P1G3 j 702 VIAVNEVGR 0.080 Table XIV-V2-HLA-A1101-9mers-(SET 1)-282P1G3 74 NPFYFTDHR 0.080 Each peptide is a portion of j SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position . for each peptide is the start I 11 IVYLMFLLL 0.080 Each peptide is a portion-of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL 877 HPKEVNILR 0.080 1113 LLTVCFVKR 0.080 396 WFPREISF 0.080 position plus eight. | 693 APFVRYQFR 0.080 Start Subsequence Scorej 317 SYQDKGNYR 0.080 Start Subsequence Score 9 KYAGLYDDI 0.012} 562 HSLKLSWSK 0.060 5 SVPKFPKEK 1.000 3 STLGEGKYA 0.007 291 NKIGGDLPK 0.060 3 VPSVPKFPK 0.600 1 ESSTLGEGK 0.006 159

Table X1V-V2-HLA-A1101-9mers-(SET 3)-282P1G3 Each peptide is a portion of SEG ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight Start Subsequence Score 6 GEGKYAGLY 0.002 4 TLGEGKYAG 0.001 8 GKYAGLYDD 0.000 5 LGEGKYAGL 0.000 2 SSTLGEGKY 0.000 7 I-J EGKYAGLYD 0.000

Table X!V-V3-A1101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified j the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 55 STSCNYVEK 1.000 46 MLAEDFIQK 0.800 27 QPSIFICSK 0.200| 61 VEKSSTFFK 0.180! 0.060) 4 GVDVINTTY 60 YVEKSSTFF } 0.020 10 TTYVSNTTY 0.020 22 ATGSPQPSI 0.010 40 SYRNRNMLA 0.008 52 IQKSTSCNY 0.006 . 59 NYVEKSSTF 0.006 11 TYVSNTTYV 0.006 12 YVSNTTYVS 0.004 31 FICSKEQEL 0.004 34 SKEQELSYR 0.004 36 EQELSYRNR 0.004 44 RNMLAEDFI 0.002 18 YVSNATGSP 0.002 16 TTYVSNATG 0.002 45 NMLAEDFIQ 0.002 6 DVINTTYVS 0.002 24 GSPQPSIFI 0.001

Table X1V-V3-A1101-9mers-1 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Start Subsequence Score 9 NTTYVSNTT 0.001 15 NTTYVSNAT 0.001 25 SPQPSIFIC 0.001 17 TYVSNATGS 0.001 33 ) CSKEQELSY 0.000 39 LSYRNRNML 0.000 51 FIQKSTSCN 0.000 14 SNTTYVSNA 0.000 7 VINTTYVSN 0.000 1 VIHGVDVIN 0.000 29 SIFICSKEQ 0.000 35 KEQELSYRN 0.000 30 IFICSKEQE 0.000 5 VDViNTTYV 0.000 47 LAEDFIQKS 0.000 43 NRNMLAEDF 0.000 32 ICSKEQELS o.ooo | 23 TGSPQPSIF o.ooo j 53 QKSTSCNYV 0.000 21 NATGSPQPS 0.000 62 EKSSTFFKI 0.000 26 PQPSIFICS 0.000 42 RNRNMLAED 0.000 54 KSTSCNYVE 0.000 38 ELSYRNRNM 0.000 57 SCNYVEKSS 0.000 37 QELSYRNRN 0.000 50 DFIQKSTSC 0.000 58 CNYVEKSST 0.000 20 SNATGSPQP 0.000 2 IHGVDVINT 0.000 8 INTTYVSNT 0.000 41 YRNRNMLAE 0.000 3 HGVDVINTT 0.000 48 AEDFIQKST 0.000 13 VSNTTYVSN 0.000 L 19 VSNATGSPQ 0.000

Table XIV-V3-A1101-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the . length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 56 TSCNYVEKS 0.000 49 EDFIQKSTS 0.000 28 PSIFICSKE 0.000

Table XIV-V4-HLA-A1101-" 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 9 LPEQPTFLK 0.600 1 VTLYSGEDL 0.015 8 DLPEQPTFL 0.001 3 t LYSGEDLPE 0.001 2 TLYSGEDLP 0.001 6 GEDLPEQPT 0.000 7 EDLPEQPTF 0.000 4 YSGEDLPEQ O.OOO 5 SGEDLPEQP | o.ooo

Table XIV-V5-HLA-A1101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 5 TVNSSNSIK 2.000 . 8 SSNSIKQRK 0.020 4 LTVNSSNSI 0.015 7 . NSSNSIKQR 0.002 3 KLTVNSSNS 0.001 6 VNSSNSIKQ 0.000 1 PMKLTVNSS 0.000 160 _ Table XIV-V5-HLA-A1101-9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Start Subsequence Score 2 MKLTVNSSN 0.000 9 SNSIKQRKP 0.000 I Table XIV-V6-HLA-A1101- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. | Start Subsequence Score 1 EEIEFIVPK 0.027 5 FIVPKLEHI 0.006 6 IVPKLEHIE 0.002 4 EFIVPKLEH 0.002 9 KLEHIEQDE 0.001 2 EIEFIVPKL 0.001 | 7 VPKLEHIEQ 0.000 3 IEFIVPKLE 0.000 8 PKLEHIEQD 0.000

Table XIV-V7-HLA-A1101- 9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 19 HPEPPRWTK 0.400 16 FTLHPEPPR 0.300 5 VIVEDNISH 0.012 10 NISHELFTL 0.012 20 PEPPRWTKK 0.006 17 TLHPEPPRW 0.004 4 HVIVEDNIS 0.003 6 IVEDNISHE 0.002

Table XIV-V7-HLA-A1101-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start] Subsequence Score 7 ) VEDNISHEL 0.001 3 FHVIVEDNI 0.000 14 ELFTLHPEP 0.000 11 ISHELFTLH 0.000 15 LFTLHPEPP 0.000 13 HELFTLHPE 0.000 2 DFHVIVEDN 0.000 8 EDNISHELF 0.000 1 HDFHVIVED o.ooo ! 12 SHELFTLHP 0.000 9 DNISHELFT 0.000 18 LHPEPPRWT 0.000

Table XV-V1-HLA-A1101-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 930 GVPEQPTFLK 18.000 11 IVYLMFLLLK 8.000 212 RTIVQKMPMK 4.500 j 342 IVEEPPRWTK 4.000 126 IVPSVPKLPK 4.000 30 SVQQVPTIIK 4.000 14 LMFLLLKFSK 2.400 33 QVPTIiKQSK 2.000 1111 LLLLTVCFVK 1.800 701 RVIAVNEVGR 1.800 948 ATLSWGLPKK 1.500 1037 KISGVNLTQK 1.200 312 KIENVSYQDK 1:200 509 SCWVENAIGK 0.800 1010 RACTSQGCGK 0.600 870 SLLDGRTHPK 0.600

Table XV-V1-HLA-A1101-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence j Score 860 GYQINWWKTK 0.600 546 HMLELHCESK 0.600 1001 ATTKYKFYLR 0.400 995 HLSNLNATTK 0.400 733 NIRVGASOPK 0.400 848 TVPKDRVHGR 0.400 947 TATLSWGLPK 0.400 283 LPTPQVDWNK 0.400 466 SPEAWSWQK 0.400 905 HLTVLAYNSK 0.400 62 NPEPTFSWTK 0.400 688 VILPLAPFVR 0.360 1196 SFIGAYAGSK 0.300 936 TFLKVIKVDK 0.300 1117 CFVKRNRGGK 0.300 51 EYFQIECEAK 0.240 532 KLRVSPKNPR 0.240 187 DLYFANVEEK 0.240 1136 HPDPEIQSVK 0.200 208 FPRLRTIVQK 0.200 529 NATKLRVSPK 0.200 844 VTWSTVPKDR 0.200 933 EQPTFLKVIK 0.180 660 EYIVEFEGNK 0.180 743 EMIIKWEPLK 0.180 1073 SIFQDVIETR 0.160 1121 RNRGGKYSVK 0.120 105 GKYRCFASNK 0.120 561 KHSLKLSWSK 0.120 300 GRETKENYGK 0.120 261 GSESSITILK 0.120 123 IEFIVPSVPK j 0.120 292 KIGGDLPKGR | 0.120 238 EIGSKANSIK 0.120 1112 LLLTVCFVKR 0.120 1057 AEHIVRLMTK 0.120 179 RVYMSQKGDL 0.120 161 , .TableXV-V1-HLA-A1101- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 295 GDLPKGRETK 0.090 451 TWGYSAFLH 0.090 939 KVIKVDKDTA 0.090 290 WNKIGGDLPK 0.080 633 NLHLSERQNR 0.080 201 | DYCCFAAFPR 0.072 523 ANLDIRNATK 0.060 834 VDVINSTLVK 0.060 148 PIVLPCNPPK 0.060 519 TAVTANLDIR 0.060 680 RVQ’GKKTTVI 0.060 552 CESKCDSHLK 0.060 370 AEGEPQPTIK 0.060 381 RVNGSPVDNH 0.060 833 GVDVINSTLV j 0.060 518 KTAVTANLDI 0.060 343 VEEPPRWTKK 0.060 90 GTFRIPNEGH 0.060 675 WEELTRVQGK 0.060 9 GLIVYLMFLL 0.054 309 KTLKIENVSY 0.045 692 LAPFVRYQFR -0.040 99 HISHFQGKYR 0.040 | 535 VSPKNPRiPK 0.040 | 858 LKGYQINWWK 0.040 738 ASQPKEMIIK 0.040 471 VSWQKVEEVK 0.040 356 AVYSTGSNGl 0.040 429 NANIDWDVR 0.040 219 PMKLTVNSLK 0.040 84 IPSNNSGTFR 0.040 792 avyapydvkv 0.040 1028 LGEGSKGIGK 0.040 190 FANVEEKDSR 0.040 726 APDRNPQNIR 0.040 413 avyqceasnv 0.040 639 RQNRSVRLTW ] 0.036

Table XV-V1-HLA-A1101- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position • plus nine. Start Subsequence Score 755 EQNGPGLEYR 0.036 842 VKVTWSTVPK 0.030 435 VDVRPLIQTK 0.030 982 NDINITTPSK 0.030 791 PAVYAPYDVK: 0.030 997 SNLNATTKYK 0.030 1123 RGGKYSVKEK 0.030 340 HVIVEEPPRW 0.030 735 RVQASQPKEM 0.030 499 RTTEEDAGSY 0.030

Table XV-V2-HLA-A1101-10mers-(SET 1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence j Score 3 IVPSVPKFPK 6.000 θ SVPKFPKEKI 0.020 9 KFPKEKIDPL 0.006 5 PSVPKFPKEK] 0.002 1 . EFIVPSVPKF | 0.001 2 FIVPSVPKFP 0,000 10 FPKEKIDPLE 0.000 4 VPSVPKFPKE 0.000 7 VPKFPKEKID 0.000 2J PKFPKEKIDP 0,000

Table XV-V2-HLA-A1101-10mers-(SET2)-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.

Start Subsequence Score 4 TLGEGKYAGL 0.004 3 STLGEGKYAG 0.003 8 GKYAGLYDDl 0.001 6 GEGKYAGLYD 0.000 5 LGEGKYAGLY 0.000 2 SSTLGEGK/A 0.000 1 ESSTLGEGKY 0.000 7 EGKYAGLYDD 0.000

Table XV-V2-HLA-A1101-10mers-(SET 3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino adds, and the end position for each peptide is the start posiiion plus nine. Start. Subsequence Score 1 EESSTLGEGK 0.018 5 TLGEGKYAGL 0.004 4 STLGEGKYAG 0.003 9 GKYAGLYDDl 0.001 10 KYAGLYDDIS 0.001 7 GEGKYAGLYD 0.000 6 LGEGKYAGLY 0.000 3 SSTLGEGKYA 0.000 2 ESSTLGEGKY 0.000 8 EGKYAGLYDD 0.000

Table XV-V3-HLA-A1101-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 61 YVEKSSTFFK 6.000 46 NMLAEDFIQK 1.200 55 KSTSCNYVEK 0.060 27 PQPSIFICSK 0.060 5 GVDVINTTYV 0.060 11' TTYVSNTTYV 0.020 10 NTTYVSNTTY 0.010 23 ATGSPQPSIF 0.010 60 NYVEKSSTFF 0.006 162

TableXV-V3-HLA-A1101-10mers-282PlG3 Table XV-V3-HLA-A1101-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius nine. Each peptide is a portion oi SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score Start j Subsequence Score Start Subsequence | Score 5 LTVNSSNSIK 1.500 53 IQKSTSCNYV 0.006 48 LAEDFIQKST 0.000 8 NSSNSiKQRK 0.020 33 ICSKEQELSY 0.004 51 DFIQKSTSCN 0.000 10 SNSIKQRKPK 0.020 34 CSKEQELSYR 0.004 38 QELSYRNRNM 0.000 4 KLTVNSSNSI 0.012( 52 FIQKSTSCNY 0.004 6 VDVINTTYVS 0.000 6 TVNSSNSIKQ 0.004( 36 KEQELSYRNR 0.004 49 AEDFIQKSTS 0.000 1 7 VNSSNSIKQR 0.004( 31 IFICSKEQEL 0.003 54 QKSTSCNYVE o.ooo 1 1 MPMKLTVNSS o.ooo) 22 NATGSPQPSI 0.002 9 | INTTYVSNTT 0.000 2 PMKLTVNSSN 0.000 17 TTYVSNATGS 0.002 21 j SNATGSPQPS 0.000 3 MKLTVNSSNS 0.000 19 YVSNATGSPQ 0.002 35 SKEQELSYRN 0.000 9 SSNSIKQRKP 0.000 13 YVSNTTYVSN 0.002 15 SNTTYVSNAT 0.000 f 62 VEKSSTFFK! 0.002 20 VSNATGSPQP 0.000 i Table XV-V6-HLA-A1101- 12 TYVSNTTYVS 0.001 3 iwm/nvtMTT n nnn &amp;#938; iuners-zozr ιυο . 43' RNRNMLAEDF 0.001 42 [YRNRNMLAED 0.000 cacn pepiiae is a puiuon ui SEQ ID NO: 13; each start •nn ELSYRNRNML 0.001 ςη ! EDFIQKSTSC 0.000 position is specified, the 56 STSCNYVEKS 0.001 I 57 TSCNYVEKSS 0.000 length of peptide is 10 amino acids, and the end position for each peptide is the start 16 NTTYVSNATG 0.001 ' 29 j PSIFICSKEQ 0.000 7 DVINTTYVSN 0.001 position pius nine. 30 SIFICSKEQE 0.001 Table XV-V4-HLA-A1101- Start Subsequence Score 41 SYRNRNMLAE 0.001 Wmers-282P1G3 10 KLEHIEQDER 0.240 0 VIHGVDVINT 0.001 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the lengt SEEIEFIVPK 0.060 I 59 CNYVEKSSTF 0.001 1 7 IVPKLEHIEQ 0.004 j 40 LSYRNRNMLA 0.001 of peptide is 10 amino acids, 4 IEFIVPKLEH 0.002 45 RNMLAEDFIQ 0.001 anu uie enu pusiuun kji eauu DeDtide is the start position 5 EFIVPKLEHI 0.001 18 TYVSNATGSP 0.001 plus nine. 6 FIVPKLEHiE 0.001 47 MLAEDFIQKS 0.000 Start Subsequence Score 2 EEiEFIVPKL 0.000 24 TGSPQPSIFl 0.000 9 DLPEQPTFLK 0.360 8 VPKLEHIEQD 0.000 8 VINTTYVSNT 0.000 1 SVTLYSGEDL 0.020 3 EiEFiVPKLE 0.000 32 FICSKEQELS 0.000 10 ! LPEQPTFLKV 0.004 9 ( PKLEHiEQDEj 0.000 26 SPQPSIHCS 0.000 7 GEDLPEQPTF 0.002 4 HGVDVINTTY 0.000 3 TLYSGEDLPE 0.002 Table XV-V7-HLA-A1101- 1 PVIHGVDVIN 0.000 2 VTLYSGEDLP f) ΡΠ9 I Ul net b-’COZ.t iQu 1 Each peptide is a portion of SEQ ID NO: 15; each start 44 NRNMLAEDFl 0.000 4 LYSGEDLPEQ 0.000 [ 28 QPSIFICSKE 0.000 8 EDLPEQPTFL 0.000 position is specified, the length 58 SCNYVEKSST 0.000 6 SGEDLPEQPT 0.000 of peptide is 10 amino acids, and the end position for each peptide is the start position 14 VSNTTYVSNA [ 0.000 5 i YSGEDLPEQP 0.000 , 25 GSPQPSIFIC 0.000 I plus nine. 37 EQELSYRNRN 0.000 Table XV-V5-HLA-A1101- SSartjl Subsequence [[Score 1Umers-2o2r1G3 [ 20 ,j HPEPPRWTKK [)0.200 163 Y Table XV-V7-HLA-A1101- 10mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start] Subsequence Score 5 HVIVEDNISH 0.060 I 16 LFTLHPEPPR 0.0401 19 LHPEPPRWTK 0.040( 7 IVEDNISHEL 0.020 17 J FTLHPEPPRW 0.015 11 | NISHELFTLH 0.004 6 VIVEDNISHE 0.001 8 VEDNiSHELF 0.001 3 DFHVIVEDNI 0.001 10 DNtSHELFTL 0.001 15 ELFTLHPEPP 0.000 14 HELFTLHPEP 0.000 18 TLHPEPPRWT 0.000 12 ISHELFTLHP 0.000 2 HDFHVIVEDN 0.000 4 FHViVEDNIS 0.000 13 SHELFTLHPE 0.000 THDFHViVED 0.000 9 EDNISHELFT 0.000 PEPPRWTKKP 0.000

Table XVl-V1-HLA-A24-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start | Subsequence Score 180 VYMSQKGDL 300.000 (1182 EYGEGDHGL 240.000 323" NYRCTASNF 100.000 823 DYPDTAPVI 90.000 [~964~ GYLLQYQII 90.000 489 1--- lYENGTLQl 75.000 1085 EYAGLYDDI 60.000 357 VYSTGSNG! 60.000 76 " FYFTDHR1I 50.000

Table XVI-V1-HLA-A24-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight Start Subsequence Score 102 HFQGKYRCF 15.000 697 RYQFRV1AV 15.000 584 RIIIDGANL 12.000 486 RYHiYENGT 12.000 968 QYQIINDTY 10.500 1004 KYKFYLRAC 10.000 ( 1052 VFEPGAEH! 9.000 1098 WFiGLMCAl 9.000 660 EYIVEFEGN 9.000 8 RGL1VYLMF 8.400 289 DWNKIGGDL 8.400 860 GYQINWWKT S.250 991 KPSWHLSNL 8.000 942 KVDKDTATL 8.000 247 KQRKPKLLL 8.000 ' 890 RNSGMVPSL 8.000 125 FIVPSVPKL 7.920 51 EYFQIECEA 7.700 414 VYQCEASNV 7.500 10 UVYLMFLL 7.200 2 EPLLLGRGL 7.200 1094 STQGWFIGL 7.200 1104 CA1ALLTLL 7.200 626 DVPDPPENL 7.200 930 GVPEQPTFL 7.200 448 NYATWGYS 7.000 793 VYAPYDVKV 6.600 214 iVQKMPMKL 6.600 1100 IGLMCAIAL 6.000 451 TWGYSAFL 6.000 1101 GLMCAIALL 6.000 1190 LFSEDGSFI 6.000 9 Γ GLIVYLMFL 6.000 154 NPPKGLPPL 6.000 796 PYDVKVQAI 6.000 419 ASNVHGTIL 6.000 959 NGNLTGYLL 6.000

Table XVl-V1-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Start j Subsequence Score 275 LLECFAEGL 6.000 261 GSESSITIL 6.000 267 TILKGEILL 6.000 753 SMEQNGPGL 6.000 901 FSEFHLTVL 6.000 743 EMIIKWEPL ( 6.000 266 ITILKGEiL 6.000 1127 YSVKEKEDL 6.000 1106 IALLTLLLL 6.000 833 GVDVINSTL 5.600 39 KQSKVQVAF 5.600 950 LSWGLPKKL 5.280 507 SYSCWVENA 5.000 109 CFASNKLGI 5.000 604 lYCCSAHTA 5.000 1172 QPTESADSL 4.800 946 DTATLSWGL 4.800 958 LNGNLTGYL 4.800 133 LPKEKIDPL 4.800 11 iVYLMFLLL 4.800 203 CCFAAFPRL 4.800 6 LGRGUVYL 4.800 810 GPDPQSVTL 4.800 1105 AlALLTLLL 4.800 954 LPKKLNGNL 4.800 245 SIKQRKPKL 4.400 163 HIYWMNIEL 4.400 542 IPKLHMLEL 4.400 692 LAPFVRYQF 4.200 359 STGSNGILL 4.000 358 YSTGSNGIL 4.000 1103 MCAIALLTL 4.000 1152 YSDSDEKPL 4.000 1001 ATTKYKFYL 4.000 864 NWWKTKSLL 4.000 151 LPCNPPKGL 4.000 1035 ( lGKISGVNL 4.000 164 . Table XVI-V1-HLA-A24-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 591 NLTISNVTL 4.000 ) 682 QGKKTTVIL 4.000 1214 GSSTATFPL ) 4.000 863 INWWKTKSL | 4.000 268 ILKGEILLL | 4.000 605 YCCSAHTAL j 4.000 988 TPSKPSWHL | 4.000 13 YLMFLLLKF 3.960 893 GMVPSLDAF 3.600 1110 TLLLLTVCF, 3.600 929 EGVPEQPTF 3.600 117 IAMSEEIEF 3.300 384 GSPVDNHPF 3.000 1183 YGEGDHGLF 3.000 450 ATVVGYSAF 3.000 687 TVILPLAPF 3.000 917 GPESEPYIF 3.000

Table XVI-V2-HLA-A24-9mers-(SET 1)-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Start) Subsequence Score 9 ' FPKEKIDPL 4.800 1 FIVPSVPKF 3.960 6 ' VPKFPKEKI 1.100 8 ' KFPKEKIDP 0.150 2 ~ Ivpsvpkfp 0.021 | 5 SVPKFPKEK’ 0.017 3 ' VPSVPKFPKi 0.010 4 ' PSVPKFPKEi 0.002 7 PKFPKEKID 0.000

Table XVI-V2-HLA-A24-9mers- (SET 2)-282P1 G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 9 AKENYGKTL 0.600 5 KGREAKENY 0.240 8 EAKENYGKT 0.132 1 GDLPKGREA 0.020 | 2 DLPKGREAK 0.015 3 . LPKGREAKE 0.011 7 REAKENYGK 0.002 6 GREAKENYG 0.002 4 PKGREAKEN 0.001

Table XVI-V2-HLA-A24-9mers-(SET 3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start | Subsequence Score 9 KYAGLYDDI 120.000 5 LGEGKYAGL 6.000 3 STLGEGKYA 0.150 --1 2 SSTLGEGKY 0.110 1 ESSTLGEGK | 0.012 4 TLGEGKYAG 0.012 6 GEGKYAGLY 0.010 7 EGKYAGLYD 0.010 I 8 GKYAGLYDD 0.001 i

Table XVl-V3-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Start Subsequence Score 59 NYVEKSSTF 180.000 17 TYVSNATGS 7.500 11 TYVSNTTYV 7.500

Table XVi-V3-HLA-A24-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence j Score 31 FICSKEQEL 5.280 40 SYRNRNMLA 5.000 39 LSYRNRNML 4.800 60 YVEKSSTFF 3.000 44 RNMLAEDFl 3.000 pF1 TGSPQPSIF 2.400 24 GSPQPSIF! 1.500 22 ATGSPQPSI 1.000 50 DFIQKSTSC 0.750 38 ELSYRNRNM 0.500 43 NRNMLAEDF 0.360 3 HGVDVINTT 0.302 47 LAEDFfQKS 0.238 · 57 SCNYVEKSS 0.210 25 SPQPSIFIC 0.180 15 NTTYVSNAT 0.168 9 NTTYVSNTT 0.168 51 FIQKSTSCN 0.150 13 VSNTTYVSN 0.150 ) 8 DVINTTYVS 0.150 | 7 VINTTYVSN 0.150 1 VIHGVDVIN 0.140 4 ' GVDVINTTY 0.140 62 EKSSTFFKI 0.132 33 CSKEQELSY 0.120 21 NATGSPQPS 0.120 56 TSCNYVEKS 0.110 10 TTYVSNTTY 0.100 14 SNTTYVSNA 0.100 32 ICSKEQELS 0.100 8 INTTYVSNT 0.100 12 YVSNTTYVS 0.100 52 IQKSTSCNY 0.100 58 CNYVEKSST 0.100 30 IFICSKEQE 0.075 35 KEQELSYRN 0.043 26 PQPSIFICS 0.025 165

Table XVI-V3-HLA-A24-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 42 RNRNMLAED 0.022 54 KSTSCNYVE 0.020 37 QELSYRNRN 0.018 19 VSNATGSPQ 0.015 36 EQELSYRNR 0.015 45 NMLAEDFIQ 0.015 5 VDVINTTYV 0.015 46 MLAEDFIQK 0.014 48 AEDFIQKST 0.014 53 QKSTSCNYV 0.012 55 STSCNYVEK 0.011 29 SIFICSKEQ 0.011 2 1HGVDVINT 0.010 16 TTYVSNATG 0.010 20 SNATGSPQP 0.010 27 QPSIFiCSK 0.010 18 YVSNATGSP 0.010 49 EDFIQKSTS 0.010 28 PSIFICSKE 0.002 34 SKEQELSYR 0.002 41 YRNRNMLAE 0.002 61 VEKSSTFFK 0.001

Table Xvi-V4-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 4 YSGEDLPEQ 0.013 6 GEDLPEQPT 0.012 2 TLYSGEDLP o.oio j Table Xvi-V5-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 4 LTVNSSNSI 1.800 3 KLTVNSSNS 0.200 8 SSNSIKQRK 0.025 2 MKLTVNSSN 0.021 5 TVNSSNSIK 0.015 1 PMKLTVNSS 0.012 6 VNSSNSIKQ 0.011 9 SNSIKQRKP 0.011 i 7 NSSNSIKQR 0.010 {

Table Xvi-V5-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 4 LTVNSSNSI 1.800 3 KLTVNSSNS 0.200 8 SSNSIKQRK 0.025 2 MKLTVNSSN 0.021 5 TVNSSNSIK 0.015 1 PMKLTVNSS 0.012 6 VNSSNSIKQ 0.011

Table Xvi-V6-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 3 IEF1VPKLE 0.001 8 PKLEHIEQD 0.000

Table Xvi-V4-HLA-A24-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 8 DLPEQPTFL 7.200 1 VTLYSGEDL 6.000 3 LYSGEDLPE 0.500 7 EDLPEQPTF 0.360 5 SGEDLPEQpl 0.022 9 LPEQPTFLK 0.015

Table Xvi-V6-HLA~A24- I 9mers-282P1G3 j Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 2 EIEFIVPKL 9.240 5 FIVPKLEHl 1.800 4 EFIVPKLEH 0.083 9 KLEHtEQDE 0.050 '6 IVPKLEHiE 0.018 7 VPKLEHIEQ 0.011 1 EEIEFIVPK 0.002

Table Xvi-V7-HLA-A24- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 10 NISHELFTL 4.000 2 DFHVIVEDN 0.700 7 VEDNISHEL 0.616 8 EDNISHELF 0.300 3 FHVIVEDNI 0.210 4 HVIVEDNIS 0.180 9 DNISHELFT 0.150 17 TLHPEPPRW 0.120 15 LFTLHPEPP 0.050 18 LHPEPPRWT 0.018 6 IVEDNISHE 10.018 I 5 VIVEDNSSH 0&amp;#908;18 19 HPEPPRWTK 0.018 11 ISHELFTLH 0.017 16 FTLHPEPPR 0.015 14 ELFTLHPEP 0.013 1 HDFHVIVED 0.002 13 HELFTLHPE 0.002 12 SHELFTLHP 0.002 20 PEPPRWTKK 0.000

Table XVI!-V1-HLA-A24-10mers-282P1G3 166

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 106 KYRCFASNKL 528.000 1126 KYSVKEKEDL 400.000 486 RYHIYENGTL 400.000 323 NYRCTASNFL 240.000 1151 EYSDSDEKPLj 240.000 j 357 VYSTGSNGIL I 200.000 604 IYCCSAHTAL 200.000 12 VYLMFLLLKF 198.000 J 454 GYSAFLHCEF 132.000 1.182 EYGEGDHGLF 120.000 975 TYEIGELNDI 90.000 507 SYSCWVENAI 84.000 124 EFIVPSVPKL 33.000 900 AFSEFHLTVL 24.000 697 RYQFRVIAVN 21.000 oqn oju NFLGTATHDF nnn l J.UUU 752 KSMEQNGPG L 14.400 957 i , KLNGNLTGYL 14.400 541 RIPKLHMLEL 13.200 1019 KPITEESSTL 12.000 1158 KPLKGSLRSL 12.000 132 KLPKEKIDPL 12.000 8 RGLIVYLMFL 12.000 1004 KYKFYLRACT &amp;#906; 2.000 875 RTHPKEVNIL 11.520 832 HGVDVINSTL 10.080 | 555 KCDSHLKHSL 9.600 489 IYENGTLQIN 9.000 317 SYQDKGNYR C 9.000 179 RVYMSQKGDL 8.000 180 VYMSQKGDLY 7.500 964 GYLLQYQIIN 7.500 46 AFPFDEYFQI 7,500 1089 LYDDISTQGW 7.200 153 CNPPKGLPPL 7.200 9 GLIVYLMFLL | 7.200 929 EGVPEQPTFL I 7.200 218 MPMKLTVNSL 7.200

Table XVI!-V1-HLA-A24-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence | Score 953 GLPKKLNGNL 7.200 274 LLLECFAEGL 7.200 142 EVEEGDPIVL . 7.200 10 LIVYLMFLLL 7.200 809 SGPDPQSVTL 7.200 270 KGEiLLLECF 7.200 1104 CAIALLTLLL 7.200 448 NYATWGYSA 7.000 849 VPKDRVHGRL 6.720 213 TIVQKMPMKL 6.600 306 NYGKTLKIEN 6.600 244 NSIKQRKPKL 6.600 1100 IGLMCAIALL 6.000 551 HCESKCDSHL 6.000 590 ANLTISNVTL 6.000 266 ITILKGEILL 6.000 267. TILKGEILLL 6.000 150 VLPCNPPKGL 6.000 987 TTPSKPSWHL 6.000 (862 QINWWKTKSL 6.000 1171 MQPTESADSL 6.000 450 ATWGYSAFL 6.000 398 FPRFLSFTNI 5.760 516 IGKTAVTANL 5.600 949 TLSWGLPKKL 5.280 1200 AYAGSKEKGS 5.000 818 LYSGEDYPDT 5.000 | 885 RFSGQRNSG M 5.000 91 TFRIPNEGHI 5.000 1085 EYAGLYDDIS 5.000 260 SGSESSITIL 4.800 798 DVKVQAINQL 4.800 627 VPDPPENLHL 4.800 1093 ISTQGWFIGL 4.800 302 ETKENYGKTL | 4.800 202 YCCFAAFPRL 4.800 5 LLGRGUVYL 4.800

Table XVil-V1-HLA-A24-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of pepiide is 10 amino acids, and the end position for each pepiide is the start position plus nine. Start Subsequence Score 1103 MCAIALLTLL 4.800 199 RNDYCCFAAF 4.800 536 SPKNPRIPKL 4.400 557 DSHLKHSLKL 4.400 972 INDTYEIGEL 4.400 (524 NLDIRNATKL 4.400 681 VQGKKTTVIL 4.000 245 SIKQRKPKLL 4.000 | 539 NPRIPKLHML 4.000 ) 1034 GIGKISGVNL 4.000 | 1105 AIALLTLLLL 4.000 | 431 NIDVVDVRPL 4.000 | 863 INWWKTKSLL 4.000 | 1099 FIGLMCAIAL 4.000' [ 1102 LMCAIALLTL 4.000 | |1213 NGSSTATFPL 4.000 | 1054 EPGAEHIVRL 4.000 | 958 LNGNLTGYLL 4.000 | 897 SLDAFSEFHL 4.000 1066 KNWGDNDSiF 4.000 418 EASNVHGTIL 4.000 1000 NATTKYKFYL 4.000 358 YSTGSNGILL 4.000 1080 ETRGREYAGL 4.000 . 616 i AADITQVTVL 4.000

Table XVS1-V2-HLA-A24- I 10mers-(SET 1)-282P1G3 ( Each peptide is a portion of I SEQ ID NO: 5; each start | position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. j Start Subsequence Score j 9 KFPKEKIDPL 60.000 | 1 EFIVPSVPKF 16.500 6 SVPKFPKEKl 1.650 2 FIVPSVPKFP 0.025 167 10 FPKEKIDPLE 0.017 3 1VPSVPKFPK 0.015 4 VPSVPKFPKE 0.013 7 VPKFPKEKID 0.010 5 PSVPKFPKEK 0.002 8 PKFPKEKIDP 0.000

Table XVH-V2-HLA-A24-10mers-{SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 4 TLGEGKYAGL 4.800 5 LGEGKYAGLY 0.150 8 GKYAGLYDDI 0.120 1 ESSTLGEGKY 0.110 2 SSTLGEGKYA 0.100 3 STLGEGKYAG 0.015 7 EGKYAGLYDD 0.010 6 GEGKYAGLYD 0.001

Table XVII-V2-HLA-A24-10mers-(SET 3)-282P1G3 Each peptide is a portion of I SEQ ID NO: 5; each start I position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. j Start Subsequence Score ] 10 KYAGLYDDIS 10.000( 5 TLGEGKYAGL 4.800 | 6 LGEGKYAGLY 0.150 ( 9 GKYAGLYDDI 0.120 2 ESSTLGEGKY 0.110 3 SSTLGEGKYA 0.100 4 STLGEGKYAG 0.015 8 EGKYAGLYDD 0.010 1 EESSTLGEGK 0.001 7 GEGKYAGLYD I 0.001

Table XVI1-V3-HL4-A24-10mers-282P1 G3

Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino adds, and the end position for each pepiide is the start position plus nine. Start Subsequence Score 60 NYVEKSSTFF 180.00 0 31 IFICSKEQEL 39.600 12 TYVSNTTYVS 7.500 43 RNRNMLAEDF 4.800 39 ELSYRNRNML 4.800 23 ATGSPQPSIF 2.000 59 CNYVEKSSTF 2.000 24 TGSPQPSIFI 1.200 22 NATGSPQPSI 1.000 51 DFIQKSTSCN 0.750 18 TYVSNATGSP 0.750 41 SYRNRNMLAE 0.500 26 ( SPQPSIFICS 0.302 4 HGVDVINTTY 0.252 48 LAEDFIQKST 0.252 37 EQELSYRNRN 0.180 15 SNTTYVSNAT 0.168 9 INTTYVSNTT 0.168 47 MLAEDFIQKS 0.158 | 25 GSPQPSIFIC 0.150 | 8 VINTTYVSNT 0.150 14 VSNTTYVSNA 0.150 7 DVINTTYVSN 0.1.50 44 NRNMLAEDFI 0.150 52 FIQKSTSCNY 0.150 58 SCNYVEKSST 0.150 57 TSCNYVEKSS 0.140 62 VEKSSTFFKI 0.132 53 IQKSTSCNYV 0.120 21 SNATGSPQPS 0.120 56 STSCNYVEKS 0.110 17 TTYVSNATGS 0.100 10 NTTYVSNTTY 0.100 2 VIHGVDVINT 0.100 5 GVDV1NTTYV 0.100 11 TTYVSNTTYV 0.100 32 FICSKEQELS 0.100 I 33 ICSKEQELSY 0.100

Table XVII-V3-HLA-A24-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 13 YVSNTTYVSN 0.100 40 LSYRNRNMLA 0.100 38 QELSYRNRNM 0.075 45 RNMLAEDFIQ 0.030 55 KSTSCNYVEK 0.022 PVIHGVDVIN 0.021 35 SKEQELSYRN 0.018 46 j NMLAEDFIQK 0.018 3 IHGVDVINTT 0.017 28 QPSIFICSKE 0.015 20 VSNATGSPQP 0.015 6 VDVINTTYVS 0.015 61 YVEKSSTFFK 0.015 34 CSKEQELSYR 0.012 50 EDF1QKSTSC 0.010 49 AEDFIQKSTS 0.010 16 NTTYVSNATG 0.010 19 YVSNATGSPQ 0.010 30 SIFICSKEQE 0.010 36 KEQELSYRNR 0.004 29 PSIFICSKEQ 0.002 . 42 YRN.RNMLAED 0.002 27 PQPS1FICSK Γ0Λ02&amp;#906; 54 QKSTSCNYVE 0.001

Table XVII-V4-HLA-A24-10mers-282P1 G3 j Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence [ Score 1 SVTLYSGEDL 4.000 8 I EDLPEQPTFL 0.720 4 I LYSGEDLPEQ 0.550 6 SGEDLPEQPT 0.216 168 '&amp;#943;- V Table XVII-V4-HLA-A24- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius nine. Start Subsequence Score 7 GEDLPEQPTF 0.200 10 LPEQPTFLKV 0.198 9 DLPEQPTFLK 0.018 2 VTLYSGEDLP 0.015 5 . YSGEDLPEQP 0.014 3 TLYSGEDLPE 0.010

Table XVII-V6-HLA-A24-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius . nine. Start Subsequence ] Score 6 FIVPKLEHIE I.1 0.022 3 ElEFIVPKLE 0.021 7 IVPKLEHIEQ 0.017 8 VPKLEHIEQD 0.010 1 SEEIEFIVPK 0.002 4 IEFIVPKLEH 0.001 9 PKLEHIEQDE 0.000

Table XVII-V5-HLA-A24- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start | Subsequence Score 4 KLTVNSSNSI 2.400 1 MPMKLTVNSS 0.180 8 NSSNSIKQRK 0.017 6 TVNSSNSIKQ 0.017 9 SSNSIKQRKP 0.017 3 MKLTVNSSNS 0.015 5 LTVNSSNSIK \0.015 O i £ PMKLTVNSSN 0.014 7 VNSSNSIKQR 0.010 10 SNSIKQRKPK 0.010

Table XVII-V6-HLA-A24- I 10mers-282P1G3 | Each peptide is a portion of I SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. | Start Subsequence Score | | 5 EFIVPKLEHI 7.500 | 2 EEIEFIVPKL 1.109 &amp;#906; 10 KLEHIEQDER 0.033 |

Table XVII-V7-HLA-A24-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each . peptide is the start position plus nine. Start) Subsequence | Score 7 IVEDNISHEL 11.088 3 DFHVIVEDNI 7.000 io [ DNISHELFTL 6.000 8 VEDNISHELF 0.200 17 FTLHPEPPRW 0.150 18 TLHPEPPRWT 0.120 .16 LFTLHPEPPR 0.050 20 HPEPPRWTKK 0.020 4 FHVIVEDNIS 0.018 6 VIVEDNISHE 0.018 5 HVIVEDNISH 0.015 9 EDNISHELFT 0.015 ) 11 NISHELFTLH 0.014 2 HDFHVIVEDN 0.014 12 ISHELFTLHP 0.012 15 ELFTLHPEPP 0.0&amp;#906;0 14 HELFTLHPEP 0.002 19 LHPEPPRWTK 0.002 1 THDFHVIVED 0.002 13 SHELFTLHPE 0.002 21 PEPPRWTKKP 0.000

Table XVIII-V1-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 539 NPRIPKLHM 300.000 151 LPCNPPKGL 120.000 988 TPSKPSWHL 120,000 2 EPLLLGRGL 80.000 133 LPKEKIDPL 80.000 991 KPSWHLSNL 80.000 1172 QPTESADSL 80.000 542 IPKLHMLEL 80.000 954 LPKKLNGNL 80.000 154 NPPKGLPPL 80.000 247 KQRKPKLLL 60.000 6 LGRGLIVYL 40.000 ' 626 DVPDPPENL 30.000 810 GPDPQSVTL 24.000 ' 695 FVRYQFRVI 20.000 11 IVYLMFLLL 20.000. 214 IVQKMPMKL 20.000 930 GVPEQPTFL 20.000 451 i WGYSAFL 20.000 159 LPPLHIYWM 20.000 1106 IALLTLLLL 12.000 1101 GLMCAIALL. 12.000 1001 ATTKYKFYL 12.000 130 VPKLPKEKI 12.000 828 APVIHGVDV 12.000 1105 AIALLTLLL 12.000 1104 CAIALLTLL 12.000 419 ASNVHGTIL 12.000 1163 SLRSLNRDM 10.000 210 RLRTIVQKM 10.000 285 TPQVDWNKI 8.000 47 FPFDEYFQI 8.000 726 APDRNPQNI 7.200 833 GVDVINSTL 6.000 772 APVEWEEET 6.000 942 KVDKDTATL 6.000 169

Tabie XVIil-V1-HLA-B7-9mers-282P1G3 Each peptide is a portion of S^Q ID MO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 795 APYDVKVQA 6.000 1100 IGLMCAIAL 4.000 398 FPREISFTN 4.000 J 863 INWWKTKSL 4.000 I 267 TILKGEILL 4.000 9 GLIVYLMFL 4.000 946 DTATLSWGL 4.000 591 NLTISNVTL 4.000 10 LIVYLMFLL 4.000 268 ILKGEILLL 4.000 1127 YSVKEKEDL 4.000 950 LSWGLPKKL 4.000 266 ITII KGFII 4,000 1214 GSSTATFPL 4.000 203 CCFAAFPRL 4.000 1103 MCAIALLTL 4.000 959 NGNLTGYLL 4.000 358 YSTGSNGIL 4.000 605 YCCSAHTAL 4.000 743 EMIIKWEPL 4.000 584 RillDGANL 4.000 125 FIVPSVPKL - 4.000 163 HiYWMNIEL 4.000 890 RNSGMVPSL 4.000 1094 STQGWFIGL 4.000 359 STGSNG1LL 4.000 1035 IGKISGVNL 4.000 682 QGKKTTVIL 4.000 245 SIKQRKPKL 4.000 I 958 LNGNLTGYL 4.000 855 HGRLKGYQ! 4.000 206 AAFPRLRT! 3.600 .730 NPQNIRVQA 3.000 111 ASNKLGIAM 3.000 433 DWDVRPU 3.000 787 RVMTPAVYA 2.250 | 250 KPKLLLPPT 2.000

Tabie XVIII-V1-HLA-B7-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start J] Subsequence Score 758 GPGLEYRVT| 2.000 352 KPQSAVYST) 2.000 208 FPRLRTIVQ 2.000 596 NVTLEDQGI 2.000 534 | RVSPKNPRI 2.000 | 30 SVQQVPTII 2.000 785 TLRVMTPAV 2.000 385 SPVDNHPFA 2.000 671 EPGRWEELT 2.000 873 DGRTHPKEV 2.000 1019 KPiTEESST 2.000 1121 RNRGGKYSV 2.000 737 QASQPKEMI 1.800 753 SMEQNGPGL 1.200 334 TATHDFHVI 1.200 916 AGPESEPYI 1.200 118 AMSEEIEFI 1.200 519 TAVTANLDI 1.200 180 VYMSQKGDL 1.200 261 GSESSITIL 1.200 738 ASQPKEMH 1.200 650 AGADHNSNI 1.200 611 TALDSAADI 1.200 901 FSEFHLTVL 1.200 1152 YSDSDEKPL 1.200 218 MPMKLTVNS 1.200 418 EASNVHGTI 1.200

Table XVlil-V2-HLA-B7-9mers-(SET 1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start . position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence ( Score 9 FPKEKIDPL ΠδΟ.ΟΟΟ

Table XVI!!-V2-HLA-B7-9mers-(SET 1)- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 6 VPKFPKEKl 12.000 3 VPSVPKFPK 0.300 5 SVPKFPKEK 0.050 2 IVPSVPKFP 0.050 i 1 FIVPSVPKF 0.020 ) 4 PSVPKFPKE 0.001 8 KFPKEKIDP 0.001 7 PKFPKEKID 0.000

Tabie XVIll-V2-HL4-B7-9mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 9 AKENYGKTL 0.360 8 EAKENYGKT 0.300 5 . KGREAKENY 0.200 3 LPKGREAKE 0.200 2 DLPKGREAK 0.015 1 GDLPKGREA 0.010 7 REAKENYGK 0.001 6 GREAKENYG 0.000 4 PKGREAKEN 0.000

Table XV!ll-V2-HLA-B7-9mers-(SET3)- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start posiiion plus eight Start Subsequence Score 5 LGEGKYAGL 1.200 3 STLGEGKYA 0.100 170

Table XVI!l-V2-HLA-B7-9mers-(SET3)- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and She end position for each peptide is the start position plus eight. Start Subsequence Score 9 KYAGLYDDI 0.040 2 SSTLGEGKY 0.020 7 EGKYAGLYD 0.010 1 ESSTLGEGK 0.010 4 TLGEGKYAG 0.010 6 GEGKYAGLY 0.002 8 GKYAGLYDD 0.001

Table XVIll-V3-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 39 LSYRNRNML 6.000 | 31 FICSKEQEL 4.000 25 SPQPSIFIC 2.000 22 ATGSPQPS! 1.800 j 44 RNMLAEDFI 1.200 38 ELSYRNRNM ,1.000 24 GSPQPSIFI 0.600 27 QPSIFICSK 0.200 8 INTTYVSNT 0.100 15 NTTYVSNAT 0.100 3 HGVDVINTT 0.100 12 YVSNTTYVS 0.100 58 CNYVEKSST 0.100 42 RNRNMLAED 0.100 6 DVINTTYVS 0.100 40 SYRNRNMLA o.ioo 14 SNTTYVSNA 0.100 9 NTTYVSNTT 0.100 21 NATGSPQPS 0.060 18 YVSNATGSP 0.050 62 EKSSTFFKl [ 0.040

Table XVlll-V3-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 60 YVEKSSTFF 0.030 4 GVDVINTTY 0.030 10 TTYVSNTTY 0.020 32 ICSKEQELS 0.020 56 TSCNYVEKS ,0.020 5 VDVINTTYV 0.020 13 VSNTTYVSN 0.020 51 FIQKSTSCN 0.020 53 QKSTSCNYV 0.020 33 CSKEQELSY 0.020- 1 VIHGVDVIN 0.020 | 57 SCNYVEKSS 0.020 | 23 TGSPQPSIF 0.020 | 7 VINTTYVSN 0.020 | 52 IQKSTSCNY 0.020 ) 11 TYVSNTTYV 0.020 J 47 LAEDFIQKS 0.018 | 16 TTYVSNATG 0.010 | 2 IHGVDVINT 0.010 [ 46 MLAEDFIQK 0.010 ( 45 NMLAEDFIQ 0.010 19 VSNATGSPQ 0.010 ( 20 SNATGSPQP 0.010 | 54 KSTSCNYVE 0.010 50 DFIQKSTSC 0.010 29 SIFICSKEQ 0.010 55 STSCNYVEK 0.010 48 AEDFIQKST 0.009 37 QELSYRNRN 0.003 j 36 EQELSYRNR 0.003 | 59 NYVEKSSTF 0.002 | 26 PQPSIFICS 0.002 j 43 NRNMLAEDF 0.002 | 35 KEQELSYRN 0.002 I 17 TYVSNATGS 0.002 | 49 EDFIQKSTS 0.002 I 61 j VEKSSTFFK 0.001

Table XVIil-V3-HLA-B7-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 28 PSIFICSKE 0.001 ) 41 YRNRNMLAE 0.001 30 IFICSKEQE 0.001 34 SKEQELSYR 0.000

Table XVIII-V4-HLA-B7-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 1 VTLYSGEDL 4.000 8 DLPEQPTFL 4.000 9 LPEQPTFLK 0.090 4 YSGEDLPEQ 0.010 2 TLYSGEDLP 0.010 6 GEDLPEQPT 0.004 f 5 SGEDLPEQP 0.003 7 EDLPEQPTF 0.002 3 LYSGEDLPE 0.001

Table XVIII-V5-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight, Start Subsequence Score 4 LTVNSSNSI 0.400 5 TVNSSNSIK 0.050 3 KLTVNSSNS 0.020 8 SSNSIKQRK 0.010 6 VNSSNSIKQ 0.010 7 NSSNSIKQR 0.010 171

Table X\/lll-V5-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 9 SNSIKQRKP 0.010 2 MKLTVNSSN 0.002 1 PMKLTVNSS 0.002

Table XVIII-V6-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end positibn for each peptide is the start position plus eight. Start Subsequence Score .2 EIEFIVPKL 1.200 5 FIVPKLEH! 0.400 7 VPKLEHIEQ 0.200. 6 iVPKLEHIE 0.050 9 KLEHIEQDE 0.003 4 EFiVPKLEH 0.002 3 iEFiVPKLE 0.001 1 EEIEFIVPK 0.001 8 PKLEHIEQD 0.000

Table XVIil-V7-HLA-B7-9mers-i 282P1G3 j Each peptide is a portion of j SEQ ID NO: 15; each start ! position is specified, the length ( of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. J Start Subsequence Score | 10 NISHELFTL 4.000 j 19 HPEPPRWTK 0.135 ( 7 VEDNISHEL 0.120-] 4 HVIVEDNIS 0.100 9 DNiSHELFT 0.100 3 FHVIVEDNI 0.040 17 TLHPEPPRW 0.020

Table XV!l!-V7-HLA-B7-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 16 FTLHPEPPR 0.015 6 IVEDN1SHE 0.015 18 LHPEPPRWT 0.015 11 ISHELFTLH 0.010 14 ELFTLHPEP 0.010 5 VIVEDNISH 0.010 8 EDNISHELF 0.002 2 DFHVIVEDN 0.002 13 HELFTLHPE 0.001 1 HDFHVIVED 0.001 15 LFTLHPEPP 0.001 12 SHELFTLHP 0.000 20 (PEPPRWTKK 0.000

Table XIX-V1-HLA-B7-10mers-| 282P1G3 [ Each peptide is a portion of ! SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, j and the end position for each ( peptide is the start position j plus nine. | Start Subsequence Score | 398 FPREISFTNL 800.000( 539 NPRIPKLHML 800.000 218 MPMKLTVNS L 240.000 1054 EPGAEHIVRL 80.000 1158 KPLKGSLRSL 80.000 849 . VPKDRVHGR i_ 80.000 536 SPKNPRIPKL 80.000 1019' KPITEESSTL 80.000 1080 ETRGREYAG L 40.000 828 APVIHGVDVI 24.000 627 VPDPPENLHL 24.000 795 APYDVKVQAI 24.000 798 DVKVQAINQL 20.000

Table XiX-V1-HLA-B7-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 179 RVYMSQKGD L 20.000 1105 AlALLTLLLL 12.000 . 693 APFVRYQFR V 12.000 752 KSMEQNGPG L 12.000 450 ATWGYSAFL 12.000 772 APVEWEEET V 12.000 1000 NATTKYKFYL 12.000 480 KPLEGRRYHI 12.000 | 590 ANLTISNVTL 12.000 418 EASNVHGTIL 12.000 2 EPLLLGRGL! 12.000 1104 CAIALLTLLL 12.000 616 AADITQVTVL 10.800 6 LGRGLIVYLM 10.000 74 NPFYFTDHRI 8.000 695 FVRYQFRVIA 7.500 356 AVYSTGSNGi 6.000 ' 150 VLPCNPPKGL 6.000 142 EVEEGDPIVL 6.000 987 TTPSKPSWH L 6.000 643 SVRLTWEAG A 5.000 735 RVQASQPKE M 5.000 780 TVTNHTLRVM 5.000 863 1NWWKTKSLL 4.000 790 TPAVYAPYDV 4.000 1034 GIGKiSGVNL 4.000 266 ITILKGEILL 4.000 1103 MCAIALLTLL 4.000 9. GL1VYLMFLL 4.000 953 GLPKKLNGNL 4.000 323 NYRCTASNFL 4.000 106 KYRCFASNKL 4.000 172

Table XIX-V1-HLA-B7-1 Omers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 862 QINWWKTKS L 4.000 274 LLLECFAEGL 4.000 541 R1PKLHMLEL 4.000 260 SGSESSITIL 4.000 949 TLSWGLPKKL 4.000 213 TIVQKMPMKL 4.000 557 DSHLKHSLKL 4.000 957 KLNGNLTGYL 4.000 1102 LMCAIALLTL 4.000 1093 ISTQGWFIGL 4.000 934 QPTFLKVIKV 4.000 132 KLPKEKIDPL 4.000 K LLGRGLIVYL A ΠΛΠ rf.UUU 8 RGLIVYLMFL 4.000 832 HGVDVINSTL 4.000 1099 FIGLMCAIAL 4.000 267 T1LKGEILLL 4.000 929 EGVPEQPTFL 4.000 516 IGKTAVTANL a r\c\r\ T.UUU 202 YCCFAAFPRL 4.000 473 WQKVEEVKP L >4.000.. 244 NSIKQRKPKL 4.000 j 373 EPQPTIKWRV 4,000 1171 MQPTESADS L 4.000 302 ETKENYGKTL 4.000 681 VQGKKTTVIL 4.000 1213 NGSSTATFPL 4.000 1100 IGLMCAIALL 4.000 809 SGPDPQSVT L 4,000 958 LNGNLTGYLL 4.000 358 YSTGSNGILL 4.000 637 SERQNRSVR L 4.000 153 CNPPKGLPPL 4.000

Table X!X-V1-HLA-B7-10mers-_282P1G3

Each peptide is a portion of SEG ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.

Start Subsequence Score 875 RTHPKEVNIL 4.000 1172 QPTESADSLV 4.000 265 . SITILKGEIL 4.000 245 SIKQRKPKLL 4.000 34 VPTI1KQSKV 4.000 10 LIVYLMFLLL 4.000 725 AAPDRNPQNI 3.600 117 IAMSEE1EFI 3.600 110 FASNKLGIAM 3.000 792 AVYAPYDVKV 3.000 413 AVYQCEASN V 3.000 129 SVPKLPKEKi 3.000 one? ZUO A A ΓΠΠΙ ητιι / M/-\rrr&lt;ur\ 11v A "7ΛΛ Z./UU 1048 HPIEVFEPGA 2.000 680 RVQGKKTTVI 2.000 27 IPSSVQQVPT 2.000 526 DIRNATKLRV 2.000 408 QPNHTAVYQ C 2.000 1Q51 EVFEPGAEHI 2.000 954 LPKKLNGNLT 2.000 208 fprlrtivqk 2.000 538 KNPRIPKLHM 1.500

Table XIX-V2-HLA-B7-10mers-1 (SET 1)-282P1G3 | Each peptide is a portion of I SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, I and the end position for each I peptide is the start position plus nine. Start Subsequence | Score j 6 SVPKFPKEK1J 3.000 J 9 KFPKEKIDPL 0.400 | 7 VPKFPKEKID 0.200 [ 4 VPSVPKFPKE 0.200 |

Table X!X-V2-HLA-B7-10mers-(SET1J-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 10 FPKEKIDPLE 0.200 3 IVPSVPKFPK 0.075 2 FIVPSVPKFP 0.010 1 EFIVPSVPKF 0.002 5 PSVPKFPKEK 0.001 8 PKFPKEKIDP ΓαοοοΠ

Table X!X-V2-HLA-B7-10mers-(SET 2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 4 TLGEGKYAGL 4.000 2 SSTLGEGKYA 0.100 θ GKYAGLYDDI 0.040 1 ESSTLGEGKY 0.020 3 STLGEGKYAG 0.010 7 EGKYAGLYDD 0.010 5 LGEGKYAGLY 0.006 6 GEGKYAGLYD o o o

Table XIX-V2-HLA-B7-10mers-(SET 3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 5 TLGEGKYAGL 4.000 3 SSTLGEGKYA 0.100 9 GKYAGLYDDI 0.040 2 ESSTLGEGKY 0.0201 I 4 STLGEGKYAG o.oio| 173

Table X!X--V2-HLA-B7-10mers-(SET 3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score) 8 EGKYAGLYDD 0.010 6 LGEGKYAGLY 0.006 10 KYAGIYDDIS 0.002) 7 GEGKYAGLYD 0.0011 1 EESSTLGEGK) 0.001!

Table XIX-V3-HLA-B7-10mers- -282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 39 ELSYRNRNML 6.000 22 NATGSPQPSI 1.800 24 TGSPQPSIF! 0.600 31 IFICSKEQEL 0.400 26 SPQPSIFICS ) 0.400 5 GVDVINTTYV ) 0.300 53 IQKSTSCNYV I 0.200 28 QPSIFICSKE -0.200 11 TTYVSNTTYV 0,200 43 RNRNMLAEDF 0.200 8 VINTTYVSNT 0.100 15 SNTTYVSNAT 0.100 58 SCNYVEKSST 0.100 38 QELSYRNRNM 0.100 9 INTTYVSNTT 0.100 14 VSNTTYVSNA 0.100 7 DVINTTYVSN 0.100 &amp;#941; ViHGVDVINT 0.100 25 GSPQPSIF1C 0.100 40 LSYRNRNMLA 0.100 13 YVSNTTYVSN 0.100 48 LAEDFIQKST 0.090 23 ATGSPQPSIF 0.060

Table X!X-V3-HLA-B7-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.- Start Subsequence Score ) 19 YVSNATGSPQ 0.050 | 62 VEKSSTFFK! 0.040 44 NRNMLAEDFl 0.040 45 RNMLAEDFIQ 0.030 17 TTYVSNATGS 0.020 47 MLAEDFIQKS 0.020 10 NTTYVSNTTY 0.020 32 FICSKEQELS 0.020 59 CNYVEKSSTF 0.020 21 SNATGSPQPS 0.020 52 FIQKSTSCNY 0.020 56 STSCNYVEKS 0.020 4 HGVDViNTTY 0.020 57 TSCNYVEKSS 0.020 33 ICSKEQELSY 0.020 61 YVEKSSTFFK 0.015 16 NTTYVSNATG 0.010 1 PVIHGVDVIN 0.010 20 VSNATGSPQP 0.010 41 SYRNRNMLAE 0.010 34 CSKEQELSYR 0.010 30 SIFICSKEQE 0.010 50 EDFIQKSTSC 0.010 55 KSTSCNYVEK 0.010 3 IHGVDVINTT 0.010 46 NMLAEDFIQK 0.010 37 EQELSYRNRN 0.009 60 NYVEKSSTFF 0.002 51 DFIQKSTSCN 0.002 12 TYVSNTTYVS 0.002 6 VDVINTTYVS 0.002 49 AEDFIQKSTS 0.002 36 KEQELSYRNR 0.001 29 psificskeo-1 0.001 54 QKSTSCNYVE 0.001 27 PQPSIFICSK 0.001 42 YRNRNMLAED 0.001

Table X!X-V3-HLA-B7-10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.

Start Subsequence Score 18 TYVSNATGSP 0.001 35 SKEQELSYRN 0.001 Table XIX-V4-HLA-B7-1 Omers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 1 SVTLYSGEDL 20.000 10 LPEQPTFLKV 1.200 8 EDLPEQPTFL 0.400 6 SGEDLPEQPT 0.045 9 DLPEQPTFLK 0.015 3 TLYSGEDLPE 0.010 5 YSGEDLPEQP Q.010 2 VTLYSGEDLP 0.010 4 LYSGEDLPEQ 0.001 7 GEDLPEQPTF 0.001

Table X!X-V5-HLA-B7-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and th,e end position for each peptide is the start position plus nine. Start Subsequence Score 1 MPMKLTVNSS 1.200 4 KLTVNSSNS! 0.400 6 TVNSSNSIKQ 0.050 10 SNSIKQRKPK 0.015 7 VNSSNSIKQR 0.010 8 NSSNSIKQRK 0.010 9 SSNSIKQRKP 0.010 174

Table XlX-V5-HLA-B7-10mers-282P1G3 Each peptide is a portion of SEQIDNO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 5 LTVNSSNSIK 0.010 2 PMKLTVNSSN 0.002 3 MKLTVNSSNS 0.002

Table XlX-V6-HLA-B7-10mers- 282P1G3. Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 2 EEIEFIVPKL 0.400 ( 8 VPKLEHIEQD 0.200 7 IVPKLEHIEQ 0.050 5 EFIVPKLEHI 0.040 6 FIVPKLEHIE 0.010 10 KLEHIEQDER 0.003 3 EIEFIVPKLE 0.003 4 IEFIVPKLEH 0.002 1 SEEIEFIVPK 0.000 9 — PKLEHIEQDE 43.000

Table X!X-V7-HLA-B7-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence | Score 7 IVEDNISHEL 6.000 10 DNISHELFTL 4.000 18 TLHPEPPRWT 0.150 20 HPEPPRWTKK 0.060 5 HVIVEDNISH 0.050 3 DFHVIVEDNI 0.040

Table XIX-V7-HLA-B7-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 17 FTLHPEPPRW 0.020 6 VIVEDNISHE 0.010 15 ELFTLHPEPP 0.010 11 NISHELFTLH 0.010 12 ISHELFTLHP 0.010 9 EDNISHELFT 0.010 19 LHPEPPRWTK 0.002 2 HDFHVIVEDN 0.002 4 FHVIVEDNIS 0.002 16 LFTLHPEPPR 0.002 14 HELFTLHPEP 0.001 8 VEDNISHELF 0.001 13 SHELFTLHPE 0.000 1 THDFHVIVED 0.000 21 PEPPRWTKKP 0.000

Table XX-V1-HLA-B3501- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence J Score 539 NPRIPKLHM 120,000 133 LPKEKIDPL 120.000 740 QPKEMIIKW 60.000 542 IPKLHMLEL 60.000 954 LPKKLNGNL 60.000 991 KPSWHLSNL 40.000 159 LPPLHIYWM 40.000 690 LPLAPFVRY 40.000 1172 QPTESADSL 40.000 130 VPKLPKEKI 24.000 299 KGRETKENY 24.000 1082 RGREYAGLY 24.000

Table XX-V1-HLA-B3501-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 47 FPFDEYFQI 24.000 197 DSRNDYCCF 22.500 151 LPCNPPKGL 20.000 1175( ESADSLVEY 20.000 390 HPFAGDWF 20.000 2 EPLLLGRGL 20.000 988 TPSKPSWHL 20.000 154 NPPKGLPPL 20.000 768 KPQGAPVEW 20.000 84 IPSNNSGTF 20.000 316 VSYQDKGNY 15.000 285 TPQVDWNKl 12.000 398 FPREISFTN 12.000 250 KPKLLLPPT 12.000 69 WTKDGNPFY 12.000 210 RLRTIVQKM 12.000 111 ASNKLGIAM 10.000 886 FSGQRNSGM 10.000 917 GPESEPYIF 9.000 I 915 GAGPESEPY 9.000 310 TLKIENVSY 9.000 1127 YSVKEKEDL 7.500 384 GSPVDNHPF 7.500 1000 NATTKYKFY 6.000 | 1019 KPITEESST 6.000 810 GPDPQSVTL 6.000 597 VTLEDQGIY 6.000 1163 SLRSLNRDM 6.000 247 KQRKPKLLL j 6.000 1214 GSSTATFPL 5.000 950 LSWGLPKKL 5.000 455 YSAFLHCEF 5.000 465 ASPEAVVSW 5.000 182 MSQKGDLYF 5.000 358 YSTGSNGIL 5.000 419 ASNVHGTIL 5.000 667 GNKEEPGRV\ 4.500 175 ’.--.Table XX-V1-HLA-B3501- I 9mers-282P1G3 j Table XX-V1-HLA-B3501-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Each peptide is a portion of SEQ ID NO: 3; each start ) position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus I eight. j Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Start) Subsequence Score 5 KGREAKENY. 24.00 0 Start Subsequence Score | Start Subsequence Score 117 1AMSEE1EF 4.500 | 812 DPQSVTLYS 2.000 8 EAKENYGKT j 1.800 268 ILKGEILLL ~450(Γ| 890 RNSGMVPSL 2.000 3 LPKGREAKE 0.600 1158 KPLKGSLRS 4.000 | 626 DVPDPPENL &amp;#943; 2.000 9 AKENYGKTL 0.030 385 SPVDNHPFA 4.000 ) 39 KQSKVQVAF 2.000 1 GDLPKGREA 0.010 853 RVHGRLKGY 4.000 ) 44 QVAFPFDEY 2.000 2 DLPKGREAK 0.010 957 KLNGNLTGY 4.000 j 730 NPQNIRVQA 2.000 7 REAKENYGK 0.003 828 APVIHGVDV | 4.000 j 283 LPTPQVDWN 2.000 4 PKGREAKEN 0.002 352 KPQSAVYST 4.000 508 YSCWVENAI 2.000 6 GREAKENYG 0.000 795 APYDVKVQA 4.000 -1 8 RGLIVYLMF 2.000 157 ( KGLPPLHIY 4.000 ( 99 HISHFQGKY 2.000 Table XX-V2-B3501-9mers-(SET 3)-282P1G3 772 APVEWEEET 4.000 | 736 VQASQPKEM 2.000 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight 629 DPPENLHLS 4.000 I 447 ENYATVVGY 2.000 212 RTIVQKMPM 4.000 I i 755 EQNGPGLEY 2.000 1104 CAIALLTLL 3.000 | 1013 TSQGCGKPI 2.000 682 QGKKTTVIL 3.000 692 LAPFVRYQF 3.000 Table XX-V2-HLA-B3501-9mers-(SET 1 )-282P1 G3 Start Subsequence Score 45 VAFPFDEYF 3.000 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. 2 SSTLGEGKY 10.00 0 441 IQTKDGENY 3.000 1106 IALLTLLLL 3.000 5 LGEGKYAGL 0.300 6 LGRGLIVYL 3.000 6 GEGKYAGLY 0.200 1035 IGKISGVNL 3.000 3 STLGEGKYA 0.150 857 RLKGYQINW , 3.000 9 KYAGLYDDI 0.080 456 SAFLHCEFF 3.000 Start Subsequence Score 1 ESSTLGEGK 0.050 758 GPGLEYRVT 3.000 9 FPKEKIDPL 120.000 584 RIIIDGANL 3.000 6 VPKFPKEKI 24.000 / EGKYAGLYD 0.030 245 SIKQRKPKL 3.000 1 FIVPSVPKF 1.000 4 ILGEgKYAG 0.020 838 NSTLVKVTW 2.500 3 VPSVPKFPK 0.200 8 OKY AGLYDD 0.001 726 APDRNPQNI 2.400 5 SVPKFPKEK 0.010 Table XX-V3-B3501-9mers-282P1G3 611 TALDSAADI 2.400 2 IVPSVPKFP 0.010 23 KAIEIPSSV 2.400 4 PSVPKFPKE 0.005 Each peptide is a portion of j SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start ' position plus eight. j 1152 YSDSDEKPL 2.250 8 KFPKEKIDP 0.003 5 LLGRGLIVY 2.000 7 PKFPKEKID 0.000 997 SNLNATTKY 2.000 738 ASQPKEMII 2.000 Table XX-V2-B3501-9mers-(SET2)-282P1G3 722 TPPAAPDRN 2.000 Star! Subsequence Score) 181 YMSQKGDLY 2.000 | 33 CSKEQELSY 60.001 657 NISEYIVEF 2.000 176

Table XX-V3-B3501-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 52 IQKSTSCNY 6.000 39 | LSYRNRNML 5.000 10 TTYVSNTTY 2.000 24 GSPQPSIFI 2.000 25 SPQPSIFIC 2.000] 38 ELSYRNRNM 2.000 31 FICSKEQEL 1.000 23 TGSPQPSIF 1.000 44 RNMLAEDFl 0.800 4 GVDVINTTY 0.600 56 TSCNYVEKS 0.500 13 VSNTTYVSN 0.500 22 ATGSPQPSI 0.400 60 YVEKSSTFF 0.300 21 NATGSPQPS 0.300 59 NYVEKSSTF 0.200 3 HGVDVINTT 0.200 27 QPSIFICSK 0.200 47 LAEDFIQKS 0.180 32 ICSKEQELS 0.150 58 CNYVEKSST 0.150 9 . NTTYVSNTT 07100 7 VINTTYVSN 0.100 54 KSTSCNYVE 0.100 15 NTTYVSNAT 0.100 8 INTTYVSNT 0.100 12 YVSNTTYVS 0.100 51 FIQKSTSCN 0.100( 43 NRNMLAEDF 0.1 ooj 57 SCNYVEKSS 0.100 1 VIHGVDVIN 10.100 14" SNTTYVSNA 0.100 6~ DVINTTYVS1 0.100 42 RNRNMLAED1 0.060 19 VSNATGSPQ 0.050 35 KEQELSYRN 0.040 62 EKSSTFFKI 0.040

Table XX-V3-B3501-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 46 MLAEDFIQK 0.030 40 SYRNRNMLA 0.030 5 VDVINTTYV 0.020 11 TYVSNTTYV 0.020 53 QKSTSCNYV 0.020 2 IHGVDVINT 0.015 45 NMLAEDFIQ 0.015 26 PQPSIFICS 0.010 49 EDFIQKSTS ! 0.010 16 TTYVSNATG 0.010 37 QELSYRNRN 0.010 55 STSCNYVEK 0.010 17 TYVSNATGS 0.010 29 SIFICSKEQ 0.010 18 YVSNATGSP 0.010 20 SNATGSPQP 0.010 50 DFIQKSTSC 0.010 28 PSIFICSKE 0.005 61 VEKSSTFFK 0.003 48 AEDFIQKST 0.003 36 EQELSYRNR 0.003 30 IFICSKEQE 0.001 41 YRNRNMLAE 0.001 34 SKEQELSYR 0.000

Table XX-V4-HLA-B3501-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 8 DLPEQPTFL 2.000 1 VTLYSGEDL 1.000 7 EDLPEQPTF 0.150 4 YSGEDLPEQ 0.150

Table XX-V4-HLA-B3501- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence Score 9 LPEQPTFLK 0.060 2 TLYSGEDLP 0.010 5 SGEDLPEQP 0.006 6 GEDLPEQPT] 0.003 3 LYSGEDLPE] 0.002

Table XX-V5-HLA-B3501- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence] Score 4 LTVNSSNSI 0.400 3 KLTVNSSNS 0.200 8 SSNSIKQRK 0.050 7 NSSNSIKQR 0.050 1 PMKLTVNSS 0.030 9 SNSIKQRKP 0.010 6 VNSSNSIKQ 0.010 2 MKLTVNSSN 0.010 5 TVNSSNSIK ο.ο&amp;#970;ο&amp;#906;

Table XX-V6-HLA-B3501-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Start Subsequence, Score 7 VPKLEHIEQ 0.900 5 FIVPKLEHI 0.400 2 EIEFIVPKL 0.300 6 IVPKLEHIE 0.010 9 KLEHIEQDE 0.006 177

Table XX-V6-HLA-B3501- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and toe end position for each peptide is the start position plus eight Start Subsequence Score 1 EEIEFIVPK 0.002 4 EFIVPKLEH 0.001 3 IEFIVPKLE 0.001 j 8 PKLEHIEQD o.ooo |

Table XX-V7-HLA-B35Q1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, toe length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Start Subsequence Score 10 NISHELFTL 1.500 17 TLHPEPPRW 0.750 4 HVIVEDNIS 0.150 11 ISHELFTLH 0.100 8 EDNISHELF 0.100 9 DNISHELFT 0.100 19 HPEPPRWTK 0.060 3 FHVIVEDNI 0.040 5 ‘ VIVEDNISH •&amp;#908;.030 7 VEDNISHEL 0.030 18 LHPEPPRWT 0.020 2 DFHVIVEDN 0.010 16 FTLHPEPPR 0.010 14 ELFTLHPEP 0.010 6 IVEDNISHE 0.006 13 HELFTLHPE 0.001 1 HDFHVIVED 0,001 15 LFTLHPEPP 0.001 12 SHELFTLHP 0.000 20 PEPPRWTKK 0.000

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, toe length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 398 FPREISFTNL 120.000 849 VPKDRVHGRL 120.000 877 HPKEVNILRF 120.000 539 NPR1PKLHML 60.000 1019 KPITEESSTL 60.000 536 SPKNPRIPKL 60.000 1158 KPLKGSLRSL 40.000 94 IPNEGHISHF 40.000 480 KPLEGRRYHl j 32.000 218 MPMKLTVNSL 20.000 1054 EPGAEHIVRL 20.000 895 VPSLDAFSEF 20.000 752 KSMEQNGPGL 20.000 568 WSKDGEAFEI 18.000 795 APYDVKVQAI 16.000 40 QSKVQVAFPF 15.000 1143 SVKDETFGEY 12.000 810 GPDPQSVTLY 12.000 499 RTTEEDAGSY 12.000 772 APVEWEEETV 12.000 996 LSNLNATTKY 10.000 758 GPGLEYRVTW 10.000 )1162 GSLRSLNRDM 10.000 297 LPKGRETKEN ' 9.000 58 EAKGNPEPTF 9.000 478 EVKPLEGRRY 9.000 627 VPDPPENLHL 9.000 828 APVIHGVDVI 8.000 74 NPFYFTDHRI 8.000 1172 QPTESADSLV 8.000 2 EPLLLGRGLI 8.000 566 LSWSKDGEAF 7.500 67 FSWTKDGNPF 7.500 110 FASNKLGIAM 6.000 309 KTLK1ENVSY 6.000 349 WTKKPQSAVY 6.000 69 WTKDGNPFYF 6.000 785 TLRVMTPAVY 6.000

Table XXI-V1-HLA-B35- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 6 LGRGLIVYLM 6.000 302 ETKENYGKTL 6.000 954 LPKKLNGNLT 6.000 1118 FVKRNRGGKY 6.000 745 IIKWEPLKSM 6.000 914 KGAGPESEPY 6.000 1211 ESNGSSTATF 5.000 244 NSIKQRKPKL 5.000 455 YSAFLHCEFF 5.000 557 DSHLKHSLKL 5.000 358 YSTGSNGILL 5.000 1093 ISTQGWFIGL 5.000 473 WQKVEEVKPL 4.500 1080 ETRGREYAGL 4.500 934 QPTFLKViKV 4.000 735 RVQASQPKEM 4.000 1077 DVIETRGREY 4.000 991 KPSWHLSNLN 4.000 693 APFVRYQFRV 4.000 373 EPQPTIKWRV 4.000 34 VPTIIKQSKV 4.000 1048 HPIEVFEPGA 4.000 538 KNPRIPKLHM 4.000 790 TPAVYAPYDV 4.000 440 LIQTKDGENY 3.000 315 NVSYQDKGNY 3.000 449 YATWGYSAF 3.000 I 916 AGPESEPYIF 3.000 I 516 IGKTAVTANL 3.000 11203 GSKEKGSVES 3.000 | 798 DVKVQAINQL 3.000 11000 NATTKYKFYL 3.000 11044 TQKTHPIEVF 3.000 j 418 EASNVHGTIL 3.000 | 596 NVTLEDQGIY 3.000 (875 RTHPKEVNIL 3.000 | 857 RLKGYQINWW 3.000

Table XXI-V1-HLA-B35- 10mers-282P1G3 178 "'Table XX1-V1-HLA-B35- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 1104 CAIALLTLLL 3.000 I 245 SIKQRKPKLL 3.000 j 725 AAPDRNPQN! 2.400 155 PPKGLPPLHI 2.400 21 FSKAIEIPSS 2.250 274 LLLECFAEGL 2.000 159 LPPLHIYWMN 2.000 957 KLNGNLTGYL 2.000 132 KIPKEKIDPL, 2.000 43 VQVAFPFDEY 2.000 29 SSVQQVPTII 2.000 264 SSITILKGEI 2.000 988 TPSKPSWHLS 2.000 260 SGSESSITIL 2.000 689 ILPLAPFVRY 2.000 158 GLPPLHIYWM 2.000 780 TVTNHTLRVM 2.000 4 LLLGRGLIVY 2.000 960 GNLTGYLLQY 2.000 ! 967 LQYQIINDTY 2.000 255 LPPTESGSES 2.000 730 NPQNIRVQAS '2.000 788 VMTPAVYAPY 2.000 8 RGLIVYLMFL 2.000 406 NLQPNHTAVY 2.000

Table XXI-V2-HLA-B3501-10mers-(SET 1)-282P1 G3 Each peptide is a portion of SEQJD NO: 5; each start posiiion is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 10 FPKEKIDPLE 1.200 7 VPKFPKEKID 0.600 6 SVPKFPKEKI 0.400

Table XXI-V2-HLA-B3501-10mers-(SET 1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 4 VPSVPKFPKE 0.200 9 KFPKEKIDPL 0.200 1 EFIVPSVPKF 0.100 3 IVPSVPKFPK1 0.010 2 FIVPSVPKFP 0.010 5 PSVPKFPKEK 0.005 8 (PKFPKEKIDP 0.000

Table XX1-V2-HLA-B3501- 10mers-(SET2)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 1 ESSTLGEGKY 10.000 4 TLGEGKYAGL 2.000 2 SSTLGEGKYA 0.750 5 LGEGKYAGLY 0.600 8 GKYAGLYDDl 0.040 7 EGKYAGLYDD 0.030 3 STLGEGKYAG . 0.010 j 6 GEGKYAGLYD 0.0011

Table XXI-V2-HLA-B3501-10mers-(SET 3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 2 ESSTLGEGKY 10.00 o 5 TLGEGKYAGL 2.000 3 SSTLGEGKYA 0.750

Table XXI-V2-HLA-B3501- 10mers-(SET3)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 6 LGEGKYAGLY 0.600 9 GKYAGLYDDl 0.040 8 EGKYAGLYDD 0.030 10 KYAGLYDDIS 0.020 4 STLGEGKYAG 0.010 I 7 GEGKYAGLYD 0.001 1 EESSTLGEGK |( 0.001

Table XXI-V3-HLA-B3501-10mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, ' and the end position for each peptide is the start position plus nine. Start Subsequence Score 43 RNRNMLAEDF 6.000 : 4 HGVDVINTTY 4.000 52 FIQKSTSCNY 2.000 ) 26 SPQPSIFICS 2.000 33 ICSKEQELSY 2.000 10 NTTYVSNTTY 2.000 22 NATGSPQPSl 1.200 39 ELSYRNRNML 1.000 59 CNYVEKSSTF 1.000 23 ATGSPQPSIF 1.000 53 IQKSTSCNYV 0.600 14 VSNTTYVSNA 0.500 | 40 LSYRNRNMLA 0.500 57 TSCNYVEKSS 0.500 35 GSPQPSIFIC 0.500 34 CSKEQELSYR 0.450 24 TGSPQPSIF! 0.400 60 . NYVEKSSTFF 0.200 28 QPSIFICSKE 0.200 11 TTYVSNTTYV 0.200 47 MLAEDFIQKS. 0.200 179 .'Table XXI-V3-HLA-B3501-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 38 QELSYRNRNM 0.200 48 LAEDFIQKST 0.180 32 FICSKEQELS 0.150 58 SCNYVEKSST 0.150 2 V1HGVDVINT 0.150 62 VEKSSTFFKl 0.120 9 iNTTYVSNTT 0.100 31 IFICSKEQEL 0.100 7 DVINTTYVSN 0.100 13 YVSNTTYVSN 0.100 17 TTYVSNATGS 0.100 21 SNATGSPQPS 0.100 55 KSTSCNYVEK 0.100 56 STSCNYVEKS 0.100 8 VINTTYVSNT 0.100 15 SNTTYVSNAT 0.100 5 GVDVINTTYV 0.060 20 VSNATGSPQP 0.050 44 NRNMLAEDFI 0.040 45 RNMLAEDFIQ 0.030 37 EQELSYRNRN 0.030 46 NMLAEDFIQK '&amp;#908;.015 19 YVSNATGSPQ 0.010 51 DFIQKSTSCN 0.010 1 PVIHGVDVIN 0.010 30 SIF1CSKEQE 0.010 16 NTTYVSNATG 0.010 6 VDVINTTYVS 0.010 12 TYVSNTTYVS 0.010 3 IHGVDVINTT 0.010 50 EDFIQKSTSC 0.010 29 PSIFICSKEQ 0.005 36 KEQELSYRNR 0.004 41 SYRNRNMLAE 0.003 49 AEDFIQKSTS 0.003 35 SKEQELSYRN 0.003 61 YVEKSSTFFK 0.003

Table XXI-V3-HLA-B3501- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 54 QKSTSCNYVE 0.001 42 YRNRNMLAED 0.001 27 PQPSIFICSK 0.001 18 TYVSNATGSP 0.001

Table XX1-V4-HLA-B35-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of pepiide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 10 LPEQPTFLKV 1.200 1 SVTLYSGEDL 1.000 8 EDLPEQPTFL 0.100 5 YSGEDLPEQP 0.100 6 SGEDLPEQPT 0.060 7 GEDLPEQPTF 0.045 9 DLPEQPTFLK 0.020 3 TLYSGEDLPE 0.015 2 VTLYSGEDLP 0.010 4 LYSGEDLPEQ 0.002 j

Table XXI-V5-HLA-B35- | 10mers-282P1G3 j Each peptide is a portion of ) SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. | Start Subsequence Score [ 1 MPMKLTVNSS 2.000 | 4 KLTVNSSNSI 0.800 8 NSSNSIKQRK 0.050 9 SSNSIKQRKP 0.050 I 2 jPMKLTVNSSN 0.030

Table XXI-V5-HL4-B35-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 6 TVNSSNSIKQ 0.010 10 SNS1KQRKPK 0.010 3 MKLTVNSSNS 0.010 7 VNSSNSIKQR 0.010 5 LTVNSSNSIK 0.010

Table XXI-V6-HLA-B35-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of pepiide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 8 VPKLEHIEQD 0.600 2 EEIEFIVPKL 0.200 5 EFIVPKLEHI 0.040 7 IVPKLEHIEQ 0.015 6 FIVPKLEHIE 0.010 10 KLEHIEQDER 0.009 3 ElEFIVPKLE 0.003 4 IEFIVPKLEH 0.001 1- SEEIEFIVPK 0.000 I 9- PKLEHIEQDE 0.000

Tabie XX1-V7-HLA-B35-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each pepiide is the start position plus nine. Start Subsequence Score 10 DNISHELFTL 1.500 17 ftlhpepprw 0.750 7 IVEDNISHEL 0.600 18 TLHPEPPRWT 0.100 J 180 Λ Table XXI-V7-HLA-B35- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peplide is 10 amino acids, and the end position for each peptide is the start position pius nine. Start Subsequence Score 12 ISHELFTLHP 0.100 20 HPEPPRWTKK 0.060 3 DFHVIVEDNI 0.040 8 VEDNISHELF 0.030 6 VIVEDNISHE 0.020 4 FHVIVEDNIS 0.015

Table XXI-V7-HLA-B35- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peplide is 10 amino acids, and the end position for each peplide is the start position plus nine. Start Subsequence j Score 5 HVIVEDNISH j 0.015 15 ELFTLHPEPP 0.010 11 NISHELFTLH 0.010 2 HDFHVIVEDN 0.010 9 EDNtSHELFT 0.010 19 LHPEPPRWTK 0.002

Table XXI-V7-HLA-B35- 10mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Start Subsequence Score 16 LFTLHPEPPR 0.001 14 HELFTLHPEP 0.001 13 SHELFTLHPE 0.000 1 THDFHVIVED 0.000 21 PEPPRWTKKP 0.000 j 181

Tables XXII-XLIX:

TableXX!l-HLA-V1-A1-9mers-282P1 G3 TableXXII-HLA-V1-A1- I 9mers-282P1G3 | TableXXll-HLA-V1-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion I of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. | Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score Pos 123456789 score| 30S 123456789 score 500 TTEEDAGSY 31 975 TYEIGELND 1S| 094 STQGWFIGL 16 1144 VKDETFGEY 29 1021 ITEESSTLG 18 1152 YSDSDEKPL 16 1078 VIETRGREY 27 1082 RGREYAGLY 18 49 FDEYFQ1EC 15 173 H|EQDERVY 26 1173 PTESADSLV 18 299 KGRETKENY 15 69 WTKDGNPFY 24 62 NPEPTFSWT 17 318 YQDKGNYRC 15 755 EQNGPGLEY 24 99 HISHFQGKY 17 326 CTASNFLGT 15 961 NLTGYLLQY 24 143 VEEGDPIVL 17 359 STGSNGILL 15 5 LLGRGLIVY 23 310 TLKIENVSY 17 466 SPEAWSWQ 15 579 GTEDGRIII 23 343 VEEPPRWTK 17 482 LEGRRYHIY 15 789 MTPAVYAPY 23 434 VVDVRPLIQ 17 580 TEDGRIIID 15 816 VTLYSGEDY 23 476 VEEVKPLEG 17 653 DHNSNISEY 15 350 TKKPQSAVY 22 479 v'KPLEGRRY 17 658 ISEYIVEFE 15 597 VTLEDQGIY 22 636 LSERQNRSV 17 747 KWEPLKSME 15 903 EFHLTVLAY 22 669 KEEPGRWEE 17 932 PEQPTFLKV 15 1154 DSDEKPLKG 22 957 KLNGNLTGY 17 972 INDTYEIGE 15 78 FTDHRIIPS 21 1052 VFEPGAEHI 17 1000 NATTKYKFY 15 145 EGDPIVLPC 21 1083 GREYAGLYD 17 1183 YGEGDHGLF 15 120 SEEIEFIVP 20 (1129 VKEKEDLHP 17 1193 EDGSFIGAY I 15 157 KGLPPLHIY 20 |l191 FSEDGSFIG 17 181 YMSQKGDLY 20 | 194 EEKDSRNDY 16 TableXXII-HLA-V2- (SET1)-A1-9mers- (SET1)-282P1G3 236 STEIGSKAH 20 ( 270 KGEILLLEC 16 316 VSYQDKGNY 20 | 336 THDFHVIVE 16 Each peptide is a portion ofSEQIDNO: 5; each 1192 SEDGSFIGA 20 | 371 EGEPQPTIK 16 44 QVAFPFDEY 19 | 393 AGDWFPRE 16 start position is 690 LPLAPFVRY 19 407 LQPNHTAVY 16 bpeuiiicu, uic icuyui ui peptide is 9 amino acids, and the end position for 915 GAGPESEPY 19 441 IQTKDGENY 16 919 ESEPYIFQT 19 447 ENYATVVGY 16 each peptide is the start position plus eight 997 SNLNATTKY 19 630 PPENLHLSE 16 Pos 123456789 score 1119 VKRNRGGKY .19 ] 786 LRVMTPAVY 16 J PSVPKFPKE 13 1175 ESADSLVEY 19 1 810 GPDPQSVTL 16 J FIVPSVPKF 8 257 PTESGSESS 16 1 853 RVHGRLKGY 16 J 489 IYENGTLQI 16 3 878 PKEVNILRF 16 TaWoYYIl-HI Δ-Χ/9- 586 IIDGANLTI 16 901 FSEFHLTVL 16 (SET2)-A1-9mers- 598 TLEDQGIYC 16 944 DKDTATLSW 16 (SET2)-282P1G3 627 VPDPPENLH π 968 QYQIINDTY 16 Each peptide is a portion of SEQ ID NO: 5; each 811 IL=== PDPQSVTLY 16 a 1022 TEESSTLGE 16 182 start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 5 KGREAKENY 15 9 AKENYGKTL 13 6 GREAKENYG 10

TableXXll-HLA-V2- (SET3)-A1-9mers- (SET3)-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight,

Pos 123456789 score 2 SSTLGEGKY 25 6 GEGKYAGLY 18 TabieXXII-HLA-V3-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. , Pos 123456789 score 33 CSKEQELSY 27 4 GVDVINTTY 26 10 TTYVSNTTY 22 52 IQKSTSCNY 15

TabieXXll-HLA-V4-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 9 LPEQPTFLK 13

TableXXil-HLA-V4-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eighL Pos 123456789 score 5 SGEDLPEQP 12 6 GEDLPEQPT 11 1 VTLYSGEDL 8 3 LYSGEDLPE 7 4 YSGEDLPEQ U

Tab!eXXII-HLA-V5-A1- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 scor e 6 VNSSNSIKQ 7 4 LTVNSSNSI 6 8 SSNSIKQRK 6 7 NSSNSIKQR 4 9 SNSIKQRKP 4 2 MKLTVNSSN 3

TableXXii-HLA-V6-A1-~1 9mers-282P1G3 j

Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of j peptide is 9 amino acids, and the end position for each peptide is the start [ position plus eight. os 123456789

EIEFIVPKL

KLEHIEQDE

EFIVPKLEH score 13 11

TabieXXil-HLA-V7-Al-9mers-282P1 G3

Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 12 SHELFTLHP 18 19 HPEPPRWTK 16 7 VEDNISHEL 11 6 tVEDNISHE 10 11 ISHELFTLH 9 16 FTLHPEPPR 8

TableXXIil-V1-HLA-A0201- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 1108 LLTLLLLTV 29 9 GLIVYLMFL 28. 125 FIVPSVPKL 28 268 ILKGELLL 28 836 VINSTLVKV 28 1101 GLMCAIALL 28 1111 LLLLTVCFV 28 4 LLLGRGUV 27 1105 AlALLTLLL 26 688 VILPLAPFV 25 118 AMSEEIEFI 24 426 ILANANIDV 24( 785 TLRVMTPAV 24( 1107 ALLTLLLLT 24| 1159 PLKGSLRSL 24| 17 LLLKFSKAl 23( 206 AAFPRLRTl 23( 275 LLECFAEGL 23( 406 NLQPNHTAV 23 .586 IIDGANLTI 23 591 NLTISNVTL 23 .826 DTAPVIHGV 23 970 QIINDTYEi 23 1106 IALLTLLLL 23 245 SIKQRKPKL 22 183 267 TILKGEILL “~22) 584 RIIIDGANL . 22 923 YIFQTPEGV 22 1027 TLGEGSKGI 22 6 LGRGLIVYL . 21 23 KAIEIPSSV 21 37 IIKQSKVQV 21 163 HIYWMNIEL 21 166 WMNIELEHI 21 219 PMKLTVNSL 21 253 LLLPPTESG 21 427 LANANIDW 21 429 NANIDVVDV 21 619 ITQVTVLDV 21 753 SMEQNGPGL 21 942 KVDKDTATL 21 1033 KGIGKISGV 21 1042 NLTQKTHPI 21 1073 SIFQDVIET 21 1104 CAIALLTLL 21 10 LIVYLMFLL 20 13 YLMFLLLKF 20 16 FLLLKFSKA 20 122 EIEFIVPSV 20 210 RLRTIVQKM 20 265 S.ITILKGE! 20 274 LLLECFAEG 20 335 ATHDFHVIV 20 585 IHDGANLT : 20 589 GANLTISNV 20 616 AADITQVTV 20 793 VYAPYDVKV 20 3 PLLLGRGLl 19 26 EIPSSVQQV 19 266 ITILKGEIL 19 451 TWGYSAFL 19 471 VSWQKVEEV 19 657 NISEYIVEF 19 680 RVQGKKTTV 19 890 RNSGMVPSL 19 935 PTFLKVIKV 19 949 TLSWGLPKK 19 957 KLNGNLTGY 19 976 YElGELNDt 19 995 HLSNLNATT 19 1088 GLYDDISTQ 19 1094 STQGWFIGL 19 1103 MCAIALLTL 19 5 LLGRGLIVY 18 11 IVYLMFLLL 18 133 LPKEKIOPL 18 214 IVQKMPMKL 18 292 KIGGDLPKG 18 515 A1GKTAVTA 18 617 ADITQVTVL 18 673 GRWEELTRV 18 700 FRViAVNEV 18· 743 EMIIKWEPL 18 840 TLVKVTWST 18 900 AFSEFHLTV 18 953 GLPKKLNGN 18 1020 PITEESSTL 18 1136 HPDPEIQSV 18 29 SSVQQVPTI 17 154 NPPKGLPPL 17 238 EIGSKANS! 17 333 GTATHDFHV 17 424 GTILANANI 17 444 KDGENYATV 17 481 PLEGRRYHI 17 514 NAIGKTAVT 17) 537 PKNPRIPKL 17 540 PRIPKLHML 17 558 SHLKHSLKL 17 611 TALDSAADI 17 810 GPDPQSVTL 17 829 PVIHGVDVI 17 833 GVDVINSTL 17 841 LVKVTWSTV 17 863 INWWKTKSL 17 870 SLLDGRTHP 17 871 LLDGRTHPK 17 875 RTHPKEVNI 17 930 GVPEQPTFL 17 946 DTATLSWGL 17 950 LSWGLPKKL 17 961 NLTGYLLQY 17 1055 PGAEHIVRL 17 1110 TLLLLTVCF 17 1121 RNRGGKYSV] 17 1163 SLRSLNRDM 17 |1166 SLNRDMQPT 17 35 PTIIKQSKV ~~16 137 KIDPLEVEE 16 161 PLHIYWMNI 16 I 216 QKMPMKLTV 16 j 252 KLLLPPTES 16 280 AEGLPTPQV 16 359 STGSNGILL 16 366 LLCEAEGEP 16 370 AEGEPQPTI 16 432 IDWDVRPL 16 463 FFASPEAW 16 525 LDIRNATKL 16 534 RVSPKNPRI 16 603 GIYCCSAHT 16 608 SAHTALDSA 16 612 ALDSAADIT 16 691 PLAPFVRYQ 16 780 TVTNHTLRV 16 788 VMTPAVYAP 16 799 VKVQAINQL 16 893 GMVPSLDAF 16 908 VLAYNSKGA 16 1001 ATTKYKFYL 16 1179 SLVEYGEGD 16 14 LMFLLLKFS 15 82 RIIPSNNSG 15 83 IIPSNNSGT 15 86 'SNNSGTFRI 15 142 EVEEGDPIV 15 254 LLPPTESGS 15 273 ILLLECFAE 15 308 GKTLKIENV 15 327 TASNFLGTA 15 349 WTKKPQSAV 15 364 GILLCEAEG 15 365 ILLCEAEGE 15 474 QKVEEVKPL 15 487 YHIYENGTL 15 546 HMLELHCES 15 579 GTEDGRIII 15 614 DSAADITQV 15 615 SAADITQVT 15 626 DVPDPPENL 15 684 KKTTVILPL 15 746 IKWEPLKSM 15 808 GSGPDPQSV 15 184 876| THPKEVNIL 15 926) QTPEGVPEQ •15 958 LNGNLTGYL 15 965 YLLQYQliN . 15 966 llqyqiin.d 15) 980 ELNDINITT 15) 991 KPSWHLSNL 15| 1092 DISTQGWFI 15) 1099 FIGLMCAIA 15| 1100 IGLMCAIAL 15| 1102 LMCAiALLT 15) 1113 LLTVCFVKR 15| 19 LKFSKAiEI 14 30 SVQQVPTII 14 107 YRCFASNKL 14 110 FASNKLGIA 14 115 LGIAMSEEI 14 150 VLPCNPPKG 14 158 GLPPLHIYW 14 185 KGDLYFANV 14 217 KMPMKLTVN 14 ,-260 SGSESSITI 14 261 GSESSITIL 14 282 GLPTPQVDW 14 305 ENYGKTLKI 14 331 FLGTATHDF 14 489 IYENGTLQI 14 504 DAGSYSCWV ' 14) 517 GKTAVTANL 14 524 NLDIRNATK 14 527 IRNATKLRV 14 542 IPKLHMLEL 14 556 CDSHLKHSL 14 569 SKDGEAFEl ; 14 697 RYQFRVIAV I 14l 702 VIAVNEVGR 14) 757 NGPGLEYRV 14] 781 VTNHTLRVM 14) 822 EDYPDTAPV 14 828 APVIHGVDV 14 940 VIKVDKDTA 14 973 NDTYE|GEL 14 1008 YLRACTSQG 14 1036 GKISGVNLT 14) 1037 KISGVNLTQ 14) 1058 FEPGAEHIV 14 1066 KNWGDNDSI 14) 1098 WFIGLMCAI 14) 1112 LLLTVCFVK 14) 1189 GLFSEDGSF 14) 1202 AGSKEKGSV 14) 1216 STATFPLRA “&amp;#906;4)

TableXXI)l-V2-(SET1)- HLA-A0201-9mers- (SET1)-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Pos 123456789 score

FIVPSVPKF

FPKEKIDPL

VPKFPKEKI

SVPKFPKEK 18 17 10

<img img-format="tif" img-content="drawing" file="IL233223AD00021.tif" id="idf0001" />

TableXXIII-V2-(SET3)- HLA-A0201-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 5 LGEGKYAGL 17 4 TLGEGKYAG 16 9 KYAGLYDDI 14 3 STLGEGKYA 13 I θ GKYAGLYDD 9

TableXX!ll-V3-HLA- A0201-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos | 123456789 score 31 FICSKEQEL 22 22 ATGSPQPSI 18 7 VINTTYVSN 14 39 1 QVDMOkIMt LO 1 t\i\i \txiVli_ 4 Λ ~T 46 MLAEDF1QK 14 &amp;#942; VIHGVDVIN 13 5 VDVINTTYV 13 47 LAEDFIQKS 13 3 HGVDVINTT 12 11 TYVSNTTYV 12 29 SIFICSKEQ 12 51 FIQKSTSCN 11| 53 QKSTSCNYV 11) 2 IHGVDVINT io) 8 INTTYVSNT w| 14 SNTTYVSNA to) 18 YVSNATGSP 10[ 24 GSPQPSIFI 10) 38 ELSYRNRNM 10 45 NMLAEDFIQ 10 55 STSCNYVEK 10 185

TabieXXIll-V4-HLA- A0201-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight Pos 123456789 ((score 8 DLPEQPTFL 21 VTLYSGEDL 16 2 TLYSGEDLP 13 4 YSGEDLPEQ 11 is the start position plus eight Pos 123456789 score 10 NISHELFTL 24 7 VEDNISHEL 14 5 VIVEDNISH 13 17 TLHPEPPRW 13 14 ELFTLHPEP 12 7ableXXIV-V6-HLA- A0203-9mers-(SET2)~ 282P1G3

<img img-format="tif" img-content="drawing" file="IL233223AD00022.tif" id="idf0002" />

NoResultsFound.

TableXX!V-V7-HLA- A0203-9mers-(SET2)~ 282P1G3

TableXXIll-V5-HLA- A0201-9mers-282P1G3

Each peptide is a portion of SEQID NO: 11; each start position is specified, the length of peptide is 9 amino adds, and the end position for each peptide is the start position plus eight.

Pos 123456789 score LTVNSSNSl

llPMKLTVNSS

[KLTVNSSNS(f 17 21 w

TabieXXII!-V6-HLA- A0201.-9mers- 282P1G3

Each peptide is a portion of SEQ ID. NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight

Pos 123456789 score 5 FIVPKLEHI 24 2 EIEFIVPKL 20

TableXXIII-V7-HLA- A0201-9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide

TableXX!V-V1-HLA- A0203-9mers- 282P1G3

Posj [123456789) (score

NoResultsFound.

TabieXXIV-V2- (SET1)HLA-A0203- 9mers-282P1G3

Pos](l23456789([score

NoResultsFound.

TableXXIV-V2- (SET2)-HLA-A0203- 9mers-282P1G3 Pos 123456789 (score NoResultsFound.

TableXXIV-V2-(SET3)-HLA-A0203-9mers-282P1 G3 Pos{ (123456789( (score

NoResultsFound.

TableXXlV-V3-HLA- A0203-9mers- 282P1G3

Pos (123456789(( score

NoResultsFound.

TableXXIV-V4-HLA- A0203-9mers-(SET2)- 282P1G3

Pos 123456789 score

NoResultsFound.

TableXXIV-V5-HLA- A0203-9mers-(SET2)- 282P1G3 (Posj (123456789 (score

NoResultsFound.

Pos[ 123456789( score

NoResultsFound.

Tab!eXXV-V1-HLA-A3- j 9mers-282P1G3 j Each peptide is a portion of SEQ SD NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 792 AVYAPYDVK 33 835 DVINSTLVK 31 436 DVRPLIQTK 30 524 NLDIRNATK 30 149 IVLPCNPPK 27 296 DLPKGRETK 27 , 843 KVTWSTVPK 27 1112 LLLTVCFVK 27 1118 FVKRNRGGK 26( 1197 FIGAYAGSK 26( 5 LLGRGLIVY 25| 677 ELTRVQGKK 25( 937 FLKVIKVDK 25( | 310 TLKIENVSY 24 (701 RVIAVNEVG 24 I 760 GLEYRVTWK 24 j 853 RVHGRLKGY 24 J 871 LLDGRTHPK 24 j 951 NLTGYLLQY 24 356 AVYSTGSNG 23 547 MLELHCESK 23 4 LLLGRGLIV 22 106 KYRCFASNK 22 pt29 SVPKLPKEK 22 209 PRLRTIVQK 22 ~413 AVYQCEASN 22 (Til AIGKTAVTA 22 186

TableXXV-V1-HLA-A3-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 584 RHIDGANL 22 680 RVQGKKTTV 22 689 ILPLAPFVR 22 949 TLSWGLPKK 22 957 klngnltgy 22 998 NLNATTKYK 22 1088 GLYDDISTQ 22 381 RVNGSPVDN 21 396 WFPREISF 21 687 TVILPLAPF 21 744 MIIKWEPLK 21) 787 RVMTPAVYA 21 882 NILRFSGQR 21 948 ATLSWGLPK 21 983 DINITTPSK 21 1008 YLRACTSQG . 21 1037 KISGVNLTQ 21 1051 EVFEPGAEH 21 1110 TLLLLTVCF 21 11 IVYLMFLLL 20 82 RilPSNNSG 20 213 TIVGKMPMK . 20 221 KLTVNSLKH 20 291 NKIGGDLPK 20 530 ATKLRVSPK 20 661 YIVEFEGNK 20 704 AVNEVGRSQ 20 733 nirvqasqp 201 942 KVDKDTATL 20 1058 EHIVRLMTK 20 )1122 NRGGKYSVK 20) 24 AIEIPSSVQ 19 44 QVAFPFDEY 19 177 DERVYMSQK 19 478 EVKPLEGRR 19 520 AVTANLDIR 19 585 IIIDGANLT 19

TableXXV-V1-HLA-A3- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length' of peptide is 9 amino acids, and the end' position for each peptide is the start position plus eight Pos 123456789 score 586 IIDGANLTI 19 591 NLTISNVTL 19 645 RLTWEAGAD 19) 829 PVfHGVDVI 19) 851 KDRVHGRLK 19 996 LSNLNATTK 19 1040 GVNLTQKTH 19 1078 VIETRGREY 19 1209 SVESNGSST 19 37 IIKQSKVQV 18 137 KIDPLEVEE 18 173 HIEQDERVY 18 179 RVYMSQKGD 18 187 DLYFANVEE 18 . 252 KLLLPPTES 18 268 ILKGEILLL 18 343 VEEPPRWTK 18' 534' RVSPKNPR1 18 j 841 LVKVTWSTV 18 ( 859 KGYQINWWK 18 ( 861 YQINWWKTK 18 j 870 SLLDGRTHP 18 J 883 ILRFSGQRN 18 | 995 HLSNLNAH 18 )1082 RGREYAGLY 18 (1107 ALLTLLLLT 18 )1108 LLTLLLLTV. 18 )1113 LLTVCFVKR 18 )1128 SVKEKEDLH 18 )1137 PDPEIQSVK 18 )1199 GAYAGSKEK 18 I 3 PLLLGRGLI 17 I 13 YLMFLLLKF 17 I 16 FLLLKFSKA 17 j 114 KLGIAMSEE 17 ) 124 EFIVPSVPK 17 ) 210 RLRTIVQKM 17

TableXXV-V1-HLA-A3-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 253 LLLPPTESG 17 340 HVIVEEPPR 17 350 TKKPQSAVY 17| 365 tLLCEAEGE 17 452 WGYSAFLH ) 17 469 AVVSWQKVE 17 488 HIYENGTLQ 17 494 TLQINRTTE 17 532 KLRVSPKNP 17 657 NISEYIVEF 17 695 FVRYQFRVI 17 702 VIAVNEVGR 17 803 AINQLGSGP 17 833 GVDVINSTL 17 857 RLKGYQINW 17 869 KSLLDGRTH 17 897 SLDAFSEFH 17 907 TVLAYNSKG 17 939 KVIKVDKDT 17 1006 KFYLRACTS 17 1025 SSTLGEGSK 17 1180 LVEYGEGDH 17 1189 GLFSEDGSF 17 8 RGLIVYLMF 16 93 RIPNEGHIS 16 220 MKLTVNSLK 16 254 LLPPTESGS 16 273 ILLLECFAE 16 274 LLLECFAEG 16 304 KENYGKTLK 16 312 KIENVSYQD 16 344 EEPPRWTKK j 16 390 HPFAGDVVF 16 421 NVHGTILAN 16 430 ANIDWDVR • 16 434 WDVRPLIQ 16 447 ENYATVVGY 16 187

TabIeXXV-V1-HLA-A3-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 472 SWQKVEEVK 16 526 DIRNATKLR 16 544 KLHMLELHC 16 563 SLKLSWSKD 16 612 ALDSAADIT 16 621 QVTVLDVPD 16 637 SERQNRSVRj '643 SVRLTWEAG .16 | 688 VILPLAPFV 16 I 735 RVQASQPKE 16 j 764 RVTWKPQGA 16 | 795 APYDVKVQA 16 j 817 TLYSGEDYP 16 I 934 QPTFLKVIK 16 (1011 ACTSQGCGK 16 (1020 PITEESSTL 16 [1038 ISGVNLTQK 16 Jl060 IVRLMTKNW 16 1077 DVIETRGRE 16 1105 AIALLTLLL 16 1119 VKRNRGGKY 16 HLA-A3-9mers-282P1G3 Each peptide is a portion ofSEQIDNO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 2 DLPKGREAK 24 7 REAKENYGK 15 5 KGREAKENY 13 9 AKENYGKTL ii|

TableXXV-V2-lSET3)- HLA-A3-9mers-282P1G3 Each peptide is a portion I of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. | Pos 123456789 scorej 4 TLGEGKYAG 14( 1 ESSTLGEGK 13| 2 SSTLGEGKY 11 6 GEGKYAGLY 10 3 STLGEGKYA 8 8 GKYAGLYDD 8 7 EGKYAGLYD 7 5 LGEGKYAGL 6 9 KYAGLYDDI ! θ

TableXXV-V3-HLA-A3- 9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 12 YVSNTTYVS 15 27 QPSIFICSK 15 55 STSCNYVEK 15 60 YVEKSSTFF 15 7 VINTTYVSN 14 18 YVSNATGSP 14 33 CSKEQELSY 13 59 NYVEKSSTF 13 38 ELSYRNRNM 12

TableXXV-V2- (SET1)HLA-A3-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 5 SVPKFPKEK 22 1 FIVPSVPKF 15 2 IVPSVPKFP 14 3 VPSVPKFPK 10

TableXXV-V4-HLA-A3- I 9mers-282P1G3 | Each peptide is a portion j of SEQ ID NO: 9; each I start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. , Pos 123456789 | score| 2 TLYSGEDLP 16| 7 EDLPEQPTF 13j 8 DLPEQPTFL 13 9 LPEQPTFLK! 10

TableXXV-V3-HLA-A3- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 46 MLAEDFIQK 25 4 GVDVINTTY 21 6 DVINTTYVS 18 1 VIHGVDVIN 15 | 10 TTYVSNTTY 15

TableXXV-V5-HLA-A3- 9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start - position plus eight

Pos 123456789 score 5 TVNSSNSIK 23 3

KLTVNSSNS 16

SSNSIKQRK 11

TabieXxTvmWA^

TableXXV-V2-(SET2)- 188 9mers-282P1G3 , Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 1 EEIEFIVPK 18 9 KLEHIEQDE 13 5 FIVPKLEHI 12 6 IVPKLEHIE 12 4 EFIVPKLEH 10 2 EIEFIVPKL 8

TableXXV-V7-HLA-A3- 9mers-282R1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and toe end position for each peptide is the start position plus eight. Pos 123456789 score 19 HPEPPRWTK 18 6 IVEDNISHE 16 20 PEPPRWTKK 16 5 VIVEDNISH 15 17 TLHPEPPRW 14 4 HVIVEDNIS v 13 10 NISHELFTL 12 14 ELFTLHPEP | 10 11 F ISHELFTLH I 8

TableXXVI-V1-HLA-A26- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 8 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 626 DVPDPPENL 27 687 "TViLPLAPF 27 105 1 EVFEPGAEH 27 119 EDGSFIGAY 27

Tab(eXXV-V7-HLA-A3- 9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight

Pos}| 123456789~~]|score| 27 903 EFHLTVLAY 26 396 WFPREISF 25 436 DVRPLIQTK 25 653 DHNSNISEY 25 946 DTATLSWGL 25 107 7 DVIETRGRE 25 117 5 ESADSLVEY 25 447 ENYATWGY 24 853 RVHGRLKGY 24 929 EGVPEQPTF 24 302 ETKENYGKT 23 433 DWDVRPLI 23 451 TWGYSAFL 23 478 EVKPLEGRR 23 500 TTEEDAGSY 23 743 EMIIKWEPL 23 779 ETVTNHTLR 23 835 DVINSTLVK 23 114 7 ETFGEYSDS 23 125 FiVPSVPKL 22 142 EVEEGDPiV 22 266 ITiLKGEiL 22 395 DWFPREIS 22 450 ATVVGYSAF 22 755 EQNGPGLEY 22 833 GVDVINSTL 22 880 EVNILRFSG 22( 109 1 DDISTQGWF 22 122 EIEFIVPSV 21 194 EEKDSRNDY 21 359 STGSNGILL 21 59/ VTLEDQGIY 21 701 EVGRSQPSC jj 21

Tab!eXXV-V7-HLA-A3- 9mers-282PlG3

Each peptide is a portion of SEQ ID NO: 15; each start position is specified! the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight

Pos)[ 123456789~j|score 826 DTAPVIHGV 21 974 DTYEIGELN 21 2 EPLLLGRGL 20 26 EIPSSVQQV 20 44 QVAFPFDEY 20j 121 EEIEFIVPS 20 289 DWNKIGGDL 20, 573 EAFEINGTE 20 778 EETVTNHTL 20 930 GVPEQPTFL 20 115 6 DEKPLKGSL 20 118 2 EYGEGDHGL 20 11 IVYLMPLLL 19 | 69 WTKDGNPFY 19 j 136 EKIDPLEVE 19, | 214 IVQKMPMKL 19( j 540 PRIPKLHML 19) 721 ETPPAAPDR 19( 798 DVKVQAINO 19, 816 VTLYSGEDY 19| 935 PTFLKVIKV 19( 942 |KVDKDTATL 19 105 8 EHIVRLMTK 19 108 0 ETRGREYAG 19 145 EGDPIVLPC 18 j 474 QKVEEVKPL 18 ( 477 EEVKPLEGR 18 ( 592 LTISNVTLE 18 (~638 ERQNRSVRL 18 | 657 NISEYIVEF 18 j 679 EEPGRWEEL 18 789 MTPAVYAPY 18 829 PVIHGVDVI 18 899 GMVPSLDAF 18 189 • Tab!eXXV-V7-HLA-A3-9mers-282P1G3 Each peptide is a portio of SEQ ID NO: 15; eac start position is specifie the length of peptide is amino acids, and the er position for each peptid is the start position plu eight. n ri, 9 d e s Pos|| 123456789 |(scc ire) 109 4 STQGWFIGL 18 10 LIVYLMFLL 17 33 QVPTIIKQS 17 175| EQDERVYMS 17 238 EIGSKANSI 17 271 GEILLLECF 17 581 EDGRIIIDG 17 584 RIIIDGANL 17 799 VKVQAINQL 17 961 NLTGYLLQY 17 977 EIGELNDIN 17 100 1 ATTKYKFYL 17 102 0 PITEESSTL 17 110 4 CAIALLTLL 17 9 GLIVYLMFL 16 51 EYFQIECEA 16 99 HISHFQGKY 16 172 EHIEQDERV 16 197 DSRNDYCCF 16 222 LTVNSLKHA 16 263 ESSITILKG 16( 277 ECFAEGLPT 16| 314 ENVSYQDKG 16( 401 EISFTNLQP 16 421 NVHGTiLAN 16( 432 IDWDVRPL 16( 511 WVENAIGKT 16 520 AVTANLDIR- 16 617 ADITQVTVL 16 622 VTVLDVPDP 16 686 TTVILPLAP 16 919 ESEPYIFQT 16 102 2 EESSTLGEG 16 103 EGSKGIGKI 16

TableXXV-V7-HLA-A3- 9mers-282P1G3 Each peptide is a portio of SEQ ID NO: 15; eac start position is specifie the length of peptide is amino acids, and the er position for each peptid is the start position plu eight. n &#906; ri, 9 id e s Pos|| 123456789 jjscc >re| °l 111( LTVCFVKRN 16 120( 9| SVESNGSST 16 5I LLGRGLIVY 15 13( YLMFLLLKF 15 35) PTIiKQSKV 15 133( LPKEKIDPL 15 144 EEGDPIVLP 15 157 KGLPPLHIY 15 178 ERVYMSQKG 15 272 EiLLLECFA 15 373 EPQPTIKWR 15( 462 EFFASPEAV 15| 468 EAWSWQKV 15( 469 AVVSWQKVE 15( 629 DPPENLHLS 15( 685 KTTVILPLA 15( 847 STVPKDRVH 15 957 KLNGNLTGY 15 980 ELNDINITT 15 1Q7 8 VIETRGREY 15 114 0 EIQSVKDET . 15 118 5 EGDHGLFSE 15 118 9 GLFSEDGSF 15 90 GTFRIPNEG 14 124 EFiVPSVPK 14 | 173 HIEQDERVY 14 | 192 NVEEKDSRN 14 | 223 TVNSLKHAN 14 | 24£ SIKQRKPKL 14 j 267 TILKGEILL 14 ( 33£ DFHVIVEEP 14 ( 34C HVIVEEPPR 14

TableXXV-V7-HLA-A3- 9mers-282P1G3 Each peptide is a portio of SEQ ID NO: 15; eac start position is specifie the length of peptide is amino acids, and the er position for each peptic is the start position plu eight. n 1 X 9 d e Pos(| 123456789 (see ire 487(- YHiYENGTL 14 525 LDIRNATKL 14 537 PKNPRIPKL 14 576 EINGTEDGR 14 582 DGRIIIDGA 14 660 EYIVEFEGN 14 676 EELTRVQGK 14 684 KKTTVILPL 14 701 RVIAVNEVG 14 ’ 704 AVNEVGRSQ 14 786 LRVMTPAVY 14 811 PDPQSVTLY 14 839 STLVKVTWS 14 844 VTWSTVPKD 14 852 DRVHGRLKG 14 867 KTKSLLDGR 14 878 PKEVNILRF 14 926 QTPEGVPEQ 14 ' 933 EQPTFLKVI 14 939 KVIKVDKDT 14 973 NDTYEIGEL 14 105 5 PGAEHIVRL 14 107 3 SIFQDVIET 14 110 3 MCAiALLTL 14 110 5 AIALLTLLL 14 112 8 SVKEKEDLH 14 6 LGRGLIVYL 13 41 SKVQVAFPF 13 4£ VAFPFDEYF 13 6t PTFSWTKDG 13 • 7£ FTDHRItPS 13 9f PNEGHISHF 13 14' DPiVLPCNP 13 ( 15: 3 HIYWMNiEL 13 190

TabieXXV-V7-HLA-A3- 9mers-282P1G3 TableXXV-V7-HLA-A3- 9mers-282P1G3 Each peptide is a portion ofSEQIDNO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 j| score -1 Pos| 123456789 |j score 219 PMKLTVNSL 13 261 GSESSITIL 13 268 ILKGEILLL 13 305 ENYGKTLK! 13 356 AVYSTGSNG 13 456 SAFLHCEFF 13 530 ATKLRVSPK 13 614 DSAADITQV 13 618 DITQVTVLD 13 619 ITQVTVLDV 13 677 ELTRVQGKK 13 775 EWEEETVTN 13 780 TVTNHTLRV 13 815 SVTLYSGED 13 876 THPKEVNIL 13 890 RNSGMVPSL 13 899 DAFSEFHLT 13 906 LTVLAYNSK 13 907 TVLAYNSKG 13 962 LTGYLLQYQ 13 968 QYQIINDTY 13 983 DINITTPSK' 13 .991 KPSWHLSNL 13 104 5 QKTHPIEVF 13 108 . 2 RGREYAGLY 13 109 2 DISTQGWF! 13 110 6 Γ&amp;#938;&amp;#938;0 9 1ALLTLLLL 13 LTLLLLTVC 13 111 9 VKRNRGGKY 13 114 4 VKDETFGEY 13 115 4 DSDEKPLKG 13 115 7 EKPLKGSLR 13 115 9 PLKGSLRSL 13

TabieXXVPV2-(SET1)- HLA-A26-9mers-(SET1)- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 1 FIVPSVPKF 22 9 FPKEKIDPL 15 2 IVPSVPKFP 11 5 SVPKFPKEK 11

TableXXVl-V2-(SET2)- HLA-A26-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 8 EAKENYGKT 15 5 KGREAKENY 12 9 AKENYGKTL 10 2 DLPKGREAK 9j

TabieXXVl-V2-(SET3)- HLA-A26-9mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 2 SSTLGEGKY &amp;#906;4 1 ESSTLGEGK 12 7 EGKYAGLYD 12 6 GEGKYAGLY 11 3 STLGEGKYA 10 5 LGEGKYAGL 9

TableXXV!-V3-HLA- A26-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789. score 4 GVDVINTTY 23 6 DVINTTYVS 22 10 TTYVSNTTY 20 60 YVEKSSTFF 18 j 59 NYVEKSSTF 17| | 49 EDFIQKSTS 16 I 31 FICSKEQEL 14) I 33 CSKEQELSY 14| j 50 DFIQKSTSC 14) ( 18 YVSNATGSP 12( j 62 EKSSTFFKI 12 23 TGSPQPSIF 11 52 IQKSTSCNY 11

TabieXXVI-V4-HLA-A26- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position-for each peptide is the start position plus eight Pos 123456789 score 7 EDLPEQPTF 20 191 8 DLPEQPTFL ~&amp;#906;δ&amp;#970; 1 VTLYSGEDL 17

TableXXV!-V5-HtA- A26-9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Pos 123456789 score

TabieXXVI-V7-HLA~ A26-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 5 VIVEDNISH 12 7 VEDNISHEL 10 HDFHVIVED 8 16 FTLHPEPPR 8

LTVNSSNSI 13

TVNSSNS1K 13

Tab!eXXVl-V6-HLA- A26-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino l acids, and the end . position for each . peptide is the start position pius eight, j Pos 123456789 scorej 2 EIEFIVPKL 29( 1 EEIEFIVPK 20( 4 EFiVPKLEH 15 5 FIVPKLEHI 14

TabieXXVI-V7-HLA- A26-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 8 EDNISHELF 18 6 tVEDNISHE 17) 10 NISHELFTL 17) 14 ELFTLHPEP 15( 2 DFHVIVEDN 14) 4 HVIVEDNIS 14( 9 DNISHELFT 14(

TafaieXXVii-VI-HLA- B0702-9mers-282P1G3 Each peptide is a portion ofj SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. J Pos 123456789 score| 988 TPSKPSWHL 26) 810 GPDPQSVTL 24( 151 LPCNPPKGL 23) 154 NPPKGLPPL 23 539 NPRIPKLHM 23 542 IPKLHMLEL 23 991 KPSWHLSNL 23 2 EPLLLGRGL 22 133 LPKEKIDPL 21 828 APVIHGVDV 21 954 LPKKLNGNL 21 390 HPFAGDWF 20 795 APYDVKVQA 20 1172 QPTESADSL 20 84 IPSNNSGTF 19 130 VPKLPKEKI 19 247 KQRKPKLLL 19 j 250 KPKLLLPPT 19 j 726 APDRNPQNl 19 j 730 NPQNIRVQA 19 | 62 NPEPTFSWT 18 j 127 VPSVPKLPK 18 I 352 KPQSAVYST 18 j 385 SPVDNHPFA 18

TableXXVll-V1-HLA- B0702-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 671 EPGRWEELT 18 758 GPGLEYRVT 18 772 APVEWEEET 18 1136 HPDPEIQSV 18 ( 690 LPLAPFVRY 17 j 890 RNSGMVPSL 17 (1019 KPITEESST 17| I 6 LGRGLIVYL 16| I 47 FPFDEYFQI 16| ( 159 LPPLHIYWM 16( J 285 TPQVDWNKI 16| 917 GPESEPYIF 16( 1105 AiALLTLLL 1G| 218 MPMKLTVNS 15) 268 ILKGEILLL 15 536 SPKNPRIPK 15 617 ADITQVTVL ( 15 6271 VPDPPENLH 15 712 QPSQPSDHH 15 723 PPAAPDRNP 15 768 KPQGAPVEW 15 942 KVDKDTATL f~~&amp;#970;δ) 11 iVYLMFLLL 14 27 IPSSVQQVP 14 208 FPRLRTIVQ 14 280 AEGLPTPQV 14 419 ASNVHGTIL 14 451 TWGYSAFL 14 682 ( QGKKTTVtL 14 681 KKTTVILPL 14 931 VPEQPTFLK 14 103' lGKISGVNL 14 105- 1 EPGAEHiVR 14 1.15( KPLKGSLRS 14 12L 1 GSSTATFPL 14 3 3 KQSKVQVAF j 13 5 3 AKGNPEPTF I 13 192

TableXXVII-V1-HLA- B0702-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each pepiide is the start position plus eight. Pos 123456789 score 71 KDGNPFYFT 13 125 FIVPSVPKL 13 143 VEEGDPiVL 13 155 PPKGLPPLH 13 203 CCPAAFPRL 13 . 205 FAAFPRLRT 13 297 LPKGRETKE 13 346 PPRWTKKPQ 13 370 aegepqPti 13 432 IDWDVRPL 13 517 GKTAVTANL 13 552 CESKCDSHL 13 558 SHLKHSLKL 13 584 RIIIDGANL 13 626 DVPDPPENL 13 628 PDPPENLHL 13 638 ERQNRSVRL 13 670 EEPGRWEEL ' 13 693 APFVRYQFR 4 9 IG 787 RVMTPAVYA 13 812 DPQSVTLYS 13 824 YPDTAPVIH'.13 921 EPYIFQTPE 13 1001 ATTKYKFYL 13 1055 PGAEHIVRL 13 1094 STQGWFIGL 13 1103 MCAIALLTL 13 (&amp;#912;&amp;#912;θ6)( IALLTLLLL I 13

Pos 123456789 score 9 FPKEKIDPL 21 6 VPKFPKEKI 19 3 VPSVPKFPK 16

TableXXV!l-V2-(SET2)- HLA-B0702-9mers- 282P1G3 Each pepiide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 3 LPKGREAKE 13 9 AKENYGKTL 13 1 GDLPKGREA 8

TableXXV!l-V2-(SET2)- HLA-B0702-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score

TableXXVIl-V2-(SET3)- HLA-B0702-9mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Posj 123456789 score 5 LGEGKYAGL 13 9 KYAGLYDD! 10 3 STLGEGKYA 9

TableXXVIl-V3-HLA- B0702-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of pepiide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 31 FiCSKEQEL 10 62 EKSSTFFKI 10 2 IHGVDVINT 9 23 TGSPQPSIF 9 38 ELSYRNRNM 9 44 RNMLAEDFI 9 48 AEDFIQKST 9 60 YVEKSSTFF 9 5 VDVINTTYV I 8 8 INTTYVSNT 8 11 TYVSNTTYV 8 40 SYRNRNMLA 8| 53 QKSTSCNYV ol °l 14 SNTTYVSNA 15 NTTYVSNAT &amp;#942; 3 HGVDVINTT 6I 9 NTTYVSNTT θ&amp;#943; 43 NRNMLAEDF θ! 58 CNYVEKSST f 6| 59 NYVEKSSTF I 5

TableXXVII-V2-(SET1)- HLA-B0702-9mers- _____ 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

TabIeXXVIl-V3-HLA- B0702-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 22 ATGSPQPS! 13 27 QPSIFICSK 12 25 SPQPSIFIC 11 39 LSYRNRNML 11 24 GSPQPSIFI io|

TableXXV!l-V4-HLA- B0702-9mers Each pepiide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each pepiide is the start position plus eight Pos 123456789 score 9 LPEQPTFLK 14 8 DLPEQPTFL 12 1 VTLYSGEDL 11 6 GEDLPEQPT 11 7 EDLPEQPTF 9 3 LYSGEDLPE 7

TableXXVII-V5-HLA- 193 B0702-9mers Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino adds, and the end position for each peptide is the start position plus eight. |Pos 123456789 ) score} 4 LTVNSSNSI 6 6 VNSSNSIKQ 2 7 NSSNSIKQR 2 9 SNSIKQRKP 2'

TableXXVl!-V6-HLA- BQ702-9mers Each peptide is a portion of SEQ ID NO: 13; each starfcposition is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start puoiuuu pjuo ciyiIi. Pos 123456789 score 2 EIEFIVPKL 13 7 VPKLEHIEQ 10 5 FIVPKLEH! 7 4 EFIVPKLEH 6

Tab!eXXV!l-V7-HLA- B0702-9mers Each peptide is a .portion j of SEQ ID NO; 15; each I start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. [ Pos 123456789 score| 19 HPEPPRWTK 15 10 NISHELFTL 12 7 VEDNISHEL 11 9 DNISHELFT 9 18 LHPEPPRWT 9 8 EDNISHELF - 7 j Each peptide is a portion ofSEQIDNO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 133 LPKEKIDPL 39 245 SIKQRKPKL 34 542 IPKLHMLEL 29 268 ILKGEILLL 28 954 LPKKLNGNL 27 849 VPKDRVHGR 26 1159 PLKGSLRSL 26 130 VPKLPKEK! 24 297 LPKGRETKE 24 855 HGRLKGYQi 24 1128 SVKEKEDLH 24 377 TIKWRVNGS 23 1203 GSKEKGSVE 23 208 FPRLRTIVQ 22 219 PMKLTVNSL 22 238 EIGSKANSI 22 246 IKQRKPKLL 22 ITILKGEIL 22 743 EMilKWEPL 22 863 INWWKTKSL 22 1035 IGKISGVNL £.£. 1042 NLTQKTHPI 22 638 ERQNRSVRL 21 670 EEPGRWEEL 21 682 QGKKTTVIL 21( 1002 TTKYKFYLR 21} 104 QGKYRCFAS 2θ| 248 QRKPKLLLP 20j 481 PLEGRRYHI 20j 530 ATKLRVSPK 20| 540 PRIPKLHML 20] j 865 WWKTKSLLD 20 I 877 HPKEVNILR 20 |1156 DEKPLKGSL 20 t 2 EPLLLGRGL 19 I 226 SLKHANDSS 19 ) 537 PKNPRIPKL ,. - II _____.____ 19 I 562 SLKLSWSKD 19 I 74C QPKEMIIKW 19

TableXXV)ll-V1-HLA-BD8- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 796 PYDVKVQA! 19 937 FLKVIKVDK 19

TableXXVIH-V2- (SET1)-HLA-B08- 9mers-(SET1)- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight

Pos 123456789 score 9 FPKEKIDPL 40 i θ VPKFPKEKI 23 T ableXXVll!-V2-(SET2)-HLA-B08-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789~} score 3 LPKGREAKE 24 8 EAKENYGKT 18 &amp;#943; I GDLPKGREA 12 6 GREAKENYG 11 9 AKENYGKTL 11

TableXXVill-V1-HLA-B08- 9mers-282P1G3

TableXXVIII-V2-(SET3)- HLA-B08-9mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each istart position is specified, 194 the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight Pos 123456789 score 5 LGEGKYAGL 20 7 EGKYAGLYD 13 4 TLGEGKYAG 9 9 SNSIKQRKP 12 3 KLTVNSSNS 7 4 LTVNSSNSI 6

TableXXVIl!-V3-HLA- B08-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the .start position plus eight. Pos 123456789 score 31 FICSKEQEL 26 38 ELSYRNRNM 18 59 NYVEKSSTF 18 40 SYRNRNMLA 17 33 CSKEQELSY 12 TableXXVIII-V4-HLA- B08-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is thd start position pius eight. Pos 123456789 score 8 DLPEQPTFL 18 1 VTLYSGEDL 12 7 EDLPEQPTF 8

TableXXVIl!-V3-HLA- B08-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the .start position plus eight. Pos 123456789 score 31 FICSKEQEL 26 38 ELSYRNRNM 18 59 NYVEKSSTF 18 40 SYRNRNMLA 17 33 CSKEQELSY 12

Tab!eXXV!i!-V6-HLA- B08-9mers~282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight Pos 123456789 score 5 FIVPKLEHI 21 7 VPKLEHIEQ 19 2 | ElEFIVPKL 17

TableXXVIII-V7-HLA- B08-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 10 NISHELFTL 14 7 VEDNISHEL 12 14 ELFTLHPEP 9 5 VIVEDNISH 8 8 EDNISHELF 8 20 PEPPRWTKK 8 3 FHViVEDNI 7 19 HPEPPRWTK 7 17 TLHPEPPRW 6

TableXXVIII-V5-HLA- B08-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 1 PMKLTVNSS 12

TableXXIX-V1-HLA- B1510-9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight

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TableXXIX-V1-HLA- B1510-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 876 THPKEVNIL 23 487 YHIYENGTL 22 558 SHLKHSLKL 21 1055 PGAEHIVRL 17 432 IDWDVRPL 16 810 GPDPQSVTL 16 . 101 SHFQGKYRC 15 143 VEEGDPIVL 15 638 ERQNRSVRL 15 6 LGRGLIVYL 14 125 FIVPSVPKL 14 172 EHIEQDERV 14 214 IVQKMPMKL 14 268 ILKGEILLL 14 336 THDFHVIVE 14 537 PKNPRIPKL 14 542 IPKLHMLEL 14 718 DHHETPPAA 14 719 HHETPPAAP 14 753 SMEQNGPGL 14 831 IHGVDVINS 14 890 RNSGMVPSL 14 988 TPSKPSWHL 14 1035 IGKiSGVNL .14 2 EPLLLGRGL 13 154 NPPKGLPPL 13 203 CCFAAFPRL 13 I 245 SIKQRKPKL 13 I 246 IKQRKPKLL 13 j 247 KQRKPKLLL 13 | 261 GSESSITIL 13 j 267 TILKGEILL 13 I 303 TKENYGKTL 13 j 591 NLTISNVTL 13 | 617 ADITQVTVL 13 j 626 DVPDPPENL 13 I 653 DHNSNISEY 13 195

TableXXIX-V1-HLA- B15l0-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 670 EEPGRWEEL 13 682 QGKKTTVIL 13 778 EETVTNHTL 13 833 GVDVINSTL 13 901 FSEFHLTVL 13 930 GVPEQPTFL) 13 1047 THPIEVFEP 13 1058 EHIVRLMTK 13 1100 IGLMCAIAL 13 1127 YSVKEKEDL 13 1156 DEKPLKGSL 13 1159 PLKGSLRSL 13 1182 EYGEGDHGL 13 9 GLIVYLMFL 12 11 IVYLMFLLL 12 133 LPKEKIDPL 12 151 LPCNPPKGL 12 174 IEQDERVYM 12 266 ITILKGEIL 12 358 YSTGSNGIL 12 389 NHPFAGDW 12 451 TWGYSAFt 12 ~474 QKVEEVKPL ““&amp;#938;2 540 PRIPKLHML 12 550 LHCESKCDS 12 552 CESKCDSHL 12 556 CDSHLKHSL 12 605 YCCSAHTAL 12 628 PDPPENLHL 12 “657 NISEYIVEF 12 783 NHTLRVMTP 12 799 VKVQAINQL 12 850 PKDRVHGRL 12 863 INWWKTKSL 12 864 NWWKTKSLL 12 878 PKEVNILRF 12 942 KVDKDTATL 12

TableXXlX-V1-HLA-B1510-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 950 LSWGLPKKL 12 973 NDTYEIGEL 12 994 WHLSNLNAT 12 1001 ATTKYKFYL 12 1020 PITEESSTL 12 1101 GLMCAIALL 12 1103 MCAIALLTL 12 1106 IALLTLLLL 12 1135 LHPDPEIQS 12 1214 GSSTATFPL 12 10 LIVYLMFLL 11 39 KQSKVQVAF 11 80 DHRHPSNN A A 1 I 84 IPSNNSGTF 11 98 GHISHFQGK 11 107 YRCFASNKL 11 162 LHIYWMNIE 11 163 HIYWMNIEL 11 180 VYMSQKGDL 11 219 PMKLTVNSL 11 228 KHANDSSSS 11 275 LLECFAEGL 11 289 DWNKIGGDL 11 324 YRCTASNFL 11 359 STGSNGILL 11 390 HPFAGDWF 11 399 PREISFTNL 11 419 ASNVHGTIL 11 459 LHCEFFASP 11 517 GKTAVTANL 11 525 LDIRNATKL 11 561 KHSLKLSWS 11 609 AHTALDSAA 11 634 LHLSERQNR 11 684 KKTTVILPL 11 743 EMIIKWEPL 11 | 854 VHGRLKGYQ 11

TableXXIX-V1-HLA- B1510-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 898 LDAFSEFHL 11 929 EGVPEQPTF 11 946 DTATLSWGL 11 954 LPKKLNGNL 11 991 KPSWHLSNL 11 1056 GAEHIVRLM 11 1081 TRGREYAGL 11 1094 STQGWFIGL 11 1105 AIALLTLLL 11 1141 IQSVKDETF 11 1152 YSDSDEKPL 11 HLA-B1510-9mers- (SET1)-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Pos 123456789 score

FPKEKIDPL

FIVPSVPKF 12 10

TableXXIX-V2-(SET2)- HLA-B1510-9mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight

Pos 123456789 score 9 AKENYGKTL 12 1 GDLPKGREA 6 196

TableXXIX-V2-(SET3)- HLA-B1510-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of pepiide is 9 amino adds, and the end position for each peptide is the start position plus eight. Pos 123456789 score 5 LGEGKYAGL 12 L· TLGEGKYAG 5

TableXXIX-V3-HLA- B1510-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, arid the end position for each peptide is the start position plus eight. Pos 123456789 score 2 IHGVDVINT —&amp;#944; 39 LSYRNRNML 12 23 TGSPQPSIF 11 31 FICSKEQEL 11 38 ELSYRNRNM 10 60 YVEKSSTFF 9 59 NYVEKSSTF 8 43 NRNMLAEDF 6

TableXXlX-V4-Hl2A- B1510-Smers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 8 DLPEQPTFL 12 7 EDLPEQPTF 11 1 VTLYSGEDL 10 start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 8 SSNSIKQRK 3 9 SNSIKQRKP 3 3 KLTVNSSNS 2 6 VNSSNS1KQ 2 7 NSSNSIKQR 2 t 1 PMKLTVNSS 1 i 5 TVNSSNSIK 1

TableXXIX-V6-HLA- B1510-9mers- 282P1G3

Each peptide is a portion of SEQ !D NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Pos 123456789 score 2 EIEFIVPKL 14

TableXXIX-V7-HLA- I B1510-9mers-282P1G3 [ Each peptide is a portion I of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 18 LHPEPPRWT 15 10 NISHELFTL 12 7 VEDN1SHEL 11 12 SHELFTLHP 11 3 FHVIVEDNt . 10 8 EDNISHELF 17 TLHPEPPRW 7

TableXXX-V1-HLA-B2705- 9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 209 PRLRTIVQK 27 7 GRGLSVYLM 25 399 PREISFTNL 25 540 PRIPKLHML 25 734 1RVQASQPK 25 1122 NRGGKYSVK 25 107 YRCFASNKL 24 533 LRVSPKNPR 24 638 ERQNRSVRL 24 324 YRCTASNFL 22 1081 TRGREYAGL 22 786 LRVMTPAVY 21 673 GRWEELTRV 20 92 FRIPNEGHI 19 261 GSESSITIL 19 301 RETKENYGK 19 485 RRYHIYENG 19 584 RIIIDGANL 19 856 GRLKGYQIN 19 859 KGYQINWWK 19 884 LRFSGQRNS 19 890 RNSGMVPSL 19 1189 GLFSEDGSF 19 1199 GAYAGSKEK 19 8 RGLIVYLMF 18 39 KQSKVQVAF 18 268 ILKGEILLL 18 271 GEILLLECF 18 291 NKIGGDLPK 18 390 HPFAGDWF 18 437 VRPLIQTKD 18 484 GRRYHIYEN 18 558 SHLKHSLKL 18 562 HSLKLSWSK 18 I 799 VKVQA1NQL 18 I e LGRGLIVYL 17 I GLIVYLMFL 17 ( 81 HRISPSNNS 17 I 125 FtVPSVPKL 17 j 247 KQRKPKLLL I v

TableXXIX-V5-HLA- B1510-9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 11; each 197

TableXXX-V1-HLA.-B2705- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start posiiion plus eighL Pos 123456789 score 267 TILKGEILL 17 284 PTPQVDWNK 17 304 KENYGKTLK 17 517 GKTAVTANL 17 525 LDIRNATKL 17 . 537 PKNPRIPKL 17 583 GRIIIDGAN 17 617 ADITQVTVL 17 679 TRVQGKKTT 17 684 KKTTVILPL 17 709 GRSQPSQPS 17 810 GPDPQSVTL 17 833 GVDVINSTL 17 893 GMVPSLDAF 17 929 EGVPEQPTF 17 1055 PGAEHIVRL 17 1101 GLMCAIALL 17 1150 GEYSDSDEK 17 1161 KGSLRSLNR 17 15 MFLLLKFSK 16 95 PNEGHISHF 16 106 KYRCFASNK 16 149 IVLPCNPPK 16 154 NPPKGLPPL 16 182 MSQKGDLYF 16 191 ANVEEKDSR 16 203 CCFAAFPRL 16 210 RLRTIVQKM 16 212 RTIVQKMPM 16 214 ivqkmpmkT 16 242 KANSIKQRK 16 245 SIKQRKPKL 16 329 SNFLGTATH 16 380 WRVNGSPVD 16 396 WFPREISF 16 424 GTILANANI 16 430 ANIDWDVR 16 436 [pVRPLIQTK 16|

TableXXX-V1-HLA-B2705- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 491 ENGTLQINR 16 534 RVSPKNPRI 16 657 NISEYIVEF 16 687 TVILPLAPF 16 760 GLEYRVTWK 16 852 DRVHGRLKG 16 874 GRTHPKEVN 16 878 PKEVNILRF 16 930 GVPEQPTFL 16 942 KVDKDTATL 16 949 TLSWGLPKK 16 954 LPKKLNGNL 16 991 KPSWHLSNL 16 1074 IFQDVIETR 16 1104 CAIALLTLL 16 1106 IALLTLLLL 16 1124 GGKYSVKEK 16 1137 PDPEIQSVK 16 11 IVYLMFLLL 15 13 YLMFLLLKF 15 41 SKVQVAFPF 15 45 VAFPFDEYF 15 98 GHISHFQGK 15 124 EFIVPSVPK P5 133 LPKEKIDPL 15 157 KGLPPLHIY 15 163 HIYWMNIEL 15 188 LYFANVEEK 15 213 TIVQKMPMK 15 220 MKLTVNSLK 15 234 SSSTEIGSK 15 239 IGSKANSIK 15 241 SKANSIKQR 15 266 ITILKGEIL 15 296 DLPKGRETK 15 300 GRETKENYG 15 316 VSYQDKGNY 15 344 [eepprwtkk I 15

TableXXX-V1-HLA-B2705-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position Is specified,-the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 450 ATWGYSAF 15 451 TWGYSA’FL 15 477 EEVKPLEGR 15 480 KPLEGRRYH 15 487 YHIYENGTL 15 527 IRNATKLRV 15 634 LHLSERQNR 15 677 ELTRVQGKK 15 ( 696 VRYQFRVIA 15 728 DRNPQNIRV 15 744 MjlKWEPLK 15 792 AVYAPYDVK 15 835 DVINSTLVK 15 853 RVHGRLKGY 15 875 RTHPKEVNI 15 876 THPKEVNIL 15 917 Qp|£SEPYIF j 15 950 LSWGLPKKL j 15 957 KLNGNLTGY j 15 973 NDTYEIGEL 15 988 TPSKPSWHL 15 996 LSNLNATTK 15 1020 PITEESSTL 1029 GEGSKGIGK 15 1030 EGSKGIGKI 15 1035 IGKISGVNL 15 1038 ISGVNLTQK 15 1040 GVNLTQKTH 15 1045 QKTHPIEVF 15 1051 EVFEPGAEH 15 "&amp;#938;058 EHIVRLMTK 15 1100 IGLMCAIAL 15 1110 TLLLLTVCF 15 1127 YSVKEKEDL 15 1159 PLKGSLRSL 15 2 EPLLLGRGL 14 12 VYLMFLLLK 14 52 AKGNPEPTF 14 198

TableXXX-V1-HLA-B2705- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 94 IPNEGHISH 14 117 IAMSEEIEF 14 129 SVPKLPKEK 14 143 VEEGDPIVL 14 171 LEHIEQDER 14 178 ERVYMSQKG 14 219 PMKLTVNSL 14 221 KLTVNSLKH 14 244 NSIKQRKPK 14 248 QRKPKLUP 14 299 KGRETKENY 14 305 ENYGKTLKI 14 323 NYRCTASNF 14 340 HVIVEEPPR 14 343 VEEPPRWTK 14 347 PRWTKKPQS 14 358 YSTGSNGIL 14 373 EPQPT1KWR 14 384 GSPVDNHPF 14 403 SFTNLQPNH 14 456 SAFLHCEFF 14 467 PEAWSWQK 14 472 SWQKVEEVK 14 474 QKVEEVKPL | 14 478 EVKPLEGRR 14 510 CWVENAIGK 14 530 ATKLRVSPK 14 542 IPKLHMLEL 14 552 CESKCDSHL 14 591 NLTISNVTL 14 628 PDPPENLHL 14 531 PENLHLSER ( 14 637 SERQNRSVR 14 661 YIVEFEGNK 14 666 EGNKEEPGR 14 690 LPLAPFVRY 14 693 APFVRYQFR 14 700 FRVIAVNEV 14

TableXXX-V1-HLA-B2705- 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos .123456789 score 727 PDRNPQNIR 14 739 SQPKEMIIK 14 756 QNGPGLEYR 14 763 YRVTWKPQG 14 776 WEEETVTNH 14 811 PDPQSVTLY 14 843 KVTWSTVPK 14 864 NWWKTKSLL 14 867 KTKSLLDGR 14 869 KSLLDGRTH 14 877 HPKEVNILR 14 882 NILRFSGQR 14 896 PSLDAFSEF 14 901 FSEFHLTVL 14 906 LTVLAYNSK 14 915 GAGPESEPY 14 948 ATLSWGLPK 14 963 TGYLLQYQI . 14 997. SNLNATTKY 14 999 LNATTKYKF 14 1001 ATTKYKFYL 14 1025 SSTLGEGSK 14 1061 VRLMTKNWG 14| 1082 RGREYAGLY 14 1083 GREYAGLYD 14 1091 DDISTQGWF 14 1105 AIALLTLLL 14 1112 LLLTVCFVK 14 1115 TVCFVKRNR 14 1120 KRNRGGKYS 14 1141 IQSVKDETF 14 1156 DEKPLKGSL 14 1172 QPTESAD&amp;amp;L 14 1182 EYGEGDHGL 14 5 LLGRGLIVY 13 1£ LKFSKAIE! 13 34 VPTIIKQSK 13 68 PEPTFSWTK 13

TableXXX-V1 -HLA-B2705-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 68 SWTKDGNPF 13 73 GNPFYFTDH 13 74 NPFYFTDHR 13 84 IPSNNSGTF 13 85 PSNNSGTFR 13 102 HFQGKYRCF 13 111 ASNKLGIAM ' 13 127 VPSVPKLPK 13 159 LPPLHIYWM 13 200 NDYCCFAAF 13 206 AAFPRLRTI 13 211 LRT1VQKMP 13 289 DWNKIGGDL 13 370 AEGEPQPTl 13 371 EGEPQPT1K 13 419 ASNVHGTIL 13 432) IDWDVRPL 13 441 IQTKDGENY 13 524 NLDIRNATK 13 556 CDSHLKHSL 13 557 DSHLKHSLK 13 597 VTLEDQGIY 13 626 DVPDPPENL 13 641 NRSVRLTWE 13( 644 VRLTWEAGA 13 653 DHNSNISEY 13 670 EEPGRWEEL 13 672 PGRWEELTR 13 676 EELTRVQGK 13 682 QGKKTTVIL 13 689 , ILPLAPFVR 13 592 LAPFVRYQF 13 721 ETPPAAPDR 13 ' 742 EMIIKWEPL 13 746 IKWEPLKSM 13 752 SMEQNGPGL 13 756 EQNGPGLEY 13 771 ETVTNHTLR I 13 199

TableXXX-V1-HLA-B2705- 9mers-282P1G3 Each peptide is a portion of SEQ !D NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 847 STVPKDRVH 13 850 PKDRVHGRL 13 ( 861 YQINWWKTK 13 863 INWWKTKSL .13 889 QRNSGMVPS 13 931 VPEQPTFLK 13 934 QPTFLKVIK 13 937 -FLKVIKVDK 13 946 DTATLSWGL 13 961 NLTGYLLQY 13 976 YEIGELNDI 13 1054 EPGAEHIVR 13 1056 GAEHIVRLM 13 1094 STQGWFIGL 13 1103 MCAIALLTL 13 1113 LLTVCFVKR 13 1153 SDSDEKPLK 13 1157 EKPLKGSLR 13 1168 |NRDMQPTES 13 1212 SNGSSTATP 13 1214 GSSTATFPL 13

TableXXX-V2-(SET1)- HLA-B2705-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score| 1 FiVPSVPKF 17 9 FPKEKIDPL 15 5 SVPKFPKEK 13 3 VPSVPKFPK 12 ‘ 6 VPKFPKEKI 10, HLA-B2705-9mers- (SET1)-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 7 REAKENYGK 19 6 GREAKENYG 15 2 DLPKGREAK 14 5 KGREAKENY 14 K AKENYGKTL 12

TableXXX-V2-(SET3)- HLA-B2705-9mers- 282P1G3 Each peptide is a portion ofSEQiDNO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 5 LGEGKYAGL 14 6 GEGKYAGLY 14 2 SSTLGEGKY 13 1 ESSTLGEGK 11 9 KYAGLYDDI 11 8 GKYAGLYDD 9

TableXXX-V3-HLA- B2705-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus I eighL ' | Pos 123456789 score. 43 NRNMLAEDF 22| 4 GVDVINTTY 16, 59 NYVEKSSTF 16 60 YVEKSSTFF 10 TTYVSNTTY 15 34 SKEQELSYR 15

TabieXXX-V3-HLA- B2705-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus J eight. Pos 123456789 score 24 GSPQPSIFI 14 27 QPSIFICSK 14 36 EQELSYRNR 14 39 LSYRNRNML 13 46 MLAEDFIQK 13 22 ATGSPQPSi 12 23 TGSPQPSIF 12 [31 FICSKEQEL 12 I 52 IQKSTSCNY 12 I 55 STSCNYVEK 12 , 33 CSKEQELSY 11 I 38 ELSYRNRNM 11 i 41 YRNRNMLAE 11 ( 44 RNMLAEDFl 11 I 61 VEKSSTFFK 11

TableXXX-V4-HLA- B2705-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight (Pos &amp;#906;23456789 j score I 7 EDLPEQPTF , 18 ! 1 VTLYSGEDL 13 , 8 DLPEQPTFL 13 j 9 LPEQPTFLK 13

TableXXX-V5-HLA- B2705-9mers-282P1G3 j TableXXX-V2-(SET2)- j 200

Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino adds, and the end position for each peptide is the start position plus eight

Pos 123456789 score 7 NSSNSIKQR 15 8 SSNSIKQRK 14 5 TVNSSNSIK 13 4 LTVNSSNSI 11

TableXXX-V6-HLA- B2705-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9. amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 1 EEIEFIVPK 17 2 EIEFIVPKL 15 4 EFIVPKLEH 14 5 FIVPKLEHl 10

TableXXX-V7-HLA- B2705-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 | score 20 PEPPRWTKK 15 16 FTLHPEPPR 14 19 HPEPPRWTK 14 5 VIVEDNISH 13 7 VEDNISHEL 13 10 NiSHELFTL 13 11 ISHELFTLH 13 . 8 EDNISHELF 11 3 FHVIVEDNI 10 1 HDFHVIVED 9

TableXXXi-Vl-HLA I 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 7 GRGLIVYLM 24 540 PRIPKLHML 22 638 ERQNRSVRL 22 673 GRWEELTRV 22 399 PREISFTNL 21 527 IRNATKLRV 21 92 FRIPNEGHI 20 107 YRCFASNKL 20 324 YRCTASNFL 20 700 FRVIAVNEV 20 728 DRNPQNIRV 20 1081 TRGREYAGL 20 485 RRYHIYENG 18 584 RiliDGANL 17 890 RNSGMVPSL 16 8 RGLIVYLMF 15 517 GKTAVTANL 15 534 RVSPKNPRI 15 583 GRIIIDGAN 15 810 GPDPQSVTL 15 856 GRLKGYQIN 15 875 RTHPKEVNt 15 . 9 GLIVYLMFL 14 11 IVYLMFLLL 14 125 FIVPSVPKL 14 203 CCFAAFPRL 14 209 PRLRTIVQK 14 210 RLRTIVQKM 14 261 GSESSITIL 14 432 IDWDVRPL 14 484 GRRYHIYEN 14 684 KKTTViLPL 14 833 GVDVINSTL 14 874 GRTHPKEVN 14 884 LRFSGQRNS 14 1083 GREYAGLYD 14 1100 . IGLMCAIAL 14 1106 j IALLTLLLL 14

TableXXXI-V1-HLA 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 1189 GLFSEDGSF 14 212 RTIVQKMPM 13 247 KQRKPKLLL 13 300 GRETKENYG 13 308 GKTLKIENV 13 424 GTILANANI 13 558 SHLKHSLKL 13 617 ADITQVTVL 13 688 VILPLAPFV 13 696 VRYQFRVIA 13 697 RYQFRVIAV 13 709 GRSQPSQPS 13 763 YRVTWKPQG 13 808 GSGPDPQSV 13 893 GMVPSLDAF 13 917 GPESEPYIF 13 930 GVPEQPTFL 13 942 KVDKDTATL 13 964 GYLLQYQII 13 991 KPSWHLSNL 13 1035 IGKISGVNL 13 1056 GAEHIVRLM 13 1101 GLMCAIALL 13 1121 RNRGGKYSV 13 1214 GSSTATFPL 13 I 2 EPLLLGRGL 12 19 LKFSKAIEI 12 | 23 KAIEIPSSV 12 j 81 HRHPSNNS 12 I 135 KEKIDPLEV 12 I 163 HIYWMNIEL 12 I 206 AAFPRLRTI 12 | 248 QRKPKLLLP 12 | 266 ITILKGEIL 12 | 267 TILKGEILL 12 ( 268 ILKGEILLL I 12 | 271 GEILLLECF 12 PRWTKKPQS 12 201

TableXXXi-V1-HLA 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 380 WRVNGSPVD 12 384 GSPVDNHPP 12 394 GDWFPREI 12 474 QKVEEVKPL 12 525 LDiRNATKL '12 533 LRVSPKNPR 12 537 PKNPRIPKL 12 542 - IPKLHMLEL 12 589 GANLTISNV 12 591 NLTISNVTL 12 628 PDPPENLHL 12 644 VRLTWEAGA 12 680 RVQGKKTTV 12 734 IRVQASQPK | 12 799 VKVQAINQL 12 822 EDYPDTAPV 12 852 DRVHGRLKG 12 889 QRNSGMVPS 12 963 TGYLLQYQ! 12 1001 ATTKYKFYL 12 1055 PGAEHIVRL 12 1061 VRLMTKNWG 12 1105 AlALLTLLL* 12 1120 KRNRGGKYS 12 1152 YSDSDEKPL 12 1172 QPTESADSL 12 4 LLLGRGUV 11 6 LGRGLIVYL 11 10 UVYLMFLL 11 26 EiPSSVQQV 11 29 SSVQQVPTI 11 37 IIKQSKVQV 11 39 KQSKVQVAF 11 45 VAFPFDEYF 11 47 FPFDEYFQ! 11 75 PFYFTDHRl 11 76 FYFTDHRI1 11 122 EiEFIVPSV 11

TableXXXI-V1-HLA 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 j score 143 VEEGDPIVL 11 154 NPPKGLPPL 11 178 ERVYMSQKG) 11 180 VYMSQKGDL| 11 185 KGDLYFANV 11 211 LRTIVQKMP 11 214 IVQKMPMKL 11 219 PMKLTVNSL 11 245 SIKQRKPKL 11 246 IKQRKPKLL 11 275 LLECFAEGL 11 280 AEGLPTPQV 11 289 DWNKIGGDL 11 305 ENYGKTLKI 11 333 GTATHDFHV 11 358 YSTGSNGIL 11 359 STGSNGILL 11 390 HPFAGDWF 11 396 WFPREISF 11 419 ASNVHGTIL 11 429 NANIDWDV 11 437 VRPLIQTKD 11 451 TWGYSAFL 11 487 YHIYENGTL 11 489 lYENGTLQl 11 498 NRTTEEDAG 11 579 GTEDGRIII 11 605 YCCSAHTAL 11 611 TALDSAADI 11 619 ITQVTVLDV 11 626 DVPDPPENL 11 679 TRVQGKKTT 11 682 QGKKTTViL 11 743 EMIIKWEPL 11 753 SMEQNGPGL 11 778 EETVTNHTL 11 780 TVTNHTLRV 11 786 LRVMTPAVY Ui

TableXXXI-V1-HLA 9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 828 APVIHGVDV 11 850 PKDRVHGRL 11 863 INWWKTKSL 11 876 THPKEVNIL 11 929 EGVPEQPTP 11 935 PTFLKVIKV 11 954 LPKKLNGNL 11 959 NGNLTGYLL 11 970 QIINDTYEI 11 973 NDTYEIGEL 11 1020 PiTEESSTL 11 1033 KGIGKISGV 11 1066 KNWGDNDSI 11 1103 MCAIALLTL 11 1104 CAIALLTLL 11 1110 TLLLLTVCF 11 1111 LLLLTVCFV 11 1127 YSVKEKEDL 11 1133 EDLHPDPEI 11 1156 DEKPLKGSL 11

TabieXXXI-V2-(SET1)- HLA-B2709-9mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start P&lt; jsition plus eight. Pos 123456789 score 1 FIVPSVPKF 12 9 FPKEKIDPL 10 6 VPKFPKEKI 8

TableXXXI-V2-(SET2)- HLA-B2709-9mers- 282P1G3 202

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. TableXXXI-V3-HLA- B2709-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 6 GREAKENYG 13 9 AKENYGKTL 11 Pos 123456789 score 1 GDLPKGREA θ 62 EKSSTFFKI 9 53 QKSTSCNYV 8 TableXXXI-V2-(SET3)- HLA-B2709-9mers- 282P1G3 60 YVEKSSTFF 8 TableXXXl-V4-HLA- B2709-9mers-282P1G3 Each peptide is a portion of SEQ iD NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 5 LGEGKYAGL 10 Pos 123456789 score 9 KYAGLYDDI 10 p VTLYSGEDL 12 8 GKYAGLYDD 6 7 EDLPEQPTF 12 6 GEGKYAGLY 4 8 DLPEQPTFL 10

Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Pos 123456789

EIEFIVPKL

FIVPKLEHI score 13 10

Tab!eXXXI-V7-HLA- B2709-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 7 VEDNISHEL 11 3 FHVIVEDNI 10 10 NISHELFTL 10 8 EDNISHELF 8

TableXXXI-V3-HLA- B2709-9mers-282P1G3 Each peptide ts a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the"end position for each peptide is the start position plus eight. Pos 123456789 score 43 NRNMLAEDF 19 39 LSYRNRNML 12 44 RNMLAEDFI 12 22 ATGSPQPSI 11 24 GSPQPSIFI 11 31 FICSKEQEL 11 41 YRNRNMLAE 11 11 TYVSNTTYV 10 5 VDVINTTYV 9 23 TGSPQPSIF 9 38 ELSYRNRNM 9 59 NYVEKSSTF 9)

TableXXXI-V5-HLA-B2709-9mers-282P1 G3 Each peptide is a portion ofSEQIDNO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 4 LTVNSSNSi 9 3 KLTVNSSNS 4

TableXXXI-V6-HLA- B2709-9mers- 282P163

TableXXXlI-Vt-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ iD NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 194 EEKDSRNDY 25 271 GEILLLECF 25 670 EEPGRWEEL 25 143 VEEGDPIVL 24 372 GEPQPTIKW 24 778 EETVTNHTL ' 24 976 YEiGELNDI 24 482 LEGRRYHIY 23 1156 DEKPLKGSL 23 370 AEGEPQPTI 22 552 CESKCDSHL 21 206 AAFPRLRT1 20 258 TESGSESSI 20j 203

TableXXXII-V1-HLA- B4402-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 121 EEIEFIVPS 19 617 ADITQVTVL 19 25 IEIPSSVQQ 18 141 LEVEEGDPl 18 144 EEGDPIVLP 18 344 EEPPRWTKK 18 537 PKNPRIPKL 18 540 PRIPKLHML 18 157 KGLPPLHtY 17 396 WFPREiSF 17 525 LDIRNATKL 17 580 TEDGRHID 17 903 EFHLTVLAY 17 1105 AiALLTLLL 17 1193 EDGSFIGAY 17 262 SESSITILK 16 268 ILKGEILLL 16 280 AEGLPTPQV 16 400 REISFTNLQ 16 465 ASPEAWSW 16 657 NISEYIVEF 16 676 EELTRVQGK 16 684 KKTTViLPL" 16 810 GPDPQSVTL ΠθΙ 893 GMVPSLDAF 16 902 SEFHLTVLA 16 929 EGVPEQPTF 16 932 PEQPTFLKV 16 933 EQPTFLKVf 16 979 GELNDINIT 16 1139 PEIQSVKDE" 16 2 EPLLLGRGL 15 6 LGRGLIVYL 15 39 (KQSKVQVAF 15 45 ( VAFPFDEYF 15 59 &#943; AKGNPEPTF 15 92 FRIPNEGHI 15 118 > AMSEEIEFI 15)

TableXXXII-V1-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is-9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 125 FtVPSVPKL 15 158 GLPPLHIYW 15 169 IELEHIEQD 15 246 IKQRKPKLL 15 343 VEEPPRWTK 15 450 ATWGYSAF 15 575 FEINGTEDG 15 628 PDPPENLHL 15 638 ERQNRSVRL 15 669 KEEPGRWEE 15 687 TVILPLAPF 15 726 APDRNPQNI 15 740 QPKEMIIKW 15 743 EMilKWEPL x t-IO 777 EEETVTNHT 15 799 VKVQAINQL 15 853 RVHGRLKGY 15 878 PKEVNILRF 15( 879 KEVNILRFS 15 , 920 SEPYIFQTP 15 950 LSWGLPKKL 15 961 NLTGYLLQY 15 997 SNLNATTKY 15 1030 EGSKGIGK! 15 1057 AEHIVRLMT 15 1100 IGLMCAIAL &amp;#943; 15 1101 GLMCAIALL 15 1104 CAIALLTLL 15 1106 IALLTLLLL 15 1175 ESADSLVEY 15 1192 SEDGSFIGA 15 5 LLGRGLIVY 14 9 GLIVYLMFL 14 11 IVYLMFLLL 14 13 YLMFLLLKF 14( 70 TKDGNPFYF 14 84 tPSNNSGTF 14 95 PNEGHISHF 14

TableXXXII-V1-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 120 SEEIEFIVP 14 123 IEFIVPSVP 14 151 LPCNPPKGL 14 200 NDYCCFAAF 14 237 TEIGSKANS 14 266 ITILKGEIL j 14 303 TKENYGKTL 14 305 ENYGKTLKI 14 350 TKKPQSAVY 14 359 STGSNGILL 14 390 HPFAGDWF 14 407 LQPNHTAVY 14 447 ENYATVVGY 14 456 SAFLHCEFF -1 Λ 1*1- 487 YHIYENGTL 14 512 VENAIGKTA 14 558 SHLKHSLKL 14 567 SWSKDGEAF 14 572 GEAFEINGT 14 599 J LEDQGIYCC 14 637 SERQNRSVR 14 653 DHNSNISEY 14 663 VEFEGNKEE 14 675 WEELTRVQG 14 720 HETPPAAPD 14 738 ASQPKEMII 14 755 EQNGPGLEY 14 759 PGLEYRVTW 14 768 KPQGAPVEW 14 838 NSTLVKVTW 14 858 LKGYQINWW 14 942 KVDKDTATL 14 944 DKDTATLSW 14 957 KLNGNLTGY 14 973 NDTYEIGEL 14 __ 1000 NATTKYKFY I 14 1023 EESSTLGEG 14 1045 QKTHPIEVF 14 204

TableXXXII-V1-HLA- B44O2-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 1055 PGAEHIVRL 14 1060 IVRLMTKNW 14 1094 STQGWFIGL 14 1098 WFIGLMCAI 14 1110 TLLLLTVCF 14 1132 KEDLHPDPE 14 1 MEPLLLGRG 13 17 LLLKFSKAI 13 50 DEYFQIECE 13 63 PEPTFSWTK 13 96 NEGHISHFQ 13 133 LPKEKIDPL 13 135 KEKIDPLEV 13 154 NPPKGLPPL 13 174 IEQDERVYM 13 203 CCFAAFPRL 13 219 PMKLTVNSL 13 245 SIKQRKPKL 13 247 KQRKPKLLL 13 261 GSESSITIL 13 267 TILKGEILL 13 282 GLPTPQVDW 13 331 FLGTATHDF’ 13 417 CEASNVHGT 13 418 EASNVHGTI 13 419 ASNVHGTIL 13( 446 GENYATWG 13 474 QKVEEVKPL 13 477 EEVKPLEGR 13 479 VKPLEGRRY 13 502 EEDAGSYSC 13 503 EDAGSYSCW 13 584 RIIIDGANL 13 591 NLTISNVTL . 13 626 DVPDPPENL 13 640 QNRSVRLTW 13 690 LPLAPFVRY . 13 692 LAPFVRYQF 13

TableXXXil-V1-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 706 NEVGRSQPS 13 742 KEMIIKWEP 13 754 MEQNGPGLE 13 761 LEYRVTWKP 13 811 PDPQSVTLY 13 821 GEDYPDTAP 13 829 PVIHGVDVI 13 833 GVDVINSTL 13 863 INWWKTKSL 13 876 THPKEVNIL | 13 890 RNSGMVPSL 13 896 PSLDAFSEF 13 915 GAGPESEPY 13 959 NGNLTGYLL 13 970 QIINDTYEI 13 986 ITTPSKPSW 13 991 KPSWHLSNL 13 1001 ATTKYKFYL 13 1050 IEVFEPGAE 13 1053 FEPGAEHIV 13 1067 NWGDNDSIF 13 1078 VIETRGREY 13 1091 DDISTQGWF 13 . 1103 MCAIALLTL 13 1119 VKRNRGGKY 13 1130 KEKEDLHPD 13 1152 YSDSDEKPL 13 1159 PLKGSLRSL 13 1174 TESADSLVE 13 1182 EYGEGDHGL 13 1205 KEKGSVESN 13 1210 VESNGSSTA 13 1212 SNGSSTATF 13 1214 GSSTATFPL 13 3 PLLLGRGLl 12 8 RGLIVYLMF - 12 19 LKFSKAIEI 12 41 SKVQVAFPF 12

TableXXXIl-V1-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 47 FPFDEYFQI 12 61 GNPEPTFSW 12 68 SWTKDGNPF 12 76 FYFTDHRII 12 99 HISHFQGKY 12 102 HFQGKYRCF 12 107 YRCFASNKL 12 117 IAMSEEIEF 12 173 HIEQDERVY 12 181 YMSQKGDLY 12 214 IVQKMPMKL 12 238 EIGSKANSI 12 260 SGSESSITl 12 304 KENYGKTLK 12 323 NYRCTASNF 12 324 YRCTASNFL 12 384 GSPVDNHPF 12 424 GTILANANI 12 432 IDWDVRPL 12 461 CEFFASPEA 12 476 VEEVKPLEG 12 489 lYENGTLQI 12 490 YENGTLQIN 12 534 RVSPKNPRI 12 542 IPKLHMLEL 12 548 LELHCESKC 12 556 CDSHLKHSL 12 569 SKDGEAFEI 12 586 IIDGANLTI 12 605 YCCSAHTAL 12 631 PENLHLSER 12 648 WEAGADHNS 12 650 AGADHNSNI '12 682 QGKKTTVIL 12 748 WEPLKSMEQ 12 753 SMEQNGPGL 12 786 LRVMTPAVY 12 796 PYDVKVQAI 12 205

TableXXXII-V1-HLA-B4402-9mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123455789 score 823 DYPDTAPVI 12 850 PKDRVHGRL 12 857 RLKGYQINW 12 864 NWWKTKSLL .12 875 RTHPKEVNI 12 901 FSEFHLTVL 12 916 AGPESEPYI 12 918 PESEPYIFQ 12 930 GVPEQPTFL 12 958 LNGNLTGYL 12 968 QYQIINDTY 12 999 LNATTKYKF 12 1022 TEESSTLGE 12 1052 VFEPGAEHI 12 (1079 1ETRGREYA 12 1082 RGREYAGLY 12 1090 YDDISTQGW 12 1141 IQSVKDETF 12 1144 VKDETFGEY 12 1183 YGEGDHGLF 12 1184 GEGDHGLFS 12. 1189 GLFSEDGSF &amp;#943; 12

TabieXXXII-V2-(SET1)- [ HLA-B4402-9mers- 282P1G3 Each pepiide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 1 F1VPSVPKF 15 9 FPKEKIDPL 13 6 VPKFPKEKI 9 7 PKFPKEKID 7

TableXXXIi-V2-(SET2)- HLAB4402-9mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 9 AKENYGKTL 17 5 KGREAKENY 11 7 REAKENYGK 10

TableXXXII-V2-(SET3)- H JVB4402-Smers- 282P1G3 Each peptide Is a portion ofSEQlDNO:5; each start position is specified, . the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 6 GEGKYAGLY 22 2 SSTLGEGKY 13 5 LGEGKYAGL 11 9 | KYAGLYDDI 10

TableXXXI!-V3-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 48 AEDFIQKST 17 23 TGSPQPSIF 15 39 LSYRNRNML 14 4 GVDVINTTY 13 37 QELSYRNRN 13 62 EKSSTFFKI 13 43 NRNMLAEDF 12 |59 NYVEKSSTF 12

TableXXXII-V3-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 10 TTYVSNiTY 14 22 ATGSPQPSI 11 33 CSKEQELSY 11 35 KEQELSYRN 11 61 VEKSSTFFK 24 GSPQPSIFI 10 31 FICSKEQEL 10 44 RNMLAEDFI 10 52 IQKSTSCNY 10 60 YVEKSSTFF 10

TableXXXII-V4-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 amino acids, and the end position for each pepiide is the start position plus eight. Pos 123456789 score 7 EDLPEQPTF 17 6 GEDLPEQPT 12 8 DLPEQPTFL 12 VTLYSGEDL 11

TableXXXII-V5-HLA- B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score ' 4 LTVNSSNSI 10 7 NSSNSIKQR 9 6 VNSSNSIKQ 4 9 SNSIKQRKP 4 206

TableXXXii-V6-HLA- B4402-9mers- 232P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start’ position plus eight. Pos 123456789( score| 1 EEIEFIVPK 19 3 IEFIVPKLE 16 2 EIEFIVPKL 15 5 FIVPKLEHI 12

TableXXXII-V7-HLA B4402-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 7 VEDNISHEL 24 20 PEPPRWTKK 16 10 NISHELFTL 14 17 TLHPEPPRW 14 8 EDNISHELF ' 13 13 HELFTLHPE. 13

TableXXXlill-V1-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position pius eight. Pos 123456789 score 611 TALDSAADI 26 206 AAFPRLRTl 25 334 TATHDFHVI 25 427 LANANIDW 25 285 TPQVDWNKI 24 418 EASNVHGTI 24

TableXXXIlll-V1-HL4- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 ( score ( 445 DGENYATW 24 519 TAVTANLD! 24 47 FPFDEYFQI 23 130 VPKLPKEKI 23 504 DAGSYSCWV 23 1106 IALLTLLLL 23 133 LPKEKIDPL 22 260 SGSESSITI . 22 429 NANIDWDV 22 616 AADITQVTV 22 23 KAIEIPSSV 21 468 EAWSWQKV 21 726 APDRNPQNl 21 823 DYPDTAPVI 21 873 DGRTHPKEV 21 963 TGYLLQYQI 21 115 LGiAMSEEl 20 139 DPLEVEEGD 20 151 LPCNPPKGL 20 154 NPPKGLPPL 20 578 NGTEDGRi! 20 589 GANLTISNV 20 737 QASQPKEMI 20 916 AGPESEPYI 20 954 LPKKLNGNL 20 1030 EGSKGIGKI 20 (1172 QPTESADSL 20 I 2 EPLLLGRGL 19 ( 305 ENYGKTLKI 19 I 542 IPKLHMLEL 19 791 PAVYAPYDV 19 j 794 YAPYDVKVQ 19 j 810 GPDPQSVTL 19 828 APVIHGVDV 19 978 IGELNDINl 19 988 TPSKPSWHL 19 1104 CAIALLTLL 19 1138 HPDPEIQSV 19

TableXXXIIli-V1-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 ) score 629 DPPENLHLS 18 650 AGADHNSNi 18 690 LPLAPFVRY 18 757 NGPGLEYRV 18 795 APYDVKVQA 18 1100 IGLMCAIAL 18 6 LGRGLIVYL 17 27 IPSSVQQVP 17 433 DWDVRPLI 17 586 IIDGANLTI 17 681 VQGKKTTVI 17 740 QPKEMIIKW | 17 ( 812 DPQSVTLYS 17 I 855 HGRLKGYQi 17 j 909 LAYNSKGAG 17 | 933 EQPTFLKVI 17 991 KPSWHLSNL 17| 1033 KGIGKISGV 17 1055 PGAEHIVRL 17 1138 DPEIQSVKD 17 17 LLLKFSKAl 16 19 LKFSKAIEI 16 75 PFYFTDHRl 16 185 KGDLYFANV 16 I 297 lpkgretkF 16 I 390 HPFAGDWF 16 | 392 FAGDVVFPR 16 I 464 j 514 FASPEAWS 16 NAIGKTAVT 16 | 573 EAFEINGTE 16) ( 695 FVRYQFRVi 16) | 877 HPKEVNiLR 16 | 899 DAFSEFHLT “ie) )1035 lGKISGVNL 16) )1199 GAYAGSKEK 16) &amp;#943; 11 IVYLMFLLL 15 I 9Z IPNEGHISH 15 14' DPIVLPCNP 1 15 207

TableXXXllll-V1-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is th e start position plus eight. Pos j 208 123456789 score FPRLRTiVQ 15 375 QPTIKWRVN 15 398 FPREISFTN 15 466 SPEAWSWQ 15 480 KPLEGRRYH 15 508 YSCWVENAI 15 614 DSAADITQV 15 682 QGKKTTVIL 15 692 LAPFVRYQF 15 703 iAVNEVGRS 15 722 TPPAAPDRN 15 728 DRNPQNIRV 15 824 YPDTAPVIH 15 826 DTAPVIHGV 15 827 TAPViHGVD' 15 829 PVIHGVDVI 15 921 EPYIFQTPE 15 927 TPEGVPEQP 15 935 PTFLKVIKV 15 976 YEicrFi Nini 1 U.L.1 'S 5-/ S 15 1048 HPIEVFEPG 15 1054 EPGAEHIVR 15 1092 DISTQGWfI 15 1111 LLLLTVCFV 15 1158 KPLKGSLRS 15 1202 AGSKEKGSV 15 4 LLLGRGLiV 14 29 SSVQQVPT! 14 30 SVQQVPTI1 14 64 EPTFSWTKD 14 76 FYFTDHRI1 14 84 IPSNNSGTF 14 141 LEVEEGDP! 14 159 LPPLHIYWM 14 255 LPPTESGSE 14 279 FAEGLPTPQ 14 283 LPTPQVDWN 14 327 TASNFLGTA 14

TableXXXIIII-V1-HLA- B5101-9mers-282P1G3 . Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 345 EPPRWTKKP 14 370 AEGEPQPTI 14 449 YATVVGYSA 14 453 VGYSAFLHC 14 527 IRNATKLRV 14 577 INGTEDGRI 14 615 SAADITQVT 14 619 ITQVTVLDV 14 673 GRWEELTRV 14 749 EPLKSMEQN 14 758 GPGLEYRVT 14 759 PGLEYRVTW 14 836 VINSTLVKV 14 849 VPKDRVHGR 14 887 SGGRNSGMV 14 950 LSWGLPKKL 14 959 NGNLTGYLL 14 1000 NATTKYKFY 14 1027 TLGEGSKGI 14 1071 NDSIFQDVI 4/i i T 1108 LLTLLLLTV 14 1190 LFSEDGSFI 14 1201 YAGSKEKGS ’ 14 62 NPEPTFSWT 13 74 NPFYFTDHR 13 110 FASNKLGIA 13 117 IAMSEEIEF 13 118 AMSEEIEFt 13 143 VEEGDPIVL 13 156 PKGLPPLHI 13 163 HlYWMNIEL 13 205 FAAFPRLRT 13 214 IVQKMPMKL 13 218 MPMKLTVNS 13 231 NDSSSSTEI 13 238 EIGSKANSI 13 256 PPTESGSES 13 258 TESGSESSI 13

TableXXXIIII-V1-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 281 EGLPTPQVD 13 357 VYSTGSNGI 13 373 EPQPTIKWR 13 388 DNHPFAGDV 13 389 NHPFAGDW 13 408 QPNHTAVYQ 13 438 RPLIQTKDG 13 471 VSWQKVEEV 13 489 IYENGTLQI 13 522 TANLDiRNA 13 529 NATKLRVSP 13 534 RVSPKNPRI 13 539 NPRIPKLHM 13 617 AD1TQVTVL 13 626 DVPDPPENL 13 680 RVQGKKTTV 13 715 QPSDHHETP 13 725 AAPDRNPQN 13 768 KPQGAPVEW 13 790 TPAVYAPYD 13 793 VYAPYDVKV 13 796 PYDVKVQA! 13 841 LVKVTWSTV 13 900 AFSEFHLTV 13 923 YIFQTPEGV 13 932 PEQPTFLKV 13 1013 TSQGCGKPI 13 1052 VFEPGAEH! 13 1056 GAEHIVRLM 13 1066 KNWGDNDSI 13 1070 DNDSIFQDV 13 1086 YAGLYDDIS 13 3 PLLLGRGLl 12 26 EIPSSVQQV 12 . 37 I1KQSKVQV 12 45 VAFPFDEYF 12 58 EAKGNPEPT 12 72 DGNPFYFTD 12 208

TableXXXliil-VTHLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is .specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 92 FRIPNEGHI 12 125 FIVPSVPKL 12 127 VPSVPKLPK 12 155 PPKGLPPLH 12 160 PPLHIYWMN 12 166 WMNIELEHI 12 190 FANVEEKDS 12 216 QKMPMKLTV 12 229 HANDSSSST 12 346 PPRWTKKPQ 12 352 KPQSAVYST 12 369 EAEGEPQPT 12 394 GDVVFPREI 12 426 ILANANIDV 12 444 KDGENYATV 12 462 EFFASPEAV 12 463 FFASPEAW 12 481 PLEGRRYHI 12 516 IGKTAVTAN 12 525 LDIRNATKL 12 558 SHLKHSLKL 12 569 SKDGEAFEi 12 571 DGEAFEING' 12 579 GTEDGRiii 12 591 NLTISNVTL 12 608 SAHTALDSA 12 627 VPDPPENLH 12 636 LSERQNRSV 12 649 EAGADHNSN 12 688 VILPLAPFV 12 700 FRVIAVNEV 12 723 PPAAPDRNP 12 730 NPQNIRVQA 12 T12 APVEWEEET 12 822 EDYPDTAPV 12 875 RTHPKEVNI 12 876 THPKEVNIL 12 895 VPSLDAFSE 12

TableXXXI!ll-V1-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start posiiion is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 901 FSEFHLTVL 12 947 TATLSWGLP 12 964 GYLLQYQII 12 1010 RACTSQGCG 12 1015 QGCGKPITE 12 1042 NLTQKTHPI 12 1044 TQKTHPIEV 12 1133 EDLHPDPEI 12 1176 SADSLVEYG 12

TableXXXill!-V2-HLA-

TableXXX!lll-V2-(SET3)- HLA-B5101-9mers- 282P1G3 Each peptide is a portion ofSEQIDNO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight Pos 123456789 score 5 LGEGKYAGL 16 9 KYAGLYDDI 11 7 EGKYAGLYD 7 B5101-9mers-(SET1}- 282P1G3

Each peptide is a portion of SEQ iD NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight.

Pos | 123456789 score 6 VPKFPKEKl 23 9 FPKEKIDPL 21 3 VPSVPKFPK 11

TableXXXIIII-V2-(SET2)- HLA-B5101-9mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 3 LPKGREAKE 15 8 EAKENYGKT 14 9 AKENYGKTL 10 5 KGREAKENY 8

TableXXXIIII-V3-HLA- B5101-9mers-282P1G3 Each peptide is a portion ofSEQIDNO:7; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eighL Pos 123456789 score 47 LAEDFIQKS 16 21 NATGSPQPS 14 62 EKSSTFFKI 14 3 HGVDVINTT 13 39 LSYRNRNML 13 24 GSPQPSIFI λ n S £ 25 SPQPSIFIC 12 27 QPSIFICSK 11 53 QKSTSCNYV 11 5 VDVINTTYV 10 10 TTYVSNTTY 10 11 TYVSNTTYV 10 22 ATGSPQPSI 10 44 RNMLAEDFI 10 16 TTYVSNATG 9 6 DVINTTYVS 8 23 TGSPQPSIF 8 31 FICSKEQEL 8

TabieXXXilil-V4-HLA- B$101-9mers-282P1G3

Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 9 209 Γ ' amino acids, and the end position for each peptide is the' start position pius eight. Pos 123456789 score 8 DLPEQPTFL 15 9 LPEQPTFLK 12 1 VTLYSGEDL 10 5 SGEDLPEQP 8

TableXXXI!ll-V5-HLAn B5101-9mers-282P1G3 [

Each peptide is a portion j of SEQ ID NO: 11; each start position is specified] the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight_j

Pos 123456789 score) 4 LTVNSSNSl 14) 2 MKLTVNSSN 7| TableXXXIIII-V6-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 5 FIVPKLEHI 14 7 VPKLEHIEQ 12 2 EIEFIVPKL 10 I 3 IEFIVPKLE

TableXXXIIII-V7-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. Pos 123456789 score 3 FHVIVEDNI 13 19 HPEPPRWTK 12

TableXXXilll-V7-HLA- B5101-9mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 9 amino acids, and the end position for each peptide is the start position plus eight. 10 NISHELFTL 10 7 VEDNISHEL 7 18 LHPEPPRWT 7 2 DFHVIVEDN 6 11 ISHELFTLH I 6

TableXXX!V-V1-HLA-A1- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 810 GPDPQSVTLY 32 1192 SEDGSFIGAY 28 193 VEEKDSRNDY 27 481 PLEGRRYHIY 27 902 SEFHLTVLAY 24 1173 PTESADSLVE 23 4 LLLGRGLIVY 22 119 MSEEIEFIVP 22 309 KTLKIENVSY 22 349 WTKKPQSAVY 22 627 VPDPPENLHL 22 754 MEQNGPGLEY 22 931 VPEQPTFLKV 22 1021 ITEESSTLGE 22 1191 FSEDGSFIGA 22 406 NLQPNHTAVY 21 499 RTTEEDAGSY 21 919 ESEPYIFQTP 21 960 GNLTGYLLQY 21 996 LSNLNATTKY 21 261 GSESSITILK 20 371 EGEPQPTIKW 20 478 EVKPLEGRRY 20 Lot GTEDGRIIID 20

TableXXXIV-V1-HLA-A1- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 788 VMTPAVYAPY 20 1143 SVKDETFGEY 20 1183 YGEGDHGLFS 20 43 VQVAFPFDEY 19 180 VYMSQKGDLY 19 689 ILPLAPFVRY 19 1118 FVKRNRGGKY 19 68 SWTKDGNPFY 18 236 STEIGSKANS 18 815 SVTLYSGEDY 18 1056 GAEHIVRLMT 18 1152 YSDSDEKPLK 18 78 FTDHRIIPSN . 17 98 GHISHFQGKY 17 343 VEEPPRWTKK 17 500 TTEEDAGSYS| 17 785 tlrvmtpavy| 17 . 824 YPDTAPVIHG I 17 901 FSEFHLTVLA j 17 1081 TRGREYAGLY) 17 134 PKEKIDPLEV 16 172 EHIEQDERVY 16 257 PTESGSESSI 16 359 STGSNGILLC 16 440 LIQTKDGENY 16 446 GENYATWGY 16 '475 KVEEVKPLEG 16 569 SKDGEAFEIN 16 612 ALDSAADITQ 16 636 LSERQNRSVR 16 652 ADHNSNISEY 16 914 KGAGPESEPY 16 967 LQYQISNDTY 16 1028 LGEGSKGIGK 16 1077 DV1ETRGREY 16 137 IqDPLEVEEG 15 , 145 EVEEGDPIVL 15 156 PKGLPPLHIY 15 210

TableXXXIV-V1-HLA-A1- I 10mers-282P1G3 | Each peptide is a portion of I SEQ ID NO: 3; each start position is specified, the I length of peptide is 10 amino acids, and the end position for each peptide is j the start position plus nine. | Pos 1234567890 scorej 298 PKGRETKENY 15| 315 NVSYQDKGNY 15 434 VVDVRPLIQT 15 580 TEDGRIIIDG 15 596 NVTLEDQGIY 15( 651 GADHNSNISE 15 852 DRVHGRLKGY 15 956 KKLNGNLTGY 15 999 LNATTKYKFY 15 1052 VFEPGAEHIV 15 1136 HPDPEIQSVK 15 1174 TESADSLVEY 15

TableXXXIV-V2-(SET1)- HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 5 PSVPKFPKEK ,. 8 8 PKFPKEKIDP 8 4 VPSVPKFPKE θ 2 FIVPSVPKFP 5 6 SVPKFPKEK! 4 1 EFIVPSVPKF 3 10 FPKEKIDPLE 3

TableXXXIV-V2-(SET2)- HLA-A1-l0mers-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino adds, and the end position for each peptide is toe start position pius nine.

Pos i 1234567890 score

TableXXXIV-V2-(SET2)- HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, toe length of peptide is 10 amino acids, and toe end position for each peptide is toe start position pius nine. Pos 1234567890 score 5 PKGREAKENY 15 10 AKENYGKTLK 13 1 GGDLPKGREA 11 7 GREAKENYGK 11

TableXXXIV-V2-(SET3}- HLA-A1-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, toe length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 6 LGEGKYAGLY 28 2 ESSTLGEGKY 21

TableXXXIV-V3-HLA-A1- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 10 NTTYVSNTTY 22 33 ICSKEQELSY 21 4 HGVDVINTTY 16 52 FIQKSTSCNY 16 26 SPQPSIFICS 13 35 SKEQELSYRN 12 61 YVEKSSTFFK 12 37 EQELSYRNRN 11 49 AEDFIQKSTS 11 56 STSCNYVEKS 11 5 GVDVINTTYV 10 48 LAEDFIQKST 10

TableXXXIV-V4-HLA-A1- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, toe length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 10 LPEQPTFLKV 21 6 SGEDLPEQPT 12 7 GEDLPEQPTF 10

TableXXXIV-V5-HL4-A1- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino adds, and toe end position for each peptide is the start position pius nine. Pos 1234567890 score 9 SSNSIKQRKP 8 5 LTVNSSNSIK 7 6 TVNSSNSIKQ 6 8 NSSNSIKQRK 4 10 SNSIKQRKPK 3

Tab!eXXX!V-V6-HLA-A1- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is toe start position plus nine. Pos 1234567890 score 1 SEEIEFIVPK 12 3 EIEFIVPKLE 12 10 KLEHIEQDER 11 4 IEFIVPKLEH 6 I 6 FIVPKLEHIE 5

TableXXXIV-V7-HLA-A1-. 10mers-282P1G3

Each peptide is.a portion of SEQ ID NO: 15; each start position is specified, toe length of peptide is 10 211 amino acids, and the end position for each peptide is the start position plus nine. (Pos 1234567890 score 20 HPEPPRWTKK 16 8 VEDNISHELF 13 13 SHELFTLHPE 12 1 THDFHVIVED 10 7 IVEDNISHEL 10 12 ISHELFTLHP 10 17 FTLHPEPPRW 7

TableXXXV-V1-HLA-A0201- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 1107 ALLTLLLLTV 31 5 LLGRGLIVYL 28 426 iLANANIDVV 28 274 LLLECFAEGL 27 1102 LMCAIALLTL 27 1105 AIALLTLLLL 27 1110 TLLLLTVCFV 26 132 KLPKEKIDPL 25 267 TILKGEILLL 25 585 IIIDGANLTI 24 635 HLSERQNRSV 24 957 KLNGNLTGYL 24 9 GLIVYLMFLL 23 615 SAADITQVTV 23 835 DVINSTLVKV 23 36 TIIKQSKVQV 22 118 AMSEEIEFIV 22 158 GLPPLHIYWM 22 431 NIDWDVRPL 22 524 NLDIRNATKL 22 840 TLVKVTWSTV 22 897 SLDAFSEFHL 22 16 FLLLKFSKAI 21 114 KLGIAMSEEI 21 ~150 VLPCNPPKGL ~21 470 WSWQKVEEV 21 "54&amp;#938; ’RIPKLHMLEL ~21

TableXXXV-V1-HLA-A0201- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 618 DITQVTVIDV 21 792 AVYAPYDVKV 21 875 RTHPKEVNIL 21 949 TLSWGLPKKL 21 953 GLPKKLNGNL 21 1034 GIGKISGVNL 21 3 PLLLGRGLIV 20 4 LLLGRGLIVY 20 10 LIVYLMFLLL 20 18 LLKFSKAIEf 20 25 IEIPSSVQQV 20 205 FAAFPRLRTI 20 213 TIVQKMPMKL 20 425 TILANANIDV 20 428 ANANtDWDV 20 488 HIYENGTLQ! 20 616 AADITQVTVL 20 862 QINWWKTKSL 20 966 LLQYQIINDT 20 1099 FIGLMCAIAL 20 1100 IGLMCAIALL 20 1189 GLFSEDGSFI 20 117 IAMSEEIEFI 19 206 AAFPRLRTtV 19 265 StTiLKGEIL 19 1135 LHPDPEIQSV 19 1158 KPLKGSLRSL 19 121 EEIEFIVPSV 18 218 MPMKLTVNSL 18 245 SIKQRKPKLL 18 260 SGSESSITIL 18 •266 ITILKGEILL 18 268 ILKGEILLLE 18 273 ILLLECFAEG 18 450 ATWGYSAFL 18 526 DIRNATKLRV 18 536 SPKNPRIPKL 18 590 ANLTISNVTL 18

TableXXXV-V1-HLA-A0201 -10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 745 IIKWEPLKSM 18 765 VTWKPQGAPV ' 18 784 HTLRVMTPAV 18 889 QRNSGMVPSL 18 900 AFSEFHLTVL 18 965 YLLQYQilND 18 972 INDTYEIGEL 18 1026 STLGEGSKGI 18 1043 LTQKTHPIEV 18 1112 LLLTVCFVKR 18 1201 YAGSKEKGSVj 18 37 IIKQSKVQVA 17 82 RIIPSNNSGT 17 137 KIDPLEVEEG 17 153 CNPPKGLPPL 17 221 KLTVNSLKHA 17 253 LLLPPTESGS 17 279 FAEGLPTPQV 17 356 AVYSTGSNGI 17 413 AVYQCEASNV 17 565 KLSWSKDGEA 17 603 GIYCCSAHTA 17 687 TV1LPLAPFV 17 696 VRYQFRViAV 17 699 QFRVIAVNEV 17 795 APYDVKVQAl 17 798 DVKVQAINQL 17 809 SGPDPQSVTL 17 836 VINSTLVKVT 17 871 LLDGRTHPKE 17 899 DAFSEFHLIV 17 941 IKVDKDTATL 17 1032 SKGIGKISGV 17 1073 SIFQDVIETR 17 1101 glmcaiallt 17 1104 CAIALLTLLL 17 1106 IALLTLLLLT 17 8 RGLIVYLMFL 16( 212

TableXXXV-V1-HLA-A0201- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 17 LLLKFSKAIE 16 22 SKAIEIPSSV 16 124 EFIVPSVPKL 16 129 SVPKLPKEKI 16 254 LLPPTESGSE 16 326 CTASNFLGTA 16 333 GTATHDFHVI 16 365 ILLCEAEGEP 16 396 WFPREISFT 16 421 NVHGTILANA, 16 443 TKDGENYATV 16 514 NAIGKTAVTA 16 518 KTAVTANLDI 16 544 KLHMLELHCE 16 576 EINGTEDGRI 16 586 IIDGANLTIS 16 610 HTALDSAADI 16 613 LDSAADITQV 16 752 KSMEQNGPGL 16 772 APVEWEEETV 16 807 LGSGPDPQSV 16 827 TAPVIHGVDV 16 857 RLKGYQINW 16 870 SLLDGRTHPK 16 915 GAGPESEPYI 16 937 FLKVIKVDKD 16 990 SKPSWHLSNL 16 1080 ETRGREYAGL 16 1094 STQGWFIGLM 16 1103 MCAIALLTLL 16 1166 SLNRDMQPTE 16 1181 VEYGEGDHGL 16 13 YLMFLLLKFS 15 141 LEVEEGDPIV 15 162 LHIYWMNIEL 15 165 YWMNIELEHI 15 179 RVYMSQKGDL 15 187 DLYFANVEEK I 15

TableXXXV-V1 -HLA-A0201 -10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 237 TEIGSKANSI 15 244 NSIKQRKPKL 15 252 KLLLPPTESG 15 282 GLPTPQVDWN 15 307 YGKTLKIENV 15 334 TATHDFHVIV 15 341 VIVEEPPRWT 15 458 FLHCEFFASP 15 464 FASPEAVVSW 15 515 AIGKTAVTAN 15 521 VTANLDIRNA 15 539 NPRIPKLHML 15 583 GRIliDGANL 15 584 RIIIDGANLT 15 588 DGANLTISNV 15 598 TLEDQGIYCC 15 661 YIVEFEGNKE 15 683 GKKTTVILPL 15 702 VIAVNEVGRS 15 725 AAPDRNPQNl 15 830 ViHGVDViNS 15 833 GVDVINSTLV 15 948 ATLSWGLPKK 15) 96&amp;#906; NLTGYLLQYQ 15) 969 YQIINDTYE! 15 977 EIGELNDINI 15 980 ELNDINITTP 15 1019 KPITEESSTL 15 1029 GEGSKGIGKI 15 1037 KISGVNLTQK 15 1108 LLTLLLLTVC 15 1120 KRNRGGKYSV 15

TabieXXXV-V2-(SET1)- HLA-A0201-10mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 6 SVPKFPKEKI 16 9 KFPKEKIDPL 15 2 FIVPSVPKFP 10

TableXXXV-V2-(SET2)- HLA-A0201-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos .1234567890 score 3 DLPKGREAKE 13 9 EAKENYGKTL 13 8 REAKENYGKT 8 1 GGDLPKGREA 7 2 GDLPKGREAK 6

TableXXXV-V2-(SET3)- HLA-A0201-10mers- 282P1G3 Each peptide is a portion ofSEQIDNO: 5;each start position is specified, the length of peptide is 10 amino acids/and the end position for each peptide is the start position plus nine. Pos 1234567890 score 3 SSTLGEGKYA 10 4 STLGEGKYAG 9 5 TLGEGKYAGL 8

TableXXXV-V3-HLA-A0201 -10tners-282P1 G3

Each peptide is a portion of SEQ iD NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 213

Pos 1234567890 score 47 MLAEDFiQKS 20 2 VIHGVDVINT 19 8 VINTTYVSNT 18 39 ELSYRNRNML 17 22 NATGSPQPSI 16 31 IFICSKEQEL 16 5 GVDVINTTYV 15 11 TTYVSNTTYV 15 3 IHGVDVINTT 13 53 IQKSTSCNYV 12 56 STSCNYVEKS 12 30 SIFICSKEQE 11 42 YRNRNMLAED 11 48 LAEDFIQKST 11 13 YVSNTTYVSN 10 14 VSNTTYVSNA 10 24 TGSPQPSIFI 10 46 NMLAEDFIQK 10 62 VEKSSTFFKI 10 7 DVINTTYVSN 9 32 FICSKEQELS 9 44 NRNMLAEDFl 9 52 FIQKSTSCNY 9

TableXXXV-V4-HLA- A0201-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. jPos 1234567890 ' score j 1 SVTLYSGEDL] 15 10 LPEQPTFLKV 14 3 TLYSGEDLPE 12 4 LYSGEDLPEQ 11 8 EDLPEQPTFL 11 9 DLPEQPTFLK 11) end position for each peptide is the start position plus nine. Pos 1234567890 | score 4 KLTVNSSNStj 21

TableXXXV-V6-HLA- A0201-I0mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 2 EEIEFIVPKL 18 6 FIVPKLEHIE 12 10 KLEHIEQDER 12 5 EFiVPKLEHl 11 7 IVPKLEHIEQ 8

TableXXXV-V7-HLA- A0201-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 iQnrm* 1 V? 7 IVEDNISHEL 19 10 &amp;#9633;NiSHELFTL 17 18 TLHPEPPRW 16 θ VtVEDNISHE

TabIeXXXVI-V1-HLA- A0203-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine Pos 1234567890 score 198 SRNDYCCFAA 19 608 SAHTALDSAA 19 717 SDHHETPPAA 19 421 NVHGTILANA 18 643 SVRLTWEAGA 18

TableXXXVI-V1-HLA- A0203-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 . score 1098 WFIGLMCAIA 18 1193 EDGSFIGAYA 18 199 RNDYCCFAAF 17 609 AHTALDSAAD 17 718 DHHETPPAAP 17 15 MFLLLKFSKA 10 37 IIKQSKVQVA 10 50 DEYFQIEGEA 10 102 HFQGKYRCFA 10 1Q9 CFASNKLGIA 10 182 MSQKGDLYFA io| 197 DSRNDYCCFA 10 221 KLTVNSLKHA 10 234 C Γ'Γ'ΤΓΙΓ' Γ&amp;#906;Ζ A OOO [ a n tv 271 GEILLLECFA 10 319 QDKGNYRCTA 10 326 CTASNFLGTA 10 347 PRWTKKPQSA 10 361 GSNGILLCEA 10 384 GSPVDNHPFA 10 404 FTNLQPNHTA 10 410 NHTAVYQCEA 10 419 ASNVHGTILA 10 441 IQTKDGENYA 10 448 NYATWGYSA 10 456 SAFLHCEFFA 10 460 HCEFFASPEA 10 496 QINRTTEEDA 10 506 GSYSCWVENA 10 511 WVENAIGKTA 10 514 NAIGKTAVTA 10 521 VTANLDIRNA 10 565 KLSWSKDGEA 10 581 EDGRIIIDGA 10 600 EDQGtYCCS/C 10 603 GIYCCSAHTA 10j 607 CSAHTALDSA 10 641 NRSVRLTWEA 10

TableXXXV-V5-HLA- A0201-10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of pepfide is 10 amino acids, and the 214

TableXXXVI-V1-HLA- A0203-10mers-282P1G3 TableXXXVI-V1-HLA- A0203-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score Pos 1234567890 score 684 KKTTVILPLA 10 420 SNVHGTILAN 9 695 FVRYQFRVIA 10 422 VHGTILANAN 9 716 PSDHHETPPA 10 442 QTKDGENYAT 9 729 RNPQNIRVQA 10 449 YATWGYSAF 9 763 YRVTWKPQGA 10 457 AFLHCEFFAS 9 '783 NHTLRYMTPA 10 461 CEFFASPEAV 9 786 LRVMTPAVYA 10 497 INRTTEEDAG 9 794 YAPYDVKVQA 10 507 SYSCWVENAI 9 819 YSGEDYPDTA 10 512 VENAIGKTAV 9 891 NSGMVPSLDA 10 515 AIGKTAVTAN 9 901 FSEFHLTVLA 10 522 TANLDIRNAT 9 907 TVLAYNSKGA 10 566 LSWSKDGEAF 9 939 KVIKVDKDTA 10 582 DGRIIIDGAN 9 992 PSWHLSNLN.A 10 601 DQGIYCCSAH 9 1002 TTKYKFYLRA 10 604 IYCCSAHTAL 9 1048 HPIEVFEPGA 10 642 RSVRLTWEAG 9 1078 VIETRGREYA 10 644 VRLTWEAGAD 9 1096 QGWFIGLMCA 10 685 KTTVILPLAP 9 1168 NRDMQPTESA 10 696 VRYQFRVIAV 9 1191 FSEDGSFIGA 10 730 NPQNIRVQAS 9 1209 SVESNGSSTA 10 764 RVTWKPQGAP 9 1215 SSTATFPLRA 10 784 HTLRVMTPAV 9 16 FLLLKFSKAI" 9 787 RVMTPAVYAP 9 38 IKQSKVQVAF 9 795 APYDVKVQA! 9 51 EYFQIECEAK 9 820 SGEDYPDTAP 9 103 FQGKYRCFAS 9 892 SGMVPSLDAF 9 110 FASNKLGIAM 9 902 SEFHLTVLAY 9 183 SQKGDLYFAN 9 908 VLAYNSKGAG 9 222 LTVNSLKHAN 9 940 V1KVDKDTAT 9 235 SSTE1GSKAN 9 993 SWHLSNLNAT 9 272 EILLLECPAE 9 1003 TKYKFYLRAC 9 320 DKGNYRCTAS 9 1049 PIEVFEPGAE 9 327 TASNFLGTAT 9 1079 IETRGREYAG 9 348 RWTKKPQSAV 9 1097 GWFIGLMCAI 9 362 SNGILLCEAE 9 1099 FIGLMCAIAL 9 385 SPVDNHPFAG 9 1169 RDMQPTESAD 9 405 TNLQPNHTAV 9 1192 SEDGSFIGAY 9 411 HTAVYQCEAS 9 1194 DGSFIGAYAG 9

TableXXXVI-V1-HLA- A0203-10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.

Pos 1210 1234567890

VESNGSSTAT score

TableXXXVI-V2-(SET1)-HLA-A0203-10mers-282P1G3 Pps]|l234567890| [score

NoResultsFound.

TableXXXV!-V2- (SET2JHLA-A0203- 10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 1 GGDLPKGREA 10 2 GDLPKGREAK 9 3 &amp;#9633;LPKGREAKE 8

Tab!eXXXVI-V2- (SET3)HLA-A0203- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius nine. Pos 1234567890 score 3 SSTLGEGKYA 10 4 STLGEGKYAG 9 5 TLGEGKYAGL '8

TableXXXVI-V3-HLA- A0203-10mers-

Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 215 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 14 VSNTTYVSNA 10 40 LSYRNRNMLA 10 15 SNTTYVSNAT 9 41 SYRNRNMLAE 9 16 NTTYVSNATG 8 42 YRNRNMLAED 8

TableXXXVI-V4-HLA- A0203-10mers-

Pos]jl234567890]jscore

NoResultsFound.

TableXXXVI-V5-HLA-' A0203-10mers-Pos]|l234567.S90j|score

NoResultsFound.

TableXXXVI-V6-HLA- A0203-10mers-

Pos[ll234567890j[score

NoResultsFound.

TableXXXVI-V7-HLA-A02Q3-10mers-Posjll234567890j [score ! NoResultsFound.

TableXXXVII-V1-A3-10mers- 282P12G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 11 IVYLMFLLLK 30 995 HLSNLNATTK 29 342 IVEEPPRWTK 28 701 RVjAVNEVGR 27 785 TLRVMTPAVY 27 1037 KISGVNLTQK 27 1111 LLLLTVCFVK 27 406 NLQPNHTAVY 26 jl121 RNRGGKYSVK 26

TabIeXXXVll-V1-A3-10mers- 282P12G3 Each peptide is a portion of SEQ ID NO: 3; each start . position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 126 IVPSVPKLPK 25 4 LLLGRGLIVY 24 33 QVPTIIKQSK 24 187 DLYFANVEEK 24 645 RLTWEAGADH 24 870 SLLDGRTHPK 24 1118 FVKRNRGGKY 24 105 GKYRCFASNKl 23 413 AVYQCEASNV 23 478 EVKPLEGRRY 23 523 ANLDIRNATK 23 689 LPLAPFVRY 23 792 AVYAPYDVKV 23 1077 DViETRGREY 23 312 KIENVSYQDK 22 688 VILPLAPFVR 22 691 PLAPFVRYQF 22 905 HLTVLAYNSK 22 1107 ALLTLLLLTV 22 1196 SFIGAYAGSK 22 30 SVQQVPTIIK 21 82 RIIPSNNSGT 21 176 QDERVYMSQK j 21 208 FPRLRTIVQK Ρ2&amp;#938; 238 EIGSKANSIK 1 21 585 IIIDGANLT1 21 680 RVQGKKTTVl | 21 704 AVNEVGRSQP 21 733 NIRVQASQPK | 21 815 SVTLYSGEDY | 21 930 GVPEQPTFLK 211 295 GDLPKGRETK 20| 381 RVNGSPVDNH 20| 532 KLRVSPKNPR 20| 707 EVGRSQPSQP 2θ| 939 KVIKVDKDTA 20| 1112 LLLTVCFVKR 20| |1136 HPDPEIQSVK 20]

TabieXXXVII-V1-A3-1 Omers-282P12G3 Each peplide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 1143 SVKDETFGEY 20 3 PLLLGRGLIV 19 24 AIEIPSSVQQ 19 83 IIPSNNSGTF 19 93 RIPNEGHISH 19 148 PIVLPCNPPK 19 179 RVYMSQKGDL 19 451 TVVGYSAFLH 19 488 HIYENGTLQI 19 584 RIIIDGANLT 19 603 GIYCCSAHTA 19 1057 AEHIVRLMTK 19 1088 GLYDDISTQG 19 36 TIIKQSKVQV 18 149 IVLPCNPPKG 18 210 RLRTIVQKMP 18 212 RTIVQKMPMK 18 252 KLLLPPTESG 18 253 LLLPPTESGS 18 268 ILKGEILLLE. 18 273 LLLECFAEG 18 .292 KIGGDLPKGR 18 426 ILANANIDVV 18 475 KVEEVKPLEG 18 481 PLEGRRYHIY 18 511 WVENAIGKTA 18 534 RVSPKNPRIP 18 596 NVTLEDQGIY 18 643 SVRLTWEAGA 18 695 fvryqfrvia 18 800 KVQAINQLGS 18 834 VDVINSTLVK 18 835 DVINSTLVKV 18 857 RLKGYQINWW 18 1166 SLNRDMQPTE 18 1209 SVESNGSSTA 18 c LLGRGUVYL 17 QVAFPFDEYF 17 .216 T ableXXXV! &amp;#943;-V1-Α3-1 Omers- 282P12G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 62 NPEPTFSWTK 17 123 IEFIVPSVPK 17 226 SLKHANDSSS 17 309 KTLKIENVSY 17 315 NVSYQDKGNY 17 322 GNYRCTASNF 17 356 AVYSTGSNGI 17 435 VDVRPLIQTK 17 436 DVRPLiQTKD 17 440 liqtkdgeny 17 469 AVVSWQKVEE 17 499 RTTEEDAGSY 17 612 ALDSAADITQ 17 687 TVILPLAPFV 17 732 QNIRVQASQP 17 735 RVQASQPKEM 17 829 PVIHGVDVIN 17 840 TLVKVTWSTV 17 853 RVHGRLKGYQ 17 942 KVDKDTATLS 17 947 TATLSWGLPK 17 1010 RACTSQGCGK 17 1060 IVRLMTKNWG 17 1073 SIFQDVIETR 17 1159 PLKGSLRSLN 17 1179 SLVEYGEGDH 17 122 EIEFIVPSVP 16 142 EVEEGDPIVL 16 254 LLPPTESGSE 16 274 LLLECFAEGL 16 370 AEGEPQPTIK 16 395 DVVFPREISF 16 396 WFPREiSFT 16 466 SPEAWSWQK 16 514 NAIGKTAVTA 16 559 HLKHSLKLSW 16 561 KHSLKLSWSK 16 633 NLHLSERQNR 16

TableXXXVli-Vl-A3-1 Omers- 282P12G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 677 ELTRVQGKKT 16 738 ASQPKEMliK 16 764 RVTWKPQGAP 16 841 LVKVTWSTVP 16 850 PKDRVHGRLK 16 882 NILRFSGQRN 16 936 TFLKVIKVDK 16 957 KLNGNLTGYL 16 980 ELNDiNITTP 16 982 NDINITTPSK 16 998 NLNATTKYKF 16 1101 GLMCAIALLT 16 1105 AlALLTLLLL 16 1108 LLTLLLLTVC 16 1128 SVKEKEDLHP 16 1134 DLHPDPEIQS 16 1140 EIQSVKDETF 16 1163 SLRSLNRDMQ 16 1189 GLFSEDGSFI 16 1197 FIGAYAGSKE 16 17 LLLKFSKAIE 15 37 iiKGSKVQVA 15 99 HISHFQGKYR 15 219 PMKLTVNSLK 15 243 ANSIKQRKPK 15 290 WNK1GGDLPK 15 310 TLKIENVSYQ 15 365 ILLCEAEGEP 15 421 NVHGTiLANA 15 433 DWDVRPLIQ 15 458 FLHCEFFASP 15 520 AVTANLDIRN 15 524 NLDiRNATKL 15 526 DIRNATKLRV 15 541 RiPKLHMLEL 15 546 HMLELHCESK 15 626 DVPDPPENLH 15 636 LSERQNRSVR 15

TabieXXXVIi-V1 -A3-1 Omers-282P12G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 639 RQNRSVRLTW 15 710 RSQPSQPSDH 15 744 MIIKWEPLKS 15 759 PGLEYRVTWK 15 773 PVEWEEETVT 15 780 TVTNHTLRVM 15 787 RVMTPAVYAP 15 806 QLGSGPDPQS 15 860 GYQINWWKTK 15 883 ILRFSGQRNS 15 894 MVPSLDAFSE 15 948 ATLSWGLPKK 15 1008 YLRACTSQGC 15 1028 LGEGSKGiGK 15 1034 GIGKISGVNL 15 1062 RLMTKNWGDN 15 16 FLLLKFSKAI 14 18 LLKFSKAIEI 14 . 23 KAIEIPSSVQ 14 42 KVQVAFPFDE 14 114 KLGIAMSEE! 14 128 PSVPKLPKEK 14 137 KIDPLEVEEG 14 158 GLPPLHiYWM 14 170 ELEHIEQDER 14 172 EHIEQDERVY 14 233 SSSSTEIGSK 14 328 ASNFLGTATH 14 331 FLGTATHDFH 14 340 HVIVEEPPRW 14 343 VEEPPRWTKK 14 349 WTKKPQSAVY 14 364 GILLCEAEGE 14 366 LLCEAEGEPQ 14 386 PVDNHPFAGD 14 439 PLIQTKDGEN 14 471 VSWQKVEEVK 14 509 SCWVENAIGK 14 217

TableXXXVli-V1-A3-1 Omers-282P12G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 547 MLELHCESKC 14 565 KLSWSKDGEA 14 660 EYIVEFEGNK 14 j 671 EPGRWEELTR 14 743 EMIIKWEPLK 14) 791 PAVYAPYDVK 14j 798 DVKVQAINQL 14 817 TLYSGEDYPD 14( 822 EDYPDTAPV! 14| 842 VKVTWStVPK 14( 848 TVPKDRVHGR 14| 880 EVNILRFSGQ 14) 907 TVLAYNSKGA 14) 933 EQPTFLKVIK 14( 960 GNLTGYLLQY 14 967 LQYQIINDTY 14 970 QIINDTYEIG 14 986 ITTPSKPSWH 14 997 SNLNATTKYK 14 1051 EVFEPGAEH! 14 1082 RGREYAGLYD 14 1123 RGGKYSVKEK 14 1156 | DEKPLKGSLR j| 14

TableXXXVII-V2-(SET1)- HLA-A3-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 3 IVPSVPKFPK 22 5 PSVPKFPKEK 14 2 FIVPSVPKFP 12 . 6 SVPKFPKEKI 11

TabieXXXVIl-V2-(SET2)- HLA-A3-10mers-232P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 2 GDLPKGREAK 17 10 akenygktlk 15 3 DLPKGREAKE 13 I 7 GREAKENYGK 12

TableXXXVH-V2-(SET3)- HLA-A3-10mers-282P1G3 Each peptide is a portion ofSEQIDNO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 5 TLGEGKYAGL 14 1 EESSTLGEGK 13 6 LGEGKYAGLY 12 2 ESSTLGEGKY 7 4 STLGEGKYAG 6 7 GEGKYAGLYD 6 9 GKYAGLYDD! 6 10 KYAGLYDDIS 6

TabieXXXVIi-V3-HLA-A3- 10mers-282P1G3 Each peptide is a portion ofSEQIDNO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 7 DVINTTYVSN 20 61 YVEKSSTFFK 20 1 PVIHGVDVIN 17 13 YVSNTTYVSN 17 19 YVSNATGSPQ 17 46 NMLAEDFIQK 17 55 KSTSCNYVEK 17

TableXXXVIi-V3-HLA-A3- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 43 RNRNMLAEDF 15 59 CNYVEKSSTF 15 52 FIQKSTSCNY 14 30 SIFICSKEQE 13 33 ICSKEQELSY 13 4 HGVDVINTTY 12 27 PQPSIFICSK 12 39 ELSYRNRNML 12 47 MLAEDFIQKS 12 5 GVDVINTTYV 11 8 VINTTYVSNT 11 10 NTTYVSNTTY 11 23 ATGSPQPSIF | 11 2 ViHGVDViNT 10 49 AEDFIQKSTS 10 34 CSKEQELSYR 9 I 41 SYRNRNMLAE 9

TableXXXVll-V4-HLA-A3- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 9 DLPEQPTFLK 21 3 TLYSGEDLPE 17 1 SVTLYSGEDL 15

TableXXXVII-V5-HLA-A3- 10mers-282P1G3

Each peptide is a portion of SEQ iD NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 218

TableXXXVII-V5-HLA-A3- 10mers-282P1G3 TableXXXV!l-V7-HLA-A3- 10mers~282P1G3 TableXXXVIII-V1-HLA-A26- 10mers-282P1G3 Each pepiide is a portion . of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide, is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score Pos 1234567890 s core Pos 1234567890 score 4 KLTVNSSNSI 15 6 VIVEDNISHE 12 315 NVSYQDKGNY 21 5 LTVNSSNSIK 14 15 ELFTLHPEPP 11 875 RTHPKEVNIL 21 10 SNSIKQRKPK 13 880 EVNILRFSGQ 21 8 NSSNSIKQRK 11 TableXXXVIII-V1-HLA-A26- 902 SEFHLTVLAY 21 6 TVNSSNSIKQ 10 iUmers-XozribJ 1182 EYGEGDHGLF 21 2 PMKLTVNSSN 7 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the 396 WFPREISFT 20 7 VNSSNSIKQR | 436 DVRPLIQTKD 20 length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 450 ATWGYSAFL 20 TableXXXVII-V6-HLA-A3- 58 EAKGNPEPTF 19 10mers-282P1G3 179 RVYMSQKGDL 19 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, Pos | 1234567890 score 277 ECFAEGLPTP 19 1077 DVIETRGREY 35 309 KTLKIENVSY 19 the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus 395 DWFPREISF 32 418 EASNVHGTIL 19 478 EVKPLEGRRY 32 626 DVPDPPENLH 19 142 EVEEGDPIVL 31 ( 721 ETPPAAPDRN 19 nine. 798 DVKVQAINQL 31 | 777 EEETVTNHTL 19 Pos 1234567890 score 302 ETKENYGKTL 30 , 974 DTYEIGELND 19 10 KLEHIEQDER 17 124 EFIVPSVPKL 27 ,1151 EYSDSDEKPL 19 1 SEEIEFIVPK 16 835 DVINSTLVKV 27 ,1211 ESNGSSTATF 19 7 IVPKLEHIEQ 12 172 EHIEQDERVY 26 44 QVAFPFDEYF “Ts, 6 FIVPKLEHIE 11 852 DRVHGRLKGY 26 213 TIVQKMPMKL 18 4 IEFIVPKLEH 10 1051 EVFEPGAEHI 26 267 TILKGEILLL 18 3 ElEFIVPKLE ' 9 1080 ETRGREYAGL 26 349 WTKKPQSAVY 18 686 TTVILPLAPF 25 401 EISFTNLQPN 18 TableXXXVII-V7-HLA-A3- 1 Omorc-OROD-I CQ 433 DWDVRPLIQ 24 557 DSHLKHSLKL 18 1140 EIQSVKDETF 24 | 618 DITQVTVLDV 18 Each peptide is a portion &amp;#972; SEQ ID NO: 15; each start 499 RTTEEDAGSY 22 | 656 SNISEYIVEF 18 position is specified, the length of pepiide is 10 amino acids, and the end position for each peptide is 779 ETVTNHTLRV 22 j 826 DTAPVIHGVD 18 815 SVTLYSGEDY 22 j 987 TTPSKPSWHL 18, 929 EGVPEQPTFL 22 | 10 LIVYLMFLLL the start position plus nine ,1118 FVKRNRGGKY 22 j 69 WTKDGNPFYF 17, Pos 1234567890 score |1143 SVKDETFGEY 22 | 98 GHISHFQGKY 17) 5 HVIVEDNISH 1i L |1147 ETFGEYSDSD | 22 I 573 EAFEINGTED ι&amp;#942; 19 LHPEPPRWTb li I 596 NVTLEDQGIY Z I 946 DTATLSWGLP 17 18 TLHPEPPRW1 1 j 707 EVGRSQPSQP 2 1 j 977 EIGELNDINI 17 20 HPEPPRWTKf (j L &amp;#970; ,1054 EPGAEHIVRL 2 ,1072 DSIFQDVIET 17 7 IVEDNISHEL 1 3 j 121 EElEFiVPSV 2 ,1105 AIALLTLLLL 17 11 NISHELFTLH 1 3 , 266 j ITILKGEILL 2 1| ,1191 SEDGSFIGAY 17 219

TableXXXVI!l-V2- (SET1)-HLA-A26- 10mers-282P1G3

Each peptide is a portion of SEQIDNO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.

Pos 1234567890 score 1 EFiVPSVPKF 27

TableXXXVIII-V2-(SET2)- HLA-A26-10mers- 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine.

Pos 1234567890 score 9 EAKENYGKTL 22 5 PKGREAKENY 10 TabieXXXViil-V2-(SET3}- HLA-A26-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 2 ESSTLGEGKY 22 8 EGKYAGLYDD 14 1 EESSTLGEGK 12 5 TLGEGKYAGL 11 6 LGEGKYAGLY 11 4 STLGEGKYAG 10

TableXXXVill-V3-HLA- A26-10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 2 EEIEFIVPKL 29 5 EFIVPKLEHI 18 I 3 EIEFIVPKLE 14

TabieXXXV!ll-V4-HLA- A26-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 1 SVTLYSGEDL 21 8 EDLPEQPTFL 19 9 DLPEQPTFLK 10

TableXXXV!II-V5-HLA- A26-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 6 TVNSSNSIKQ 14 5 LTVNSSNSIK 13 7 VNSSNSIKQR 6

TableXXXVIi!-V6-HLA- A26-10mers-282P1G3

Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 1

Pos 1234567890

EEIEFIVPKL EFIVPKLEH!

EIEFIVPKLE score 29 18

U

TableXXXV!ll-V7-HLA- A26-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 10 DNISHELFTL 26 7 IVEDNISHEL 19 5 HVIVEDNISH 16 6 ViVEDNISHE 15 15 ELFTLHPEPP 14

TableXXXlX-V1-HLA- B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is ihe start position plus nine. Pos 1234567890 score 1054 EPGAEHIVRL 25 398 FPREISFFNL 24 627 VPDPPENLHL 24 218 MPMKLTVNSL 23 27 IPSSVQQVPT 22 539 NPRIPKLHML 22 1158 KPLKGSLRSL 22 536 SPKNPRiPKL 21 1019 KPITEESSTL 21 155 PPKGLPPLH1 20 795 APYDVKVQAI 20 828 APVIHGVDV! 20 849 VPKDRVHGRL 20 895 VPSLDAFSEF 19 927 TPEGVPEQPT 19 931 VPEQPTFLKV 19 2 EPLLLGRGL1 18 373 EPQPT1KWRV 18 480 KPLEGRRYHl 18 693 APFVRYQFRV 18 772 APVEWEEETV 18 877 HPKEVNILRF 18 94 IPNEGHISHF 17 220 '· Tab!eXXXIX-V1-HLA-B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 790 TPAVYAPYDV 17 934 QPTFLKVIKV j 17 954 LPKKLNGNLT 17 1048 HPIEVFEPGA 17 34 VPTIIKQSKV 16 74 NPFYFTDHRI 16 160 PPLHIYWMNI 16 616 AADITQVTVL 16 900 AFSEFHLTVL 16 1080 ETRGREYAGL 16 1172 QPTESADSLV 16 84 IPSNNSGTFR 15 390 HPFAGDVVFP 15 681 VQGKKTTVIL 15 1105 AIALLTLLLL 15 208 FPRLRTIVQK 14 418 EASNVHGTIL 14 450 ATWGYSAFL 14 .541 RIPKLHMLEL 14 590 ANLTISNVTL 14 637 SERQNRSVRL 14 671 EPGRWEELTR 14 715 QPSDHHETPP 14 723 PPAAPDRNPQ 14 758 GPGLEYRVTW 14 768 KPQGAPVEWE 14 810 GPDPQSVTLY 14 929 EGVPEQPTFL 14 957 KLNGNLTGYL 14 1034 GIGKISGVNL 14 1104 CAIALLTLLL 14 1151 EYSDSDEKPL 14 1213 NGSSTATFPL 14 5 LLGRGLIVYL 13 10 LIVYLMFLLL 13 106 KYRCFASNKL 13 124 EFIVPSVPKL 13 127 VPSVPKLPKE 13

TableXXXIX-V1-HLA- B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 132 KLPKEKIDPL 13 153 CNPPKGLPPL 13 246 IKQRKPKLLL 13 260 SGSESSITIL 13 267 TILKGEILLL 13 297 LPKGRETKEN 13 323 NYRCTASNFL 13 346 PPRWTKKPQS 13 375 QPTIKWRVNG 13 431 NIDVVDVRPL 13 516 IGKTAVTANL 13 604 IYCCSAHTAL 13 683 GKKTTVILPL 13 726 APDRNPQNIR 13 742 KEMIIKWEPL 13 752 KSMEQNGPGL 13 875 RTHPKEVNIL 13 921 EPYIFQTPEG 13 941 IKVDKDTATL 13 988 TPSKPSWHLS 13 991 KPSWHLSNLN 13 1102 LMCAIALLTL 13 1126 KYSVKEKEDL 13 1136 HPDPEIQSVK.13 8 | RGLIVYLMFL 12 64 EPTFSWTKDG 12 142 EVEEGDPIVL 12 154 NPPKGLPPLH 12 202 YCCFAAFPRL 12 244 NSIKQRKPKL 12 250 KPKLLLPPTE 12 345 EPPRWTKKPQ 12 357 VYSTGSNGIL 12 358 YSTGSNGILL 12 428 ANANIDWDV 12 473 WQKVEEVKPL 12 524 NLDIRNATKL 12 555 KCDSHLKHSL 12

TableXXXIX-V1-HLA- B0702-10mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 557 DSHLKHSLKL 12 629 DPPENLHLSE 12 669 KEEPGRWEEL 12 680 RVQGKKTTVl 12 690 LPLAPFVRYQ 12 712 QPSQPSDHHE 12 730 NPQNIRVQAS 12 749 EPLKSMEQNG 12 809 SGPDPQSVTL 12 824 YPDTAPVIHG 12 889 QRNSGMVPSL 12 897 SLDAFSEFHL 12 945 KDTATLSWGL 12 349 TLSWGLPKKL 12 972 INDTYEIGEL 12 1093 ISTQGWFIGL 12 1099 FIGLMCAIAL 12 1100 IGLMCAIALL 12 1103 MCAIALLTLL 12 1181 VEYGEGDHGL ) 12

TableXXXIX-V2-(SET1)- HLA-B0702-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius nine. Pos 1234567890' score 9 KFPKEKIDPL 13 10 FPKEKIDPLE 11 7 VPKFPKEKID 10 1 EFIVPSVPKF 9 ! 6 SVPKFPKEKI 7 221

TableXXXIX-V2-(SET2)- HLA-B0702-10mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length-of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 4 LPKGREAKEN 12 9 EAKENYGKTL 11 8 REAKENYGKT 9 1 GGDLPKGREAi 7

TableXXXiX-V2-(SET3)- HLA-B0702-10mers- . 282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 5 TLGEGKYAGL 12 9 GKYAGLYDDI 7 3 SSTLGEGKYA 6

TableXXXIX-V3-HLA- B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7j»each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 7 DVINTTYVSN 23 10 NTTYVSNTTY 20 39 ELSYRNRNML 19. 23 ATGSPQPSIF 18 4 HGVDVINTTY 16 50 EDFIQKSTSC 15 1 PVIHGVDVIN 14 52 FIQKSTSCNY 14 56 STSCNYVEKS 14 60 NYVEKSSTFF 14 51 DFIQKSTSCN 13

TableXXX!X-V3-HLA- B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 19 YVSNATGSPQ 12 31 IFiCSKEQEL 12 33 ICSKEQELSY 12 13 YVSNTTYVSN 11

TableXXX!X-V4-HLA- B0702-10mers-282P1G3 Each peptide is a portion ofSEQIDNO:9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 10 LPEQPTFLKV 19 8 EDLPEQPTFL 14 1 SVTLYSGEDL 10

TableXXXlX-VS-HLA- B0702-10mers-282P1G3 Each peptide is a portion ofSEQIDNO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 1 MPMKLTVNSS 13 4 KLTVNSSNSI 7

TableXXXIX-V6-HLA- B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score ~2 EEIEFIVPKL.13 8 VPKLEHIEQD 10 5 EFIVPKLEHI 7

TabieXXXIX-V7-HLA- B0702-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 20 HPEPPRWTKK 12 7 IVEDNISHEL 11 9 EDNISHELFT 10 10 DNISHELFTL 10 8 VEDNISHELF 7 18 TLHPEPPRWT 7 3 DFHVIVEDNI 6

TableXL-V1-HLA-B08- 10mers-282PlG3

Posjj-I234567890jjscore|

NoResultsFound. |

TableXL-V2-(SET1)-HLA-B08-1 Omers-282P1G3

Pos]jl 234567890||score

NoResulisFound.

TabieXL-V2-(SET2)- HLA-B08-10mers- 282P1G3

Pos (1234567890( score

NoResultsFound.

TableXL-V2-(SET3)- HLA-B08-10mers- 282P1G3

Pos)|l234567890(jscore

NoResultsFound.

Tab!eXL-V3-HLA-B08-~] 10mers-282P1G3 |

Pos||1 234567890) score NoResultsFound. 222

TableXL.-V4-HLA. 10mers-282P1G3

Pos|jl234567890[jscore

NoResultsFound.

TableXL-V5-HLA-BO8- 10mers-282P1G3

Pos] 1234567890 score

NoResultsFound.

TableXL-V6-HLA-B08-10mers-282P1G3 Pos|[l 234567890] jscore

NoResultsFound.

TableXL-V7-HLA-B08- 10mers-282P1G3

Pos]]l234567890[lscore

NoResultsFound.

TableXLI-V1-HLA- B1510-10mers- 282P1G3

Pos]|l234567890|]score

NoResultsFound.

TabteXLi-V4-HLA- B1510-10mers- 282P1G3 TableXLII-V3-HLA- B2705-10mers- 282P1G3 Pos ’l234567890|(score Pos|(l23456789t)j|score NoResultsFound. NoResultsFound. TableXLI-V5-HLA- TableXLII-V4-HLA- B1510-10mers- B2705-10mers- 282P1G3 282P1G3 Pos 1234567890||score Pos 1234567890( score NoResultsFound. NoResultsFound. TableXLI-V6-HLA- TableXLII-V5-HLA- B1510-10mers- B2705-10mers- 282P1G3 282P1G3 Pos((l234567890(|score Posjjl234567890jjscore NoResultsFound. NoResultsFound. TableXLI-V7-HLA- TableXLII-V6-HLA- B1510-10mers- B2705-10mers- 282P1G3 282P1G3 Pos (1234567890( (score Pos (1234567890( (score NoResultsFound. NoResultsFound.

TabieXLI-V2-(SET1)- HLA-B1510-10mers- 282P1G3

Pos) |l234567890| (score

NoResultsFound.

TableXL!-V2-(SET2)- HL4-B1510-10mers- 282P1G3

Pos((l234567890( (score

NoResultsFound.

TableXL!-V2-(SET3)- HLA-B1510-10mers- 282P1G3

Pos](l234567890|[score

NoResultsFound.

TableXLI-V3-HLA- B1510-10mers-(SET3)- 282P1G3

Pos 1234567890 (score

TableXLII-V1-HLA- B2705-1Qmers- 282P1G3 Tab!eXLII-V7-HLA- B2705-10mers- 282P1G3 Posj 1234567890j|score Pos(|l234567890||score NoResultsFound. NoResultsFound. | TableXLII-V2-(SET1)- TableXLili-V1-HLA- HLA-B2705-10mers- B2709-10mers- 282P1G3 282P1G3 Pos||l234567890|)score Pos(jl234567890|]score NoResultsFound. NoResultsFound. TableXLII-V2-(SET2)- TableXLIII-V2-(SET1)- HLA-B2705-10mers- HLA-B2709-10mers- 282P1G3 282P1G3 Pos 1234567890(|score Pos 1234567890 (score NoResultsFound. NoResultsFound. TableXLll-V2-(SET3)- TableXLIII-V2- HLA-B2705-10mers- (SET2)HLA-B2709- 282P1G3 10mers-282P1G3 ' Posj(l234567890(|score Pos(|l234567890((score( NoResultsFound. NoResultsFound. TabteXLII-V3-HLA- Tab!eXLII!-V2-{SET3)- B2705-10mers- HLA-B2709-10mers- 282P1G3 282P1G3 Pos j (123456789O] [s core Pos 1234567890 score

NoResultsFound. 223 Λ pableXL!ll-V2-(SET3)-HLA-B2709-10mers- 282P1G3 [Pos[[t23456789Q[[score [ NoResultsFound.

TableXLIII-V3-HLA- B2709-10mers- 282P1G3

Pos)[l234567890[[score

NoResuttsFound.

TableXL!ll-V4-HLA- B2709-10mers- 282P1G3

Pos[jl^4567390j [score

NoResultsFound. j

TableXLl)!-V5-HLA- B270S-10mers- 282P1G3

Pos[)l234567890[[score

NoResultsFound.

TableXLlll-V6-HLA- B2709-10mers- 282P1G3

Posj|l234567890 [score

NoResultsFound.

TableXLI!!-V7-HLA- B2709-10mers- 282P1G3

Pos[[l234567890[[score

NoResultsFound.

TabfeXLIV-V1-HLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ iD NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score [1192 SEDGSFIGAY 28 902 SEFHLTVLAY 27 777 EEETVTNHTL 25 932 PEQPTFLKV! 25 237 TEIGSKANSI 24 [669 KEEPGRWEEL 24|

TableXLlV-V1 -HLA-B4402-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for ei ich peptide is the start rosition plus nine. Pos 1234567890 score 1 MEPLLLGRGL 23 502 EEDAGSYSCW 23 1174 TESADSLVEY 23 193 VEEKDSRNDY 22[ 304 KENYGKTLK! 22[ 446 GENYATWGY 22) 637 SERQNRSVRL 22) 742 KEMIIKWEPL 22( 754 MEQNGPGLEY 22| 1029 GEGSKGIGKI 22| 1181 VEYGEGDHGL 22) 928 PEGVPEQPTF 211 1132 KEDLHPDPEl 21 344 EEPPRWTKKP 20 417 CEASNVHGTi 19 25 IEIPSSVQQV 18 371 EGEPQPTIKW 18 656 SNISEYIVEF 18 1084 REYAGLYDD! 18 124 EFIVPSVPKL 17 172 EHIEQDERVY 17 262 SESStTILKG 17 281 EGLPTPQVDW 17| 590 ANLTISNWL 17j 652 ADHNSNISEY 17[ 739 SQPKEM1IKW 1105 AIALLTLLLL 121 EEIEFIVPSV 16| 143 VEEGDPIVLP 16) 157 KGLPPLHIYW 16( 266 ITiLKGEiLL 16) 267 TILKGEILLL 16( 280 AEGLPTPQVD 16) 372 GEPQPTIKWR 16[ 383 NGSPVDNHPF 16 406 NLQPNHTAVY 16 464 FASPEAVVSW 16 478 ) EVKPLEGRRY I 16

TableXLIV-V1 -HLA-B4402-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 536 SPKNPR1PKL 16 580 TEDGR1IIDG 16 616 AADITQVTVL 16 810 GPDPQSVTLY 16 900 AFSEFHLTVL 16 929 EGVPEQPTFL 16 1019 KPITEESSTL 16 1054 EPGAEHIVRL | 16 1104 CAIALLTLLL 16 1151 EYSDSDEKPL 16 4 LLLGRGLIVY 15 5 LLGRGUVYL 15 .60 KGNPEPTFSW 15 120 L. SEEIEFIVPS 15 132 KLPKEK1DPL 15 , 142 EVEEGDPiVL 15 144 EEGDPIVLPC 15 153 CNPPKGLPPL 15 244 NSIKQRKPKL 15 245 SIKQRKPKLL 15 260 SGSESSITIL 15 302 ETKENYGKTL 15 330 NFLGTATHDF 15 400 REISFTNLQP 15 461 CEFFASPEAV 15 627 VPDPPENLHL 15 670 EEPGRWEELT 15 676 EELTRVQGKK 15 683 GKKTTVILPL 15 691 PLAPFVRYQF 15 795 APYDVKVQA! 15 798 DVKVQAINQL 15 809 SGPDPQSVTL 15 822 EDYPDTAPV! 15 857 RLKGYQINWW 15 875 RTHPKEVNIL, 15 892 SGMVPSLDAF 15 916 AGPESEPYIF ! 15 224

TableXLIV-V1-HLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end posiiion for each peptide is the start position plus nine. Pos 1234567890 ) score 918 PESEPYIFQT 15 949 TLSWGLPKKL 15 960 GNLTGYLLQY 15 972 INDTYEIGEL 15 1044 TQKTHPIEVF 15 1057 AEHIVRLMTK 15 1099 FIGLMCAIAL 15 1100 IGLMCAIALL 15 1211 ESNGSSTATF 15 2 EPLLLGRGL! 14 9 GLIVYLMFLL 14 12 VYLMFLLLKF 14 16 FLLLKFSKA! 14 58 EAKGNPEPTF 14 98 GHISHFQGKY 14 101 SHFQGKYRCF 14 150 VLPCNPPKGL 14 162 LHIYWMNIEL 14 199 RNDYCCFAAF 14 271 GEILLLECFA 14. 340 HVIVEEPPRW 14 343 VEEPPRWTKK 14 370 AEGEPQPTIK·· 14 389 NHPFAGDWF 14 393 AGDVVFPREI 14 418 EASNVHGTiL 14 431 NIDWDVRPL 14 524 NLDIRNATKL 14 575 FEINGTEDGR 14 585 IIIDGANLTI 14 625 LDVPDPPENL 14 639 RQNRSVRLTW 14 689 ILPLAPFVRY 14 720 HETPPAAPDR 14 725 AAPDRNPQN! 14 758 |GPGLEYRVTW 14 837 | INSTLVKVTW 14 877 | HPKEVNILRF 14

TableXLIV-V1jHLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end posiiion for each peptide is the start position plus nine. Pos 1234567890 score 956 KKLNGNLTGY 14 976 YEIGELNDIN 14 979 GELNDINITT 14 1053 FEPGAEHIVR 14 1059 HIVRLMTKNW 14 1077 DVIETRGREY 14 1109 LTLLLLTVCF 14 1156 DEKPLKGSLR 14 1158 KPLKGSLRSL 14 1210 VESNGSSTAT 14 10 LIVYLMFLLL 13 38 IKQSKVQVAF 13 46 AFPFDEYFQI 13 63 PEPTFSWTKD 13 94 IPNEGHISHF 13 106 KYRCFASNKL 13 123 lEFIVPSVPK 13 135 KEKIDPLEVE 13 156 PKGLPPLHIY 13 194 EEKDSRNDYC 13 196 KDSRNDYCCF 13 218 MPMKLTVNSL 13 246 IKQRKPKLLL 13 264 SSITILKGEI 13 309 KTLKIENVSY 13 358 YSTGSNGILL 13 450 ATWGYSAFL 13 473 WQKVEEVKPL 13 507 SYSCWVENAI 13 539 NPRIPKLHML 13 548 lelhceskcd 13 552 CESKCDSHLK 13 555 KCDSHLKHSL 13 557 DSHLKHSLKL 13 583 GRI1IDGANL 13 666 EGNKEEPGRW 13 748 WEPLKSMEQN 13 761 LEYRVTWKPQ 13

TableXLlV-V1-HLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 767 WKPQGAPVEW 13 774 VEWEEETVTN 13 778 EETVTNHTLR 13 788 VMTPAVYAPY 13 828 APVIHGVDVI 13 852 DRVHGRLKGY 13 862 QINWWKTKSL 13 879 KEVNILRFSG 13 895 VPSLDAFSEF 13 941 IKVDKDTATL 13 943 VDKDTATLSW 13 957 KLNGNLTGYL 13 990 SKPSWHLSNL 13 996 LSNLNATTKY 13 999 LNATTKYKFY 13 1023 EESSTLGEGS 13 1026 STLGEGSKGI 13 1051 EVFEPGAEHI 13 1079 IETRGREYAG 13 1080 ETRGREYAGL 13 1081 TRGREYAGLY 13 1089 LYDDISTQGW 13 1102 LMCAIALLTL 13 1139 PEIQSVKDET 13 1140 EIQSVKDETF 13 1143 SVKDETFGEY 13 1171 MQPTESADSL ' 13 1182 EYGEGDHGLF 13 |1213 NGSSTATFPL 13

TableXLIV-V2-(SET1)-HLA 10mers- . 282P1G3

Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. 225

Pos 1234567890 score 1 EFIVPSVPKF 17 9 KFPKEKIDPL 15 I 6 SVPKFPKEKI j 11

TableXLIV-V2-(SET2)- HLA-B4402-1 Omers-282P1G3 Each peptide is a portion |of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 9 EAKENYGKTL 15 5 PKGREAKENY 11 8 REAKENYGKT 11 2 GDLPKGREAK 7

TableXLIV-V2-(SET3)- H LA-B4402-1 Omers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 2 ESSTLGEGKY 15 1 EESSTLGEGK 13 6 LGEGKYAGLY 13 7 GEGKYAGLYD 11 5 TLGEGKYAGL 10 9 GKYAGLYDD! 8

TableXLIV-V3-HLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 62 VEKSSTFFKl 20 39 ELSYRNRNML 15 49 AEDFIQKSTS 15

TableXLIV-V5-HLA- I B4402-10mers-282P1G3 | Each peptide is a portion I ofSEQIDNO: 11; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. j Pos 1234567890 score) 4 KLTVNSSNS! 10

Tab!eXLIV-V3-HLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 23 ATGSPQPSIF 14 24 TGSPQPSIFI 13 31 IFICSKEQEL 13 4 HGVDVINTTY 12 10 NTTYVSNTTY 12 33 ICSKEQELSY 12 36 KEQELSYRNR 12 38 QELSYRNRNM 12 43 RNRNMLAEDF 12 59 CNYVEKSSTF 11 60 NYVEKSSTFF 11 22 NATGSPQPSI 10 52 FIQKSTSCNY 10 44 NRNMLAEDF! L®

TableXL!V-V4-HLA- B4402-10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position pius nine. Pos 1234567890 score 7 GEDLPEQPTF 23 8 EDLPEQPTFL 17 1 SVTLYSGEDL 12 7 VNSSNSIKQR 10 SNSIKQRKPK 5

TableXLIV-V6-HLA 1 Omers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of ' peptide is 10 amino acids, and the end · position for each peptide is the start position pius nine. Pos 1234567890 score 2 EEIEFIVPKL 27 1 SEEIEFIVPK 15 5 EFIVPKLEHI 14 4 IEFIVPKLEH 13

TableXUV-V7-HLA-B4402- 10mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 10 amino acids, and the end position for each peptide is the start position plus nine. Pos 1234567890 score 8 VEDNISHELF 23 21 PEPPRWTKKP 18 10 &amp;#9633;NISHELFTL 15 7 IVEDN1SHEL 12 A T i / FTLHPEPPRW 12 14 Tektlhpep 11

TableXLV-V1-HLA- B5101-10mers- 282P1G3

Pos)[l234567890||score

NoResultsFound.

TableXLV-V2-(SET1)- HLA-B5101-10mers- 282P1G3 P5s]pl234567890j|score

NoResultsFound.

TableXLV-V2-(SET2)- HLA-B5101-10mers- 282P1G3 226

<img img-format="tif" img-content="drawing" file="IL233223AD00024.tif" id="idf0004" />

NoResultsFound. [

TableXLV-V2-(SET3)- HLA-B5101-10mers- 282P1G3

Posj(l 234567890() score

NoResultsFound.

TableXLV-V3-HLA- B5101-10mers-(SET3)- 282P1G3

Pos|(l 234567890) score NoResultsFound.

TableXLV-V4-HLA- B5101-10mers- 282P1G3

Pos 1234567890 score

NoResultsFound.

TabieXLV-V5-HLA- B5101-10mers- 282P1G3

Posfll234567890||score

NoResultsFound.

TableXLV-V6-HLA- B5101-10mers- 282P1G3

Pos((l234567890|[score

NoResultsFound.

TableXLV-V7-HLA- B5101-10mers- 282P1G3

Pos([l234567890]|score

NoResultsFound.

TableXLVI-V1 -DRB1 -0101 -15mers- 282P1G3 Each pepiide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each pepiide is the start position plus fourteen. Pos 123456789012345 score 263 ESSITILKGEILLLE 36 287 QVDWNKIGGDLPKGR 36 920 SEPYIFQTPEGVPEQ 33 446 GENYATWGYSAFLH 32

TableXLV!-V1-DRB1 15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 1032 SKGIGKISGVNLTQK 32 1097 GWFIGLMCAIALLTL 31 120 SEEIEF1VPSVPKLP 29 522 TANLDIRNATKLRVS 29 831 IHGVDVINSTLVKVT 29 13 YLMFLLLKFSKAIEI | 28 470 WSWQKVEEVKPLEG 28 104 QGKYRCFASNKLGIA 27 127 VPSVPKLPKEKIDPL 27 461 CEFFASPEAWSWQK 27 476 VEEVKPLEGRRYHIY 27 940 VIKVDKDTATLSWGL 27 981 LNDINITTPSKPSWH 27 11 IVYLMFLLLKFSKAI 26 16 FLLLKFSKAIE1PSS 26 187 DLYFANVEEKDSRND 26 272 EILLLECFAEGLPTP 26 321 KGNYRCTASNFLGTA 26 539 NPRIPKLHMLELHCE 26 697 RYQFRVIAVNEVGRS 26 742 KEMIIKWEPLKSMEQ 26 748 WEPLKSMEQNGPGLE 26 764 RVTWKPQGAPVEWEE 26 883 ILRFSGGRNSGMVPS 26 . 1083 GREYAGLYDDISTQG 26 1096 QGWFIGLMCAIALLT 26 1 MEPLLLGRGLIVYLM 25 8 RGLIVYLMFLLLKFS 25 78 FTDHRIIPSNNSGTF 25 112 SNKLGIAMSEEIEFI 25 138 IDPLEVEEGDPIVLP 25 148 PIVLPCNPPKGLPPL 25 163 HIYWMNIELEHIEQD 25 208 FPRLRTIVQKMPMKL 25 354 QSAVYSTGSNGILLC 25 401 E1SFTNLQPNHTAVY 25 411 HTAVYQCEASNVHGT 25 509 SCWVENAIGKTAVTA 25 581 EDGRIIIDGANLTIS 25

TableXLVl-V1 -DRB1 15mers-_282P1G3

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of pepiide is 15 amino acids, and the end position for each peptide is the start position plus fourteen.

Pos 123456789012345 score 619 ITQVTVLDVPDPPEN 25 575 WEELTRVQGKKTTVI 25 685 KTTVILPLAPFVRYQ 25 838 NSTLVKVTWSTVPKD 25 905 HLTVLAYNSKGAGPE 25 993 SWHLSNLNATTKYKF 25 1049 PIEVFEPGAEHIVRL 25 1103 MCAIALLTLLLLTVC 25 1108 LLTLLLLTVCFVKRN 25 14 LMFLLLKFSKAIEIP 24 34 VPTIIKQSKVQVAFP 24 123 IEFIVPSVPKLPKEK 24 156 PKGLPPLHIYWMNIE 24 178 ERVYMSQKGDLYFAN 24 205 FAAFPRLRTIVQKMP 24 211 LRTIVQKMPMKLTVN 24 243 ANSIKQRKPKLLLPP 24 249 RKPKLLLPPTESGSE 24 328 ASNFLGTATHDFHVI 24 336 THDFHVIVEEPPRWT 24 601 DQGIYCCSAHTALDS 24 693 APFVRYQFRVIAVNE 24 702 VIAVNEVGRSQPSQP 24 745 IIKWEPLKSMEQNGP 24 750 PLKSMEQNGPGLEYR ( 24 798 DVKVQAINQLGSGPD 24( 800 KVQAINQLGSGPDPQ 24) 801 VQAINQLGSGPDPQS 24( 839 STLVKVTWSTVPKDR 24| 843 KVTWSTVPKDRVHGR 24( 852 DRVHGRLKGYQINWW 24| 860 GYQINWWKTKSLLDG 24| 892 SGMVPSLDAFSEFHL 24( 937 FLKVIKVDKDTATLS 24( 947 TATLSWGLPKKLNGN I 24 956 KKLNGNLTGYLLQYQ 24 975 TYEIGELNDINITTP 24 978 IGELNDINITTPSKP 24 1003 TKYKFYLRACTSQGC 24 227

TableXLVI-V1 -DRB1 -0101 -15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peplide is 15 amino acids, and the end position for each peplide is the start position plus fourteen. Pos 123456789012345 score 1057 AEHIVRLMTKNWGDN 24 1087 AGLYDDISTQGWFIG 24 1105 AIALLTLLLLTVCFV 24 1187 DHGLFSEDGSFIGAY 24 38 IKQSKVQVAFPFDEY 23 89 SGTFRIPNEGHISHF 23 144 EEGDPIVLPCNPPKG 23 153 CNPPKGLPPLHIYWM 23 215 VQKMPMKLTVNSLKH 23 348 RWTKKPQSAVYSTGS 23 351 KKPQSAVYSTGSNGI 23 416 QCEASNVHGTILANA 23 429 NANIDWDVRPLIQT 23 486 RYHIYENGTLQINRT 23 532 KLRVSPKNPRIPKLH 23 616 AADITQVTVLDVPDP 23 678 LTRVQGKKTTVILPL 23 733 NIRVQASQPKEMIIK 23 758 GPGLEYRVTWKPQGA 23 796 PYDVKVQAINQLGSG I 23 955 PKKLNGNLTGYLLQY 23 1107 ALLTLLLLTVCFVKR 23 1165 RSLNRDMQPTESADS 23 1168 NRDMQPTESADSLVE 23 1204 SKEKGSVESNGSSTA ' 23 1207 KGSVESNGSSTATFP 23 27 1PSSVQQVPTIIKQS 22 81 HRIIPSNNSGTFRIP 22 132 KLPKEKIDPLEVEEG 22 140 PLEVEEGDPIVLPCN 22 277 ECFAEGLPTPQVDWN 22 376 PTIKWRVNGSPVDNH 22 468 EAWSWQKVEEVKPL 22 484 GRRYHIYENGTLQIN 22 686 TTVILPLAPFVRYQF 22 705 VNEVGRSQPSQPSDH 22 706 NEVGRSQPSQPSDHH 22 730 NPQNIRVQASQPKEM 22 731 PQNIRVQASQPKEM1 22

TableXLVI-V1 -DRB1 -0101 -15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 783 NHTLRVMTPAVYAPY 22 825 PDTAPVIHGVDVINS 22 828 APVIHGVDVINSTLV 22 878 PKEVNILRFSGQRNS 22 902 SEFHLTVLAYNSKGA 22 973 NDTYEIGELNDINIT 22 1100 IGLMCAIALLTLLLL 22 1102 LMCAIALLTLLLLTV | 22 1138 DPEIQSVKDETFGEY 22 346 PPRWTKKPQSAVYST 21 391 PFAGDVVFPREISFT 21 431 NIDVVDVRPLIQTKD 21 529 NATKLRVSPKNPRIP 21 641 NRSVRLTWEAGADHN 21 683 GKKTTVILPLAPFVR 21 881 VNILRFSGQRNSGMV 21 889 QRNSGMVPSLDAFSE 21 1095 TQGWFIGLMCAIALL 21 1166 SLNRDMQPTESADSL 21 1198 IGAYAGSKEKGSVES 21 10 LIVYLMFLLLKFSKA 20 18 LLKFSKAIEIPSSVQ 20( 28 PSSVQQVPTIIKQSK 20| 44 QVAFPFDEYFQIECE 20( 73 GNPFYFTDHRIIPSN 2θ| 109 CFASNKLGIAMSEEI 20[ 362 SNGILLCEAEGEPQP 20[ 421 NVHGTILANANIDW 20| 434 WDVRPLIQTKDGEN 20| 473 WQKVEEVKPLEGRRY 20| 572 GEAFEINGTEDGRII 20 582 DGRIIIDGANLTISN 20 593 TISNVTLEDQGIYCC 20 684 KKTTVILPLAPFVRY 20 692 LAPFVRYQFRVIAVN 20 782 TNHTLRVMTPAVYAP 20 908 VLAYNSKGAGPESEP 20 928 PEGVPEQPTFLKVIK 20 966 LLQYQIINDTYEIGE 20

TableXLVi-V1-DRB1-Q101-15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos | 123456789012345' score 1039 SGVNLTQKTHPIEVF 20 1117 CFVKRNRGGKYSVKE 20 32 QQVPTIIKQSKVQVA 19 75 PFYFTDHRIIPSNNS 19 122 EIEFIVPSVPKLPKE 19 265 SITILKGEILLLECF 19 268 ILKGEILLLECFAEG 19 377 TIKWRVNGSPVDNHP 19 455 YSAFLHCEFFASPEA 19 602 QGIYCCSAHTALDSA 19 659 SEYIVEFEGNKEEPG 19 898 LDAFSEFHLTVLAYN 19 922 PYIFQTPEGVPEQPT 19 932 PEQPTFLKVIKVDKD 19 952 WGLPKKLNGNLTGYL 19 1028. LGEGSKGIGK1SGVN 19 1038 ISGVNLTQKTHPIEV 19 1061 VRLMTKNWGDNDSIF 19 |11O6 IALLTLLLLTVCFVK 19 [1124 GGKYSVKEKEDLHPD 19 11149 FGEYSDSDEKPLKGS 19 I 4 LLLGRGLIVYLMFLL 18 | 64 EPTFSWTKDGNPFYF 18 I 74 NPFYFTDHRIIPSNN 18 ( wo "iSHFQGKYRCFASNK 18 I 107 YRCFASNKLG1AMSE 18 114 KLG1AMSEE1EFIVP 18 I 130 VPKLPKEKIDPLEVE 18 199 RNDYCCFAAFPRLRT 18 209 PRLRTIVQKMPMKLT 18 216 QKMPMKLTVNSLKHA 18 219 PMKLTVNSLKHANDS 18 251 PKLLLPPTESGSESS 18 270 p&lt;G0LLLECFAEGLP 18 300 GRETKENYGKTLKIE 18 355 SAVYSTGSNGILLCE 18 393 AGDWFPREISFTNL 18 452 WGYSAFLHCEFFAS 18 46C HCEFFASPEAVVSWQ I 18 228

TableXLVt-V1 -DRB1 15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos ( 123456789012345 ( score 492 NGTLQINRHEEDAG 18 505 AGSYSCWVENAIGKT 18 524 NLDIRNATKLRVSPK 18 542 IPKLHMLELHCESKC 18 566 LSWSKDGEAFEINGT 18 574 AFEINGTEDGRIIID 18 645 RLTWEAGADHNSNIS 18 672 PGRWEELTRVQGKKT 18 743 EMHKWEPLKSMEQN 18 763 YRVTWKPQGAPVEWE 18 778 EETVTNHTLRVMTPA 18 784 HTLRVMTPAVYAPYD 18 813 PQSVTLYSGEDYPDT 18 862 QINWWKTKSLLDGRT 18 866 WKTKSLLDGRTHPKE 18 907 TVLAYNSKGAGPESE 18 909 LAYNSKGAGPESEPY 18 934 QPTFLKVIKVDKDTA 18 951 SWGLPKKLNGNLTGY 18 979 GELNDiNITTPSKPS 18 996 LSNLNATTKYKPYLR 18 1006 KFYLRACTSQGCGKP 18| 1021 ITEESSTLGEGSKGI 18( 1024 ESSTLGEGSKGIGKI 18( 1050 IEVFEPGAEH1VRLM •18 1116 VCFVKRNRGGKYSVK 18| 1126 KYSVKEKEDLHPDPE 18) 1161 KGSLRSLNRDMQPTE 18j 1180 LVEYGEGDHGLFSED 18| 1194 DGSFIGAYAGSKEKG 18 6 LGRGUVYLMFLLLK 17( 12 VYLMFLLLKFSKAIE 17 20 KFSKAIEIPSSVQQV 17 22 SKAIEIPSSVQQVPT 17 35 PTilKQSKVQVAFPF 17 42 KVQVAFPFDEYFQIE 17 49 FDEYFQIECEAKGNP 17 90 GTFRIPNEGHISHFQ 17 97 EGHISHFQGKYRCFA 17

TableXLVi-V1-DRB1 -0101 -15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 ( score 135 KEKIDPLEVEEGDPI 17 .150 VLPCNPPKGLPPLHI 17 171 LEHIEQDERVYMSQK 17 177 DERVYMSQKGDLYFA 17 179) RVYMSQKGDLYFANV 17 212 RTIVQKMPMKLTVNS 17 221 KLTVNSLKHANDSSS 17 222 LTVNSLKHANDSSSS 17 224 VNSLKHANDSSSSTE 17 232 DSSSSTEIGSKANSI 17 240 GSKANSIKQRKPKLL 17 242 KANSIKQRKPKLLLP 17 269 LKGEILLLECFAEGL 17 276 LECFAEGLPTPQVDW 17 290 WNKiGGDLPKGRETK 17 305 ENYGKTLKIENVSYQ 17 326 CTASNFLGTATHDFH 17 356 AVYSTGSNGILLCEA 17 364 GILLCEAEGEPQPTI 17 375 QPTIKWRVNGSPVDN 17 385 SPVDNHPFAGDWFP 17 396 WFPREISFTNLQPN 17 442 QTKDGENYATVVGYS 17 449 YATVVGYSAFLHCEF 17 453 VGYSAFLHCEFFASP 17 494 TLQINRTTEEDAGSY 17( 510 CWVENAiGKTAVTAN 17 519 TAVTANLDIRNATKL 17 561 KHSLKLSWSKDGEAF 17 575 FEINGTEDGRIIIDG 17 584 RIIIDGANLTISNVT 17 608 SAHTALDSAADITQV 17 633 NLHLSERQNRSVRLT 17 643 SVRLTWEAGADHNSN 17 700 FRViAVNEVGRSQPS 17 740 QPKEMIIKWEPLKSM 17 761 LEYRVTWKPQGAPVE 17 762 EYRVTWKPQGAPVEW 17 | 790 TPAVYAPYDVKVQAI 17

TabieXLVl-V1-DRB1 15mers- 282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 795 APYDVKVQAINQLGS 17 802 QAINQLGSGPDPQSV 17 833 GVDVINSTLVKVTWS 17 836 ViNSTLVKVTWSTVP 17 891 NSGMVPSLDAFSEFH 17 903 EFHLTVLAYNSKGAG 17 943 VDKDTATLSWGLPKK 17 961 NLTGYLLQYQllNDT 17 962 LTGYLLQYQilNDTY 17 967 LQYQIINDTYEIGEL 17 1009 LRACTSQGCGKPITE 17 1010 RACTSQGCGKPITEE 17 1058 EHIVRLMTKNWGDND 17 1072 DSIFQDVIETRGREY 17 1075 FQDVIETRGREYAGL 17 1076 QDVIETRGREYAGLY 17 1154 DSDEKPLKGSLRSLN 17 1178 DSLVEYGEGDHGLFS 17 1188 HGLFSEDGSFIGAYA 17 1195 GSFIGAYAGSKEKGS 17 1210 VESNGSSTATFPLRA || 17

TableXLVI-V2-(SET1)-HLA-DRB1 15mers-2B2P1 G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 2 SEElEFiVPSVPKFP 29 5 lEFIVPSVPKFPKEK 24 14 KFPKEKIDPLEVEEG 22 12 VPKFPKEKIDPLEVE 20 4 EIEFIVPSVPKFPKE 19 9 VPSVPKFPKEKIDPL 19 3 EEIEFIVPSVPKFPK 15 &amp;#943; 6 EFIVPSVPKFPKEKl 14 229

TableXLVI-V2-(SET2)-HLA-DRB1- 0101-15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. Pos 123456789012345 ! score 4 KIGGDLPKGREAKEN 18 12 GREAKENYGKTLKIE 18 2 WNKIGGDLPKGREAK 17 14 EAKENYGKTLKIENV 16 6 GGDLPKGREAKENYG 11 7 GDLPKGREAKENYGK 11 3 NKIGGDLPKGREAKE 8

TableXLVI-V2-(SET3)-HLA- DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 13 EGKYAGLYDDISTQG 26 6 EESSTLGEGKYAGLY 20 8 SSTLGEGKYAGLYDD 18 1 GKPITEESSTLGEGK 16

TableXLVI-V3-HLA-DRB1 -0101 - 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 8 IHGVDVINTTYVSNT 29 15 NTTYVSNTTYVSNAT 25 21 NTTYVSNATGSPQPS 25 46 SYRNRNMLAEDFIQK 24 2 PDTAPVIHGVDVINT 22 27 NATGSPQPSIFICSK 20 20 SNTTYVSNATGSPQP 19 9 HGVDViNTTYVSNn 18 34 PSIFICSKEQELSYR 18 47 YRNRNMLAEDFIQKS 18 35 SIFICSKEQELSYRN 17

TabIeXLVI-V3-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of pepiide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 50 RNMLAEDFIQKSTSC 17 22 TTYVSNATGSPQPSI 16 23 TYVSNATGSPQPSIF 16 42 EQELSYRNRNMLAED 16 53 LAEDFIQKSTSCNYV 16 54 AEDFIQKSTSCNYVE 16 55 EDFIQKSTSCNYVEK 16 14 INTTYVSNTTYVSNA 15 52 MLAEDFIQKSTSCNY 15 5 APVIHGVDVINTTYV 14 24 YVSNATGSPQPSIFI 14 26 SNATGSPQPSIFICS 14 32 PQPSIFICSKEQELS 14 62 I TSCNYVEKSSTFFKI 14

TabieXLVI-V4-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 4 PQSVTLYSGEDLPEQ 26 12 GEDLPEQPTFLKVIK 20 3 DPQSVTLYSGEDLPE 15 11 SGEDLPEQPTFLKVI 15 8 TLYSGEDLPEQPTFL 14

TableXLVI-V5-HLA-DRB1 I 15mers-282P1G3 ( Each peptide is a portion of SEQ I ID NO: i 1; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. ] Pos 123456789012345 score) 15 SNSIKQRKPKLLLPP 24) 3 VQKMPMKLTVNSSNS ~23, 7 PMKLTVNSSNSiKQR 23,

TableXLVI-V5-HLA-DRB1-0l01- 15mers-282P1G3 Each pepiide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is ' 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 6 MPMKLTVNSSNSIKQ 20 4 QKMPMKLTVNSSNSI 18 12 VNSSNSIKQRKPKLL 17 14 SSNSIKQRKPKLLLP 17 9 KLTVNSSNSIKQRKP 16

TableXLVI-V6-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 15 amino acids, and the end position for each pepiide is the start position plus fourteen. Pos 123456789012345 score 6 SEEIEFIVPKLEHIE 22 10 EFIVPKLEHIEQDER 19 8 EIEFIVPKLEHIEQD 18 2 GIAMSEEIEFIVPKL 16 3 iAMSEEIEFIVPKLE 15 13 VPKLEHIEQDERVYM 15 14 PKLEHIEQDERVYMS 11

TableXLVl-V7-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 18 SHELFTLHPEPPRWT 30 6 THDFHVIVEDNISHE 24 10 HVIVEDNISHELFTL 22 15 DNISHELFTLHPEPP 22 7 hdfhvivednishel 19 24 LHPEPPRWTKKPQSA 16 21 LFTLHPEPPRWTKKP 15 11 VIVEDNISHELFTLH 14

TableXLVII-Vl-HLA-DRBl 15mers-282P1G3 230

Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 171 LEHiEQDERVYMSQK 28 1132 KEDLHPDPEIQSVKD 28 66 TFSWTKDGNPFYFTD 26 114 KLGIAMSEElEFiVP 26 191 ANVEEKDSRNDYCCF 26 594 ISNVTLEDQGIYCCS 26 951 SWGLPKKLNGNLTGY 26 1164 LRSLNRDMQPTESAD 26 177 DERVYMSQKGDLYFA 25 313 IENVSYQDKGNYRCT 25 393 AGDWFPREISFTNL 25 689 ILPLAPFVRYQFRVl 25 895 VPSLDAFSEFHLTVL 25 996 LSNLNATTKYKFYLR 25 582 DGRillDGANLTISN 24 265 SiTILKGEILLLECF 23 938 LKVIKVDKDTATLSW 23) 623 TVLDVPDPPENLHLS 22 2 EPLLLGRGLiVYLMF 21 7 GRGLIVYLMFLLLKF 21 8 RGLIVYLMFLLLKFS 21 243 ANSIKQRKPKLLLPP 21 272 EiLLLECFAEGLPTP 21 290 WNKIGGDLPKGRETK 21 476 VEEVKPLEGRRYHIY 21 687 TVILPLAPFVRYQFR 21 786 LRVMTPAVYAPYDVK 21 813 PQSVTLYSGEDYPDT 21 940 VIKVDKDTATLSWGL 21 968 QYQIINDTYEIGELN 21 1032 SKGIGKISGVNLTQK 21 1103 MCAIALLTLLLLTVC 21 3 PLLLGRGLIVYLMFL 20 20 15 MFLLLKFSKAIEiPS 179 RVYMSQKGDLYFANV 20 20 211 LRTIVQKMPMKLTVN 263 ESSITiLKGEILLLE 20 404 FTNLQPNHTAVYQCE 20 631 PENLHLSERQNRSVR 20 748 WEPLKSMEQNGPGLE 20 783 NHTLRVMTPAVYAPY 20

TableXLVll-V1-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 796 PYDVKVQAiNQLGSG 20 846 WSTVPKDRVHGRLKG 20 867 KTKSLLDGRTHPKEV 20 947 TATLSWGLPKKLNGN 20 1071 NDSIFQDVIETRGRE 20 1075 FQDVIETRGREYAGL 20 1086 YAGLYDDISTQGWFI 20 . 1097 GWFIGLMCAIALLTL 20 1116 VCFVKRNRGGKYSVK 20 1138 DPEIQSVKDETFGEY 20 1172 QPTESADSLVEYGEG 20 1188 NGLFSEDGSFIGAYA 20 34 VPTIIKQSKVQVAFP 19 44 QVAFPFDEYFQIECE 19 81 HRIIPSNNSGTFRIP 19 122 EIEFIVPSVPKLPKE 19 124 EFiVPSVPKLPKEKI 19 130 VPKLPKEKIDPLEVE ! 19 140 PLEVEEGDPIVLPCN 19 148 PIVLPCNPPKGLPPL 19 217 KMPMKLTVNSLKHAN 19 251 PKLLLPPTESGSESS 19 434 VVDVRPLIQTKDGEN: 19 438 RPLIQTKDGENYATV , 19 439 PLIQTKDGENYATVV 19 467 PEAVVSWQKVEEVKP 19 520 AVTANLDIRNATKLR 19 522 TANLDIRNATKLRVS 19 530 ATKLRVSPKNPRIPK 19 539 NPRIPKLHMLELHCE 19 557 DSHLKHSLKLSWSKD 19 576 EiNGTEDGRIIIDGA 19 624 VLDVPDPPENLHLSE 19 641 NRSVRLTWEAGADHN 19 762 EYRVTWKPQGAPVEW 19 860 GYQINWWKTKSLLDG 19 881 VNILRFSGQRNSGMV 19 893 GMVPSLDAFSEFHLT 19 955 PKKLNGNLTGYLLQY 19

TableXLVII-V1-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 1058 EHIVRLMTKNWGDND 19 1100 IGLMCAIALLTLLLL 19 1141 IQSVKDETFGEYSDS 19 1150 GEYSDSDEKPLKGSL 19 1157 EKPLKGSLRSLNRDM 19 1177 ADSLVEYGEGDHGLF 19 12 VYLMFLLLKFSKAIE 18 24 AiEIPSSVQQVPTII 18 42 KVQVAFPFDEYFQIE 18 80 DHRIIPSNNSGTFRI 18 127 VPSVPKLPKEK1DPL 18 146 GDPIVLPCNPPKGLP 18 264 SSITiLKGEILLLEC 18 307 YGKTLKIENVSYQDK 18 328 ASNFLGTATHDFHVI 18 340 HVIVEEPPRWTKKPQ 18 363 NG1LLCEAEGEPQPT 18 389 . NHPFAGDWFPRE1S 18 423 HGTiLANANIDVVDV 18 429 NANIDWDVRPLIQT 18 430 ANIDWDVRPUQTK 18 479 VKPLEGRRYHIYENG 18 524 NLDIRNATKLRVSPK 18 545 LHMLELHCESKCDSH 18 565 KLSWSKDGEAFEING 18 583 GRIIIDGANLTISNV 18 588 DGANLTISNVTLEDQ 18 693 APFVRYQFRVIAVNE 18 699 QFRVIAVNEVGRSQP 18 702 VIAVNEVGRSQPSQP 18 741 PKEMIIKWEPLKSME 18 806 QLGSGPDPQSVTLYS 18 906 LTVLAYNSKGAGPES 18, 977 EIGELNDINITTPSK 18, 983 DIN1TTPSKPSWHLS 18, 1025 SSTLGEGSKGIGKIS 18, 1064 MTKNWGDNDSIFQDV 18, 1112 LLTVCFVKRNRGGKY 18| 1161 KGSLRSLNRDMQPTE 18, 231 " TableXLVI 1-V1 -HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 31 VQQVPTllKQSKVQV 17 36 TiiKQSKVQVAFPFD 17 52 YFQIECEAKGNPEPT 17 96 NEGHISHFQGKYRCF 17 j 116 GIAMSEEIEFIVPSV 17 164 IYWMN1ELEHIEQDE 17 168 NIELEHIEQDERVYM 17 208 FPRLRTIVQKMPMKL 17 236 STEIGSKANSIKQRK 17 244 NSIKQRKPKLLLPPT 17 273 1LLLECFAEGLPTPQ 17 294 GGDLPKGRETKENYG 17 375 QPTIKWRVNGSPVDN 17 j 547 MLELHCESKCDSHLK 17 j 625 LDVPDPPENLHLSER 17 633 NLHLSERQNRSVRLT 17 647 TWEAGADHNSNISEY 17 660 EYIVEFEGNKEEPGR 17 722 TPPAAPDRNPQNIRV 17 771 GAPVEWEEETVTNHT 17 792 AVYAPYDVKVQAINQ 17 798 DVKVQAINQLGSGPD 17 851 KDRVHGRLKGYQINW 17 898 LDAFSEFHLTVLAYN 17 921 EPYIFQTPEGVPEQP 17 934 QPTFLKVIKVDKDTA 17 937 FLKVIKVDKDTATLS 17 1038 ISGVNLTQKTHPIEV 17 1076 QDVIETRGREYAGLY 17 50 DEYFQIECEAKGNPE 16 56 ECEAKGNPEPTFSWT 16 74 NPFYFTDHRliPSNN 16 170 ELEHIEQDERVYMSQ. 16| 202 YCCFAAFPRLRTIVQ 16 242 KANSIKQRKPKLLLP 16 283 LPTPQVDWNKIGGDL 16 460 HCEFFASPEAVVSWQ 16 494 TLQINRTTEEDAGSY 16 553 ESKCDSHLKHSLKLS 16

TableXLVIl-V1-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos j 123456789012345 score 969( YQIINDTYEIGELND 16 46 AFPFDEYFQIECEAK 15 89 SGTFRIPNEGHISHF 15 160 PPLHIYWMNIELEHI 15 187 DLYFANVEEKDSRND 15 270 KGEILLLECFAEGLP 15 296 DLPKGRETKENYGKT 15 355 SAVYSTGSNGILLCE 15 381 RVNGSPVDNHPFAGD 15 484 GRRYHIYENGTLQiN 15 659 SEYiVEFEGNKEEPG 15 662 IVEFEGNKEEPGRWE 15 830 VIHGVDVINSTLVKV 15( 861 YQINWWKTKSLLDGR 15| 926 QTPEGVPEQPTFLKV 15( 998 NLNATTKYKFYIRAC 15l 1050 IEVFEPGAEHIVRLM 15] 1115 TVCFVKRNRGGKYSV 15) 1124 GGKYSVKEKEDLHPD 15 1153 SDSDEKPLKGSLRSL 15( 1 MEPLLLGRGUVYLM 14 10 LIVYLMFLLLKFSKA 14( 14 LMFLLLKFSKAIEIP 14( 18 LLKFSKAIEIPSSVQ 14( 100 ISHFQGKYRCFASNK 14 147 DPIVLPCNPPKGLPP 14 215 VQKMPMKLTVNSLKH 14 221 KLTVNSLKHANDSSS 14 250 KPKLLLPPTESGSES 14 271 GEILLLECFAEGLPT 14 336 THDFHVIVEEPPRWT 14 362 SNGILLCEAEGEPQP 14 551 HCESKCDSHLKHSLK 14 742 KEMilKWEPLKSMEQ 14 775 EWEEETVTNHTLRVM 14 880 EVNILRFSGQRNSGM 14 883 ILRFSGQRNSGMVPS 14 891 NSGMVPSLDAFSEFH 14 965 YLLQYQIINDTYEIG 14

TableXLVII-V1-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each pepfide is the start position pius fourteen. Pos 123456789012345 score . 1018 GKPiTEESSTLGEGS 14 1072 DSIFQDVIETRGREY '14 1088 GLYDDISTQGWFIGL 14 1105 AIALLTLLLLTVCFV 14 1110 TLLLLTVCFVKRNRG 14 1126 KYSVKEKEDLHPDPE 14 1149 FGEYSDSDEKPLKGS 14 9 GLIVYLMFLLLKFSK 13 13 YLMFLLLKFSKAIEI 13 35 PTIiKQSKVQVAFPF 13 123 IEFIVPSVPKLPKEK 13 141 LEVEEGDPIVLPCNP 13 181 YMSQKGDLYFANVEE 13 266 ITILKGEILLLECFA 13 339 FHVIVEEPPRWTKKP . 13 354 QSAVYSTGSNGILLC 13 449 YATWGYSAFLHCEF 13 473 WQKVEEVKPLEGRRY 13 486 RYHIYENGTLQINRT 13 544 KLHMLELHCESKCDS 13 595 SNVTLEDQGIYCCSA 13 608 ( SAHTALDSAADITQV 13 621 QVTVLDVPDPPENLH . 13 685 KTTVILPLAPFVRYQ rt O 1&amp;#908; 686 TTVILPLAPFVRYQF 13 833 GVDVINSTLVKVTWS 13 928 PEGVPEQPTFLKVIK 13 935 PTFLKVIKVDKDTAT 13 959 NGNLTGYLLQYQIIN 13 963 TGYLLQYQIINDTYE 13 1098 WFIGLMCAIALLTLL 13 1106 IALLTLLLLTVCFVK 13 1107 ALLTLLLLTVCFVKR 13 1108 LLTLLLLWCFVKRN 13 1109 LTLLLLTVCFVKRNR 13 1128 SVKEKEDLHPDPEIQ 13 1148 TFGEYSDSDEKPLKG 13 1168 NRDMQPTESADSLVE 13 232 -. TabIeXLVII-V2-(SET1)-HLA-DRB1-0301 -15mers-282P1 G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 j score 4 EIEFIVPSVPKFPKE 19 6. EFIVPSVPKFPKEKI 18 9 VPSVPKFPKEKIDPL 18 12 VPKFPKEKIDPLEVE 17 5 IEFIVPSVPKFPKEK 12 15 FPKEKIDPLEVEE-GD 12 2 SEEIEFIVPSVPKFP 10

TableXLVIFV2-(SET2)-HLA-DRB1- 030i-15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 2 WNKIGGDLPKGREAK 21 6 GGDLPKGREAKENYG 18 8 DLPKGREAKENYGKT 15 5 IGGDLPKGREAKENY 11 9 LPKGREAKENYGKTL 10 12 GREAKENYGKTLKIE 10

TableXLVli-V2-(SET3)-HLA- DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 | score 8 SSTLGEGKYAGLYDD 21 5 TEESSTLGEGKYAGL 16 1 GKPITEESSTLGEGK 14 15 KYAGLYDDISTQGWF 12 7 ESSTLGEGKYAGLYD 10

Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. Pos 123456789012345 score 34 PSIFICSKEQELSYR 25 42 EQELSYRNRNMLAED 25 50 RNMLAEDFIQKSTSC 23 35 SIFICSKEQELSYRN 19 55 EDFIQKSTSCNYVEK 19 33 QPSIFICSKEQELSY 17 13 VINTTYVSNTTYVSN 16 7 VIHGVDVINTTYVSN 15 36 IFICSKEQELSYRNR 15 4 TAPVIHGVDVINTTY 12 10 GVDVINTTYVSNTTY 12 49 NRNMLAEDFIQKSTS 12

TableXLVII-V4-HLA-DRB1-03Q1- 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 4 PQSVTLYSGEDLPEQ 21 10 YSGEDLPEQPTFLKV 16 6 SVTLYSGEDLPEQPT 13 12 GEDLPEQPTFLKVIK 13 8 TLYSGEDLPEQPTFL 12 11 SGEDLPEQPTFLKVI 11 I 5 QSVTLYSGEDLPEQP 10

TableXLVII-V5-HLA-DRB1 . 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos| 123456789012345 score 15 SNSIKQRKPKLLLPP 21 5 KMPMKLTVNSSNSIK 18 14 SSNSIKQRKPKLLLP 16 3 VQKMPMKLTVNSSNS 14 7 PMKLTVNSSNSIKQR 13

TableXLVII-V5-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 9 KLTVNSSNSIKQRKP 12

TableXLVIII-V2-{SET1)-HLA- 0401-15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is foe start position plus fourteen. Pos 123456789012345 score 12 VPKFPKEKIDPLEVE 22 6 EFIVPSVPKFPKEKI 20 9 VPSVPKFPKEKIDPL 20 3 EEIEFIVPSVPKFPK 18 2 SEEIEFIVPSVPKFP 14 1 MSEEIEFIVPSVPKF 12 14 KFPKEKIDPLEVEEG 12 4 EIEFIVPSVPKFPKE 10

TableXLV!ll-V2-(SET2)-HLA-G401- 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 2 WNKIGGDLPKGREAK 14 11 KGREAKENYGKTLKI 12 14 EAKENYGKTLKIENV 12 6 GGDLPKGREAKENYG 8 5 IGGDLPKGREAKENY 7 10 PKGREAKENYGKTLK 7 3 NKIGGDLPKGREAKE 6 4 KIGGDLPKGREAKEN 6 8 DLPKGREAKENYGKT 6 9 LPKGREAKENYGKTL 6 12 GREAKENYGKTLKIE 6 13 REAKENYGKTLKIEN I 6

TableXLVII-V3-HLA-DRB1 15mers-282P1G3 233

TabieXLVIII-V2-(SET3)-HLA- 0401-15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 13 EGKYAGLYDDiSTQG 22 1 GKPITEESSTLGEGK 20 8 SSTLGEGKYAGL.YDD 14 15 KYAGLYDDISTQGWF 12

TabieXLVIII-V3-HLA 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 15 amino acids,'and the end position for each peptide is the start position pius fourteen. Pos 123456789012345 score 8 IHGVDVINTTYVSNT 26 15 NTTYVSNTTYVSNAT 22 5 APVIHGVDVINTTYV 20 22 TTYVSNATGSPQPSI 20 49 NRNMLAEDFIQKSTS 20 50 RNMLAEDFIQKSTSC 20 32 PQPSIFICSKEQELS 18 38 ICSKEQELSYRNRNM 18 51 NMLAEDFIQKSTSCN 18 54 AEDFIQKSTSCNYVE 17 21 NTTYVSNATGSPQPS 16 34 PSIFICSKEQELSYR 16 35 SIFICSKEQELSYRN 15 42 EQELSYRNRNMLAED 15 4 TAPVIHGVDVINTTY 14 10 GVDV1NTTYVSNTTY 14 11 VDVINTTYVSNTTYV 14 16 TTYVSNTTYVSNATG 14 55 EDFIQKSTSCNYVEK 14 1 YPDTAPViHGVDVIN 12 2 PDTAPVIHGVDVINT 12 6 PVIHGVDVINTTYVS 12 7 VIHGVDVINTTYVSN 12 9 HGVDVINTTYVSNTT 12 12 DVINTTYVSNTTYVS 12 13 VINTTYVSNTTYVSN 12|

TableXLVIil-V3-HLA 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 14 INTTYVSNTTYVSNA 12 18 YVSNTTYVSNATGSP 12 19 VSNTTYVSNATGSPQ 12 25 VSNATGSPQPSIFIC 12 27 NATGSPQPSIFICSK 12 30 GSPQPSIFICSKEQE 12 40 SKEQELSYRNRNMLA 12 41 KEQELSYRNRNMLAE 12 43 QELSYRNRNMLAEDF 12 47 YRNRNMLAEDFIQKS 12 48 RNRNMLAEDFIQKST 12 52 MLAEDFIQKSTSCNY 12 61 STSCNYVEKSSTFFK 12 I 62 TSCNYVEKSSTFFKI 12

Tab!eXLVIII-V4-HLA-G401- 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. Pos 123456789012345 ) score 7 VTLYSGEDLPEQPTF 22 12 GEDLPEQPTFLKVIK 20 4 PQSVTLYSGEDLPEQ 14 3 DPQSVTLYSGEDLPE 12 9 LYSGEDLPEQPTFLK 12 11 SGEDLPEQPTFLKVI 12 15 LPEQPTFLKVIKVDK 12

TableXLVIII-V5-HLA 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 5 KMPMKLTVNSSNSIK 20

TabieXLVIII-V5-HLA 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 7 PMKLTVNSSNSIKQR 20 9 KLTVNSSNSIKQRKP 20 6 MPMKLTVNSSNSIKQ 18 3 VQKMPMKLTVNSSNS 15 4 QKMPMKLTVNSSNSI 12 8 MKLTVNSSNSIKQRK 12 12 VNSSNSIKQRKPKLL 12 15 SNSIKQRKPKLLLPP 9

TableXLVIII-V6-HL4 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. Pos 123456789012345 score 10 EFIVPKLEHIEQDER 26 2 GIAMSEEIEFIVPKL 20 13 VPKLEHIEQDERVYM’ 20 8 EIEFIVPKLEHIEQD 16 6 SEEIEFIVPKLEHIE 14 1 LGIAMSEE1EFIVPK 12 4 AMSEEIEFIVPKLEH 12 5 MSEEIEFIVPKLEHI 12 14j|PKLEHIEQDERVYMS 12

TableXLVII!-V7-HLA-04Q1- 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 22 6 THDFHVIVEDNISHE 8 DFHVIVEDNISHELF 20 10 HVIVEDNISHELFTL 20 21 LFTLHPEPPRWTKKP 20 2 LGTATHDFHVIVEDN 18( 234 „ TableXLVIII-V7-HLA-0401 - 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start posiiion plus fourteen. Pos 123456789012345 score 9 FHVIVEDNISHELFT 14 14 EDNISHELFTLHPEP [ 14 18 SHELFTLHPEPPRWT 14 5 ATHDFHVIVEDNISH 12 7 HDFHVIVEDNISHEL 12 11 VIVEDNISHELFTLH 12 15 DNISHELFTLHPEPP 12 22 FTLHPEPPRWTKKPQ 12 19 HELFTLHPEPPRWTK 10

TableXLlX-V1-HLA-DRB1-1101 - 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 aiiiiiivj tfviuo, auu uic duu puciuuii iUi each peptide is the start position plus fourteen. Pos 123456789012345 score 672 PGRWEELTRVQGKKT 30 1113 LLTVCFVKRNRGGKY 28 74 NPFYFTDHRIIPSNN 26 702 V1AVNEVGRSQPSQP 26 843 KVTWSTVPKDRVHGR 26 937 FLKVIKVDKDTATLS 26 1058 EHIVRLMTKNWGDND 26 336 THDFHV1VEEPPRWT 25 760 GLEYRVTWKPQGAPV 25 100 ISHFQGKYRCFASNK 24 446 GENYATWGYSAFLH 24 934 QPTFLKVIKVDKDTA 24 949 TLSWGLPKKLNGNLT 24 1072 DSIFQDVIETRGREY 24 13 YLMFLLLKFSKAIEI 23 287 QVDWNKIGGDLPKGR 23 470 WSWQKVEEVKPLEG 23 1083 GREYAGLYDDISTQG 23 1096 QGWFIGLMCAIALLT 23 187 DLYFANVEEKDSRND 22 12 VYLMFLLLKFSKAIE 21

TableXLIX-V1-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start posiiion plus fourteen. Pos 123456789012345 score 120 SEEIEFIVPSVPKLP 21 127 VPSVPKLPKEKIDPL 21 619 ITQVTVLDVPDPPEN 21 693 APFVRYQFRVIAVNE 21 1025 SSTLGEGSKGIGKIS 21 31 VQQVPTIIKQSKVQV 20 52 YFQIECEAKGNPEPT | 20 73 GNPFYFTDHRIIPSN 20 94 IPNEGHISHFQGKYR 20 124 EFIVPSVPKLPKEKI 20 202 YCCFAAFPRLRTIVQ 20 208 FPRLRTIVQKMPMKL 20 221 KLTVNSLKHANDSSS 20 547 MLELHCESKCDSHLK 20 739 SQPKEMIIKWEPLKS nn ZU 877 HPKEVNILRFSGQRN 20 906 LTVLAYNSKGAGPES 20 1029 GEGSKGIGKISGVNL 20 1038 ISGVNLTQKTHPIEV 20 1076 QDVIETRGREYAGLY 20 1161 KGSLRSLNRDMQPTE 20 1124 GGKYSVKEKEDLHPD 19 1180 LVEYGEGDHGLFSED 19 11 IVYLMFLLLKFSKAI 18 75 PFYFTDHRIIPSNNS 18 135 KEKIDPLEVEEGDPI 18 304 KENYGKTLKIENVSY 18 401 EISFTNLQPNHTAVY ( 18 452 WGYSAFLHCEFFAS 18 473 WQKVEEVKPLEGRRY 18 602 QGIYCCSAHTALDSA 18 748 WEPLKSMEQNGPGLE 18 798 DVKVQAINQLGSGPD 18 828 APVIHGVDVINSTLV 18 978 IGELNDINFTTPSKP 18 1002 TTKYKFYLRACTSQG 18 1115 TVCFVKRNRGGKYSV 18 49 FDEYFQIECEAKGNP 17 | 5C DEYFQIECEAKGNPE 17

TableXLlX-V1 -HLA-DRB1 -1101 - 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score 107 YRCFASNKLGIAMSE 17 205 FAAFPRLRTIVQKMP 17 461 CEFFASPEAWSWQK 17 697 RYQFRVIAVNEVGRS 17 1040 GVNLTQKTHPIEVFE 17 1188 HGLFSEDGSFIGAYA 17 18 LLKFSKAIEIPSSVQ 16 64 EPTFSWTKDGNPFYF 16 163 HIYWMNIELEHIEQD 16 209 PRLRTIVQKMPMKLT 16 291 NKIGGDLPKGRETKE 16 373 EPQPTIKWRVNGSPV 16 392 FAGDWFPRE1SFTN 16 428 ANANIDWDVRPLIQ 16 455 YSAFLHCEFFASPEA 16 524 NLDIRNATKLRVSPK 16 572 GEAFEINGTEDGRII 16 645 RLTWEAGADHNSNIS 16 662 IVEFEGNKEEPGRWE 16 689 1LPLAPFVRYQFRVF 16 745 IIKWEPLKSMEQNGP 16 792 AVYAPYDVKVQAINQ 16 835 DVINSTLVKVTWSTV 16 849 VPKDRVHGRLKGYQI . 16 863 INWWKTKSLLDGRTH 16 966 LLQYQIINDTYEIGE 16 983 DINITTPSKPSWHLS 16 1005 YKFYLRACTSQGCGK 16 1054 EPGAEHIVRLMTKNW 16 1087 AGLYDDISTQGWFIG 16 |1198 IGAYAGSKEKGSVES 16 j 15 MFLLLKFSKA1EIPS 15 i 24 AIEIPSSVQQVPTII 15 I 123 IEFIVPSVPKLPKEK 15 j 145 IVLPCNPPKGLPPLH 15 j 215 PMKLTVNSLKHANDS 15 | 263 i| ESSITILKGEILLLE 15 | 381 VNGSPVDNHPFAGDV 15 | 47f VEEVKPLEGRRYHIY 15 235

-l)!GGDLPKGREAKENYG!j 7|) • \TableXLIX-V1-HL4-DRB1 15mers-282P1G3 TabieXL!X-V1-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. Each peptide is a portion of SEQ ID NO: 3; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. TabieXL!X-V2-(SET3)-HLA- DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the Pos 123456789012345 score Pos 123456789012345 score 530 ATKLRVSPKNPRIPK 15 491 ENGTLQINRTTEEDA 14 start position plus fourteen. 554 SKCDSHLKHSLKLSW 15 510 CWVENAIGKTAVTAN 14 Pos 123456789012345 score 661 YIVEFEGNKEEPGRW 15 526 DIRNATKLRVSPKNP 14 13 EGKYAGLYDDISTOG 23, 675 WEELTRVQGKKTTVI 15 532 KLRVSPKNPRIPKLH 14 1 GKPITEESSTLGEGK 15 682 QGKKTTVILPLAPFV 15 536 SPKNPRIPKLHMLEL 14 7 ESSTLGEGKYAGLYD 14 683 GKKTTV1LPLAPFVR 15 543 PKLHMLELHCESKCD 14 700 FRVIAVNEVGRSQPS 15) 557 DSHLKHSLKLSWSKD 14 TabieXLIX-V3-HLA-DRB1.-1101 -15mers-282P1G3 758 GPGLEYRVTWKPQGA 15 616 AADITQVTVLDVPDP 14 Each peptide is a portion of SEQ ID NO: 7; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. 824 YPDTAPVIHGVDVIN 15 631 PENLHLSERQNRSVR 14 859 KGYQIN WWKTKSLLD 15 656 SNISEYIVEFEGNKE 14 869 KSLLDGRTHPKEVNI 15 712 QPSQPSDH'HETPPAA 14 882 NILRFSGQRNSGMVP 15 727 PDRNPQNiRVQASQP.- , , , — 14 903 EFHLTVLAYNSKGAG 15 762 EYRVTWKPQGAPVEW 14 Pos 123456789012345 score 948 ATLSWGLPKKLNGNL 15 783 NHTLRVMTPAVYAPY 14 52 MLAEDFIQKSTSCNY 20 996: LSNLNATTKYKFYLR 15 794 YAPYDVKVQAtNQLG 14 15 NTTYVSNTTYVSNAT 17 1018 GKPITEESSTLGEGS 15 831 IHGVDVINSTLVKVT 14 21 NTTYVSNATGSPQPS 16 1106 iALLTLLLLTVCFVK 15 836 V1NSTLVKVTWSTVP 14 1 YPDTAPVIHGVDVIN 15 1157 EKPLKGSLRSLNRDM 15 839 STLVKVTWSTVPKDR 14 33 QPSIFICSKEQELSY 15 1197 F1GAYAGSKEKGSVE 15 845 TWSTVPKDRVHGRLK 14 19 VSNTTYVSNATGSPQ 14 34 VPTIIKQSKVQVAFP 14 851 KDRVHGRLKGYQINW 14 42 EQELSYRNRNMLAED 14 91 TFRiPNEGHiSHFQG 14 867 KTKSLLDGRTHPKEV 14 61 jSTSCNYVEKSSTFFK 14 129 SVPKLPKEKIDPLEV 14 921 EPYIFQTPEGVPEQP 14 8 1HGVDVINTTYVSNT 13 165 YWMNIELEHIEQDER 14 935 PTFLKVIKVDKDTAT 14 35 S1FICSKEQELSYRN 13 171 LEHIEQDERVYMSQK 14 1128 SVKEKEDLHPDPEIQ 14 50 RNMLAEDFIQKSTSC 13 177 DERVYMSQKGDLYFA j 14 Γ~5&amp;#912; APVIHGVDVINTTYV 12 186 GDLYFANVEEKDSRN j 14 1 TableXLIX-V2-(SET2)-HLA-DRB1 15mers-282P1G3 34 PSIFICSKEQELSYR 10 234 SSSTEIGSKANSIKQ 14 40 SKEQELSYRNRNMLA 10 Each peptide is a portion of SEQ iD NO: 5; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. 240 GSKAN SIKQRKPKLL 14 44 ELSYRNRNMLAEDFI 10 262 SESSITILKGEILLL 14 54 AEDFIQKSTSCNYVE 10 284 PTPQVDWNKiGGDLP 14 4 TAPVIHGVDVINTTY 9 313 IENVSYQDKGNYRCT 14 317 SYQDKGNYRCTASNF 14 PfableXLlX-V4-HLA-DRB1 j 15mers-282PlG3 | Pos 123456789012345 score 329 SNFLGTATHDFHVIV 14 3 NKSGGDLPKGREAKE 16 | 340 HVIVEEPPRWTKKPQ 14 Each peptide is a portion of SEQ I ID NO; 9; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen, j 13 REAKENYGKTLKIEN 9 344 EEPPRWTKKPQSAVY 14 5 IGGDLPKGREAKENY 8 375 QPTIKWRVNGSPVDN 14 8 DLPKGREAKENYGKT 8 .408 QPNHTAVYQCEASNV 14 1 DWNKIGGDLPKGREA 7 429 NANIDWDVRPLIQT 14 4 [kTggdlpkgreakbT 7 Poe ; Ρ&amp;#938;23456789012345 jjscorej 467 PEAWSWQKVEEVKP 236 -7abieXLIX-V4-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 9; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos 123456789012345 score pf GPDPQSVTLYSGEDL 12 I 7 VTLYSGEDLPEQPTF 10 15 LPEQPTFLKVIKVDK 9 4 PQSVTLYSGEDLPEQ 3 5 QSVTLYSGEDLPEQP1 7 12 GEDLPEQPTFLKVIK 7 3 DPQSVTLYSGEDLPE 6 6 SVTLYSGEDLPEQPT, 6 8 TLYSGEDLPEQPTFL 6 9 |LYSGEDLPEQPTFLK 6

TableXLIX-V5-HLA-DRB1 _15mers-282P1 G3_

Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen.

Pos j 123456789012345 score 12 j VNSSNSIKQRKPKLL 14

TableXLIX-V5-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 11; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position pius fourteen. Pos 123456789012345 score 3 VQKMPMKLTVNSSNS 12 4 QKMPMKLTVNSSNSI 12 6 MPMKLTVNSSNSIKQ 12 11 TVNSSNSIKQRKPKL 10 7 PMKLTVNSSNSIKQR 9 14 SSNSIKQRKPKLLLP 9 1 TIVQKMPMKLTVNSS 8 5 KMPMKLTVNSSNSIK 8 13 NSSNSIKQRKPKLLL 8 2 iVQKMPMKLTVNSSN 7 9 KLTVNSSNSIKQRKP 7 15 SNSIKQRKPKLLLPP 7

TableXLIX-V6-HLA-DRB1 15mers-282P1G3_

Each peptide is a portion of SEQ ID NO: 13; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen.

Pos 123456789012345 score 10 EFIVPKLEHIEQDER 20 6 SEEIEFIVPKLEHIE 15 7 EEIEFIVPKLEHJEQ 15 3 IAMSEEIEFIVPKLE 13 13 VPKLEHIEQDERVYM 12 8 EIEFIVPKLEHIEQD 11

TableXLIX-V7-HLA-DRB1 15mers-282P1G3 Each peptide is a portion of SEQ ID NO: 15; each start position is specified, the length of peptide is 15 amino acids, and the end position for each peptide is the start position plus fourteen. Pos) 123456789012345 score 6 THDFHVIVEDNISHE 19 18 SHELFTLHPEPPRWT 19 11 VIVEDNISHELFTLH 15 17 ISHELFTLHPEPPRW 14 26 PEPPRWTKKPQSAVY 14 7 HDFHVIVEDNISHEL 13 15 DNISHELFTLHPEPP 12 19 HELFTLHPEPPRWTK 12 2 LGTATHDFHVIVEDN 11 237 d Table L: Protein Characteristics of 282P1G3 282PlG3v.l Bioinformatic Program URL Outcome ORF Protein length ORF finder 1224 aa Transmembrane region TM Pred HMMTop http://www.ch.embneLorg/ http://www.enzim.hu/hmmiop/ 2TM.aa.6-25, 1098-1116 one TM, aa 1098-1117 Sosui TMHMM http://www.genome.ad.jp/SOSui/ http://wtvw.cbs.dtu.dk/services/TMHMM 2TM,aa3-25, 1096-1118 oneTM, aa 1097-1119 Signal Peptide Signal P http://www.cbs.dtu.dk/services/SignalP/ yes, cleave aa 24-25 pi pI/MW tool http://www.expasy.ch/tools/ pi 5.54 Molecular weight pVMW tool http://www.expasy.ch/tools/ 136.6 kD Localization PSORT PSORT Π http://psortnibb.ac.jp/ http://psortnibb.ac.jp/ 46% plasma membrane, 10% micobody 44% endoplasmic, 11% vacuolar Motifs Pfam Prints Blocks http://www.sanger.ac.uk/Pfam/ http://www.biocbem.ucl.ac.uk/ http://www.blocks.fhcrc.org/ Ig domain, Fibronectin type HI repeat Cadherin, Fibronectin type III repeat Fibronectin type III repeat v.3 Bioinformatic Program URL Outcome ORF Protein length ORF finder S93aa Transmembrane region TMPred http://www.ch.embnei.org/ one TM, aa 3-19, N-terminus in HMMTop Sosui TMHMM bttp://www.erizim.hu/hmmtop/ http://www.genome.ad.jp/SOSui/ http://www.cbs.dtu.dk/services/TMHMM one TM, aa 1-25, N-terminus out one TM, aa 3-25 none Signal Peptide Signal P http://www.cbs.dtu.dk/services/SignalP/ none pi pI/MWtool http://www.expasy.ch/tools/ pi 5.49 Molecular weight pI/MW tool http :H www.expasy. ch/too Is/ 100.2kD Localization PSORT PSORT II http://psortnibb.ac.jp/ http://psort.nibb. ac.jp/ 78% secreted, 19% lysosomal 52% nuclear, 17% mitochondreal Motifs Pfain Prints Blocks http://www.sanger.ac.uk/Pfam/ http://www.biochem.ucl.ac.uk/ http://www.blocks.fhcrc.org/ Ig domain, Fibronectin type III repeat Cadherin, Fibronectin type III repeat Fibronectin type HI repeat 238

Table LI: Exon boundaries of transcript 282P1G03 v.1

Exon Number Start End Length 1 1 97 97 2 98 177 80 3 178 362 185 4 363 468 106 5 469 656 188 6 657 779 123 7 . 7S0 950 171 8 951 998 48 9 999 1119 121 10 1120 1304 185 11 1305 1436 132 12 1437 1577 141 13 . 1578 1689 112 14 1690 1906 217 15 1907 2022 116 16 2023 2147 125 17 2148 2249 102 18 2250 2447 198 19 2448 2518 71 20 2519 2741 223 21 2742 2857 116 22 2858 3062 205 23 3063 3185 123· 24 3186 3365 180 25 3366 3524 159 26 3525 3656 132 27 3657 3729 73 28 3730 7650 j 3921

Table Lila. Nucleotide sequence of transcript variant 282P1G03 v.2 (SEQ ID NO: 151) cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact aatcgtatat cta.atgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt tccaaaattc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt SO 12 0 180 240 300 360 420 480 540 600 660 720 780 840 239 L . "cg.caaacgtg gaagaaaagg acagtcgcaa fcgactacfcgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 a9999aaa.tc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaagca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa aoccctggag ggcaggcggt atcatatcta 174 0· tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacfctgt ctgaaagaca gaacaggagt gtfccggctga cctgggaagc 2220 tSSaSctgac c'acaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 999a9cccca- gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc 3000 ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg 3060 agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt 3120 atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca 3180 gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc 3240 aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag 3300 ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga 3360 agggaaatat gctggtttat atgatgacat ctccactcaa ggctggttta ttggactgat 3420 gtgtgcgatt gctcttctca cactactatt attaactgtt tgctttgtga agaggaatag 3480 aggtggaaag tactcagtta aagaaaagga agatttgcat ccagacccag aaattcagtc 3540 agtaaaagat gaaacctttg gtgaatacag tgacagtgat gaaaagcctc tcaaaggaag 3600 ccttcggtcc cttaataggg atatgcagcc tactgaaagt gctgacagct tagtcgaata 3660 cggagaggga gaccatggtc tcttcagtga agatggatca tttattggtg cctacgctgg 3720 atctaaggag aagggatctg ttgaaagcaa tggaagttct acagcaactt ttccccttcg 3780 ggcataaaca caacatatgt aagcaacgct actggttcac cccaaccttc catatttatc 3840 tgttcaaagg agcaagaact ttcatatagg aatagaaaca tgctggccga agatttcatc 3900. cagaagtcaa catcctgcaa ttatgttgaa aagagtagta ctttcttcaa aatataaaat 3960 gccaagcact tcaggcctat gttttgctta tattgttttc aggtgctcaa aatgcaaaac 4020 acaaaacaaa tcctgcattt agatacacct caactaaatc caaagtcccc attcagtata 4080 ttccatattt gcctgatttt actattcggt gtgtttgcat agatgttgct acttggtggg 4140 tttttctccg tatgcacatt ggtatacagt ctctgagaac tggcttggtg actttgcttc 4200 actacaggtt aaaagaccat aagcaaactg gttatttaaa atgtaaaaag gaatatgaaa 4260 gtcttattaa aacacttcat tgaaaatata cagtctaaat ttattattta aatrtttacta 4320 gcaaaagtct taggtgaaca atcaactagt atttgttgag ctcctatttg cccagagatg 4380 gtcatattta aacagaagta tacgfcttttc agtttcaaca tgaatttttt tatttctgtc 4440 agttatgaca tccacgagca tcactttttg tgtctgtttt tttttttttc ttggactaaa 4500 ttcaactgca tggaagcggt ggtcagaagg ttgttttata cgagaacagg cagaaagtgc 4560 ccattgttca ggattctaat agctacatct acttaatatc ttcatttcta aattgactgc 4620 240 ,.fctttaccttt ttctcatgtt tatataatgg tatgcttgca tatatttcat gaatacattg 4 68 0 tacatattat gttaatattt acacaattta aaatatagat gtgttttatt ttgaagtgag 4740 aaaatgaaca ttaacaggca tgtttgtaca gctagaatat attagtaaga tactgttttt 4800 cgtcattcca gagctacaac taataacacg aggttccaaa gctgaagact ttgtataaag 4860 tatttgggtt ttgttcttgt attgctttct ttcaacagtt tcaaaataaa atatcataca 4920 aatattgagg gaaatgtttt catatttttc aaaataggtt tttattgttg aatgtacatc 4980 taccccagcc cctcaaaaga aaaactgttt acatagaaat tcctacacat acgtttgcgt 5040 atatgttatt ttaaacatct ttgtggtgag aattttttcc ccgatattct ccttctgtca 5100 aagtcagaac aaattcaggg aatttatttt ctggcagttg tgctccagtc cttttaaaat 5160 tgtacatgaa catgttttag aaacaatatg gaggatgatg catacatgtc ggtcaagttc 5220 agcgctcgac attttatgga aagatttttt taaccttacc acgaaatact taactactgt 5280 ttaagtgaat tgacttattt cactttagtt tttgaactgt gattattggt atactgttat 5340 atcctcaact tggatttatg gtaacccctt ttagttcatg gagaccaaaa tttggggtat 5400 ttataatagt cagcgcagga atgcacatgg aatatctact tgtccttttg aacctcacga 5460 gtcatccaga atgtatagac aggaaaagca tgtcttattt aaaactgtaa tttatgggct 5520 caggatctga ccgcagtccc gggagtaagc atttcaaagg gggaaggcag tgtggtccct 5580 accctgtgtg aatgtgagga tgtagacatc catcagtgca actcg'agctc catcctcctc 5640 cgatttctaa ggctccagtt ttctggaggg acagtcatca tgttttgatt tatctgggag 5700 aaaactgtgg tgcacagctt gtgaggaggg caaggttgtg acgttcgagc ttagttctgg 5760 tgttattctg tctcctcttc tttgtcatca gccaaaacgt ggtttttaaa gagagtcatg 5820 caggttagaa ataatgtcaa aaatatttag gaatttaata acctttaagt cagaaactaa 5880 aacaaatact gaaatattag ctcttcctac acttcgtgtt cccctttagc tgcctgaaaa 5940 tcaagattgc tcctactcag atcttctgag tggctaaaac ttatggatat gaaaaatgag 6000 attgaatgat gactatgctt tgctatcatt gttacctttc ctcaatacta tttggcaact 6060 actgggactc ttcagcacaa aaggaataga tctatgattg accctgattt taattgtgaa 6120 attatatgat tcatatattt tatgaatcag aataaccttc aaataaaata aatctaagtc 6180 ggttaaaatg gatttcatga ttttccctca gaaaatgagt aacggagtcc acggcgtgca 6240 afcggtaatta taaattggtg atgcttgttt gcaaattgcc cactcgtgat aagtcaacag 6300 ccaatattta aaactttgtt cgttactggc tttaccctaa ctttctctaq tctactgtca 6360 atatcatttt aatgtaattg attgtatata gtctcaagaa tggttggtgg gcatgagttc 6420 ctagagaact gtccaagggt tgggaaaatc caaattctct tcctggctcc agcactgatt 6480 ttgtacataa acattaggca ggttgcttaa cctttttatt tcaaactctc tcaactctaa 6540 agtgctaata ataatctcag ttaccttatc tttgtcacag ggtgttcttt tttatgaaga 6600 aaaatttgaa aatgataaaa gctaagatgc cttctaactt cataagcaaa cctttaacta 6660 attatgtatc tgaaagtcac ccccacatac caactcaact tttttcctgt gaacacataa 6720 atatattttt atagaaaaac aaatctacat aaaataaatc tactgtttag tgagcagtat 6780 gacttgtaca tgccattgaa aattattaat cagaagaaaa ttaagcaggg tctttgctat 6840 acaaaagtgt tttccactaa ttttgcatgc gtatttataa gaaaaatgtg aatttggtgg 6900 ttttattcta tcggtataaa ggcatcgata ttttagatgc acccgtgttt gtaaaaafcgt 6 960 agagcacaat ggaattafcgc tggaagtctc aaataatatt tttttcctat tttatactca 7020 tggaagagat aagcfaaaga ggggacaata atgagaaatg ttggtgtgct tttctaagca 7080 tttaaaacat aattgccaat tgaaacccta aatatgttta cataccatta agatatgatt 7140 catgtaacaa tgttaaatta attataatgg gattgggttt gttatctgtg gtagtatata 7200 tcctagtgtt cctatagtga aataagtagg gttcagccaa agctttcttt gttttgtacc 7260 ttaaattgtt cgattacgtc atcaaaagag atgaaaggta tgtagaacag gttcacgtga 7320 ttaccttttt cttttggctt ggattaatat tcatagtaga actttataaa acgtgtttgt 7380 attgtaggtg gtgtttgtat tatgcttatg actatgtatg gtttgaaaat attttcatta 7440 tacatgaaat tcaactttcc aaataaaagt tctacttcat gtaatccaaa a 7491

Table Lilia. Nucleotide sequence alignment of 282P1G03 v.1 (SEQ ID NO: 152) and 282P1G03 v.2 (SEQ ID NO: 153) v.l 1 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg | 1 | 1 | I | | 1 I I 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 If 1 I 1 1 1 1 1 1 1 1 l| t I 1 I 1 J 1 I 50 V.2 1 1 1 1 1 1 1 1 1 I 1 1 1 1 i 1 i i i i i i i i i 1 I i i i &#943; i i i 1 I 1 1 I 1 I I 1 1 1 I 1 1 I 1 1 CGGACCCTGCGCGCCCCCGTCCCGGCTCCCGGCCGGCTCGGGGGAGAAGG 50 v. 1 51 cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg 1 I 1 I 1 I 1 I I 1 1 11 I 111 I 1 I I 11 1 1 I 1 1 1 1 111 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 100 v.2 51 l i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ) 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I i 1 1 I l 1 1 1 1 1 1 1 1 1 1 CGCCCGAGGGGAGGCGCCGGACAGATCGCGTTTCGGAGGCGGCGCA-GGTG 100 v.1 101 ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcatag II 1 1 1 1 1 I 1 1 1 1 1 1 1 ) 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 15 0 V.2 101 1 1 11 11 1 1 1 i11 1 I 11 1 1 1 1 1 1 II 1 1N 1 II 1111 1 II i 1 1 &#943; &#943; 1 i 1 1 1 1 I CTGTAAACTGCAAACCATAATCCTGTCTTAATACTGCAAACAAATCATAG 150 V.1 151 tggaactaaggggaacttaatttactgtttccaggttaactaaggtctca 200 241 v.2 151 TGGAACTAAGGGGAACTTAATTTACTGTTTCCAGGTTAACTAAGGTCTCA 200 v.l 201 gctgtaaaccaaaagtgagagaagacattaagattttcattcttaccggg j I I|11 I 1 Η I II III II III II II11 I I I 1 1 I H ! 1 ! 1 11 I Η I I I 1 1 I 250 v.2 201 Η &#943; I i &#943; I &#943; * Μ &#943; &#943; Μ N &#943; H i i I 1 &#943; 1 &#943; N Η » Η N « I » &#943; &#943; &#943; j t &#943; j i i H GCTGTAAACCAAAAGTGAGAGGAGACATTAAGATTTTCATTCTTACCGGG 250 v.l 251 ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact I 1 1 I i &#943; II (I i 1 I 1 1 i i | i i 1 I j I 1 j II (I 1 1 1 1 1 1 1 I I 1 1 I 1 1 1 I II 1 1 300 v.2 251 1 1 1 I 1 i Η &#943; 1 1 1 1 1 I I 1 I I i I 1 I 1 1 1 &#943; &#943; I 1 I J 1 1 1 1 1 I I I 1 1 U 1 1 1 1 1 1 TTGTCTTCTTCCTGAAGAGCAATGGAGCCGCTTTTACTTGGAAGAGGACT 300 v.l 301 aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa I 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 350 v.2 301 1 i 1 1 t 1 1 I I 1 I 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I 1 I 1 1 1 1 1 ll 1 1 i 1 1 1 1 I I J [ 1 AATCGTATATCTAATGTTCCTCCTGTTAAAATTCTCAAAAGCAATTGAAA 350 v.l 351 taccatcttcagttcaacaggttccaaeaatcataaaacagtcaaaagtc 1111111 I 11 I 1111111 I 1 11111II1111!Ii11 I 1 1 1 1 1 1 1 I 1 It 1 1 400 v.2 351 &#943; Η N 1 &#943; I ) i 11 I i I 1 ) H I I 1 I I I 1 1 1 I 1 1 ) 1 ) I I 1.1 It 1 I I I I &#943; 1 I 1 1 TACCATCTTCAGTTCAACAGGTTCCAACAATCATAAAACAGTCAAAAGTC 400 v.l 401 caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagctaa II (I 1 II 1 I II 11 1 II 1 1 1 II I i 11 ) j 1 I 1 1 1 1 1 I j 1 1 1 1 1 1 I 1 1 1 II 1 1 450 v.2 4.01 1 1 1 1 t j ! 1 Π I 1 1 I &#943; I i &#943; 1 i J I ι I I Π 1 I ι i 1 I I &#943; I &#943; U II 1 1 ii 1 U II CAAGTTGCCTTTCCCTTCGATGAGTATTTTCAAATTGAATGTGAAGCTAA 450 v.l 451 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 11II11111111111II1II11II11Ii(11II1II1 &#943; I i! 11111 It 11 500 v.2 451 AGGAAATCCAGAACCAACATTTTCGTGGACTAAGGATGGCAACCCTTTTT 500 v.l 501 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg 1 I j 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 11 1 1 1 1 550 v.2 501 ι i i 1 i 1 l i ι 1 1 1 I 1 i i 1 1 I 1 I 1 I I I I I I &#943; 1 1 1 I 1 I 1 i i I I 1 1 i 1 ! I 1 1 I I ATTTCACTGACCATCGGATAATTGCATCGAACAATTGAGGAACATTCAGG 550 v. 1 551 atcccaaacgaggggcacatatctcacttteaagggaaataccgctgctt I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 600 v.2 551 II 1 1 I 1 Η Η 1 11 1 N 1 Η &#943; 1 1 1 1 J 1 1 I 1 i 1 I 1 1 1 1 J I 1 J 1 j 1 1 1 I 1 1 1 1 ATCCCAAACGAGGGGCACATATCTCACTTTCAAGGGAAATACCGCTGCTT 600 v. 1 601 tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag 1 1 1 II II 1 1 1 1 III 11 1 ! 1 I II I 1 I I II 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 650 v. 2 601 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TGCTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650 v. 1 651 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg 1 1 I I 1 It 1 1 il 1 I 1 I 1 j i ! 1 1 II j 1 ( 1 1 1 1 1 1 1 1 1 1 1 1 1 It 1 1 1 1 1 1 1 1 700 v.2 651 t 1 1 1 1 J 1 l 1 1 I 1 I 1 1 1 1 - 1 I 1 1 I I 1 1 1 1 I 1 1 1 I 1 I 1 i I I 1 I 1 II I I I 1 1 &#943; ttccaSgtgttccaaaat'tcccaaaagaaaaaattga.ccctcttgaagtg 700 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 750 v.2 701 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 11.1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 II 1 1 1 1 1 1 II GAGGAGGGAGATCCAATTGTCCTCCCATGCAATCCTCCCAAAGGCCTCCC 750 v.l 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 800 v.2 751 Πι &#943; Η 1 1f &#943; 1 1 ) 1 1 1 &#943; Π ! &#943; 1 J Π &#943; Π !&#943; Η i 1i 1&#943; 1 1 1 1 1 1 1 I ) 1 t! ) ACCTTTACACATTTATTGGATGAATATTGAATTAGAACACATCGAACAAG 800 v.l 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 ! 1 1 1 17 1 1 1 1 1T 1 1 850 v.2 801 I 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg 850 v.l 851 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 900 v.2 851 ι I II ι 1 I i II I 111 1 1111111 1 II I 1 1 1111 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag 900 v.l 901 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt II 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 950 v.2 901 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTAAGGACTATTGTACAGAAAATGCCAATGAAACTAACAGTTAACAGTT 950 242 rv.1 951 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca tiI1|η&#943;1ii| | | | |i | &#943; &#943; &#943; η &#943; &#943; &#943; &#943; &#943; η &#943; η &#943; ii I | &#943; η | I | jl I |i | 1000 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 I 1 v .2 951 TAAAGCATGCTAATGACTCAAGTTCATCCACAGAAATTGGTTCCAAGGCA 1000 v.l 1001 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag 1N 11111II11 Π 1 I 1 1 1 1 1 1 1 1 I 1 1 II1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 ! 1 1 1 1 1050 &#943; I 1 I I I 1 i 1 1 &#943; j 1 Ι &#943; 1 1 1 I &#943; 1 i i ) &#943; I J , &#943; ) 1 &#943; I 1 ! ) I ) ) 1 ) ) 1 ) ) I i 1 I 1 V.2 1001 AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG 1050 v.l 1051 tggcagtgagtcttcaattaccatcctcaaaggggaaatcttgctgcttg II I || 1 1 &#943; I I I II || Π II Η II I I I j 1 1 II 1 l| 1 II l| II 1 1 1 j 1 1 1 1 1 1100 I!1 11 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 I I 1 11 I I 1 1 1 l 1 II 1 1 1 II 1 1 1 1 1 11 v.2 1051 TGGCAGTGAGTCTTCAATTACCATCCTCAAAGGGGAAATCTTGCTGCTTG 1100 v.l 1101 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt I 1 1 1 11 1 1 1 II 1 1 1 II 1 1 II 1 1 1 1 1 1 1 II 1 1 1 1 1 1 II I II 1 1 1 II 1 1 1 Π 1150 1 I 1 1 1 1 1 1 I 1 1 1 1 I I 1 I 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 ! 1 1 1 1 1 v.2 1101 AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGGAACAAAATT 1150 v.l 1151 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac II || II II Η 1 i || 1 I 1| Η II II III | 1 | 1 1 1 | 1 1 I Ι&#906; 1 1 1 1 | 1 11 I I 1200 1 1 1 1 1 I! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 · 1 1 1 1 1 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 v.2 1151 GGTGGTGACTTACCAAAGGGGAGAGAAgCAAAAGAAAATTATGGCAAGAC 1200 v.l 1201 tttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca | I I I I I I 1 1 I I 1 1 1 1 1 1 1 1 I ) 1 1 1 11 1 II 1 1 II 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 1250 II 1 1 1 1 1 1 11 I 1 1 I 1 1 1 1 II 1 1 1 1 1 1 1 1 1 ! l 1 1 1 1 1 1 1 1 II 1 1 II 1 1 1 1 1 v.2 12 01 TTTGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA 1250 v.l 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta II I II I |l I 1 I j| || 1 II 1 1 1 II II II 1 1 1 |l l| 1 1 |l j 1 II II 1 1 1 II 1 1300 1 I 1 1 1 1 I 111 II 1 11 1 II 1 1 1 1 1 1 11111 II 1 1 1 II I 1II I 1 1 1 1 I II 1 I v.2 1251 CAGCCAGCAATTTCTTGGGAACAGCCACTCACGATTTTCACGTTATACTA 1300 v.l 1301 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtataqcac 11111 1 1 1 III II II II II 1 1 1 II 1 II 1 1 1 1 1 II II II II II 1 1 1 II 1 1 1 1350 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l l 1 1 1 v.2 13 01 GAAGAGCCTCCTCGCTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCAC 1350 v.l 1351 cggaagcaatqgcatcttgttatgtgagqctgaagqagaacctcaaccca 11li 11 11111 i! 11 il 111II11111! 11 n 11111111II11! 11111 v.2 1351 CGGAAGCAATGGCATCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCA 1400 1400 v.l 1401 caatcaagtggagagtcaatggctccccagttgacaatcatccatttgct | I I 1 I 1 ! I 1 1 1 1 1 H 1 1 1 1 1 1 1 1 j I 1 i 1 1 I I I 1 I I 1 5 i 1 I 1 H I i | &#943; 1 I 5 1450 1 I ι ι I ι ι1i1 1 ι 1 1 1 1 ι ι 1 ι ι &#943;ι&#943;Ili11 &#943; 1 1 I I I 11 &#943; !1 1&#943; 1 I 1 1 i I 1 ι v.2 14 01 CAATCAAGTGGAGA.GTCAATGGCTCCCCAGTTGACAATCATCCATTTGCT 1450 v.l 1451 ggtgatgttgtcttccccagggaaatcagttttaccaaccttcaaccaaa Hit! HI 11! HI 1111 Η! 1 H ! HI 11 Hi I HI 11 111 1II &#943; 11111 v.2 1451 GGTGATGTTGTCTTCCeCAGGGAAATCAGTTTTACCAACCTTCAACCAAA 1500 1500 v.l 1501 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc | 1 1 I 1 1 1 II 1 II II j 1 1 1 1 |] 1 1 1 1 II 1 | I | | | j | | I | | 1 11 |l 1 1 1 1 II 1550 1 i I 1 1 1 ! 1 I 1 1 I S I 1 1 ! 1 I I 1 1 1 1 I 1 I 1 1 i 1 1 1 * 1 1 I ι 1 I 1 i 1 1 1 I ! > 1 i v.2 1501 TCATACTGCTGTGTACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCC 1550 v.l 1551 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc | I I I I I I I I 1 I I I II 11 I I 1 I 1 II 1 I I I I I i I I |j I I I I |j II || 1 1 1 I 1 1600 II 1 1 1 1 1 1 11111 11 11111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1111 1 1 v.2 1551 TTGCCAATGCCAATATTGATGTTGTGGATGTCCGTCCATTGATACAAACC 1600 v.l 1601 aaagatggagaaaattacgctacagtqgttqggtacaqtgctttcttaca NIIH i 1 11 1 II II II II 1 1 li 1 1 1 II 1 1 1 II 1 I 1 111 II 1 II 1 ) 1 1 II 1650 1 1 1 1 1 1111II1111 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 Π 1 1 Π 1 1 1 111II Π 111 V.2 1601 AAAGATGGAGAAAATTACGCTACAGTGGTTGGGTACAGTGCTTTCTTACA 1650 v.l 1651 ttgcgagttctttqcttcacctgaqqcaqtcgtgtcctggcagaaqqtqq ι Η π I Π 11 1 1 II Η H 1 H ill III IIIIIIIHI Η Η II II Hill 1700 1 1 1 s 1 1 ι l t 1 1 1 1 1 1 1 l I 1 t ) 1 1 1 1 l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 l-v.2 1651 TTGCGAGTTCTTTGCTTCACCTGAGGCAGTCGTGTCCTGGCAGAAGGTGG 1700 v.l 1701 aagaagtgaaacccctggagggcaggcggtatcatatctatgaaaatggc | II II 1 1 II II 1 II II II 1 II II |l 1 II 1 II 1 II 1 II II II II ]| II II 1 1750 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 111111111 v.2 17 01 AAGAAGTGAAACCCCTGGAGGGCAGGCGGTATCATATCTATGAAAATGGC 1750 243 v. 1 1751 acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg 1 I I I II 1 1 I ! 1 I I 1 1 1 1 1 II 1 I 1 1 1 1 I 1 1 1 I 1 1 1 II ! 1 1 II II II II I I 1 1800 v.2 1751 1 1 1 1 I 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 ACATTGCAGATCAACAGAACCACCGAAGAAGATGCTGGGTCTTACTCATG 1800 v. 1 1801 ttgggtagaaaatgctataggaaaaactgcagtcacagccaatttggata 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 11 1 1 i 1 1 1 1 1 1 1 1 I i 1 1 1 1 1 1 1 i 1 S 1 1850 v.2 1801 1 II 1 I 1 1 I 1 1 11 II 1 1 I 1 1 1 ! 1 ! 1 ! ! I ! 1 I I ! 1 ! I 1 ! 1 1 1 I 1 I I ! I ! 1 1 1 ttgggtagaaaatgctataggaaaaactgcagtcacagccaatttggata 1850 v.1 1851· ttagaaatgctacaaaacttagagtttctcctaagaatcctcgtatcccc 1 1 1 1 I I II II II 1 1 II 1 ) I 1 I 1 I 1 1 1 1 1 I 1 1 1 I 1 I 1 I I I I 1 I 1 1 1 1 1 1 1 1 190 0 v.2 1851 1 1 1 I 1111 ! 1 1 if 1 1 1 I 1 1 1 II I II 1 1 1 1 1 11 11 1 I I 11 1 11 1 II 1 1 1 I 1 TTAGAAATGCTACAAAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCC 1900 v.1 1901 aaattgcatatgcttgaattacattgtgaaagcaaatgtgactcacattt | 1 1 |l It 1 I 1 I 1 1 1 1 1 1 1 1 II 1 ( ! 1 I I I 1 I j 1 1 1 II 1 1 II II 1 1 II 1 1 1 1 1950 v.2 1901 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 i 1 1 1 1 1 AAATTGCATATGCTTGAATTACATTGTGAAAGCAAATGTGACTCACATTT 1950 v.1 1951 gaaacacagtttgaagttgtcctggagtaaagatggaaaagcctttqaaa 1 I I 1 I ] 1 Π 1 I II 1 || I || I I I I || || I I I 11 I 1 I I || I || I 1 I 111 I I I 2000 v.2 1951 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 II 1 1 1 I 1 1 I GAAACACAGTTTGAAGTTGTCCTGGAGTAAAGATGGAGAAGCCTTTGAAA 2000 v. 1 2001 ttaatggcacagaagatggcaggataattattgatggagctaatttgacc 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2050 v.2 2001 111 1 1 II1 1 1 11 1 1 1 1 1 1 1 1 1 1 I 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 I 1 1 1 TTAATGGCACAGAAGATGGCAGGATAATTATTGATGGAGCTAATTTGACC 2050 v.1 2051 atatctaatgtaactttagaggaccaaggtatttactgctgttcagctca II II 1 1 1 I j I II 1 I 1 II 1 I II 1 I 1 1 1 II I 1 I 1 1 1 II 1 I j 1 1 1 1 I 1 1 I I ! 1 2100 v.2 2051 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 ATATCTAATGTAACTTTAGAGGACCAAGGTATTTACTGCTGTTCAGCTCA 2100 v.1 2101 tactgctctagacagtgctgccgatataactcaagtaactgttcfctgatg | I 1 1 1 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 II 1 1 ) 1 1 II 1 1 1 1 1 1 1 II 1 1 1 1 I I 1 1 1 1 2150 v.2 2101 I I 11 1 ! 1 I I 1 II 1 1 1 II II II I 1 1 I 1 1 III 1 I II 1 !II 111 II 1 1 1 11 TACTGCTCTAGACAGTGCTGCCGATATAACTCAAGTAACTGTTCTTGATG 215 0 v. 1 2151 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt 1 1 111 I 11111 1 1 1 1 I 1 1 1 1 I I11111 1 I 111I11 11 1 1 1 1 1 1 1 1 II 1 1 1 2200 v.2 2151 1 1 1 1 1 11 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TTCCGGATCCACCAGAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGT 2200 v. 1 2201 gttcggctgacctgggaagctggagctgaccacaacagcaatattagcga 1 I i II 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 111111111111111 1111 1 1 1 1 1 1 1 1 1 1 1 2250 v.2 2201 I 1 1 II 11 1 1 1 I 1 I 1 I 1 1 ! 1 1 11 1 1 1 11 I 1 11 11 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 GTTCGGCTGACCTGGGAAGCTGGAGCTGACCACAACAGCAATATTAGCGA 2250 v.1 2251 gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg 11 Η 1 HI II I I I II 1 II 1 1 II I } 1 I j I I 1 1 1 j I 1 II I 1 I 1 1 1 1 1 1 1 I I ! 2300 v.2 2251 1 I it 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 i 1 1 1 1 I f 1 1 1 1 1 1 1 1 GTATATTGTTGAATTTGAAGGAAACAAAGAAGAGCCTGGAAGGTGGGAGG 2300 v. 1 2301 aactgaccagagtccaaggaaagaaaaccacagttatcttacctttggct 11 I 1 111 1 1 1 1 1 11 1 1 111 I 11 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 II 1 1 1 1 II 1 1 1 1 2350 v.2 2301 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AACTGACCAGAGTCCAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCT 2350 v.1 2351 ccatttgtgagataccagttcagggtcatagccgtgaacgaagtagggag 1 1 1 1 1 1 l 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2400 v.2 2351 1 1 111 1 it II Ii 1 I It 1 i 1 i i 11 ii I is I I i i 1 1 I I 1 1 I 1 1 1 I II i I I 1 I CCATTTGTGAGATACCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAG 2400 v.1 2401 aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc 1 II I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 111 1 1 1 I 1 1 l 1 1111 I 1 1 1 1 1 1 111 I 1 1 1 1 1 2450 v.2 2401 AAGTCAGCCTAGCCAGCCGTCAGACCATCATGAAACACCACCAGCAGCTC 2450 v.1 2451 cagataggaatccacaaaacataagggttcaagcctctcaacccaaggaa | I 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 I II 1 1 1 J 1 1 1 1 1 I 1 1 1 1 I 1 | 1 I 1 1 I 1 1 II II 2500 v.2 2451 II 1 1 1 1 1 1 1 I 1 1 II 1 1 1 11 II 1 1 I 1 1 1 1. 1 I i 1 I 1 1 II 1 I II 1 1 I ! I 1 II 1 CAGATAGGAATCCACAAAACATAAGGGTTCAAGCCTCTCAACCCAAGGAA 2500 v. 1 2501 atgattataaagtgggagcctttgaaatccatggagcagaatggaccagg 2550 244 fv,.· 2 2501 ATGATTATAAAGIGGGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGG 2550 V.1 2551 cctagagtacagagtgacctggaagccacagggagccccagtggagtggg j i I | I 1 i I | | j I 1 i I I 1 It I I I i 1 I I I 1 1 i I 1 It 1 1 I &#943; 1 | i ) II I 1 ! II 1 2600 v . 2 2551 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 CCTAGAGTACAGAGTGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGG 2600 v.1 2601 aagaagaaacagtcacaaaccacacattqcqgqtqatqacgcctqctgtc II I I I I I | I | I I I | I 1 III 1 I I 1 i 1 I 1 1 III I III 1 || tt|| 1 Ml l| I I 2650 v . 2 2601 I 11111 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 i i I 1 i 1 1 1 1 1 1 1 I 1 I i i i 1 I i Ii1 I 1 I AAGAAGAAACAGTCACAAACCACACATTGCGGGTGATGACGCCTGCTGTC 2650 v.1' 2651 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I IS I 1 1 1 1 II 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 2700 v. 2 2651 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 1 1 1 1 1 1 |.| TATGCCCCTTATGATGTCAAGGTCCAGGCTATCAATCAACTAGGATCTGG 2700 v.1 2701 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata 1 II 1 II 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 2750 v.2 2701 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 II 1 I II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GCCTGACCCTCAGTCAGTGACTCTCTATTCTGGAGAAGACTATCCTGATA 2750 v.1 2751 cagctccagtgatccatggggtggacgttataaacagtacattagttaaa I I 1 1 1 I 1 1 1 1 1 I 1 1 1 1 IS 1 II 1 1 1 1 1 ! 1 1 ! 1 1 I 1 1 1 1 1 1 1 1 H 1 1 1 1 I 1 1 2800 v.2 2751 I 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 i 1 1 1 1 1 I I 1 CAGCTCCAGTGATCCATGGGGTGGACGTTATAAACAGTACATTAGTTAAA 2800 v.1 2801 gttacctggtcaacagttccaaaggacagagtacatggacgtctqaaaqq 111 H 1 INI II 1 1 III 1 1 1 11 II III III II 1 1 1 II II III Hill III 2850 v.2 2801 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 j 1 1 1 - GTTACCTGGTCAACAGTTCCAAAGGACAGAGTACATGGACGTCTGAAAGG 2850 v. 1 2851 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac 11111111111111 I 111111II11 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 2900 v.2 2851 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 ! 1 1 CTATCAGATAAATTGGTGGAAAACAAAAAGTCTGTTGGATGGAAGAACAC 2900 v.1 2901 atcccaaagaagtgaacattctaagattttcaggacaaagaaactctgga II 1 II I 1 1 1 1 I I 1 1 1 I 1 I 1 II I I I 1 1 I 1 J 1 1 I I I 1 I I I 1 I I I I I I I I I I 1 2 95 0 v.2 2901 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATCCCAAAGAAGTGAACATTCTAAGATTTTCAGGACAAAGAAACTCTGGA 2950 v.1 2951 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 H II 1 1 1 1 1 1 II 1 3000 v.2 2951 t 1 I I I 1 1 1 1 I 1 I I 1 ! 1 I 1 1 l 1 1 1 1 I! 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATGGTTCCTTCCTTAGATGCCTTTAGTGAATTTCATTTAACAGTCTTAGC 3000 v.1 3001 ctataactctaaaggagctggtcctgaaagtgagccttatatatttcaaa 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l 1 1 1 I 1 1 1 1 1 1 1 3050 v. 2 3001 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 CTATAACTCTAAAGGAGCTGGTCCTGAAAGTGAGCCTTATATATTTCAAA 3050 v. 1 3051 caccagaaggagtacctgaacagccaact-tttctaaaggtca-tcaaagtt 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 3100 v.2 3051 N 1 1 1 It 1 1 II 1 II 1 1 II II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I CACCAGAAGGAGTACCTGAACAGCCAACTTTTCTAAAGGTCATCAAAGTT 3100 v.1 3101 gataaagacactgccactttatcttggggactacctaagaaattaaatgg 1 1 1 1 1 1 ! 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 3150 v.2 3101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GATAAAGACACTGCCACTTTATCTTGGGGACTACCTAAGAAATTAAATGG 3150 v.1 3151 aaacttaactggctatcttttgcaatatcagataataaatgacacctacg < I 1 ! 1 1 1 ! 1 1 1 I 1 I 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 3200 v.2 3151 i 1 &#943; i i i ii1 I 1 I II I 1 II i I I II 1 11111 1 111 11 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 AAACTTAACTGGCTATCTTTTGCAATATCAGATAATAAATGACACCTACG 3200 v.1 3201 agattggagaattaaatgatattaacattacaactccatcaaagcccagc | 1 I I 1 I I I 1 I 1 I I 1 || i 1 | 1 I I I II I 1 1 1 I 1 I i I I I I 1 1 I I I I I I i j I I I 3250 v.2 3201 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AGATTGGAGAATTAAATGATATTAACATTACAACTCCATCAAAGCCCAGC 3250 v.1 3251 tggcacctctcaaacctgaatgcaactaccaagtacaaattctacttgag 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3300 V . 2 3251 I 1 I I 1 1 1 1 1 1 1 I 1 1 I I 1 II 11 II 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 I I 1 1 1 1 1 I TGGCACCTCTCAAACCTGAATGCAACTACCAAGTACAAATTCTACTTGAG 3300 v.1 3301 ggcttgcacttcacagggctgtggaaaaccgatcacggaggaaagctcca 3350 245

I v.2 3301 GGCTTGCACTTCACAGGGCTGTGGAAAACCGATCACGGAGGAAAGCTCCA 3350 v.l 3351 ccttaggagaagggagtaaaggtatcgggaagatatcaggagtaaatctt 1 I I | 1 1 If ! I 1 | ] J ! 3400 Ι &amp;#943; 1 1 l &amp;#943; Π ! ) Η 1 &amp;#943; &amp;#943; v.2 3351 CCTTAGGAGAAGGGA----------------------------------- 3365 v.l 3401 actcaaaagactcacccaatagaggtatttgagccgggagctgaacatat 3450 v.2 3366-------------------------------------------------- 3365 v.l 3451 agttcgcctaatgactaagaattggggcgataacgatagcatttttcaag 3500 v.2 3366 -------------------------------------------------- 3365 v.l 3501 atgtaattgagacaagagggagagaatatgctggtttatatgatgacatc I 1 II II I I I 1 1 1 1 1 II 1 I 1 1 1 1 11 1 1 3550 1 i 1 I 1 1 I 1 1 1 il 1 1 1 1 1 H I 1 1 1 I II v.2 3 3 66 ------------------------AATATGCTGGTTTATATGATGACATC 3391 v.l 3551 tccactcaaggctggtttattggactgatgtgtgcgattgctcttctcac | I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 11 1 1 1 I j 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 I II 1.1 1 II i 3600 1 1 l 1 1 1 J 1 1 1 1 1 1 1 1 i I I 1 1 I 1 t 1 1 1 1 1 1 I 1 1 1 I 1 1 1 S 1 I 1 I ! 1 1 ! 1 1 ι &amp;#943; v.2 3392 TCCACTCAAGGCTGGTTTATTGGACTGATGTGTGCGATTGCTCTTCTCAC 3441 v.l 3601 act/ictattattaactgtttgctttgtgaagaggaatagaggtggaaagt 111111111111! il 1IIII11! II111111II il 1.1 II 1II Ii il 1111 v.2 3442 ACTACTATTATTAACTGTTTGCTTTGTGAAGAGGAATAGAGGTGGAAAGT 3650 3491 v.l 3651 actcagttaaagaaaaggaagatttgcafcccagacccagaaattcagtca 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 3700 1 I i 1 E 1 1 ι I 1 I ) 1 1 I 1 1 t 1 1 t 1 1 I I 1 1 I 1 1 1 1 t 1 1 1 I 1 1 i i 1 I 1 ! 1 1 I 1 s v.2 3492 ACTCAGTTAAAGAAAAGGAAGATTTGCATCCAGACCCAGAAATTCAGTCA 3541 v.l 3701 gtaaaagatgaaacctttggtgaatacagtgacagtgatgaaaagcctct 1 1 1 1 1 1 1 1 1 1 ! I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3750 1 1 1 11 1 11 1 1 i 1 I 1 1 1 1 1 1 1 111 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 v.2 3542 GTAAAAGATGAAACCTTTGGTGAATACAGTGACAGTGATGAAAAGCCTGT 3591 v.l 3751 caaagqaagccttcqqtcccttaatagggatatgcagcctactgaaagtg 1 1 1 1 II I II 1 1 1 1 II II 1 HI I II 1 111 II111II Ml Ml 1II11 Mil 3800 ι I 1 ! J 1 ι 1 1 1 1 &amp;#943; ι 1 II I 1 1 1 1 1 I I I I 1 1 1 1 1 1 1 l &amp;#943; 1 t II 1 1 It l-l ι 1 1 1 I v.2 3592 CAAAGGAAGCCTTCGGTCCCTTAA.TAGGGATATGCAGCCTACTGAAAGTG 3641 v.l 3801 ctgacaqcttagtcqaatacggagagggagaccatggtctcttcagtgaa Η II UN 11 Η 1111! 11II1! II1 Η Η Η 11IIΗ IIII!! 11 Η 11 V.2 3642 CTGACAGCTTAGTCGAATACGGAGAGGGAGACCATGGTCTCTTCAGTGAA 3850 3691 v.l 3851 gatggatcatttattggtgcctacgctggatctaaggaqaagggatctgt 1 1 III 1 1 1 1 1 1 1 1 1 II III 1II 1 II 1 II 111 1 1 1IIII II 11 II 1 II III 3900 1 1 1 1 I 1 I I &amp;#943; Η 1 ι 1 1 i S 1 i 1 I 1 I i ι 1 1 1 Η I! 1 1 Π 1 &amp;#943; 1 1 1 { 1 1 1 1 I 1 1 I V.2 3692 GATGGATCATTTATTGGTGCCTACGCTGGATCTAAGGAGAAGGGATCTGT 3741 v.l 3901 tgaaagcaatggaagttctacagcaacttttccccttcgggcataaacac | II I 1 1 1 II 1 1 I 1 I I 1 1 1 11 I 1 1 1 1 1 | | 1 1 1 1 1 1 1 1 1 1 1 1 I 1 11 1 1 I 1 II 3950 1 1 I 1 1 1 1 1 1 1 1 ι 1 I i I 1 I 1 II 1 1 I I I 1 I 1 I l &amp;#943; 1 1 { 1 1 1 I 1 I 1 1 il 1 1 1 1 1 v.2 3742 TGAAAGCAATGGAAGTTCTACAGCAACTTTTCCCCTTCGGGCATAAACAC 3791 v.l 3951 aacatatgtaagcaacgctactggttcaccccaaccttccatatttatct 1 1 1 I 1 I 1 1 1 11 1 I 1 1 1 1 1 1 111 1T1 1 1 1 1 1 II 1 II 1 1 1 i 1 1 1 1 II 1 1 II 1 4000 ' 1 1 I ι t I 1 I 1 1 ι 1 t 1 I 1 1 I I &amp;#943; ι H 1 1 1 1 I i i ! I I i 1 I i 1 1 1 1 1 1 1 1 1 I i 1 v.2 3 792 AACATATGTAAGCAACGCTACTGGTTCACCCCAACCTTCCATATTTATCT ’ 3841 v.l 4001 gttcaaaggagcaagaactttcatataggaatagaaacatgctggccgaa I II ι ι ι ι ι ι ι i ii iiιι) ι ιΜ 1II 1 Η 11II11II111 1 II II II 1 II 1 4050 II II 1 11 II 1 I 1 1 I 1 1 1 1 1 I 1 I 1 I N 1 1II11 II 1 1 II 11 1 1 1 II 1 1 II ι v.2 3842 GTTCAAAGGAGCAAGAACTTTCATATAGGAATAGAAACATGCTGGCCGAA 3891 v.l 4051 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac 1 1 ! 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 II 1 1 1 ! 1 1 1 I 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 4100 1 1 11 1 1 1 11 1 1 1 1 1 ! 1 1 1 1 1i1 1 1 1 1 i II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II v.2 3892 GATTTCATCCAGAAGTCAACATCCTGCAATTATGTTGAAAAGAGTAGTAC 3941 246 4101 tttcttcaaaatataaaatgccaagcacttcaggcctatgttttgcttat I I I 11 I I II I 1 I 1 1 I I II 1 I 1 II I 1 1 I 1 I 1 1 1 1 ] I I I 1 1 I 1 I 1 1 j 1 I 1 1 I 4150 v.2 3942 1 1 I 1 1 1 11 I 1 1 1 1 1111 1 1 I 1 1 1 I 1 1 11 l1 11 I 1 1 1 1 1 1 11 1 1 1 1 t 1 1 1 1 TTTCTTCAAAATATAAAATGCCAAGCACTTCAGGCCTATGTTTTGCTTAT 3991 v.l 4151 attgttttcaggtgctcaaaatgcaaaacacaaaacaaatcctgcattta 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 i 1 1 1 1 I 1 1 1 1 1 i 1 1 i 1 I 1 1 1 1 1 1 1 1 1 i 1 1 1 11 1 1 1 4200 v.2 3992 1 1 1 l Η 1 1 1 1 H 1 I I i I I 1 I I 1 I 1 1 I 1 I 1 1 1 l 1 t ι 1 1 1 ! 1 I I l ι 1 1 1 1 1 1 ATTGTTTTCAGGTGCTCAAAATGCAAAAGACAAAAGAAATCCTGCATTTA 4041 v.l 4201 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg I I 1 1 1| I I I I II I I II I I I I 1 1 1 II i I I 1 I j I 11 I 1 II 1 II II 1 I 1! I 1 I 4250 v.2 4042 j } 1 I 1 1 j 1 I I 1 i i II j 1 I I i 1 II 1 1 i I ! 1 1 1 1 l i t 1 I 1 1 1 1 1 l ι I ι 1 1 I 1 GATACACCTCAACTAAATCCAAkGTCCCCATTCAGTATATTCCATATTTG 4091 v.l 4251 cctgattttactattcggtgtgtttgcafcagatgttgctacttggtgggt 1 1 1 11 1 1 1 1 1 1 1 I 1 1 ! 1 1 1 1 1 1 II 1 1 1 1 1 11 1 1 111 1 1 1 1 I 1 1 1 1 1 1 11 1 4300 v.2 4092 1 1 1 1 i 1 i 1 1 ι ι Ι ι 1 1 ι i f t ( 1 ι ι ι ι 1 1 1 ! &amp;#943; I ι 1 1 , 1 I 1 1 1 ! 1 ι ι I 1 ι 1 ι I CCTGATTTTACTATTCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGT 4141 v.l 4301 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga 1 1 1 1 1 1 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 4350 ' v.2 4142 Π ι I &amp;#943; &amp;#943; ! Η Η .1 II 1 I 11 1 1 ι &amp;#943; 1 I 1 I J j ( ) &amp;#943; Π H ! 1 I J 1 H 1 I 1 &amp;#943; I J 1 1 TTTTCTCCGTATGCACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGA 4191 v.l 4351 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa I 1 II I II 1 I I 1 I I I I 1 I I 1 1 I I 1 I 1 I 1 I 1 1 1 1 1 I 1 1 I 1 I I I i I 1 1 I I 1 1 1 4400 v.2 4192 ι I I ι 1 1 1 I 1 1 1 I 1 1 1 ! 1 1 I I 1 I ( 1 1 1 1 1 1 I I ’ ι I i 1 1 1 t 1 1 1 ι ι 1 I 1 1 i I CTTTGCTTCACTACAGGTTAAAAGACCATAAGCAAACTGGTTATTTAAAA 4241 V.l 4401 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac 1! I! Η II (111! IIII! 1IIIIIIII1!111II11Ii!Η II111 Η II TGTAAAAAGGAATATGAAAGTCTTATTAAAACACTTCATTGAAAATATAC 4450 V.2 4242 4291 v.l 4451 agtctaaattfcattatttaaattttactagcaaaagtcttaggtgaacaa 1 I Η Η 1 1 1 i 1 i i i i ii i 1 i i i i i i i i ii &amp;#943; i i &amp;#943; &amp;#943; i i &amp;#943; i i i 1 1 1 1 i i 1 I 1 I 4500 v.2 4292 1 ι I 1 I i 1 I 1 1 1 I 1 &amp;#943; ι 1 1 1 1 ! I 1 1 1 1 1 1 1 I 1 I Η ι I 1 1 I ) 1 1 I 1 ι 1 1 1 I 1 1 AGTCTAAATTTATTATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAA 4341 v.l 4501 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa I 1 1 1 1 I I I 1 1 I II I 1 I 1 I 1 1 1 1 I 1 1 I i 1 1 1 I I 1 I 1 I 1 1 1 1 1 1 I I 1 1 1 I -i j 4550 v.2 4342 &amp;#943; 1 1 I 1 ! 1 I 1 1 1 1 1 I 1 1 1 1 1 I 1 ι I U i 1 1 I I ι I 1 ι i 1 ! 1 t 1 1 1 1 1 1 ι &amp;#943; &amp;#943; i I TCAACTAGTATTTGTTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAA 4391 v.l 4551 acagaagtatacgtttttcagtttcaacatgaatttttttatttctgtca Ii 1II11111IIIIII Η 1! 11 Η I! Η Η Η 11111111II111! 1! 11 4600 v.2 4392 ACAGAAGTATACGTTTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCA 4441 v.l 4501 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct 11111 m 1111 η ι m ι u ι i-ι n u 11 u ι u 111 ιι η 11 h u n GTTATGACATCCACgAGCATCACTTTTTGTGTCTGTTTTTTTTTTTTTCT 4650 v.2 4442 4491 v.l 4651 tggactaaattcaactqcatgqaagcggtggtcagaaggttgttttatac Π Π Π Η Η Π 1 1 1 Π II INI II II II II 1 i in nil HI II 1 Η Π 4700 v.2 4492 1 1 ! i 1 1 I ! 1 I 1 1 1 ! 1 ! ι 1 ! 1 l ι 1 I 1 1 1 1 1 1 I I I 1 I 1 1 1 1 1 1 &amp;#943; Ι ι ι 1 1 &amp;#943; 1 I TGGACTAAATTCAACTGCATGGAAGCGGTGGTCAGAAGGTTGTTTTATAC 4541 V.l 4701 gagaacaggcagaaagtgcccattgttcaggattctaatagctacatcta !| II II 1 II 1 ! I 1 i 1 ! I I 1 I I I ! I 1 I I II I || II I ! I 11 II I 1 I I II 1 1 1 4750 v.2 4542 II 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 111 I 11 1 ! 1 1 I 1 1 1 II 1 1 ! i l 1 1 i i 1 ι 1 1 ι GAGAACAGGCAGAAAGTGCCCATTGTTCAGGATTCTAATAGCTACATCTA 4591 V.l 4751 cttaatatcttcatttctaaattgactgcttttacctttttctcatgttt i 1]11111II1II11! Π 111111!1II11Ii11111III Π I111II11 4800 V.2 4592 CTTAATATCTTCATTTCTAAATTGACTGCTTTTACCTTTTTCTCATGTTT 4641 v.l 4801 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg Π Π Π II 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1IIII II 1 II II 1 1 1 1 1 1 1 1 i 1 1 4850 v.2 4642 I 1 ! ! 1 1 ι 1 l ι ι I I I I I I j I I I j I I ! I 1 1 1 1 » I » 1 1 » I ! I 1 1 1 1 ! I 1 1 I ! 1 ATATAATGGTATGCTTGCATATATTTCATGAATACATTGTACATATTATG 4691 v.l 4851 ttaatatttacacaatttaaaatatagatgtgttttattttgaagtgaga 1 1 I 1 I I 1 I 1 1 1 1 I 1 1 1 1 1 1 1 111 i 1 1 I I 11 i 1 II 1 I 1 ! 1 ! 1 1 1 I 1 1 1 1 i 1 4900 v.2 4692 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TTAATATTTACACAATTTAAAATATAGATGTGTTTTATTTTGAAGTGAGA' 4741 247 ‘ v.'l v.2 v.1 v.2 v. 1 v.2 v.1 v.2 v.1 v.2 v.1 v.2 v. 1 v.2 v.1 v.2 v.1 v.2 v.1 - v.2 v.1 v.2 v.1 v.2 v.1 V.2 v.1 v.2 v.1 v.2 4901 4742 4951 4792 5001 4842 5051 4892 5101 4942 5151 4992 5201 5042 5251 5092 5301 5142 5351 5192 5401 5242 5451 5292 5501 5342 5551 5392 5601 5442 V.1 5651 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat

III II1 it III11IIIIII(I I! 11111II111IIfii I Ii 1111! 11II

AAATGAACATTAACAGGCATGTTTGTACAGCTAGAATATATTAGTAAGAT actgtttttcgtcattccagagctacaactaataacacgaggttccaaag 1111 i 111111111111111111111111111111 i 11111111111111

ACTGTTTTTCGTCATTCCAGAGCTACAACTAATAACACGAGGTTCCAAAG cfcgaagactttgtataaagtatttgggttttgttcttgtattgctttctt 11II111111111111! III11111111IIIIII!1111i 11II111II1

CTGAAGACTTTGTATAAAGTATTTGGGTTTTGTTCTTGTATTGCTTTCTT tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc 1111II1111111 H 11111II 111 11! i HI 11II1111111 Π 1111 i

TCAACAGTTTCAAAATAAAATATCATAcAAATATTGAGGGAAATGTTTTC atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc HI 1111 II 1 H 1111 i 11111III Η 111 Π 1111 f 11 Η Π ! i 11 i 11

ATATTTTTCAAAATAGGTTTTTATTGTTGAATGTACATCTACCCCAGCCC ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta II11IIII11II11111II1III11II I!1111111111111111111&amp;#938;Ι

CTCAAAAGAAAAACTGTTTACATAGAAATTCCTACACATACGTTTGCGTA tatgttattttaaacatctttgtggtgagaattttttccccgatattctc cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt IIIIIIIIIIIIII111II11II111II11II111111II11IIIII111

CTTCTGTCAAAGTCAGAACAAATTCAGGGAATTTATTTTCTGGCAGTT.GT gctccagtccttttaaaattgtacatgaacatgttttagaaacaatatgg IIIi 111II11111II1111IIII11111IIII11II11II11111II11

GCTCCAGTCCTTTTAAAATTGTACATGAACATGTTTTAGAAACAATATGG

I aggatqatqcatacs-tgtcqqtcaaqttcaqcqctcqacattttat-gqaa 1111111111111111111111111111111111111111111 i 111111

AGGATGATGCATACATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAA agattt'ttttaaccttaccacgaaatacttaactactgtttaagtgaatt

II Η 11 Η Η Η I Η Η Η Π Η 11II H i I &amp;#943; 111 i 1111II Η Η Η H

AGATTTTTTTAACCTTACCACGAAATACTTAACTACTGTTTAAGTGAATT gacttatttcactttagtttttgaactgtgattattggtatactgttata

11111111II11IIIIII111 (11111 i IIIII11II1111111IIIIII

GACTTATTTCACTTTAGTTTTTGAACTGTGATTATTGGTATACTGTTATA tcctcaacttggatttatggtaaccccttttagttcatggagaccaaaat lllillllllllllllllllllllllllllllllllllllllllllllll

TCCTCAACTTGGATTTATGGTAACCCCTTtTAGTTCATGGAGACCAAAAT ttggggtatttataatagtcagcgcaggaatgcacatggaatatctactt IIIIII! 111111II111111111II11111111II11111111111111

TTGGGGTATTTATAATAGTCAGCGCAGGAATGCACATGGAATATCTACTT gtccttttgaacctcacgagtcatccagaatgtatagacaggaaaagcat

Ii I H I 11 11II111111111II11IIIIII11II11 IS 11II111II H

GTCCTTTTGAACCTCACGAGTCATCCAGAATGTATAGACAGGAAAAGCAT gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg 4950 4791 5000 4841 5050 4891 5100 4941 5150 4991 5200 5041 5250 5091 5300 5141 5350 5191 5400 5241 5450 52.91 5500 5341 5550 5391 5600 5441 5650 5491 5700 248 V. 2 5492 GTCTTATTTAAAACTGTAATTTATGGGCTCAGGATCTGACCGCAGTCCCG 5541 v.1 5701 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga II II I) I 11 II I 1 |1 II II 1 1 I 1 11 II j II I II II II I 1 j 1 1 ] 1 1 1 It II 5750 ν. 2 5542 t 1 ! i 1 I I 1 &#943; I i I H I ! f i 1 1 1 I 1 1 I I l i &#943; i &#943; E I I ! &#943; i 1 Η H U U Η i &#943; ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga 5591 v.1 5751 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc i II 1 1 1 I 1 1 I 1 1 II I 1 1 1 1 II 1 II I 1 I 1 1 1 II II ( j 1 1 1 1 j 1 1 1 II 1 1 5800 v.2 5592 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I I &#943; I s 1 f 1 I 1 I II 1 I 1 1 1 111 I II i I 1 1 I H I 1 1 H ATGTGAGGATGTAGACATCCATCAGTGCAACTCGAGCTGCATCCTCCTCC 5641 v.1 5801 gatttctaaggctccagttttctggagggacagtcatcatgttttgattt l| I 1 1 1 I I 1 1 1 1 1 1 1 1 , 1 I 1 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 II 1 II 1 1 1 5850 v.2 5642 I I j 1 1 1 1 I I 1 l I I 1 I 1 I 1 II 1 II I 1 1 1 1 1 1 I I 1 I I 1 11 1 11 1 1 I I I i 11 t GATTTCTAAGGcTCCAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTT 5691 v.1 5851 atctgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 II 1 1 II 1 1 1 1 1 1 1 1 1 5900 v.2 5692 f &#943; II Η &#943; I &#943; &#943; &#943; 1 1 I I N E &#943; I 1 it Η Η &#943; Η &#943; 1 j Π Π J N 1 J 1 Η 1 I 1 J i ATCTGGGAGAAAACTGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGA 5741 v.1 5901 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcag | I II II I I j I I 1 1 1 1 1 11 1 1 1 II 1 i 1 1 1 1 1 II 1 j 1 1 1 1 1 1 I 1 1 .| II 1 1 ) 1 5950 v.2 5742 I I ! 1 1 1 1 1 1 I 1 ! 1 1 I 1 1 1 i 1 1 1 I 1 1 H l &#943; 1 &#943; &#943; &#943; &#943; 11 1 ! ι 1 ( I ! 1 1 1 i 1 &#943; I CGTTCGAGCTTAGTTCTGGTGTTATTCTGTCTCCTCTTCTTTGTCATCAG 5791 v.1 5 951 ccaaaacgtggtttttaaagagagtcatgcaggttagaaataatgtcaaa | 1 1 ,| 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 [ 1 1 1 1 1 I I 1 1 1 1 1 II 1 6000 v.2 5792 &#943; &#943; ! I I i i 1 I I 1 > 1 1 I 1 i I 1 1 1 i 1 1 t 1 1 1 I i 1 1 { i i 1 &#943; i I 1 1 i 1 I 1 1 1 1 1 1 CCAAAACGTGGTTTTTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAA 5841 v. 1 6001 aatatttaggaatttaataacctttaagtcagaaactaaaacaaatactg | 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 II I 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 6050 v.2 5842 1 1 1 &#943; j 1 I I 1 i 1 i 1 &#943; 1 1 1 1 1 ι 1 &#943; 1 1 1 J 1 1 1 1 1 1 1 1 1 1 I I 1 j I 1 1 I 1 ] 1 1 1 1 AATATTTAGGAATTTAATAACCTTTAAGTCAGAAACTAAAACAAATACTG 5891 v.1 6051 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat | I I I I II I I I 1 1 1 1 1 1 j 1 1 1 1 1 1 1 1 1 1 II 1 1 I 1 1 1 1 1 1 ) 1 1 1 1 1 1 1 j 1 1 1 6100 v.2 5892 &#943; f ( 1 1 I U I 1 Η 1 Π π 1 1 N 1 It Π 1 1 i H 1 1 ( 1 I Π II 1 1 1 Ν &#943; 1 I 1 1 AAATATTAGCTCTTCCTACACTTCGTGTTCCCCTTTAGCTGCCTGAAAAT 5941 v.1 6101 caagattgctcctactcagatcttctgagtggctaaaacttatggatatg | 1 1 1 1 1 1 1 II I 1 II 11 1 II II 1' 1 II 1 II 1 II 1 !| 1 1 1 II 1 1 1 1 1 I 1 II II 6150 v.2 5942 I 1 1 U 1 ι 1 U I I I II 1 1 1 1 I I I 1 1 II U 1 1 1 U U 1 1 1 t ι Η 1 1 1 H I H CAAGATTGCTCCTaCTCAGATCTTCTGAGTGGCTAAAACTTATGGATATG 5991 v.1 6151 aaaaatgagattgaatgatgactatgctttgctatcattgttacctttcc II II I 1 1 1 II 1 1 1 1 1 I II 1' II 1 1 1 1 1 1 1 1 1 1 ] 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 6200 v.2 5992 Il 1 l 1 H II l 11 I 11 1 1 1 I 1 Η II II H l Η Π 1 1 1 1 1 Η 1 1 1 I 1 I 1. ι II AAAAATGAGATTGAATGATGACTATGCTTTGCTATCATTGTTACCTTTCC 6041 v.1 6201 tcaatacfcatttggcaactactgagactcttcagcacaaaaggaatagat 1 1 1 1 1 1 t t 1 1 1 t 1 1 1 1 1 I 1 1 1 1 t I I 1 1 1 I 1 i 1 11 t 1 1 1 1 1 I It 1 1 1 1 1 I 1 6250 v.2 6042 Η H 1 I Η 1 j J I 1 11 11 Π 1 1 Η Η 11 11 1 1 i 1 I 1 1 ι 1 i II I 1 1 1 t 1 1 1 1 TCAATACTATTTGGCAACTACTGGGACTGTTCAGCACAAAAGGAATAGAT 6091 v.1 6251 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt ! I 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 11111i111M 1 1 1 1 1 i i!111 Iil1 6300 v.2 6092 Η I I 1 i 1 1 ! i i 1 1 1 1 i i H i I ( 1 1 U 1 1 1 &#943; 1 i 1 I I 1 i ) &#943; H t Η 1 i H 2 ) CTATGATTGACCCTGATTTTAATTGTGAAATTATATGATTCATATATTTT 6141 v.1 6301 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg 1 1 111 I I 1 I 11i111 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 II 111 II11 I I 1 1 1 1 1 1 1 1 6350 v.2 6142 1 I 1 I 1i I 1 I I 1 1 I 1 1 1 1 1 1 I 1 1 1 I I 1 I ! II 1 1 I 1 I 1 1 I ! I 1 1 ! ! II 1 I II ATGAATCAGAATAACCTTCAAATAAAATAAATCTAAGTCGGTTAAAATGG 6191 v.1 6351 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa 1 1 1 11111111!!! 1 1 1 1 1 1 1 1111 1 11 1 1 > 1 111111 I 1 1 1 1 1 I 1 1 1 1 1 6400 v.2 6192 I I 1 1 II 11 I i II 1 1 I Η I 1 II I I II I 11 { I s 1 1 i 11 1 11 | 1 1 1 1 1 I 1 1 II ATTTCATGATTTTCCCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAA 6241 v.1 6401 tggtaafctataaattggtgatgcttgtttgcaaattgcccactcgtgata H ! m H 1 HI))!) 111 m 1) 1 Η 1! Ill 1H i Η 1111 Π i Η Η 1 6450 v . 2 62^2 TGGTAATTATAAATTGGTGATGCTTGTTTGCAAATTGCCCACTCGTGATA 6291 v-l 6451 agtcaacagccaatafcttaaaactttgttcgttactggctttaccctaac 6500 249 v.2 6292 v.l 6501 v.2 6342 v.l 5551 v.2 6392 v.l 66 01 v.2 6442 v.l 5651 v.2 6492 V. 1 6701 v.2 6542 v.l 6751 v.2 6592 v.l 6801 v.2 6642 v.l 6851 v. 2 5692 v.l 6901 V.2 6742 v.l 6951 v.2 6792 v. 1 7001 v.2 6842 v.l 7051 v.2 6892 v.l 7101 v.2 6942 v. 1 7151 v.2 6992 v.l 7201 v.2 7042

AGTCAACAGCCAATATTTAAAACTTTGTTCGTTACTGGCTTTACCCTAAC tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag ΠΗΠΠΠΗΠΠΠΠΗΠΠΠΠΠΠΙΠΠΗ HUH!!!

TTTCTCTAGTCTACTGTCAATATCATTTTAATGTAATTGATTGTATATAG tctcaagaatggttggtgggcatgagttcctagaqaactgtccaagggtt 11! I il IIIIHI! Il I! III11.) 1111 (I III Π I 11II11111! I H 1

TCTCAAGAATGGTTGGTGGGCATGAGTTCCTAGAGAACTGTCCAAGGGTT gggaaaatccaaattctcttcctggctccagcactgattttgtacataaa

II Π IIIII ΠII Π Π IIII111 Π II Π IIΗ II Π 11 Π I Π Π Π I

GGGAAAATCCAAATTCTCTTCCTGGcTCCAGCACTGATTTTGTACATAAA cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa 11II11 Π Η 111Π 111111II11! 1111.11111111II! 1111 i 1111

CATTAGGCAGGTTGCTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAA gtgctaataataatctcagttaccttatctttgtcacagggtgttctttt UUiMiMTiiiCTUiUUiHIUUlUUUUUU'il-iii'i ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc

II1111IIIII I!I i i 1111IIIil1II11111II1111 il fl 11111II

TTATGAAGAAAAATTTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTC ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc

11111II11II11 III IIII11IIII1111111II111111! 111111II

ATAAGCAAACCTTTAACTAATTATGTATCTGAAAGTCACCCCCACATACC aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca ΙΗΠΙΠΗΗΠΠΠΗΠΙΠΙΠΠΙΗΠΗΗΠΠΠΠΠΙ

AACTCAACTTTTTTCCTGTGAACACATAAATATATTTTTATAGAAAAACA aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat ΠΠΙΠΙΠΠΠΗΠΠΠΗΠΠΠΗΗΙΗΙΠΠΗΠΠΠ

AATCTACATAAAATAAATCTACTGTTTAGTGAGCAGTATGAcTTGTACAT gccattgaaaattattaatcagaagaaaattaaqcaqggtctttgctata 1111 U 11IIIIIIII111IIII11 H 111 III &amp;#938;ΙΙ&amp;#938;ΙIIII1111II11

GCCATTGAAAATTATTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATA caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga II111 Η IIIIII1111 II 111II11III Η Η 11111IIII11111111

CAAAAGTGTTTTCCACTAATTTTGCATGCGTATTTATAAGAAAAATGTGA atttggtggttttattctatcggtataaaggcatcgatattttagatgca III II II IIIIIII Π II Π II IIIIIIII Π II 11 IIII I) IIIIII11

ATTTGGTGGTTTTATTCTATCGGTATAAAGGCATcGATATTTTAGATGCA cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca

Π Π 111111 Π Π Π IIIIIIII1111 Π I! 111! 1 Π 11 Π II11 Π I

CCCGTGTTTGTAAAAATGTAGAGCACAATGGAATTATGCTGGAAGTCTCA aataatatttttttcctattttatactcatggaagagataagctaaagag ΠΠ1ΠΠΙΗΗΠΠΗΗΠΠΗΠΗΗΠΙΠΠΠΠΠΠΙ

AATAATATTTTTTTCCTATTTTATACTCATGGAAGAGATAAGCTAAAGAG gggacaataatgagaaatgttggtgtgcttttctaagcatttaaaacata IIIIIHIHHIIIinillllllllllHIIIIIIlllllinillll

GGGACAATAATGAGAAATGTTGGTGTGCTTTTCTAAGCATTTAAAACATA 6341 6550 63 91 6600 6441 6650 6491 6700 6541 6750 6591 6800 6641 6850 6691 6900 6741 6950 6791 7000 6841 7050 6891 7100 6941 7150 6991 7200 7041 7250 7091 250 .Λ-1 7251 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc I 1 I II 1 1 1 I 1 I ! I 1 1 1 1 1 1 I 1 1 I 1 I 1 1 I 1 1 1 1 1 || 1 1 I I II 1 I 1 j II i 1 I 7300 v.2 7092 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 i i 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 ATTGCCAATTGAAACCCTAAATATGTTTACATACCATTAAGATATGATTC 7141 v.l 7301 atgtaacaatgttaaattaattataatgggattgggtttgttatctgtgg 1 1 1 I 1 ) I 1 1 ) I I 1 1 1 II 1 I 1 1 I II 1 1 1 1 1 1 1 1 1 1 1 1 t| 1 1 1 I 1 II 1 1 I 1 1 7350 v.2 7142 ] 1 1 H U 1 N U Η 1 &amp;#943; i 1 ) i ! 1 1 ! Η H i I 1 1 I i ι 1 i i ! S i 1 ! 1 i i 1 I H atgtaacaatgttaaattaattatamggqattgggtttgttatctgtgg 7191 v.l 7351 tagtatatatcctagtgttcctatagtgaaataagtagggttcagccaaa 1 1 1 1 1 1 1111!11 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1111 I 11 1 1 1 1 1 1 7400 v.2 7192 ι J I ι I I Η I ι ι ι ι Η 1 i 1 I I I 1 1 1 1 I I 1 &amp;#943; 1 ι 1 I 1 1 Η I 1 1 1 I It 1 Η 1 11 TAGTATATATC CTAGTGTTCCTATAGTGAAATAAGTAGGGTTCAGC CAAA 7241 v.l 7401 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7450 v.2 7242 I 1 1 &amp;#943; | 1 1 1 I 1 1 1 1 1 1 I I I 1 1 I I 1 t I I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 t I 1 II 1 1 &amp;#943; 1 ι GCTTTCTTTGTTTTGTACCTTAAATTGTTCGATTACGTCATCAAAAGAGA 7291 v.l 7451 tqaaaqgtatgtagaacaggttcacgtgattacctttttcttttggcttg 11111II11111111111111 III 11111111111 III 111111111111 7500 v.2 7292 TGAAAGGTATGTAGAACAGGTTCACGTGATTACCTTTTTCTTTTGGCTTG 7341 v.l 7501 gattaatattcatagtagaactttataaaacgtgtttgtattgtaggtgg II I I 1 1 I I 1 I I I 1 1 I I I 1 I I I 1 1 II I I I 1 1 1 I I I II 1 1 1 1 I I 1 I I I I 1 I 1 7550 V.2 7342 1 1 II 1 I 1 1 1 1 I 1 1 1111111111 I 1111111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11111 GATTAATATTCATAGTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGG 7391 v.l 7551 tgtttgtattatgcttatgactatgtatggtttgaaaatattttcattat I I II 1 II II 1 1 I 1 II 1 II 1 II I I II ] 1 I j 1 1 1 I 1 1 1 I 1 I 1 1 I 1 1 1 1 1 1 1 1 7600 v.2 7392 1 1 1 I 1 J 1 1 1 1 1 &amp;#943; I 1 ι I 1 I ι U 1 1 I 1 ι l &amp;#943; &amp;#943; l ι 1 1 I i { 1 1 I! I I J I I 11 I II TGTTTGTATTATGCTTATGACTATGTATGGTTTGAAAATATTTTCATTAT 7441 v.l 7601 acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa ι ι i ι η η ι ι ι ι ι η ι ii | πιη ι ii ii 1 1 1 1 1 II II 1 II 1 1 1 1 II 1 1 1 7650 v.2 7442 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ACATGAAATTCAACTTTCCAAATAAAAGTTCTACTTCATGTAATCCAAAA 7491

Note: Two ΞΝΡ at 668 and 1178.

Table LIVa. Peptide sequences of protein coded by 282P1G03 v.2 (SEQ ID NO: 154) MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 50 GNPEPTFSKT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 120 EEIEFIVPSV PKFPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV 180 YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSLKHA NDSSSSTEIG 240 SKANSIKQRK PKLLLPPTES GSESSITILK GEILLLECFA EGLPTPQVDW NKIGGDLPKG 300 REAKENYGKT LKIENVSYQD KGNYRCTASN FLGTATHDFH VIVEEPPRWT KKPQSAVYST 3 60 GSNGILLCEA EGEPQPTIKW RVNGSPVDNH PFAGDWFPR EISFTNLQPN HTAVYQCEAS 42 0 NVHGTILANA NIDWDVRPL IQTKDGENYA TWGYSAFLH CEFFASPEAV VSWQKVEEVK 480 PLEGRRYHIY ENGTLQINRT TEEDAGSYSC WVENAIGKTA VTANLDIRNA TKLRVSPKNP 54 0 RIPKLHMLEL HCESKCDSHL KHSLKLSWSK DGEAFEINGT EDGRIIIDGA NLTISNVTLE 600 DQGIYCCSAH TALDSAADIT QVTVLDVPDP PENLHLSERQ NRSVRLTWEA 'GADHNSNISE 660 YIVEFEGNKE EPGRWEELTR VQGKKTTVIL PLAPFVRYQF RVIAVNEVGR SQPSQPSDHH 72 0 ETPPAAPDRN PQNIRVQASQ PKEMIIKWEP LKSMEQNGPG LEYRVTWKPQ GAPVEWEEET 780 VTNHTLRVMT PAVYAPYDVK VQAINQLGSG PDPQSVTLYS GEDYPDTAPV IHGVDVINST 84 0 LVKVTWSTVP KDRVHGRLKG YQINWWKTKS LLDGRTHPKE VNILRFSGQR NSGMVPSLDA 900 FSEFHLTVLA YNSKGAGPES EPYIFQTPEG VPEQPTFLKV IKVDKDTATL SWGLPKKLNG 960 NLTGYLLQYQ IINDTYEIGE LNDINITTPS KPSWHLSNLN ATTKYKFYLR ACTSQGCGKP 1020 ITEESSTLGE GKYAGLYDDl STQGWFIGLM CAIALLTLLL LTVCFVKRNR’GGKYSVKEKE 108 0 DLHPDPEIQS VKDETFGEYS DSDEKPLKGS LRSLNRDMQP TESADSLVEY GEGDHGLFSE . 1140 DGSFIGAYAG SKEKGSVESN GSSTATFPLR A 1171

Table LVa. Amino acid sequence alignment of 282P1G03 v.1 (SEQ ID NO: 155) and 282P1G03 v.2 (SEQ ID NO: 158) v.l 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD 50 v.2

1 MEPLLLGRGLI VYLMFLLLKFSKAIE IPS S VQQVPTIIKQS KVQVAFPFD 50 v.l

51 BYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 251 v.2 51 EYFQIECEAKGKPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 v.l 101 SHFQGKYRCFASNKLGIAMSEEXEFIVPSVPKLPKEKIDPLEVEEGDPIV 1 ! &#943; I ! Η 1 Η I ! 1 1 1 1 i 1 1 1 I 1 I 1 1 1 1 I 1 Η 1 1 1 1 I 1 1 1 1 ! 1 1 1 1 1 1 1 1 150 v.2 101 1 1 1 1 &#943; 1 1 1 1 1 ! I I 1 1 I 1 1 1 I 1 H 1 1 1 1 1 &#943; 1 1 1 - 1 1 1 i 1 &#943; I 1 ! &#943; 1 1 1 1 1 &#943; ! SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKFPKEKIDPLEVEEGDPIV 150 v.1 151 LPCHPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN 1 I I I 1 1 1 I 1 1 1 I 1 1 1 1 I 1 1 1 II I 1 [ II 1 1 II 1 1 ( 1 1 1 1 I 1 1 1 1 II II li 1 200 v.2 151 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 i 1 1 1 1 1 i 1 1 i 1 1 1 1 1 1 LPCWPPKGLPPLHIYWMNIELEHIEQDERVyMSQKGDLYFANVEEKDSRN 200 v. 1 201 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKMiSIKQRK I 1 I I It I 1 1 I I I 1 II II 1 I 1 1 1 1 1 II 1 1 1 1 1 1 1 1 II II II 1 1 1 1 II 1 1 1 1 250 v.2 201 1 1 1 1 I 1 ! 1 ! 1 1 1 1 1 1 I 1 1 1 1 I 1 I 1 1 I 1 1 1 1 I 1 1 1 1 ! I 1 1 1 1 ! 1 1 ! 1 1 1 1 1 D YCCFAAFPRLRTIVQKMPMKLTVNSLKBAKDS Ξ S STEIGS KANSIKQRK 250 v.1 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG ! &#912; 1 1 1 ! 1 1 I 1 1 1 II 1 1 1 H li 1 i 1 1 1 1 1 1! II 1 &#943; 1 1 1 1 1 1 1 1 1 1 1 1 1 HI 300 v.2 251 1 11111IIII 1 1 1 II II 1 1 II 1 I 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 I 1 1 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPOVDWNKIGGDLPKG 300 v.1 301 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT II 1 1 II I 1 1 1 1 1 II 1 1 1 1 1 II II II 1 1 1 1 1 1 1 ! 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 350 v.2 301 1 I ’ 1 1 1 1 1 1 1 1 1 i l 1 1 1 1 I 1 1 1 { 1 1 1 1 1 U &#943; II 1 I 1 f I 1 I 1 1 1 1 1 t I I II REAKEKYGKTLKIENVSYQBKGNYP.CTASNFLGTATHDFHVIVBEPPKWT 350 v.1 351 KKPQSAVYSTGSNGILLCEAEGEPQPTXKWRWGSPVDNHPFAGDWFPR I I 1 I I I 1 I 1 II 1 I I 1 II I I I 1 I 1 1 I I 1 I II 1 1 I j I I 1 1 I I I 1 I 1 I I 1 I 1 1 400 v.2 351 1 1 II 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 II 1 1 1 1 I 1 1 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR 400 v.1 401 EIS FTNLQPNHTAVYQCEASNVHGTILANANIDYVDVRPLIQTKDGENYA II111 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 111 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 450 v.2 401 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 EIS FTNLQPNHTAVYQCE ASNVHGTILANANID WDVRPLIQTKDGENYA 450 v.1 451 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT 1 1 1 1 1 II 1 II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 500 v.2 451 1 1 1 1 1 II 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 i 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 TWGYSAFUiCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENGTLQINRT 500 v.1 501 TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPKN'PRIPKLHMLEL I I 1 1 I II 1 II 1 1 1 1 I 1 1 1 1 II 1 II 1 I 1 1 1 II 1 II 1 II 1 11 II 1 1 1 I 1 1 1 j 550 v.2 SOI 1 II 1 1 1 I I 1 I 1 I 1 II 1 1 1 1 1 1 II 1 1 1 I 1 I 11 11 1 1 1 1 II 1 II 1 II II 1 1 I TEEDAGSYSCWVENAIGKTAVTAKLQIOTATKLRVSPKNPRIPKLHMLEL 550 v.l 551 HCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE I 1 1 11 1 1 1 1 II 1 1 1 1 1 1 1 1 II 1 1 I j 1 II 1 1 1 1 1 1 1 1 1 I 1 1 II 1 1 1 1 1 &#943; &#943; 1 600 v.2 551 1 1 II 1 II 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 II 1 1 1 11 II II HCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE 600 v.1 601 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENIHLSERQNRSITRLTWEA I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 650 v.2 601 1 1 1 II 1 1 1 1 1 1 1 1 II11 1 II 1 1 1 1 I 1 I 1 1 1 1 1 1 I 1 1 1 11 1 1 II 1 1 1 1 1 1 1 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA 650 v.1 651 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 1 1 I I I I 1 1 I 1 1 1 1 j I I 1 1 I 1 I 1 1 1 I I I 1 1 I 1 I 1 I 1 1 I I I 1 1 I 1 1 1 I 1 1 1 1 700 v.2 651 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 700 v.1 701 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 11 1 1 1 II 1 ) 1 1 1 1II1i 11 1 750 v.2 701 1 1 1 II 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 II 1 I 1 1 1 1 1 1 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 750 v.l 751 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 li 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 I 1 I II 800 V.2 751 1 1 1 II II 1 1 1 1 1 I 1 1 ! 1 1 1 1 1 1 1 1 I 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 800 v.l 801 vqainqlgsgpdpqsvtlysgbdypdtapvibgvdvinstlvkvtwstvp 1 I I 1 1 1 1 1 1 ! 1 I 1 1 1 1 II I 1 1 1 1 1 1 1 11 I 1 1 1 I 1 1 I I 1 1 I 1 1 I 1 1 1 1 1 H 850 V.2 801 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 VQAXNQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLVKVTWSTVP 850 252 > i 851 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVtilLRFSGQRNSGMVPSLDA ι ι ι 1 I 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 I 1 1 900 v.2 851 11 i 1 1 1 i 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 i 1 1 1 11 1 1 1 i 1 1 1 1 1 1 ! 1 1 1 1 1 1 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSGQRNSGMVPSIxDA 900 v.1 901 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL· | 1 I ! I 1 i j I j I 1 1 1 I 1 1 1 j I 1 1 1 I I 1 I 1 1 1 1 I I I 1 1 1 1 1 1 I I II 1 i II 1 1 950 v.2 901 11 1 1 1 I 1 1 1 1 1 1 1111II11111!1111 I 1 11 11) i 1 1 1 1 1 1 1 1 1 1 1 1 I 1 Ρ3ΕΡΗΕΤν&#912;ιΑΥΝ3ΚσΑσΡΕ3ΕΡΥΙΡ0ΤΡΕανΡΕ0ΡΤΡΕΚν&#912;ΚνηΚ&#944;Τ·ΑΤη 950 v.1 951 SWGLPKKANGNLTGYLLQYQIIiroTYEIGELNDINITTPSKPSWHLSNLN 1 1 1 ! I 1 J 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 ) 1 1 ) 1 1 1 1 1 1 1 1 ! 1 i 1 1 1 1 1000 v.2 951 11111111 I 1 1 1 1 I 1 1 1 1 1 II 1 1 11 1 1 1 I 1 1 1 II 1 I ItN 11 11 1 1 1 1 II S WGLPKK1NGMLTGYLLQYQIXNBTYEIGELNDINITTP SKP S WHLSNL.N 1000 v.1 1001 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNETQKTHPI 1 1 1 1 1 t I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 i 1050 v.2 1001 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTKYKFYLRACTSQGCGKPITEESSTLGEG------------------- 1031 v. 1 1051 EVFEPGAEHIVRLMTKNWGBNDSIFQDVIETRGREYAGLYDDISTQGWFI . I 1 I I I I I I II 1 1 1 I I 1100 v.2 1032 • 1 1 1 1 1 1 1 ! 1 1 1 i 1 1 1 ----------------------------------KYAGLYDDISTQGWFI 1047 v.1 1101 GLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPDPEIQSVKDETFG 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 115 0 v.2 1048 1 1 1 1 1 1 I 1 1 II 1 111 1 111 II 1 II 1 II 1 1 1 11 It 1 1 1 1 1 11 1 1 1 1 1 1 1 11 GLMCAIALLTLLLLTVCFVKRNRGGKYSITKEKEDLHPDPEIQSVKDETFG 1097 v.1 1151 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1200 v.2 1098 1 1 1 1 II 1 II 1 1 11II11111 11i 1 1 1 II II 1 I II 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1147 v.1 1201 YAGSKEKGSVESNGSSTATFPLRA 1224 } i ] I is | η ] j | s j ! | ι ι | ι { }{ 1 v.2 1148 1 1 1 1 1 1 1 1 I 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 YAGSKEKGSVESNGSSTATFPLRA 1171

Table LJlb. Nucleotide sequence of transcript variant 282P1G03 v.3 (SEQ ID NO: 157) cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg 'caaaccataa tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt ccaggttaac fcaaggtctca gctgtaaacc aaaagtgaga ggagacatta‘agattttcat tcttaccggg ttgtcttctt cctgaaqagc aatggagccg cttttacttg gaagaggact aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt ateatatcta tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 253 ft-fcgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc I860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacacaac atatgtaagc aacgctactg gttcacccca 2820 accttccata tttatctgtt caaaggagca agaactttca tataggaata gaaacatgct 2880 ggccgaagat ttcatccaga agtcaacatc ctgcaattat gttgaaaaga gtagtacttt 2940 cttcaaaata taaaatgcca agcacttcag gcctatgttt tgcttatatt gttttcaggt 3000 gctcaaaatg caaaacacaa aacaaatcct gcatttagat acacctcaac taaatccaaa 3060 gtccccattc agtatattcc atatttgcct gattttacta ttcggtgtgt ttgcatagat 3120 gttgctactt ggtgggtttt tctccgtatg cacattggta tacagtctct gagaactggc 3180 ttggtgactt tgcttcacta caggttaaaa gaccataagc aaactggtta tttaaaatgt 3240 aaaaaggaat atgaaagtct tattaaaaca cttcattgaa aa.tatacagt ctaaatttat .3300 tatttaaatt ttactagcaa aagtcttagg tgaacaatca actagtattt gttgagctcc 3360 tatttgccca gagatggtca tatttaaaca gaagtatacg tttttcagtt tcaacatgaa 3420 tttttttatt tctgtcagtt atgacatcca cgagcatcac tttttgtgtc tgtttttttt 3480 tttttcttgg actaaattca actgcatgga agcggtggtc agaaggttgt tttatacgag 3540· aacaggcaga aagtgcccat tgttcaggat tctaatagct acatctactt aafcatcttca 3600 tttctaaatt gactgctttt acctttttct catgtttata taatggtatg cttgcatata 3660 tttcatgaat acattgtaca tattatgtta atatttacac aatttaaaat atagatgtgt 3720 tttattttga agtgagaaaa tgaacattaa caggcatgtt tgtacagcta gaatatatta 3780 gtaagatact gtttttcgtc attccagagc tacaactaat aacacgaggt tccaaagctg 3840 aagactttgt ataaagtatt tgggttttgt tcttgtattg ctttctttca acagtttcaa 3900 aataaaatat catacaaata ttgagggaaa tgttttcata tttttcaaaa taggttthta 3960 ttgttgaafcg tacatctacc ccagcccctc aaaagaaaaa ctgtttacat agaaattcct 4020 acacatacgt ttgcgtatat gttattttaa acatctttgt ggtgagaatt ttttccccga 4080 tattctcctt ctgtcaaagt cagaacaaat tcagggaatt tattttctgg cagttgtgct 4140 ccagtccttt taaaattgta catgaacatg ttttagaaac aatatggagg atgatgcata 4200 catgtcggtc aagttcagcg ctcgacattt tatggaaaga tttttttaac cttaccacga 4260 aatacttaac tactgtttaa gtgaattgac ttatttcact ttagtttttg aactgtgatt 4320 afctggtatac tgttatatcc tcaacttgga tttatggtaa ccccttttag ttcatggaga 4380 ccaaaatttg gggtatttat aatagtcagc gcaggaatgc acatggaata tctacttgtc 4440 cttttgaacc tcacgagtca tccagaatgt atagacagga aaagcatgtc ttatttaaaa 4500 ctgtaattta tgggctcagg atctgaccgc agtcccggga gtaagcattt caaaggggga 4560 aggcagtgtg gtccctaccc tgtgtgaatg tgaggatgta gacatccatc agtgcaactc 4620 gagctccatc ctcctccgat ttctaaggct ccagttttct ggagggacag tcatcatgtt 4680 ttgatttatc tgggagaaaa ctgtggtgca cagcttgtga ggagggcaag gttgtgacgt 4740 tcgagcttag ttctggtgtt attctgtctc ctcttctttg tcatcagcca aaacgtggtt 4800 tttaaagaga gtcatgcagg ttagaaataa tgtcaaaaat atttaggaat ttaataacct 4860 ttaagtcaga aactaaaaca aatactgaaa tattagctct tcctacactt cgtgttcccc 4920 tttagctgcc tgaaaatcaa gattgct.cct actcagatct tctgagtggc taaaacttat 4980 ggatatgaaa aatgagattg aatgatgact atgctttgct atcattgtta cctttcctca 5040 atactatttg gcaactactg ggactcttca gcacaaaagg aatagatcta tgattgaccc 5100 tgattttaat tgtgaaatta tatgattcat atattttatg aatcagaata accttcaaat 5160 aaaataaatc taagtcggtt aaaatggatt tcatgatttt ccctcagaaa atgagtaacg 5220 gagtccacgg cgtgcaatgg taattataaa ttggtgatgc ttgtttgcaa attgcccact 5280 cgtgataagt caacagccaa tatttaaaac tttgttcgtt actggcttta ccctaacttt 5340 ctctagtcta ctgtcaatat cattttaatg taattgattg tatatagtct caagaatggt 5400 tggtgggcat gagttcctag agaactgtcc aagggttggg aaaatccaaa ttctcttcct 5460 ggctccagca ctgattttgt acataaacat taggcaggtt gcttaacctt tttatttcaa 5520 actctctcaa ctctaaagtg ctaataataa tctcagttac cttatctttg tcacagggtg 5580 254 tt'Otttttta tgaagaaaaa tttgaaaatg ataaaagcta agatgccttc taacttcata 5640 agcaaacctt taactaatta tgtatctgaa agtcaccccc acataccaac tcaacttttt 5700 tcctgtgaac acataaatat atttttatag aaaaacaaat ctacataaaa taaatctact 5760 gtttagtgag cagtatgact tgtacatgcc attgaaaatt attaatcaga agaaaattaa 5820 gcagggtctt tgctatacaa aagtgttttc cactaatttt gcatgcgtat ttataagaaa 5880 aatgtgaatt tggtggtttt attctatcgg tataaaggca tcgatatttt agatgcaccc 5940 gtgtttgtaa aaatgtagag cacaatggaa ttatgctgga agtctcaaat aatatttttt 6000 tcctatttta tactcatgga agagataagc taaagagggg acaataatga gaaafcgttgg 6060 tgtgcttttc taagcattta aaacataatt gccaattgaa accctaaata tgtttacata 6120 ccattaagat atgattcatg taacaatgtt aaattaatta taatgggatt gggtttgtta 6180 tctgtggtag tatatatcct agtgttccta tagtgaaata agtagggttc agccaaagct 6240 ttctttgttt tgtaccttaa attgttcgat tacgtcatca aaagagatga aaggtatgta 6300 gaacaggttc acgtgattac ctttttcttt tggettggat taatattcat agtagaactt 6360 tataaaacgt gtttgtattg taggtggtgt ttgtattatg cttatgacta tgtatggttt 6420 gaaaatattt tcattataca tgaaattcaa ctttccaaat aaaagttcta cttcatgtaa 6480 tccaaaa 6487

Table Llllb. Nucleotide sequence alignment of 282P1G03 v.1 (SEQ ID NO: 158) and 282P1G03 v.3 (SEQ ID NO: 159) v.l 1 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg j I 1 i I 1 I 1 I 1 I II 1 1 1 1 11 1 1 I I I I II 1 |l I 1 I 1 || I 1 t| 1 1 1 I 11 1 II I 50 v.3 1 II 1 j Π 1 1 1 1 1 { 1 Ii 1 1 1 1 I I II 1 1 II ι H 1 1 II ι 1 1 1 I 1 1 1 S I Η ι ι ll CGGACCCTGCGCGCCCCCGTCCCGGCTCCCGGCCGGCTCGGGGGAGAAGG 50 v.l 51 cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg f I Π | 1 1 1 I Η 1 1 1 1 1 I I 1 1 1 1 1 I 1 &#943; Μ 1 &#943; 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 100 v.3 51 I 1 1 I I 1 1 I 1 J 1 1 1 I 1 i 1 1 l 1 1 1 1 1 1 I II I 1 1 1 I U II I 1 1 1 1 I 1 1 I 1 1 1 1 CGCCCGAGGGGAGGCGCCGGACAGATCGCGTTTCGGAGGCGGCGCAGGTG 100 v.l 101 ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcatag I I I I 1 1 1 I I I I I I 1 1 j I |l I 1 1 I 1 1 1 ) 1 jl 1 1 1 1 11 1 1 1 1 11 I I 1 I II 1 1 150 v.3 101 I f 1 1 1 1 1 1 II 1 I I 1 1 II 1 I 1 1 1 I I 1 II 1 1 l 1 1 i 1 II 1 I 1 1 1 I 1 1 I 1 1 1 II CTGTAAACTGCAAAGCATAATCCTGTCTTAATACTGCAAACAAATCATAG 150 v.l 151 tggaactaaggggaacttaatttactgtttccaggttaactaaggtctca | 1 1 1 II 1 1 Γ I 1 1 I t 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 ! 1 1 1 I 1 1 1 1 1 1 I 1 I 1 1 1 1 '200 v.3 151 Π 1 1 II I 1 1 1 J 1 H ! i 1 1 1 1 1 1 ! II &#943; 1 1 1 1 II 1 1 1 1 Π 1 1 1 II J 1 1 1 1 II TGGAACTAAGGGGAACTTAATTTACTGTTTCCAGGTTAACTAAGGTCTCA 200 v.l 201 gctgtaaaccaaaagtgagaggagacattaagattttcattcttaccggg 11 11 1 1 1 1 II 1 I 1 I 1 1 1 1 1 1 II 1 1 1 1 11111 11 11 1 II I 1 1 1 1 1 1 1 1 1 11 250 v.3 201 Η Π 1 II H II 1 1 II 1 -1 1 II II 1 ! I 1 1 1 I -II 1 ! 1 1 Π 1 1 1 1 1 I I 1 i 1 1 Π GGTGTAAACCAAAAGTGAGAGGAGACATTAAGATTTTCATTCTTACCGGG 250 v.l 251 ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact I | | I I 1 I I I | &#943; (I | II 1 | | II 1 1 1 1 1 I I I ll || I I | 1 I 1 ] I || t I I I | 11 300 v.3 251 1 II11111111111111 I 1111111 II 1 1 II 11 I 1 1 1 1 1 II 1 1 1 1 1 1 II l TTGTCTTCTTCCTGAAGAGCAATGGAGCCGCTTTTACTTGGAAGAGGACT 300 v.l 301 aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa II I 1 I 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 I 1 1 I 1 1 II 1 1 1 1 1 I 1 1 I 1 1 [ 1 1 ( I 1 1 1 1 1 1 350 v.3 301 1 i I H ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 II 1 1 I 1 1 H 1 s 1 1 I 1 U I 1 1 I 1 I 1 1 1 AATCGTATATCTAATGTTCCTCCTGTTAAAATTCTCAAAAGCAATTGAAA 350 v. 1 351 taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc I 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 400 v.3 351 1 1 II 1 } 1 1 II 1 1 1 1 I 1 I I 1 1 1 1 1 1 1 H 1 1 I I 1 I I 1 1 I 1 I 1 I 1 1 1 1 1 1 II I TACCATCTTCAGTTCAACAGGTTCCAACAATCATAAAACAGTCAAAACTC 400 V.l 401 caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagctaa 1111 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 11111111111 I Iιι&#970;illΙ&#938;11 1 1 450 v.3 401 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 CAAGTTGCCTTTCCCTTCGATGAGTATTTTCAAATTGAATGTGAAGCTAA 450 V.l 451 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt mmimimmimmimmummimmim 500 v . 3 451 AGGAAATCCAGAACCAACATTTTCGTGGACTAAGGATGGCAACCCTTTTT 500 v.l 501 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 550 V.3 501 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1111 1 1 1 1 1 II111111 I 1111 1 I 1 1 1 1 1 I I 1 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg 550 255 &#970;. y.- 1 551 atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt | I II I | I 1 I I I II |l 1 1 1 11 1 I | | II 11 1 t II II I I II I 1 1 I II | j I j 1 I 600 v. 3 551 II N II 1 1 1 1 1 1 1 II 1 II II 1 II 1111111111111111 1 1 1 1 1 1 1 1 1 1 1 ATCCCAAACGAGGGGCACATATCTCACTTTCAAGGGAAATACCGCTGCTT 600 v.l 601 tgcttcaaataaactggqaatcgctatgtcagaagaaatagaatttatag 1 1 I 1 I 1 I j I 1 I |l I 1 I 1 II II 1 I 1 II 1 1 11 1 1 1 1 II ] 1 1 11 1 II 1 1 1 11 1 650 v.3 601 II1II 1 1 1 II 111N 1 1 N 1 N 1 1 1 J I 111 1 1 1 1 1 I 1 1 1111 111 11111 TGCTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650 v.l 651 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg ( I 1 ! I I I 1 I I , II I I I II I I I I I I II j I l| I I I 1 I I I I 1 ! II II 1 1 1 1 II 700 v. 3 651 I 1 i i 1 ! i 1 1 i 1 1 1 1 i &#943; I I 1 1 I 1 1 1 1 ι I 1 i ( i ! 1 1 t i ( 1 &#943; &#943; 1 1 I < I I i 1 1 > TTCCAAGTGTTCCAAAAcTCCCAAAAGAAAAAATTGACCCTCTTGAAGTG 700 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc II 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 II | I | I | | 1 II 1 1 II Ij 1 1 1 1 1 1 II II 750 v.3 701 1 1 1 i 1 I 1 ι 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 I 1 1 1 ι 1 1 1 1 ! I 1 I Η I 1 1 1 1 I ι 1 GAGGAGGGAGATCCAATTGTCCTCCCATGCAATCCTCCCAAAGGCCTCCC 750 v.l 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 1 I 1 || I I || I I I I j ! I ] 1 ] 1 I 1 I I j I I I 1 1 1 1 I 1 1 1 1 1 1 1 j 1 1 1 1 1 1 II 1 800 v.3 751 i 1 II i Η 1 1 1 1 i 1 1 1 i i 1 I 1 &#943; i 1 ι I i i f i i i &#943; 1 ι ι 1 ι ι ι ι 1 ι ι I s I &#943; 1 1 1 ACCTTTACACATTTATTGGATGAATATTGAATTAGAACACATCGAACAAG 800 v.l 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg I 1 1 1 1 1 1 1 1 1 1 1 1 II j 1 1 1 II 1 II II 1 1 1 1 1 II 1 ]| 1 1 1 II 1 1 1 1 II 1 1 1 850 v.3 801 1 I 1 1 1 1 1 II 1 1 II 1 1 1 1 1 1 II 1 1 II 1 1 1 1 ! 1 1 1 1 1 1 ! 1 1 1 1 I 1 1 1 1 1 1 1 1 ATGAAAGAGTATACATGAGCCAAAAGGGAGATCTATACTTCGCAAACGTG 850 v.l 851 gaaqaaaaqqacagtcgcaatgactactgfctgctttgctgcatttccaag 1111 11 1 II IN III IIIIII IIII II II III II 1 IIII 111 II I! IIII 900 v.3 851 I 1 1 1 1 1 1 I 1 I 1 1 I II 1 1 11 1 1 1 1 1 1 1 1 1 II 1 1 I 1 1 I 1 1 1 1 I I f 1 11 1 1 1 1 GAAGAAAAGGACAGTCGCAATGACTACTGTTGCTTTGCTGCATTTCCAAG 900 v.l 901 attaaggactattgtacagaaaatgccaatgaaactaacaqttaacaqtt 11 1 II II Π 1 1 1 1 N N II II 1 1 II II II N 1 II 1 1 1 NΙ&#938; 1 N II 1 N 1 950 v.3 901 II II II II 1 1 11 1 II 1 II 1 1 1 1 1 1 1 1 1 II 1 1 II 1 II 11 1 1 1 1 1 1 1 1 1 1 I 1 ATTAAGGACTATTGTACAGAAAATGCCAATGAAACTAACAGTTAACAGTT 950 V.l 951 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca II 1 II 1 |l 1 II l| II II II II I II II 1 |] II II II 1 I II II 1 II II 1 1 II 1000 v.3 951 1 I It II 1 1 1 1 1 1 1 I I II 1 1 II 1 1 1 1 1 II 1 1 1 I 1 1 1 1 1 I 1 I 1 1 I l.l II 1 1 1 TAAAGCATGCTAATGACTCAAGTTCATCCACAGAAATTGGTTCCAAGGCA 1000 v.l 1001 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag N 1 1 N N i i i N i 1 N i ' 1 1 i 1 1 N i N N &#943; N 1 N N 1 N N N 1 N &#912; 1050 v.3 1001 1 I 1 ι ι i I ι 1 N II II ι It N 1 ι 1 N N 1 ι 1 1 ι &#943; I I 1 N N N N 11 N 1 1 AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG 1050 v.l 1051 tggcagtgagtcttcaattaccatcctcaaaggggaaatcttgctgcttg II i { I Pl II II II || II II j|J II II I I I I) I |j I) |j 1 ) II 1 |j II 1 II 1100 v.3 1051 1 1 I I 1 1 II I N N N N N N 1 II N 1 II II I II 1 1 1 1 1 1 1 N 1 N II 1 I TGGCAGTGAGTCTTCAATTACCATCCTCAAAGGGGAAATCTTGCTGCTTG 1100 v.l 1101 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt II 11 II 1 II II II |l 1 II 1 II 1 1 II II 1 II 1 II l| II II II II 1 II II II 1150 v.3 1101 1 1 1 I 1 I 111 1 11II1 I II 1 11 1N1II1 I 1 1 1 1 II 1 1 II 1 1 II 1 1 II 1 1 1 AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGGAACAAAATT 1150 v.l 1151 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac || | |||||| | , η|| ||| |N11 IIII1 1 II Π II II II N N II 1 N II 1200 v.3 1151 111 11111 1 1 11 I IIII IIN1N1 II1 II 1 1 1 I II II II II II II II II GGTGGTGACTTACCAAAGGGGAGAGAAACAAAAGAAAATTATGGCAAGAC 1200 v.l 1201 fcttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca II 11 j Π 1 I 11 II II ! II II 11 II II II II II 1 1 II II I 1 1 II II 11 1 11 1250 v.3 1201 1 I 1 11 1 111 1 1 1 1 1 II 1 II II 1 11 N II 1 1 1 1 1 I II11 11 II II I! II II TTTGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA 1250 v.l 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta 1 1 111 I 1111 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 N 1 N II 1 111111111 i1 13 00 v.3 1251 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! ι 1 1 1 1 I 1 I | | 1 1 1 I ! 1 1 1 1 CAGCCAGCAATTTCTTGGGAACAGCCACTCACGATTTTCACGTTATAGTA 13 00 v.l 1301 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtatagcac 1 Η Η | Π | | ι Η ι ι |i | μ | | | | π | | I || |1 || || η | π |j | | η || 1350 v.3 1301 1 1 I 1 I 1 1 I ι ι ι | I I | | | 1 I I I 1 1 1 1 1 1 1 ! 1 1 1 I 1 1 1 1 1 I | I 1 1 1 I I | I I 1 GAAGAGCCTCCTCGCTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCAC 1350 256 I""· ' v.l 1351 cggaagcaatggcatcttgttatgtgaggctgaaggagaacctcaaccca 1111111111111111111111111111111111111111 III 1111111

v . 3 13 51 CGGAAGCAATGGCATCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCA v.l 1401 caatcaagtqqagagtcaatggctccccagttgacaatcatccatttgct

! II1) IIIII! III! Hl Hl! II ! I! I II III! 11 HI I Π 111 &amp;#943; II! I

v.3 1401 CAATCAAGTGGAGAGTCAATGGCTCCCCAGTTGACAATCATCCATTTGCT v.l 1451 ggtgatgttgtcttccccagggaaatcagttttaccaaccttcaaccaaa

11II11II11IIII111II111IIII1111IIII ili III111II II 1II

v.3 1451 GGTGATGTTGTCTTCCCCAGGGAAATCAGTTTTACCAACCTTCAACCAAA v.l 1501 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc 111111IIII11IIII11111111 H IIII11 H 111II11II111II11

v.3 15 01 TCATACTGCTGTGTACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCC v.l 1551 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc III IIIIIIIIII11111II11II11111111IIIIIII111IIIIII11

v.3 1551 TTGCCAATGCCAATATTGATGTTGTGGATGTCCGTCCATTGATACAAACC v.l 1601 aaagatqgaqaaaattacgctacagtggttgggtacaqtgctttcttaca 11111111111111111111111111111111111111111111111111

v.3 1601 AAAGATGGAGAAAATTACGCTACAGTGGTTGGGTACAGTGCTTTCTTACA v.l 1651 ttgcgagttctttgcttcacctgaggcagtcgtgtcctggcagaagqtgg 11II1111111! I! II11II11IIIII11 Ii 111111 III 1111IIII11

v.3 1651 TTGCGAGTTCTTTGCTTCACCTGAGGCAGTCGTGTCCTGGCAGAAGGTGG v.l 1701 aagaagtgaaacccctggagggcaggcggtatcatatctatgaaaatggc II i Iii III1111IIII11II111111IIIIIII11II11II111II111

v.3 17 01 AAGAAGTGAAACCCCTGGAGGGCAGGCGGTATCATATCTATGAAAATGGC v.l 1751 acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg

II111111II11II111 i 11111111111111II11111111111111II

v.3 1751 ACATTGCAGATCAACAGAACCACCGAAGAAGATGCTGGGTCTTACTCATG v.l 1801 ttgggtagaaaatgctataggaaaaactqcagtcacaqccaatttggata 11111111111 111 11111II1111II1111111111111111II SI 111

V.3 1801 TTGGGTAG AAAATGCTATAGGAAAAACTGCAGTCACAGCCAATTTGGATA v.l 1851 ttagaaS-tgctacaaaacttagagtttctcctaagaatcctcgtatcccc

I &amp;#943; II111 Μ 11 N IIIIIIIII ii I &amp;#943;! I! Ii III INI Nl II11 ii III

v.3 1851 TTAGAAATGCTACAAAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCC v.l 1901 aaattgcatatgcttgaattacattgtgaaagcaaatgtgactcacattt

11111111111111! 11111111111111111II11111II11il IIIII

v.3 1901 AAATTGCATATGCTTGAATTACATTGTGAAAGCAAATGTGACTCACATTT v.l 1951 gaaacacagtttgaagttgtcctggagtaaagatggagaagcctttgaaa

IIIII HI III 111 11 III 111111 III III I 111 111 HI 111II HI I

v.3 1951 GAAAC ACAGTTTGAAGTTGTCCTGGAGTAAAGATGGAGAAGCCTTTGAAA v.l 2001 ttaatggcacagaagatggcaggataattattgatggagctaatttgacc

H H 1111 n11)i11!111]11J H1 111 J111111!11111 H 111&amp;#938;I

V.3 2001 TTAATGGCACAGAAGATGGCAGGATAATTATTGATGGAGCTAATTTGACC v.l 2051 atatctaatgtaactttagaggaccaaggtatttactgctgttcagctca II1111II111 HI 11111 HI II11 HI IIIIIII111IIIIIII III 1

v.3 2 051 ATATCTAATGTAACTTTAGAGGACCAAGGTATTTACTGCTGTTCAGCTCA v.l 2101 tactgctctagacagtgctgccgatataactcaagtaactgttcttgatg 1400 1400 1450 1450 1500 1500 1550 1550 1600 1600 1650 1650 17 00 1700 1750 1750 1800 1800 1850 1850 1900 1900 1950 1950 2000 2000 2050 2050 2100 2100 2150 257 1 . 2101 TACTGCTCTAGACAGTGCTGCCGATATAACTCAAGTAACTGTTCTTGATG 2150 v.l 2151 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt I &amp;#943; 1 1 I I I 1 11 1 1 [11II 1 II 1 II 1 1 I I 1 II 1 Π II 1 1 1 1 1 1 1 I 1 1 I 1 1 I! 2200 1 I i 1 l 1 II 1 1 I 1 1 J i I II 1 1 1 1 1 I I 1 I 1 Hi I I 1 1 H I I 1 I I 1 II 1 &amp;#943; I 1 1 v.3 2151 TTCCGGATCCACCAGAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGT 2200 v.l 2201 gttcggctgacctqggaagctggagctgaccacaacagcaatattagcga Til HI II II II I H 1 Hill II 11 1 Π 1 I II II Η Π II II! II Π II 1 2250 Η Η i 1 1 1 1 I 1 1 1 1 1 1 1 I 1 I I 1 1 1 ! 1 H 1 1 1 1 I ! I 1 1 1 1 1 I I 1 1 1 II 1 1 I v.3 22 01 GTTCGGCTGACCTGGGAAGCTGGAGCTGACCACAACAGCAATATTAGCGA 2250 v.l 2251 gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg Η | ii ii ! i| ii I il I || I t I Π I Π II II Π II II Η Π II Π II Η II 2300 1 H N 1 I 1 1 II 1 1II I 1 1 1 1 j 1 II 1 H I 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v, 3 2251 GTATATTGTTGAATTTGAAGGAAACAAAGAAGAGCCTGGAAGGTGGGAGG 2300 v.l 2301 aactgaccagagtccaaggaaagaaaaccacagttatcttacctttggct II 1 1 1 1 1 II 1 II 1 II I II 1 I 1 1 II II 1 11 I II |l 1 1 II t| 1 II It I |( II 2350 1 1 I &amp;#943; 1 1 &amp;#943; ι 1 &amp;#943; ι 1&amp;#943; I 1 t 1 1 1 H I I i &amp;#943; H 1 II 1 1 1 1 1 ι 1 I 1 I 1 II 1 i 1 I It I v.3 2301 AACTGACCAGAGTCCAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCT 2350 v.l 2351 ccatttgtqaqataccagttcagggtcatagccgtgaacgaagtagggag 1 I f 1 I Η I f &amp;#943; &amp;#943; Π &amp;#943; ( Η U &amp;#943; π&amp;#912;&amp;#943; &amp;#943; &amp;#943; U Η i U &amp;#943; Η &amp;#943; Η 1 Η 1 &amp;#943; ΗTl N 2400 1 H 1 1 1 ι 1 1 1 1 1 1 l Π I 1 1 ! I 1 i 1 !·! 1 1 ! 1 1 1 1 1 I I N S i ! ! Η 1 ! i H 1 v.3 2351 CCATTTGTGAGATACCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAG 2400 v.l 2401 aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc II Hlill III III III lllll lllll Illlllllll II mill HIM v.3 24 01 AAGTCAGCCTAGCCAGCCGTCAGACCATCATGAAA.CACCACCAGCAGCTC 2450 2450 v.l 2451 cagataggaatccacaaaacataagggttcaagcctctcaacccaaggaa Π Π II 1 1 1 1 1 1 1 1 II Π Η 1 1 II 1 1 Η II II Η 1 II Π II 1 Η Η II H 2500 1 1 1 1 1 1 11 11 i 111 H 1 i 1 1 I 1 J } 1 1 II il I I I 1 U 1 I 1 II i 1 1 1 1 l 1 ι 1 v.3 2451 CAGATAGGAATCCACAAAACATAAGGGTTCAAGCCTCTCAACCCAAGGAA 2500 v.l 2501 atgattataaagtgggagcctttgaaatccatggagcagaatggaccagg IIIIII111IIIIIIIIII111 III 1 III 1 1 III II1 II 11 II 111 II II 2550 i 1 1 I 1 1 1 1 1 1 1 1 ι 1 1 &amp;#943; ι 1 ι ι &amp;#943; ι 1 { ι I I 1 I &amp;#943; ι &amp;#943; &amp;#943; &amp;#943; Η 1 &amp;#943; &amp;#943; Η &amp;#943; ι Η N &amp;#943; 1 ι v.3 2 5 01 ATGATTATAAAGTGGGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGG 2550 t v.l 2551 cctagagtacagagtgacctggaagccacagggagccccagtggagtggg Π II Π I 1 II Π 1 1 II 1 1 I! 1 II 1 11111 I 1111 I 11II II 1 1 1 I I II II 2600 1 1 i i 1 1 &amp;#943; | i ! 1 1 i 1 ! 1 ι 1 II ! 1 II 1 1 1 1 ! &amp;#943; 1 1 I 1 t I 1 II ι ι I II ι 1 1 ι 1 ( v.3 25 51 CCTAGAGTACAGAGTGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGG· 2600 v.l 2601 aagaagaaacagtcacaaaccacacattgcgggtgatgacgcctgctgtc . I 1 II |l 1 II 1 II l| II l| 1 1 II 1 1 1 1 II II II II 1 l| 1 |l II |l II 1 1 II 2650 l ι &amp;#943; ι 1 1 l 1 l 1 I 1 11 1 1 1 l &amp;#943; 11 I 11 I 1 I ll 1 1 II 1 1 1 II &amp;#943; 1 1 1 Η 1 11 II 1 v.3 2601 AAGAAGAAACAGTCACAAACCACACATTGGGGGTGATGACGCCTGCTGTC 2650 v.l 2551 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg Π I! 111 1 1 I 1 1 I! II II II II 1 II H I 111 111 I 11 I 1 II 1 Η Π Π Π 2700 1 N 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Π 1 1 1 1 1 1 1 1 1 1 I ) 1 1 i 1 ι H 1 l &amp;#943; 1 1 Η Η 1 1 v.3 2651 TATGCCCCTTATGATGTCAAGGTCCAGGCTATCAATCAACTAGGATCTGG 2700 v.l 2701 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata 1 1 11 II 1 1 II 1 1 1 1 II II 1 1 1 1 1 1 H I II 1 1 I I 1 II 1 1 IIII! Γ Π 1 1 H 2750 1 1 1 1 i 1 U S 1 I 1 I 1 ι II 1 l I 1 1 1 1 1 ι 1 II 1 I N I 1 I 1 i 1 { I 1 N Η 1 &amp;#943; H v.3 2701 GCCTGACCCTCAGTCAGTGACTCTCTATOCTGGAGAAGACTATCCTGATA 2750 v.l 2751 cagctccagtgatccatggggtggacgttataaacagtacattagttaaa | 1 1 1 1 | 1 1 1 1 1 1 1 1 | 1 I 1 1 1 1 1 1 1 ! 1 1 1 1 2800 I I 1 I 1 1 U i 1 i 1 1 i 1 1 I ! I ! i 1 i 1 M I i i v.3 2751 CAGCTCCAGTGATCCATGGGGTGGACGTT--------------------- 2779 v.l 2801 gttacctggtcaacagttccaaaggacagagtacatggacgtctgaaagg 2850 v.3 2780 -------------------------------------------------- 2779 v.l 2851 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac 2900 v.3 2780 -------------------------------------------------- 2779 v.l 2901 atcccaaagaagtgaacattctaagattttcaggacaaagaaactctgga 2950 258 1. ,. -1 v.3 2780 -------------------------------------------------- 2779 v.1 2951 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc 3000 v.3 2780 -------------------------------------------------- 2779 v.1 3001 ctataactctaaaggagctggtcctgaaagtgagccttatatatttcaaa 3050 v.3 2780 ---------- 2779 v.1 3051 caccagaaggagtacctgaacagccaacttttctaaaggtcatcaaagtt 3100 v.3 2780 -------------------------------------------------- 2779 v.l 3101 gataaagacactgccactttatcttggggactacctaagaaattaaatgg 3150 v.3 2780 ------------------------------------------------ 2779 v.l 3151 aaacttaactggctatcttttgcaatatcagataataaatgacacctacg 3200 v.3 2780’------------------ --------------------------- 2779 v.l 3201 agat'tggagaattaaatgatattaacattacaactccatcaaagcccagc 3250 v.3 2780 --------------------------------- 2779 v.l 3251 tggcacctctcaaacctgaatgcaactaccaagtacaaattctacttgag 3300 v.3 2780 --- 2779 v.l 3301 ggcttgcacttcacagggctgtggaaaaccgatcacggaggaaagctcca 3350 v.3 2780 -------------------------------------------------- 2779 v.l 3351 ccttaggagaagggagtaaaggtatcgggaagatatcaggagtaaatctt 3400 v.3 2780 ----------------------------_____----------------- 2779 v.l 3401 actcaaaagactcacccaatagaggtatttgagccgggagctgaacatat 3450 V.3 2780 -------------------------------------------------- 2779 v.l 3451 agttcgcctaatgactaagaattggggcgataacgatagcatttttcaag 3500 v.3 2780 --------------- 2779 v.l 3501 atgtaattgagacaagagggagagaatatgctggtttatatgatgacatc 3550 V.3 2780 -------------------------------------------------- 2779 v.l 3551 tccactcaaggctggtttattggactgatgtgtgcgattgctcttctcac 3600 v.3 2780 --------------------------------------------'------- 2779 v.l 3601 actactattattaactgtttgctttgtgaagaggaatagaggtggaaagt 3650 V.3 2780 -------------------------------:-----------------------, 2779 v.l 3651 actcagttaaagaaaaggaagatttgcatccagacccagaaattcagtca 3700 V.3 2780 -------------------------------------------- 2779 259 _v.l 3701 gtaaaagatgaaacctttggtgaatacagtgacagtgatgaaaagcctct v.3 2780 -------------------------------------------------- v.l 3751 caaaggaagccttcggtcccttaatagggatatgcagcctactgaasgtg v.3 2780 -------------------------------------------------- v.l 3801 ctgacagcttagtcgaatacggagagggagaccatggtctcttcagtgaa v.3 2780 --------------------------------------------------- v.l 3851 gatggatcatttattggtgcctacgctggatctaaggagaagggatctgt v.3 2780 ---------- --------------------------------------- v.l 3901 tgaaagcaatggaagttctacagcaacttttccccttcgggcataaacac llllllll

v.3 27 80 ------------------------------------------ATAAACAC v.l 3951 aacatatgtaagcaacgctactggttcaccccaaccttccatatttatct

, 111111111111111111111111111!II11111111! 111111 II III

v.3 27 8 8 AACATATGTAAGCAACGCTACTGGTTCACCCCAACCTTCCATATTTATCT v.l 4001 gttcaaaggagcaagaactttcatataggaatagaaacatgctggccgaa 111111111111 I’ll 111111 i 1111111111111111111111111111

v.3 2838 GTTCAAAGGAGCAAGAACTTTCATATAGGAATAGAAACATGCTGGCCGAA v.l 4051 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac 111111111111 i 1111111 iIi111111 iIII11i 111 i I i 11111 i 11

v.3 2888 GATTTCATCCAGAAGTCAACATCCTGCAATTATGTTGAAAAGAGTAGTAC v.l 4101 tttcttcaaaatataaaatgccaagcacttcaggcctatgttttgcttat 11111111111111111II1111111111111111111111111111111

v.3 2938 TTTCTTCAAAATATAAAATGCCAAGCACTTCAGGCCTATGTTTTGCTTAT v.l 4151 attgttttcaggtgctcaaaatgcaaaacacaaaacaaatcctgcattta 111111111111111111111111II11111II11111II1111111111

V.3 2988 ATTGTTTTCAGGTGCTCAAAATGCAAAACACAAAACAAATCCTGCATTTA v.l 4201 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg 11111 Π 1111111II1111II111II11 Η 1111111 Η 1111111111

v.3 3038 GATACACCTCAACTAAATCCAAAGTCCCCATTCAGTATATTCCATaTTTG v.l 4251 cctgattttactattcggtgtgtttgGatagatgttgctacttggtgggt 11111111111111111 111 111111111IIIII111111II11111111

v.3 3088 CCTGATTTTACTATTCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGT v.l 4301 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga

1II! 11111II1111 111 III11II111111!I ill 1!IIII1111!III

v.3 3138 TTTTCTCCGTATGCACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGA v.l 4351 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa 111111111111111111111IIIII111111111111111111111111

v.3 318 8 CTTTGCTTCACTACAGGTTAAAAGACCATAAGCAAACTGGTTATTTAAAA v.l 4401 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac

11111111111 ii 111111II11111 H II II11II I! I! IIIII1111.I

v.3 323 8 TGTAAAAAGGAATATGAAAGTCTTATTAAAACACTTCATTGAAAATATAC v.l 4451 agtctaaatttattatttaaattttactagcaaaagtcttaggtgaacaa 111111111111II11!111II1II111II!IIIII I!111111II I! 11

v.3 32 8 8 AGTCTAAATTTATTATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAA 3750 2779 3800 2779 3850 2779 3900 2779 3950 2787 4000 2837 4050 2887 4100 2937 4150 2987 4200 3037 4250 3087 4300 313 7 4350 3187 4400 3237 4450 32 87 4500 3337 260 k · -er v.l 4501 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa 1 I I I I I I I 1 I I I I I I 1 | I I I I I | I 1 | I I 1 I | I I I I I I 1 I I j 1 | I 1 ] I II I 4550 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.3 3338 TCAACTAGTATTTGTTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAA 3387 v.l 4551 acagaagtatacgtttttcagtttcaacatgaatttttttatttctgtca I I II II I I II ! 1 | 1 1 ! II 1 1 H 1 1 1 ! 1 11 1 1 1 1 I I 1 II I I || 1 I 1 1 1 1 4600 1 1 1 1 1 1 1 l 1 il 1 l &amp;#943; ! 1 1 1 1 1 1 1 1 I 1 1 I ! 1 &amp;#943; 1 I I i 1 1 i 1 1 J ι s 1 i &amp;#943; h ι t ι v.3 3388 ACAGAAGTATACGTTTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCA 3437 v.l 4601 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct i ( I &amp;#943; II I 1 1 II I II 1 1 II | | II II IIII I 1 1 I II 1 I II 1 1 1 1 1 1 1 1 II II 4650 1 1 1 J 1 { 1 1 El 1 1 1 1 I 1 1 1 s ι ι 1 1 1 i I I 1 1 i 1 1 1 I 1 ι 1 &amp;#943; I 1 SI 1 &amp;#943; 1 1 ι 1 &amp;#943; ι v.3 343 8 GTTATGACATCCACgAGCATCACTTTTTGTGTCTGTTTTTTTTTTTTTCT 3487 v.l 4651 tggactaaattcaactgcatggaagcggtggtcagaaggttgttttatac I II I I 1 I 1 I II 1 I II I I I I I 1 1 1 I I I I I 1 I I 1 II 1 1 1 I I 1 I 1 1 1 I I I I 1 1 4700 1 Π 1 N N 1 I N 1 I I N 1 1 1 1 I ι &amp;#943; &amp;#943; 1 1 1 I J Η I Η 1 i I 1 1 1 I 1 M 1 1 I 1 I v.3 348 8 TGGACTAAATTCAACTGCATGGAAGCGGTGGTCAGAAGGTTGTTTTATAC 3537 v.l 4701 gagaacaggcagaaagtgcccattgttcaggattctaatagctacatcta I 1 I I I 1 I I II I II 1 || 1 1 I I 1 1 I I I I I I 1 1 1 1 1 1 I 1 I 1 1 1 1 I I 1 1 II I i 1 4750 I i 1 1 I 1 i ι 1 I 1 1 1 i 1 I ! 1 ι 1 1 1 ( 1 U 1 ! H 1 i t t 1 1 ! 1 1 ! I 1 1 i I 1 N 1 I v.3 353 8 GAGAACAGGCAGAAAGTGCCCATTGTTCAGGATTCTAATAGCTACATCTA 3587 v.l 4751 cttaatatcttcatttctaaattgactgcttfctacctttttctcatgttt ! 1 1II II11 1 1 1 1 1 1 1 1 ! 1 II 1 1 1 1 11 1 1 1 1 1 1 1 11 1 1 11 11 1 1 1 1 1 1 1 1 4800 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.3 35 88 CTTAATATCTTCATTTCTAAATTGACTGCTTTTACCTTTTTCTCATGTTT 3637 v.l 4801 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4850 1 1 ι ι 1 1 1 ι 1 ι 1 ι t 1 ι ι ι i 1 1 ! 1 1 I I I 1 I i &amp;#943; &amp;#943; I 1 { 1 1 &amp;#943; !! ! 1 ι ι I 1 ι 1 i 1 1 v.3 3 63 8 ATATAATGGTATGCTTGCATATATTTCATGAATACATTGTACATATTATG 3687 v.l 4851 ttaatatttacacaatttaaaatatagatgtgttttattttgaagtgaga II 1 II 1 II 1 I 1 1 I I I 1 II 1 1 1 II 1 I I I I 1 1 1 II 1 1 I 1 1 1 I I 1 1 11 I I I 1 I 4900 iTT 1 1 1 1 I 1 1 1 l ι 1 I I 1 ι &amp;#943; 1 I f 1 1 1 1ιI 1 1 I i 1 1 1 ι I 1 1 ι I 1 1 ι 1 I 1 1 1 1 v.3 368 8 TTAATATTTACACAATTTAAAATATAGATGTGTTTTATTTTGAAGTGAGA 3737 v.l 4901 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat 1 1 1 1 1 1 1 I 1 1 1 I 1 1 I 1 1 1 1 1 1 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 I 1 I 1 1 1 1 4950 1 1 I 1 1 1 I ! I 1 1 I 1 1 j 1 ! 1 1 J 1 1 I 1 1 1 1 1 1 1 1 I 1 1 ι 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 v.3 3738 AAATGAACATTAACAGGCATGTTTGTACAGCTAGAATATATTAGTAAGAT 3787 v.l 4951 actgtttttcgtcattccagagctacaactaataacacgaggttccaaag ! 1 I 1 I I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I I 1 I 1 1 1 1 I 1 1 1 ! I I I I I I I I I 1 I ! 1 ! 5000 1 ι 1 1 1 1 1 1 I ! 1 1&amp;#906; 1 Η 1 1 1 1 11 1 I ι 1 1 1 I ι 1 1 1 1 1 i 1 1 1 i ι ι i ι ι Η 1 ι ι v.3 378 8 ACTGTTTTTCGTCATTCCAGAGCTACAACTAATAACACGAGGTTCCAAAG 3837 v.l 5001 ctgaagactttgtataaagtatttgggttttgttcttgtattgctttctt ι nm mm i immmimimi mm mi nm ii! v.3 3838 CTGAAGACTTTGTATAAAGTATTTGGGTTTTGTTCTTGTATTGCTTTCTT 5050 3887 v.l 5051 tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc 1 1 1 11 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 II 1 II 1 1 il 1 1 1 1 1 i I 5100 1 1 1 11 1 I 1 1 1 1 1 1 1 11 111 1 1 1 1 1 1 11 1 1 1 111 1 1 1 1 1 1 111 11 1 1 1 1 1 1 v.3 3888 TCAACAGTTTCAAAATAAAATATCATAcAAATATTGAGGGAAATGTTTTC 3937 v.l 5101 atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc | 1 1 1 1 11 11 II 1 1 1 l| 1 1 1 1 l| 1 1 1 1 II 1 1 1 1 1 II 1 1 1 1 1 1 1 I II II I I 1 5150 l ι I 1 1 1 I I I ι ι Π I ι H 1 ι 1 &amp;#943; l 1 H 1 ι &amp;#943; ( 1 I 1 1 Η &amp;#943; 1 ι ι &amp;#943; I &amp;#943; I I ι ι Η H v.3 3 93 8 ATATTTTTCAAAATAGGTTTTTATTGTTGAATGTACATCTACCCCAGCCC 3987 v.l 5151 ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta 1 I I I I i j 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 I 1 1 I 1 1 1 1 1 1 5200 1 ! 1 1 I 1 1 1 1 I 11 1 I 1 1 1 1 1 I 1 1 I 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.3 3988 CTCAAAAGAAAAACTGTTTACATAGAAATTCCTACACATACGTTTGCGTA 4037 v.l 5201 tatgttattttaaacatctttgtggtgagaattttttccccgatattctc | II 1 1 1 1 Η 1 II 1 1 1 1 1 1 1 1 II Π Η 1 1 1 1 1 II 1 1 II 1 1 II 1 1 I 1 1 1 111 5250 1 1 1 I 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 &amp;#943; ι 1 t 1 1 1 &amp;#938; I ! 1 1 1 1 1 I 1 &amp;#943; 1 ! i 1 t Si I ! 1 1 1 4087 v.l 5251 cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt mimuiimmmmmmmmtmmmmm 5300 261 V73 408 8 CTTCTGTCAAAGTCAGAACAAATTCAGGGAATTTATTTTCTGGCAGTTGT 4137 v.l 5301 gctccagtccttttaaaattgtacatgaacatgttttagaaacaafcatgg t I I j H 1 I 1 1 1 1 1 1 1 1 1 I It I 1 1 1 1 1 I I I I I j 1 I I I 1 1 1 1 II 1 I I ] 11 II 5350 U 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 I v.3 4138 GCTCCAGTCCTTTTAAAATTGTACATGAACATGTTTTAGAAACAATATGG 4187 v.l 5351 aggatgatgcatacatgtcggtcaagttcagcgctcgacattttatggaa 1 1 1 ) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 f ( 1 I f f f 1 1 1 1 ( 1 1 i I 1 1 i 1 5400 I N Η I I S Η I I i I I h ! ! i I i 1 i 1 1 1 I &amp;#970; N 1 1 1 I I 1 i 1 1 1 1 1 1 I l Π I S V.S 4188 AGGATGATGCATACATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAA 4237 v. 1 5401 agatttttttaaccttaccacgaaatacttaactactgtttaagtgaatt 1 1 1 1 1 1 1 1 1 1 1 1 111111 1 1 1 1 1 I 1 11 1 1 1 1 ! 1 1 1 1 11 1 1 1 1 1 1 i I ! 1 1 1 5450 1 N H / Η Π ) / N ) ) 1 ) ) ) i Π I 1 1 Ii 1 1 1 I 1 I N 1 1 j I 1 1 1) I 1 1 1 1 1 v.S 4238 AGATTTTTTTAACCTTACCACGAAATACTTAACTACTGTTTAAGTGAATT 4287 v.l 5451 gacttatttcactttagtttttgaactgtgattattggtatactgttata 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 ! 1 5500 I 1 1 1 1 1 1 i i { i I It i 1 i i N 1 I 11 i I 1 ι 1 i Η II I I 11 1 1 1 I I 1 I 1 I i » 1 V.3 42 88 GACTTATTTCACTTTAGTTTTTGAACTGTGATTATTGGTATACTGTTATA 4337 v.l 5501 tcctcaacttggatttatggtaaccccttttagttcatggagaccaaaat I I I I I II I I I II II I 1 II 1 II 1 1 1 II I |l I I II I II I 1 I II 11 1 1 I) 11 1 5550 I I M i I 1 1 i l 1 1 1 I I 1 I 1 1 1 I 1 1 I 1 I 1 U I I 1 I 1 II ι I 1 H t I I Η II H v.S 4 S 3 8 TCCTCAACTTGGATTTATGGTAACCCCTTtTAGTTCATGGAGACCAAAAT 4387 v.l 5551 ttqgggtatttataatagtcagcgcaggaatgcacatggaatatctactt 1 1 INI 111 11! 11 11 IIII II II1II II 1II1II 1IIII 111II11111 5600 I I Η ι 1 I 1 ι ι ι ι { i ι ι ι ι ι ι &lt; ι t i 1 1 ι ι I 1 ι 1 I i ι 1 1 ι I I 1 1 I-1 1 I I I I 1 V.3 4388 TTGGGGTATTTATAATAGTCAGCGCAGGAATGCACATGGAATATCTACTT 4437 v.l 5601 gtccttttgaacctcacgagtcatccagaatgtatagacaggaaaagcat 1 I 1 1 1 j 1 1 I 1 1 I 1 1 I 1 1 1 I 1 II 1 1 I 1 11 1 1 1 1 II 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 5650 H 1 1 1 1 1 i 1 I 1 1 1 I I 1 1 1 Π I 1 I 1 i 1 1 1 1 I 1 I I I 1 i I I 1 1 1 1 I I 1 1 I 1 I I V.3 4438 GTCCTTTTGAACCTCACGAGTCATCCAGAATGTATAGACAGGAAAAGCAT 4487 v.l 5651 gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg | II I I 1 1 I I I I I I I I I I II I I I I I 1 I I I I I I 1 I 1 1 1 I 1 1 I It 1 1 1 I 1 1 1 j 5700 I I I I l ι Η I 1 1 1 I I i 1 &amp;#943; ι 1 I 1 Η 1 1 1 1 1 1 1 Η I 1 1 i 1 1 1 I ! 1 1 I 1 1 1 I 1 J v.S 4488 GTCTTATTTAAAACTGTAATTTATGGGCTCAGGATCTGACCGCAGTCCCG 4537 v.l 5701 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga I III || IN 11 1 11II III 111 till II Nil Nil 1 11 II 1 N (IN II 5750 I i 1 I 1 I 1 1 I l ι 1 I 1 I.I ι 1 ι 1 ι I t H f I l &amp;#943; &amp;#943; &amp;#943; I ( I 1 &amp;#943; &amp;#943; Ι ι &amp;#943; ι 1 f N ι ι ι ι ι v.S 4538 GGAGTAAGCATTTCAAAGGGGGAAGGCAGTGTGGTCCCTACCCTGTGTGA 4587 v.l 5751 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc ill 1 1 1 1 1 1 1 1 11(1111111111111111111111111 1 1 II II 1 1 1 11 5800 ι ι ι I I I I 1 ι H 1 1 1 1 ι l ι &amp;#943; ι ι 1 I I 1 1 ι ι ι ι Η I 1 I 1 1 1 1 I I I 1 I I H 1 1 1 v.3 45 8 8 ATGTGAGGATGTAGACATCCATCAGTGCAACTCGAGCTCCATCCTCCTCC 4637 v.l 5801 gatttctaaqgctccagttttetggaqgqacagtcatcatgttttgattt II1 π t IιII I II π||IIιI 1 μ 1I|111|||111|1| | 1 || 1 II 1 111 5850 Η 1 1 1 1 Η 1 1 l i I i 1 1 i 1 I I i 1 &amp;#943; Η i 1 i H 1 s 1 Π Η I ι 1 1 I Η I Η Η 1 v.S 4 63 8 GATTTCTAAGGcTCCAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTT 4687 v.l 5851 atctgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga luuunuuiuuiuuuuuuuuuimuumu v.3 468S ATCTGGGAGAAAACTGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGA 5900 4737 v.l 5901 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcag II II I ! 1 I | 1 | | | | | ι | 1 1 1 1 1 1 1 1 1 1 1 I 1 |[ 1 |l II II II II 1 )| II 1 1 5950 1 i &amp;#943; m ι 1 ι I &amp;#943; ι I i 1 J 1 1 1 1 1 II 1 II. 1 &amp;#943; 1 1 1 S 1 I I I 1 I 1 1 i ! 1 ! 1 I 1 i ! J 1 v.3 4738 CGTTCGAGCTTAGTTCTGGTGTTATTdTGTCTCCTCTTCTTTGTCATCAG 4787 v.l 5951 ccaaaacgtggttttfcaaagagagtcatgcaggttagaaataatgtcaaa 1 1 1 I 1 1 1 1 1 1 1 I 11 1 1 111 1 1 1 I 111 I 1 I 111111&amp;#906; i 11111II11II11 6000 i1i) I i i1 l It i l I 1 ι 111 I I I 11 11 1 1 ι ι I &amp;#943; Η I 1 I II I I I I I 1 I l ι i 1 v.3 4788 CCAAAACGTGGTTTTTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAA 4837 v.l 6001 aatatttaggaatttaataacctttaagtcagaaactaaaacaaatactg I I 1 I i 1 II 1 1 1 1 Ι&amp;#906; 1 I 1 1 1 1 1 1 1 1 Π 1 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 1 1 1 Μ I 6050 I 1 ι &amp;#943; 1 I I I 1 1 Η 1 I i &amp;#943; 1 1 i 1 1 1 Η 1 I H I 1 i 1 ! i I 1 1 1 ι 1 ι ι 1 ι H 1 i H v.3 4 83 8 AATATTTAGGAATTTAATAACCTTTAAGTCAGAAACTAAAACAAATACTG 4887 v.l 6051 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat 6100 262

v.3 4 8 88 AAATATTAGCTCTTCCTACACTTCGTGTTCCCCTTTAGCTGCCTGAAAAT v.l 6101 caagattgctcctactcagatcttctgagtggctaaaacttatggatatg )1I 11111111 Η 111 Η I Η 1111111!I!1111II Η III 11 Π Π 11

v.3 4938 CAAGATTGCTCCTaCTCAGATCTTCTGAGTGGCTAAAACTTATGGATATG v.l 6151 aaaaatqaqattgaatgatgactatgctttgctatcattgttacctttcc

&amp;#912;Η&amp;#912;&amp;#943;&amp;#943;ΗππΗΗΗΗΗΗπ immmmmmmH

v.3 4988 AAAAATGAGATTGAATGATGACTATGCTTTGCTATCATTGTTACCTTTCC v.l 6201 tcaatactatttggcaactactgggactcttcagcacaaaaggaatagat 111111111111111111111111 N 111111111111111111111 i 11

v.3 5038 TCAATACTATTTGGCAACTACTGGGACTCTTCAGCACAAAAGGAATAGAT v.l 6251 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt

111111111111111II1111111II111111II11 III 111 ill 111 II

v.3 50 8 8 CTATGATTGACCCTGATTTTAATTGTGAAATTATATGATTCATATATTTT v.l 6301 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg 1111 Η II Η II II 11111 HI 1111 Η 1II111III Η Η 11II11111

v.3 513 8 ATGAATCAGAA.TAACCTTCAAATAAAATAAATCTAAGTCGGTTAAAA.TGG v.l 6351 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa 111111111 Ii I! 11111 Ii 111!11111i11111! 11!!1111111111

V.3 518 8 ATTTCATGATTTTCCCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAA v.l 6401 tggtaattataaattggtgatgcttgtttgcaaattgcccactcgtgata 111! 1111111111111II11111111111111II111111111111111

V.3 5238 TGGTAATTATAAATTGGTGATGCTTGTTTGCAAATTGCCCACTCGTGATA v.l 6451 agtcaacagccaatatttaaaactttgttcgttactggctttaccctaac &amp;#943; II HI 1111! 11II11II Nil IIIII &amp;#943;! 11111II111III! II1111

v.3 52 8 8 AGTCAACAGCCAATATTTAAAACTTTGTTCGTTACTGGCTTTACCCTAAC v.l 6501 tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag 1111111111iII111Π111II11111111111! 1111II1111 H 111

v.3 53 3 8 TTTCTCTAGTCTACTGTCAATATCATTTTAATGTAATTGATTGTATATAG v.l 6551 tctcaaqaatggttggtgggcatgagttcctagagaactgtccaagggtt

111111J11111111111111111 III 11II111111II11111111 III

v.3 53 8 8 TCTCAAGAATGGTTGGTGGGCATGAGTTCCTAGAGAACTGTCCAAGGGTT v.l 66 01 gggaaaatccaaattctcttcctggctccagcactgattttgta>cataaa

IIII11! IIIIIII11IIIIIIIIIIIIIIIII I! III11111IIIIIII

v.3 5438 GGGAAAATCCAAATTCTCTTCCTGGcTCCAGCACTGATTTTGTACATAAA v.l 6651 cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa 11! III1111111111II1111II11II1IIII11 Si 1 H 111! 11 111 1

v.3 5488 CATTAGGCAGGTTGCTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAA v.l 6701 gtgctaataataatctcagttaccttatctttcjtcacagggtgfctctttt v 3 553 8 v.l 6751 ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc

i Η ! I Ml Η Η 111 HI I III Η II Η I &amp;#943; II N &amp;#943; Η Η &amp;#943; Η UΗ Η U

v.3 5588 TTATGAAGAAAAATTTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTC v.l 6801 ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc

1111II111II11 IS 111II11 HI 11 IS II111II111II I! 11IIIII

v.3 563 8 ATAAGCAAACCTTTAACTAATTATGTATCTGAAAGTCACCCCCACATACC 4937 6150 4987 6200 5037 6250 5087 6300 5137 6350 5187 640 0 5237 6450 5287 6500 5337 6550 5387 6600 5437 6650 5487 6700 . 5537 6750 5587 6800 5637 6850 5687 263 ,ν. 1 6851 aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca ill! Ill Hill II nil 11 III IIII mill IIIIII III Ulll III 6900 v.3 5 fo 3 8 AACTCAACTTTTTTCCTGTGAACACATAAATATATTTTTATAGAAAAACA 5737 v. 1 6901 aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat I Η Π Π 1 Η Η II II II Π Π Π 1 I Π 1 II Π Η II 1 II Π II Π Π H 6950 v.3 5738 &amp;#943; i &amp;#943; Η Η Η 1 Η 1 I J &amp;#943; 1 II H }1 I 1 I j i 1 1 1 I I 1 ι I I 11 1 i 1 S 1 l I 1 1 1 i AATCTACATAAAATAAATCTACTGTTTAGTGAGCAGTATGAcTTCTACAT 5787 v.l 6951 gccattgaaaattattaatcagaagaaaattaagcagggtctttgctata I II II II II II I I I 1 1 1 I | II I 1 1 II 1 1 II II 1 1 II I II I I 11 1 I I 1 I 7000 V. 3 5788 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 II I I 1 II 1 II I 1 II 1 ! II 1 1 1 1 1 1 &amp;#943; 1 ! 1 1 1 1 1 1 GCCATTGAAAATTATTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATA 5837 v.l 7001 caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga Η Π 1 II N 1 1 1 II II II 1 N 1 1 Η II 1 N 1 I II Π Π Π 1 II II 1 1 II 1 7050 v.3 5838 l I I II 1 1 I 1 l I l &amp;#943; 1 I 1 I 1 I 1 1 1 1 I 1 I 1 1 1 ! II 1 I 1 1 1 I 1 1 1 1 1 I I 1 I t I 1 GAAAAGTGTTTTCCACTAATTTTGCATGCGTATTTATAAGAAAAATGTGA 5887 v.l 7051 atttggtggttttattctatcggtataaaggcatcgatattttagatgca 1 1 1 1 I II I 1 1 1 1 1 1 II 1 1 II II 1 II 1 1 1 1 II 1II 1 1 I Π 1 1 1 1 1 1 I 1 1 II 7100 v.3 5888 I 1 I 1 1 1 il i 1 1 I 1 I I 1 I 1 ι 1 I I 1 1 1 &amp;#943; 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I 1 1 I 1 I I ATTTGGTGGTTTTATTCTATCGGTATAAAGGCATcGATATTTTAGATGCA 5937 v.l 7101 cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7150 v. 3 5938 1 1 I I j ι Η Η I I 1 1 H 1 1 1 &amp;#943; J Η J 1 I I 1 ) ) 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I I 1 i I 1 CCCGTGTTTGTAAAAATGTAGAGCACAATGGAATTATGCTGGAAGTCTCA 5987 v.l 7151 aataatatttttttcctattttatactcatggaagagataagctaaagag ι η ι m m m m n m m m i m ι m ι m m m m 11 7200 v. 3 5988 AATAATATTTTTTTCCTATTTTATACTCATGGAAGAGATAAGCTAAAGAG 6037 v.l 7201 ggqacaataatgagaaatgttggtgtgcttttctaagcatttaaaacata Till IIIIII 1 IIII11II1 I IIII II I 1 1 1 1 1 1 1 III 1 1 1 1 1 1 11 1 1 1 1 7250 v.3 6038 1 i 1 S 1 I 1 1 1 I l &amp;#943; 1 1 1 1 1 1 1 1 1 I I 1 I 1 1 i ! I H i I 1 1 1 1 I 1 I I 1 I I 1 1 1 I 1 GGGACAATAATGAGAAATGTTGGTGTGCTTTTCTAAGCATTTAAAACATA 6087 v.l 7251 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc 1 1 1 1 1 1 1 1 11 1 1 1II 11 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 I 1 1!1 1 1 1 I 1111 1 1 1 I 7300 v.3 6088 it 1 I 1 11 1 1 1 1 1 1 1 U 1 1 1 1 1 1 1 1 t I 1 t 11 I 1 1 I 1 1 1 I I } 1 t ! i 1 I 1 1 1 1 ATTGCCAATTGAAACCCTAAATATGTTTACATACCATTAAGATATGATTC 6137 v.l 7301 atgtaacaatqttaaattaattataatgggattgqgtttgttatctgtgg η N HI I 1 1 INI III IH II ! Hl l| Hl 1 IN II I IU 1 I III HI 1 7350 v.3 6138 I i II J 1 1 1 1 II &amp;#912; II 1 Η 1 f J 1 &amp;#943; N 1 1 i 1 11 1 S i 1 1 m i 1 1 ii 11 I 1 ! 1 U ATGTAACAATGTTAAATTAATTATAATGGGATTGGGTTTGTTATCTGTGG 6187 v.l 7351 tagtatatatcctagtgttcctatagtgaaataagtagggttcagccaaa | I N 1 ΓII1II1 II II II I II II 1 1 II 1 I II 11 H II 1 1 II II 1 1 1 1 1 II 7400 v.3 6188 1 It ! 1 &amp;#943; 1 H 1 i 1 1 ! it 1 l &amp;#943; 1 i 1 t I i t 1 I 1 I 1 1 i ι &amp;#943; 1 ι 1 1 1 1 J 1 1 i i &amp;#943; 1 1 1 TAGTATATATCCTAGTGTTCCTATAGTGAAATAAGTAGGGTTCAGCCAAA 6237 v.l 7401 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga 1 I II H 1 II H II 1 1 11 1 Π Π 1 II II II 11 II I H IIII I 1 II II 1 II 1 7450 v.3 5238 i U i 1 1 I I i 1 1 i i 1 i ι 1 I i 1 1 1 I i i i i I 1 1 1 1 I 1 H i i t 1 1 I i 1 i 1 1 I 1 1 GCTTTCTTTGTTTTGTACC'TTAAATTGTTCGATTACGTCATCAAAAGAGA 6287 v. 1 7451 tgaaaggtatgtagaacaggttcacgtgattacctttttcttttggcttg 11 III 111 III II III III 1II N1N11NIII III 1II1 III 1 III II 7500 v. 3 62 8 8 TGAAAGGTATGTAGAACAGGTTCACGTGATTACCTTTTTCTTTTGGCTTG I v. 1 7501 gattaatattcatagtagaactttataaaacgtgtttgtattgtaggtgg | I Η II j l| I I 11 I II II 1 I I I 1 1 il II |l 1 II || II 11 1 1 1 I 1 11 1 I I I 755 0 v.3 6338 1 1 1 1 1 1 1 1 1 H 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1. II 1 1 1 1 1 1 GATTAATATTCATAGTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGG 6387 v. 1 7551 tgtttgtattatgcttatgactatgtatggtttgaaaatattttcattat II Μ Π 1 1 1 II II 1 II Μ l| II 1 I II II II 1 1 II j 1 1 1 1 1 1 1 II &amp;#943; II |l j 7600 v. 3 6388 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 t 1 I 1 111 I H II II II II I II II 1 TGTTTGTATTATGCTTATGACTATGTATGGTTTGAAAATATTTTCATTAT . 6437 V. 1 7601 acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa | 1 H 111II111111111 11IIII II II II il II II I 1 1 1 II 1 1 1 1 1 1 II 7650 v. 3 6438 H i I 11 π 1 1 1 1 I 1 I I H I 1 1 I 1 1 1 1 H 1 I I 1 { I I { I | 111 | 1 1 I u 1 1 | acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa 6487 264

Table LIVb. Peptide sequences of protein coded by 282P1G03 v.3 (SEQ ID NO: 160) MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 60 GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 12 0 EEIEFIVPSV PKLPREKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV 180 YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSLKHA NDSSSSTEIG 240 SKANSIKQRK PKLLLPPTES GSESSITILK GEILLLECFA EGLPTPQVDW NKIGGDLPKG 300 RETKENYGKT LKIENVSYQD KGNYRCTASN FLGTATHDFH VIVEEPPRWT KKPQSAVYST 3 60 GSNGILLCEA EGEPQPTIKW RVNGSPVDNH PFAGDWFPR EISFTNLQPN HTAVYQCEAS 42 0 NVHGTILANA NIDWDVRPL IQTKDGENYA TWGYSAFLH CEFFASPEAV VSWQKVEEVK 4 80 PLEGRRYHIY ENGTLQINRT TEEDAGSYSC WVENAIGKTA VTANLDIRNA TKLRVSPKNP 54 0 RIPKLHMLEL HCESKCDSHL KHSLKLSWSK DGEAFEINGT EDGRIIIDGA NLTISNVTLE 600 DQGIYCCSAH TALDSAADIT QVTVLDVPDP PENLHLSERQ NRSVRLTWEA GADHNSNISE 660 YIVEFEGNKE EPGRWEELTR VQGKKTTVIL PLAPFVRYQF RVIAVNEVGR SQPSQPSDHH 720 ETPPAAPDRN PQNIEVQASQ PKEMIIKWEP LKSMEQNGPG LEYRVTWKPQ GAPVEWEEET 7 80 VTNHTLRVMT PAVYAPYDVK VQAINQLGSG PDPQSVTLYS GEDYPDTAPV IHGVDVINTT 84 0 YVSNATGSPQ PSIFICSKEQ ELSYRNRNML AEDFIQKSTS CNYVEKSSTF FKI 8 93

Table LVb. Amino acid sequence alignment of 282P1G03 v.1 (SEQ ID NO: 161) and 282P1G03 v.3 (SEQ ID NO: 162) v.l 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD | I I I I I I ] I j I I I I 1 1 I 1 I I I I I I I 1 I I I I I 1 I I I 1 I 1 I I I I 1 I I I 1 1 1 1 50 v.3 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 MEPLLLGRGLTVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD 50 v.l 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 1 1 1 1 1 1 1 1 1 1 1 1 I 1 II 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 U 1 1 I 1 1 1 1 1 1 1 1 1 1 I 100 V.3 51 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 V.l 101 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV I 1 1 II 1 j II 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 150 v.3 101 1 1 1 11111111 &amp;#943;111111 I 1IIII111 I 1111 1 II 1 II II 1 1 1 II 1 II 1 1 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV 150 v.l Xb X LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN I I I 1 I I I I I I 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 I II II 1 1 1 1 1 II 1 1 1 II 200 v.3 151 1 1 1 I 111111111111 1 1 1 1111II1111 1 I 11 1111 1 I 1 1 1 II 1 1 1 1 1 1 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVBEKDSRN 200 V.l 2 01 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK 1 1 I 1 i 1 1 1 1 1 1 1 i i 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 250 V.3 201 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK 250 v.l 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG I I I I 1 1 I i 1 1 | i ii i i i i i 1 i 1 j | , &amp;#943; &amp;#943; i I I I ! &amp;#943; &amp;#943; I I i &amp;#943; &amp;#943; &amp;#943; &amp;#943; i &amp;#943; ; ι ι | ι ι ι 3 00 v.3 251 I i 1 i 1 i &amp;#943; i 1 1 1 i i 1 i 1 i &amp;#943; 1 li li-1 1 1 I i I 1 i I 1 1 I 1 i i 1 ! I I Tl 1 1 1 1 1 1 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG 300' v.l 301 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT II 1 I 1 1 1 II II II II ! 1 1 1 1 1 1 1 1 1 II I II 1 I i 1 1 1 1 1 1 1 1 I 1 1 1 1 II 1 I 350 v.3 301 1 1 I 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 I 1 I 1 I 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT 350 v.l 351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR | I 1 1 1 1 I 1 1 1 I 1 1 1 I I 1 I II 1 I 1 1 1 I 1 1 1 1 1 1 |l I 1 1 1 1 1 1 1 1 II II 1 1 1 400 v.3 351 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1II1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 11 1 1 I 1 II 1 I l KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR 400 v.l 401 e i s finlqpnhtavyqceasnvhgtilananidvvdvr.pl IQTKDGENYA | 1 I 1 1 1 1 1 1 1 I 1 1 II 1 1 I II 1 1 1 l| I 1 I 1 1 1 1 1 1 I 1 1 1 1 I 1 1 II 1 1 1 II 1 450 v.3 401 1 1 1 1111 1 1 111 111 1111111 11 1 1 111 111 1 11 111 1 11 1 1 11 11111 · EISFTNLQPNHTAVYQCEASNVHGTILANANIDWDVRPLIQTKDGENYA 450 v.l 451 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT i 1 1 1 1 1 ) 1 ! 1 1 1 1 1 1 1 i 1 11 1 1 1 1 1 1 i 1 1 1 1 1 i 1 1 I 1 1 1 1 ) 1 1 1 1 i 1 1 1 1 ’ 500 v. 3 451 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 N 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT 500 v.l 501 TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPKNPRTPKT.HMT.ET, 550 i 11ii 111111IIfl II11li1111)&amp;#943;II Η I Μ liIU liII I II I! 265 V.-3 .- 501 TEEDAGS YS CWVENAIGKTAVTANLDIRNATKLRVS PKNPRIPKLHMLEL 550 v.l 551 HCESKCDSHLKHSLKLSWSKDGEAFEIIiGTEDGRIIIDGANLTISNVTLE 1 1 1 1 1 1 1 1 1 ) 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 600 v. 3 551 1 111 11 I 11 ι &amp;#943; 11' IIII11 1 11 &amp;#943; IIII11II1II II III 11 II I l 11 11 1 HCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE 600 v. 1 601 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA I 1 1 1 1 II 1 1 II t II I II II 1 1 II 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 650 v.3 601 111 1 1 1 1 1 I ! 11 11 11 I 111 I 1 ! i ! 1 1 1 1 I II 1 i 1 1 1 1 I II 1 1 1 1 1 ! 1 1 1 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA 650 v. 1 651 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVTLPLAPFVRYQF 1 1I 1 1 1 II 1 1II I11 1 11 I 1 1 1 1 1 11111 111 111 1 1 1 1 II 1 1 1 I 1 1 1 1 I 700 v.3 651 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 i 1 1 1 1 1 1 I 1 1 I 1 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 700 v. 1 701 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11111i 11 1 11 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 750 v.3 701 1 1 II II 1 1 1 1 II 1 1 11 1 1 1 1 1 1 1111 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 750 v.1 751 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 11 1 ! 1 1 1 I 1 1 1 I 1 1 1 800 v. 3 751 1 11 I 11 1 1 1IIIIII1 1 1 II 1 1 II 1 II 1 1 11 1 II1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 800 v.1 801 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLV-KVTWSTV I I 1 I I 1 I I I 1 I I 1 I II I I I I 1 I I I I I I 1 1 II 1 1 II II I . 1 I 1 1 849 v.3 801 111II 1 11111111 111111 1 1 1 1 1 1 111111 1 11 1 1 1 - I · 1 ·· 1 - 1 · · VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINTTYVSNATGSPQ 850 v.1 850 P 850 1 v.3 851 1 P 851

Table Life. Nucleotide sequence of transcript variant 282P1G03 v.4 (SEQ ID NO: 163) cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggegeegg acagatcgcg ttteggagge ggcgcaggtg ctgtaaactg caaaccataa tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact aategtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt tccaaaactc ccaaaagaaa aaattgaccc tettgaagtg gaggagggag atccaattgt cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atetataett egeaaaegtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac tttgaagata gagaatgtet cctaccagga caaaggaaat tategetgea cagccagcaa tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac aaagaagect cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc tgaaggagaa cctcaaccca caatcaagtg gagagteaat ggctccccag ttgacaatca tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaceaacc ttcaaccaaa tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattaege tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta tgaaaatggc acattgeaga tcaacagaac caccgaagaa gatgctgggt cttactcatg ttggStagaa aatgetatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgeata tgettgaatt 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 266 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2150 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa . 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa· ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac ttacctgaac agccaacttt 2760 tctaaaggtc atcaaagttg ataaagacac tgccacttta tcttggggac tacctaagaa 2820 attaaatgga aacttaactg gctatctttt gcaatatcag ataataaatg acacctacga 2880 gattggagaa ttaaatgata ttaacattac aactccatca aagcccagct ggcacctctc 2940 aaacctgaat gcaactacca agtacaaatt ctacttgagg gcttgcactt cacagggctg 3000 tggaaaaccg atcacggagg aaagctccac cttaggagaa gggagtaaag gtatcgggaa 3060 gatatcagga gtaaatctta ctcaaaagac tcacccaata gaggtatttg agccgggagc 3120 tgaacatata gttcgcctaa tgactaagaa ttggggcgat aacgatagca. tttttcaaga 3180 tgtaattgag acaagaggga gagaatatgc tggtttatat gatgacatct ccactcaagg 3240 ctggtttatt ggactgatgt gtgcgattgc tcttctcaca ctactattat taactgtttg 3300 ctttgtgaag aggaatagag gtggaaagta ctcagttaaa gaaaagga.ag atttgcatcc 3360 agacccagaa attcagtcag taaaagatga aacctttggt gaatacagtg acagtgatga - 3420 aaagcctctc aaaggaagcc ttcggtccct taatagggat atgcagccta ctgaaagtgc 3480 tgacagctta gtcgaatacg gagagggaga ccatggtctc ttcagtgaag atggatcatt 3540 tattggtgcc tacgctggat ctaaggagaa gggatctgtt gaaagcaatg gaagttctac 3600 agcaactttt ccccttcggg cataaacaca acatatgtaa gcaacgctac tggttcacce 3660 caaccttcca tatttatctg ttcaaaggag caagaacttt catataggaa tagaaacatg 3720 ctggccgaag atttcatcca gaagtcaaca tcctgcaatt atgttgaaaa gagtagtact 3780 ttcttcaaaa tataaaatgc caagcacttc aggcctatgt tttgcttata ttgttttcag 3840 gtgctcaaaa tgcaaaacac aaaacaaatc ctgcatttag atacacctca actaaatcca 3900 aagtccccat tcagtatatt ccatatttgc ctgattttac tattcggtgt gtttgcatag 3960 atgttgctac ttggtgggtt tttctccgta tgcacattgg tatacagtct ctgagaactg 4020 gcttggtgac tttgcttcac tacaggttaa aagaccataa gcaaactggt tatttaaaat 4080 gtaaaaagga atatgaaagt cttattaaaa cacttcattg aaaatataca gtctaaattt 4140 attatttaaa ttttactagc aaaagtctta ggtgaacaat caactagtat ttgttgagct 4200 cctatttgcc cagagatggt catatttaaa cagaagtata cgtttttcag tttcaacatg 4260 aattttttta tttctgtcag ttatgacatc cacgagcatc actttttgtg tctgtttttt 4320 tttttttctt ggactaaatt caactgcatg gaagcggtgg tcagaaggtt gttttatacg 4380 agaacaggca gaaaijtgccc attgttcagg attctaatag ctacatctac ttaatatctt 4440 catttctaaa ttgactgctt ttaccttttt ctcatgttta tataatggta tgcttgcata 4500 tatttcatga atacattgta catattatgt taatatttac acaatttaaa atatagatgt 4560 gttttatttt gaagtgagaa aatgaacatt aacaggcatg tttgtacagc tagaatatat 4620 tagtaagata ctgtttttcg tcattccaga gctacaacta ataacacgag gttccaaagc 4680 tgaagacttt gtataaagta tttgggtttt gttcttgtat tgctttcttt caacagtttc 4740 aaaataaaat atcatacaaa tattgaggga aatgttttca tatttttcaa aataggttbt 4800 tattgttgaa tgtacatcta ccccagcccc tcaaaagaaa aactgtttac atagaaatt'c 4 860 ctacacatac gtttgcgtat atgttatttt aaacatcttt gtggtgagaa ttttttcccc 4920 gatattctcc ttctgtcaaa gtcagaacaa attcagggaa tttattttct ggcagttgtg 4980 ctccagtcct tttaaaattg tacatga,aca tgttttagaa acaatatgga ggatgatgca 5040 tacatgtcgg tcaagttcag cgctcgacat tttatggaaa gattttttta accttaccac 5100 gaaatactta actactgttt aagtgaattg acttatttca ctttagtttt tgaactgtga 5160 ttattggtat actgttatat cctcaacttg gatttatggt aacccctttt agttcatgga 5220 gaccaaaatt tggggtattt ataatagtca gcgcaggaat gcacatggaa tatctacttg 5280 tccttttgaa cctcacgagt catccagaat gtatagacag gaaaagcatg tcttatttaa 5340 aactgtaatt tatgggctca ggatctgacc gcagtcccgg gagtaagcat ttcaaagggg 5400 gaaggcagtg tggtccctac cctgtgtgaa tgtgaggatg tagacatcca tcagtgcaac 5460 tcgagctcca tcctcctccg atttctaagg ctccagtttt ctggagggac agtcatcatg 5520 ttttgattta tctgggagaa aactgtggtg cacagcttgt gaggagggca aggttgtgac 5580 gttcgagctt agttctggtg ttattctgtc tcctcttctt tgtcatcagc caaaacgtgg 5640 tttttaaaga gagtcatgca ggttagaaat aatgtcaaaa atatttagga atttaataac 5700 267 &amp;#943; , ctfctaagtca gaaactaaaa caaatactga aatattagct cttcctacac ttcgtgttcc 5760 cctttagctg cctgaaaatc aagattgctc ctactcagat cttctgagtg gctaaaactt 5820 atggatatga aaaatgagat tgaatgatga ctatgctttg ctatcattgt tacctttcct 5880 caatactatt tggcaactac tgggactctt cagcacaaaa ggaatagatc tatgattgac 5940 cctgatttta attgtgaaat tatatgattc atatatttta tgaatcagaa taaccttcaa 6000 ataaaataaa tctaagtcgg ttaaaatgga tttcatgatt ttccctcaga aaatgagtaa 6060 cggagtccac agcgtgcaat gataattata aattggtgat gcttgtttqc aaattgccca 6120 ctcgtgataa gtcaacagcc aatatttaaa actttgttcg ttactggctt taccctaact 6180 ttctctagtc tactgtcaat atcattttaa tgtaattgat.tgtatatagt ctcaagaatg 6240 gttggtgggc atgagttcct agagaactgt ccaagggttg ggaaaatcca aattctcttc 6300 ctggctccag cactgatttt gtacataaac attaggcagg ttgcttaacc tttttatttc 6360 aaactctctc aactctaaag fcgctaataat aatctcagtt accttatctt tgtcacaggg 6420 tgttcttttt tatgaagaaa aatttgaaaa tgataaaagc taagatgcct tctaacttca 6480 taagcaaacc tttaactaat tatgtatctg aaagtcaccc ccacatacca actcaacttt 6540 tttcctgtga acacataaat atatttttat agaaaaacaa atctacataa aataaatcta 6600 ctgtttagtg agcagtatga cttgtacatg ccattgaaaa ttattaatca gaagaaaatt 6660 aagcagggtc tttgctatac aaaagtgttt tccactaatt ttgcatgcgt atttataaga 6720 aaaatgtgaa tttggtggtt ttattctatc ggtataaagg catcgatatt ttagatgcac 6780 ccgtgtttgt aaaaatgtag agcacaatgg aattatgctg gaagtctcaa ataatatttt 6840 tttcctattt tatactcatg gaagagataa gctaaagagg ggacaataat gagaaatgtt 6900 ggtgtgcttt tctaagcatt taaaacataa ttgccaattg aaaccctaaa tatgtttaca 6960 taccattaag atatgattca tgtaacaatg ttaaattaat tataatggga ttgggtttgt 7020 tatctgtggt agtatatatc ctagtgttcc tatagtgaaa taagtagggt tcagccaaag 7080 ctttctttgt tt'tgtacctt aaattgttcg attacgtcat caaaagagat gaaaggtatg 7140 tagaacaggt tcacgtgatt acctttttct tttggcttgg attaatattc atagtagaac 7200 tttataaaac gtgtttgtat tgtaggtggt gtttgtatta tgcttatgac tatgtatggt 7260 ttgaaaatat tttcattata cafcgaaattc aactttccaa ataaaagttc tacttcatgt 7320 aatccaaaa 7329

Table Lille. Nucleotide sequence alignment of 282P1G03 v.1 (SEQ ID NO: 164) and 282P1G03 v.4 (SEQ ID NO: 165) v.1 1 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg I I II I ) I 1 II I II 1 I I 1 I I 1 1 I I I I I 1 I 1 I 1 I I I 1 I I I I 1 1 1 1 I II 1 I I 1 50 v. 4 1 1 J I 1 I &amp;#943;ι i 1 1 1 &amp;#943;11ι I 1 1 II ι 1 1 i ! 1 1 1 1 1 1 I I J 1 1 I j 11 I 11 S 1! 1 I 1 I CGGACCCTGCGCGCCCCCGTCCCGGCTCCCGGCCGGCTCGGGGGAGAAGG 50 v. 1 51 cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg 1 1 1 1 1 1 1 1 1 1 1 1 1! 1 11 11 1 1 1 1 1 1 1 1 1 I 11 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 100 v . 4 51 1 1 J 1 1 i 1 1 1 I S 1 I I 1 I 1 1 i 1 1 1 N ι II I I 1 U I J ι 1 I II 1 1 1 f I ! Π ι (I CGCCCGAGGGGAGGCGCCGGACAGATGGCGTTTCGGAGGCGGCGCAGGTG 100 v.1 101 ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcatag I I 1 II 1 I I 1 I |l I I 1 1 11 1 I 1 1 1 1 I 1 II 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 II 1 1 j 1 150 V - 4 101 i 1 i ι 1 h4 S 1 i 1 t I I 1 1 ι Η Η I I 1 1 Η 1 ι 1 &amp;#943; I 1 I 1 I ι 1 i 1 E I 1 1 I I 1 ι l i CTGTAAACTGCAAACCATAATCCTGTeTTAATACTGCAAACAAATCATAG 150 v. 1 151 tggaactaaggggaacttaatttactgtttccaggttaactaaggtctca | I I 1 I I 1 I I I I I I II I I I I 1 1 1 I || 1 1 I 1 1 1 I 1 I 1 I I ! I 1 1 I I 1 1 I 1 1 II 200 v.4 151 1 1 1 1 1 1 1 1 1 1 1 1 11 I 1111 I 1 1 1 1 I 1 1 1 I II 1 1 1 ι 1 1 1 1 1 1 1 1 1 II 1 1 1 1 TGGAACTAAGGGGAACTTAATTTACTGTTTCCAGGTTAACTAAGGTCTCA 200 v.1 201 gctgtaaaccaaaagtgagaggagacattaagattttcattcttaccggg II 1 1 1 II 1 1 1 I 1 1 1 1 1 1 j I I 1 j I 1 1 ) I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 I 1 250 v.4 201 H 1 I 1 i l 1 I I ! I 11 Ηι Η 1 Η II I I 1 &amp;#943; 1 I 1 1 II 1 I 1 11 1 I i 1 1 1 I II 1 i GCTGTAAACCAAAAGTGAGAGGAGACATTAAGATTTTCATTCTTACCGGG 250 v.1 251 ttgtcttcttcctgaagaqcaatqgacccgcttttacttaaaaaagqact 11 Hl 11111111111111111 i II i i 1! 111II11II1! IIII1 Mil 1 300 v . 4 251 TTGTCTTCTTCCTGAAGAGCAATGGAGCCGCTTTTACTTOGAAGAGGACT 3 00 v. 1 301 aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa | I 1 1 1 II 1 1 1 1 1 1 1 I IS 1 1 1 11 1 1 M I |] 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 If I I I 350 v.4 3 01 1 I 1 1 1 I 1 1 1 1 t 1 11 1 I i 1 1 1 1 1 I 1 I I II I 1 1 1 1 1 1 II l 1 1 1 1 ll I 1 ι ι I I aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa 350 v.1 351 taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc | 1 1 1 1 1 1 1 1 1 1 j 1 1 1 1 1 11 1 1 II 1 1 1 1 1 1 II 1 1 I 1 1 1 1 1 1 1 1 1 | | | 1 1 I 1 400 v. 4 351 1 1 I 1 1 II 1 1 II 1 1 1 I I 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 TACCATCTTCAGTTCAACAGGTTCCAACAATCATAAAACAGTCAAAAGTC 400 268 ν·.ι 401 caagttgcetttcccttcgatgagtattttcaaattgaatgtgaagctaa I 1 I I 1 I 1 I II 1 1 II II 1 1 1 1 1 1 II 1 1 ii II I 1 1 I [ 1 II it 1 (I II II 1 II 450 V. 4 401 1 1 1 ! 1 1 II 1 1 1 1 1 II 1 1 1 1 I 11 11 I 1 1 1 1 1 1 II 11 1 I 1 1 1 1 1 1 1 1 1 11 1 1 CAAGTTGCCTTTCCCTTCGATGAGTATTTTCAAATTGAATGTGAAGCTAA 450 v. 1. 451 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 1 i i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 N 1 1 I 1 1 1 1 1 1 I 1 I 1 t 1 1 1 50 0.v.4 451 II 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 ! 1 1 II II I 1 1 1 1 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 500 v.l 501 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg 1 1 1 I 1 1 1 1 1 1 I I I I 1 1 I j 1 1 1 1 1 1 I 1 I i 1 1 1 II I 1 I 1 I ) I 1 I 1 1 1 1 1 1 I 1 550 v. 4 501 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1II11 1 1111II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTTCACTGACCATCGGATA4TTCCATCGAACAATTCAGGAACATTCAGG 550 v. 1 551 atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt II 1 I I I I I 1 1 I I I 1 I 1 1 1 1 1 II I 1 I 1 1 1 II j 1 I 1 1 1 1 I 1 1 I 1.1 1 I I ] 1 1 1 600 v. 4 551 Ii 1 t ι ! t Ii I 1 I 1 I 1 1 1 1 1 1 ! 1 t 1 1 1 1 1 1 ι I 1 1 I I t &amp;#943; [ &amp;#943; 1 &amp;#943; &amp;#943; 1 &amp;#943; I &amp;#943; Η &amp;#943; ι ATCCCAAACGAGGGGCACATATCTCACTTTCAAGGGAAATACCGCTGCTT 600 v.l 601 tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag 1 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 65 0 v. 4 601 1 1 1 1 I I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 TGCTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650 v. 1 651 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg 1 1 1 II 1 1 1 1 1 1 1 11II 1111 1 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 I 1 1 1 700 v. 4 651 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 TTCCAAGTGTTCCAAAAcTCCCAAAAGAAAAAATTGACCCTCTTGAAGTG 700 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 750 v. 4 701 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GAGGAGGGAGATCCAATTGTCCTCCCATGCAATCCTCCCAAAGGCCTCCC 750 v.l 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 1 1 1 1 1 1 1 1 I !1 11 1 1 1 1 1 II 1 1 11 1 1 1 111 1 1 1 1 1 I 1 1 1 1 1 1 1 1 i 1 1 1 1 1 800 v.4 751 1 1 1 111 11 1 11 11 1 1 1 1 1 1 1 1 I 1 1 1 1 1 11 1 1 1 1 1 1 I 11 1 1 111 1 1 1 1 1 1 1 ACGTTTACACATTTATTGGATGAATATTGAATTAGAACACATCGAACAAG 800 v.l 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg 1 1 1 1 1 1 1 I II 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 850 v.4 801 1 1 1 II 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATGAAAGAGTATACATGAGCCAAAAGGGAGATCTATACTTCGCAAACGTG 850 v.l 851 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag 1 1 1 I I 1 1 1 I 1 I I 1 I 1 1 j 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 900 V-4 851 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 ι I 1 1 ι ι 1 1 1 i 1 1 ι 1 1 1 1 1 ι 1 1 1 i 1 ι 1 1 1 1 ι 1 1 1 1 ι GAAGAAAAGGACAGTCGCAATGACTACTGTTGCTTTGCTGCATTTCCAAG 900 V.l 901 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt 1 1 1 1 1 11!! 1 1 1 1 1 1 1 1 11111111111111111111111 1 111 1 11111 950 v. 4 901 1 1 1 1 I 1 1II 1 I 1 I 1 1 I 1 II 1 I I ! 11 1 II II 1 1 11 1 1 1 I 1 1 11 1 1 1 1 11 I 1 ATTAAGGACTATTGTACAGASAATGCCAATGAAACTAACAGTTAACAGTT 950 V.l 951 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1000 v.4 951 1 1 1 I 1 1 I 1 ι ι &amp;#943; I 1 1 1 I 1 J 1 1 J &amp;#943; 1 1 1 I l 1 1 1 1 &amp;#943; I ! &amp;#943; 1 ι 1 ι ι &amp;#943; 1 1 &amp;#943; ι I j ι 1 &amp;#943; TAAAGCATGCTAATGACTCAAGTTCATCCACAGAAATTGGTTCCAAGGCA 1000 v. 1 1001 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1050 v. 4 1001 1 1 1 I &amp;#943; 1 1 1 1 ! 1 1 1 1 1 1 I 1 ι 1 1 1 1 1 1 i I i 1 I I 1 1 1 I 1 1 I 1 s i I I 1 ! ι 5 I 1 1 AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG 1050 v. 1 1051 tggcagtgagtcttcaattaccatcctcaaaggggaaatcttgctgcttg II 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 11111111II!I 11111 11 1 1 1 1 1 1 1 1 1 I 111 1100 V.4 1051 1 1 1 1 1 1 1 1 II 1 1II II 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 TGGCAGTGAGTCTTCAATTACCATCCTCAAAGGGGAAATCTTGCTGCTTG 1100 v.l 1101 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt | I j 1 II II 1 1 1 1 1 I l| 1 1 1 1 1 1 II 1 I 1 1 1 I 1 II I 1 1 1 1 1 l| I 1 1 1 1 1 1 1 1 1150 v.4 1101 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 11 1 II 1 1 1 1 1 AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGGAACAAAATT 1150 v.l 1151 ggtsgtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 i 1 ! 1 1200 V . 4 1151 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GGTGGTGACTTACCAAAGGGGAGAGAAACAAAAGAAAATTATGGCAAGAC 1200 269 v.l 1201 t'ttgaagatagagaatgtctccfcaccaggacaaaggaaattatcgctgca Il I 1 I 1 1 1 I 1 1 1 I 1 I 1 II II l| 1 j 1 1 I 1 II 11 II |j 1 1 1 1 1 1 1 11 1 1 I 1 1 1250 v.4 1201 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 TTTGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA 1250 v. 1 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta I 1 j 1 1 1 I 1 1 I I ] I ! ! I 1 1 1 I 1 1 I 1 I I ! I ! I 1 I I 1 1 j 1 1 I I 1 1 j 1 1 1 1 1 I j 1300 v.4 1251 1 1 I I 1 1 ! 1 1 ! I 1 I 1 1 ! 1 I 1 I 1 I I 1 I 1 I 1 I I 1 1 1 1 1 1 1 I 1 1 1 1 I I 1 1 I I 1 1 CAGCCAGCAATTTCTTGGGAACAGCCACTCACGATTTTCACGTTATAGTA 1300 v.l 1301 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtatagcac in ii in η π 11 η π 11 hihiihh iiiiimiim 11 η u 1350 V.4 1301 I 1 I 1 I II 1 1 Ii 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GAAGAGCCTCCTCGCTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCAC 1350 v.l 1351 cqqaaqcaatqqcatcttgttatgtgaggctgaaggaqaacctcaaccca II π II1 I I III! I | I | |( 1 I 1111I1ΠII Π Π II Π 1 II Π II II 11 1400 V. 4 1351 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 1 1 1 1 II 1 1 II 1 1 1 II II 1 1 II I 1 1 CGGAAGCAATGGCATCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCA 1400 v.l 1401 caatcaagtggagagtcaatggctccccagttgacaatcatccatttgct | I I I II I 1 I 1 I II I I II I 1 1 II 1 j 1 I 1 II 1 1 j II I II 1 II II 1 II II II I 1450 v.4 1401 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 CAATCAAGTGGAGAGTGAATGGCTCCCCAGTTGACAATCATCCATTTGCT 1450 v. 1 14 51 ggtgatgttgtcttccccagggaaatcagttttaccaaccttcaaccaaa II 11 I I 1 I 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 | I II II 1 1 1 1 I 1 1 1 1 1 11 1 II 1 1 1500 V.4 1451 J i j ! ι 1 ! i ι i ι 1 1 &amp;#943; ι 1 ι 1 i ι ι ι &amp;#943; ι t ι ! I t 1 ! ι t I 1 ι I I I ii 1 » 1 1 &amp;#943; ι I I 1 GGTGATGTTGTCTTCCCCAGGGAAATCAGTTTTACCAACCTTCAACCAAA 1500 v.l 1501 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc 1) 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 II 1 I 1 II 1 1 1 1 1 1 1 1 1 1 1 II II I 1550 v.4 1501 II 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TCATACTGCTGTGTACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCC 1550 v.l 1551 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc II II Η II I I I I I I I II 1 Π 1 1 1 1 1 II II II l| II 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1600 v.4 1551 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 1 1 I 1 1 1 1 1 1 1 1 1 II 11 1 1 TTGCCAATGCCAATATTGATGTTGTGGATGTCCGTCCATTGATACAAACC 1600 v.l 1601 aaagatgqagaaaattacgctacagtggttgggtacagtqctttcttaca II Π 1 II II 11 1 1 1 1 i 1 III Π 1 HI III III II 1 1 II II II II II 1 II 1 1650 v.4 1601 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 AAAGATGGAGAAAATTACGCTACAGTGGTTGGGTACAGTGCTTTCTTACA 1650 v.l 1651 ttgcgagttctttgcttcacctgaggcagtcgtgtcctggcagaaggtgg II 1 1 1 1T 1 1 &amp;#943; 1 1 1 1 1 1 1 1 1 1 1 1 11111111111111 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1700 v.4 1651 1 1 I 1 1 1 1 ! I 1 1 ! 1 I 1 I I 1 1 1 1 1 1 1 ! ! 1 1 1 i 1 I 1 I 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 ! TTGCGAGTTCTTTGCTTCACCTGAGGCAGTCGTGTCCTGGCAGAAGGTGG 1700 v.l 1701 aagaagLgaaacccctqgagggcaggcggtatcatatctatgaaaatggc II Η Η ι || II ! J t ! ΜΗ II 11! Hi 111 1 Η Η Η Η Η ! II Η Η H 1750 v.4 1701 1 1 I 1 1 1 1 1 I 1 1 1 I 1 I 1 1 1 II 1 1 1 1 I 1 II 1 i ! N 1 1 1 1 1 i 1 II 1 I 1 1 1 i 1 1 AAGAAGTGAAACCCCTGGAGGGCAGGCGGTATCATATCTATGAAAATGGC 1750 v.l 1751 acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg Η Η' Η Π I 1 1 1 1 I 1 1 1 1 Η Η 1 1 &amp;#943; Η 1 Η Η 1 Η Η 1 1 1 1 1 Η 1 1 1 Π I 1800 V.4 1751 I I 1 1 1 1II 1 1 1 11 1 1 1 111 111II1 1 1 1 1 1 1 1 11 1 1 i 1 1 1 1 1 111 II 1 1 1 ACATTGCAGATCAACAGAACCACCGAAGAAGATGCTGGGTCTTACTCATG 1800 v.l 1801 ttgggtagaaaatgctataggaaaaactgcagtcacagccaatttggata 1 1 Π Π 1 1 111!Η Π 1111 11111 1 1 1 Η 111II1 Η Η 1 1 1 I 1 1 II 1 1850 V.4 1801 1 ι I II 1 1 I 1 1 1 1 ι ι 1 1 1 1 1 11 111ι11 I 1 ι I 1 1 1 11 1 ι 1 ι 1 1 1 11 1 11 1 1 TTGGGTAGAAAATGCTATAGGAAAAACTGCAGTCACAGCCAATTTGGATA 1850 v. 1 1851 ttagaaatgctacaaaacttagagtttctcctaagaatcctcgtatcccc II I I 11 II I I I I I I I I II 1 I II I I I I I I I II II II l| 1 II 1 II 1 1 [| I 1 1 1900 v.4 1851 1 II11II111 11 1 1 1 II 1 1 1 1II I I 111111II I 111 1 1 1 1 1 1 1 1 1 1 1 1 1 TTAGAAATGCTACAAAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCC 1900 v.l 1901 aaattgcatatgcttgaattacattgtgaaagcaaatgtgactcacattt II II I 1 II 11 |] 1 II II 1 l| ! II II II 1 11 II 11 IS 11 II 1 II 1 1 11 1 1 '1 1950 v.4 1901 1 I 1 1 1 1 1 I 1 1 1 II 1 1 ! II I 11 1 111 1 1 II 1 I II 1 1 I 1 1 1 I I 1 I I 1 1 1 1 1 1 AAATTGCATATGCTTGAATTACATTGTGAAAGCAAATGTGACTCACATTT 1950 v.l 1951 gaaacacagtttgaagttgtcctggagtaaagatggagaagcctttgaaa 2000 270

v.4 1951 GAAACACAGTTTGAAGTTGTCCTGGAGTAAAGATGGAGAAGCCTTTGAAA v.l 2001 ttaatggcacagaagatggcaggataattattgatggagctaatttgacc

11II11!1111 II II! I 11 IIIIII11 II 1III!ill 11 IS 111 i IIIII

v.4 2001 TTAATGGCACAGAAGATGGCAGGATAATTATTGATGGAGCTAATTTGACC v.l 2051 atatctaatgtaactttagaggaccaaggtatttactgctgttcagctca 111111i 1111111111II1111111111111111111111111111111

v.4 2051 ATATCTAATGTAACTTTAGAGGACCAAGGTATTTACTGCTGTTCAGCTCA v.l 2101 tactgctctagacagtgctgccgatataactcaagtaactgttcttgatg 1111111111111111111111111111II11111111111111111111

v.4 2101 TACTGCTCTAGACAGTGCTGCCGATATAACTCAAGTAACTGTTCTTGATG v.l 2151 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt 1IIII111II11111II11II I! Ill 111IIIII111111II11111111

V.4 2151 TTCCGGATCCACCAGAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGT v.l 2201 gttcggctgacctgggaagctggagctgaccacaacagcaatattagcaa

IIIII11IIII1!11II1111111111 111 1111IIII11111111! III

v.4 2201 GTTCGGCTGACCTGGGAAGCTGGAGCTGACCACAACAGCAATATTAGCGA v.l 2251 gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg 11U 111111111111IIIIIII11II111111II1111IIIII111111

v.4 2251 GTATATTGTTGAATTTGAAGGAAA.CAAAGAAGAGCCTGGAAGGTGGGAGG v.l 2301 aactgaccagagtccaaggaaagaaaaccacagttatcttacctttggct 1111111111111111111 '11111111111111II111111111111111

v.4 23 01 AACTGACCAGAGTCCAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCT v.l 2351 ccatttgtgagataccagttcagggtcatagccgtgaacgaagtagggag lllllllllllllllllllllllllllllllllllillllllllllllll

v.4 2351 CCATTTGTGAGATACCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAG v.l 2401 aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc llllllllllllllliliUlllllllHIIIlillllilllllllllll

v.4 2401 AAGTCAGCCTAGCCAGCCGTCAGACCATCATGAAACACCACCAGCAGCTC v.l 2451 caqataggaatccacaaaacataagggttcaagcctctcaacccaagqaa 1111111-111II Hill II III II III! llllllll III ii ι mi Nil

v.4 2451 CAGATAGGAATCCACAAAACATAAGGGTTCAAGCCrCTCAACCCAAGGAA v.l 2501 atgattataaagtgggagcctttgaaatccatggagcagaatggaccaqq lilSliSlillllllllilllliHimilllHIIIMlililillii

v.4 2501 ATGATTATAAAGTGGGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGG v.l 2551 cctagagtacagagtgacctggaagccacagggagccccagtagagtggg

III 11II Hill Hill 111111111111111111111111 III 1111II

v.4 2551 CCTAGAGTACAGAGTGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGG v.l 2601 aagaagaaacagtcacaaaccacacattgcggg.tgatgacgcctgctgtc 11111111111111II111111111111111111111111111111111 r

v.4 2601 AAGAAGAAACAGTCACAAACCACACATTGCGGGTGATGACGCGTGCTGTC v.i 2651 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg

I! 111II 111 11111! II i 1111111111IIII IS II1111IIII11III

v.4 2 651 TATGCCCCTTATGATGTCAAGGTCCAGGCTATCAATCAACTAGGATCTGG v.l 2701 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata

Iiii 1111111111111111 Π111111111111111111! v.4 27 01 GCCTGACCCTCAGTCAGTGACTCTCTATTCTGGAGAAGACT--------- v.l 2751 cagctccagtgatccatggggtggacgttataaacagtacattagttaaa 2000 2050 2050 2100 2100 2150 2150 2200 2200 2250 2250 2300 2300 2350 2350 2400 2400 2450 2450 2500 2500 2550 2550 2600 2600 2650 2650 2700 2700 2750 2741 2800 271 v.4 2742 ----------------'---------------------------------- v.l 2801 gttacctggtcaacagttccaaaggacagagtacatggacgtctgaaagg v.4 2742 -------------------------------------------------- v.l 2351 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac v.4 2742 -------------------------------------------------- v.l 2901 atcccaaagaagtgaacattctaagattttcaggacaaagaaactctgga v.4 2742 -------------------------------------------------- v.l 2951 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc v.4 2742 -------------------------------------------------- v.l 3001 ctataactctaaaggagctggtcctgaaagtgagcctfcatatatttcaaa v.4 2742 -------------------------------------------------- v.l 3051 cacc&amp;amp;gaagaagtacctgaacagccaacttttctaaaggtcatcaaagtt 11! 11! I! II li III1111111111 Η I!II! 11! II!

v.4 274 2 ------------TACCTGAACAGCCAACTTTTCTAAAGGTCATCAAAGTT v.l 3101 gataaagacactgccactttatcttggggactacctaagaaattaaatgg

I!III1111! 1IIII1111 i!I!11IIIII11) 11! IIIIII i I i III i I

v.4 27 8 0 GATAAAGACACTGCCACTTTATCTTGGGGACTACCTAAGAAATTAAATGG v.l 3151 aaacttaactggctatcttttgcaatafccagataataaatgacacctacg

11 III III I! Ill II! HI III III 11 III HI I III III III HI III I

v.4 2830 AAACTTAACTGGCTATCTTTTGCAATATCAGATAATAAATGACACCTACG v.l 3201 agattggagaattaaatgatattaacattacaactccatcaaagcccagc ΗΗ&amp;#943;ΠΙΝΗΠΠΠΗΠΗΠΠΠΠΠΠΠΠΠΠΠΠΗ

v.4 2880 AGATTGGAGAATTAAATGATATTAACATTACAACTCCATCAAAGCCCAGC v.l 3251 tggcacctctcaaacctgaatgcaactaccaagtacaaattctacttgag ι m ι u 11 m 1111111 η i m m 1111 m ι η ι i m m ι m

v.4 2330 TGGCACCTCTCAAACCTGAATGCAACTACCAAGTACAAATTCTACTTGAG v.l 3301 ggcttqcacttcacagggctgtggaaaaccgatcacqqaqqaaagctcca mmmsm mm ii mu mm mins m ι mu I!

v.4 2980 GGCTTGCACTTCACAGGGCTGTGGAAAACCGATCACGGAGGAAAGCTCCA v.l 3351 ccttaqqaqaaqqqaqtaaaggtatcgggaagatatcaqqagtaaatctt immimmimmmimmiimmmimsm

v.4 3 03 0 CCTTAGGAGAAGGGAGTAAAGGTATCGGGAAGATATCAGGAGTAAATCTT v.l 3401 actcaaaaqactcacccaatagaggtatttgagccgggagctgaacatat immiimimmmmmmmimmmmm v.4 3080 ACTCAAAAGACTCACCCAATAGAGGTATTTGAGCCGGGAGCTGAACATAT v.l 3451 agttcgcctaatgactaagaattggggcgataacgatagcatttttcaag mimmmmmmmmmmmmimmm V.4 3130 AGTTCGCCTAATGACTAAGAATTGGGGCGATAAcGATAGCATTTTTCAAG v.l 3501 atgtaattgagacaagagggagagaatatgctggtttatatgatgacatc iiimiimmmmmmmmmmmmmm

v.4 3180 ATGTAATTGAGACAAGAGGGAGAGAATATGCTGGTTTATATGATGACATC 2741 2850 2741 2900 2741 2950 2741 3000 2741 3050 2741 3100 2779 3150 2829 3200 2879 3250 2929 3300 2979 3350 3029 3400 3079 3450 3129 3500 3179 3550 3229 272 v.‘l 3551 .f''' ’ tccactcaaggctggtttattggactgatgtqtqcgattgctcttctcac 1 1 1 1 II Η II II II 11 1 II HI II 1 II 1 lllll III 1 II 1 ΠΠ 1 1 I 1 &amp;#943; 1 3600 v.4 3230 1 1 1 1 1 ! 1 i 1 &amp;#943; ι I t i 1 1 &amp;#943; I &amp;#943; ι t ι ι 1 ι I ι I 1 1 I 1 ! I t ι ι 1 1 i i i 1 ! I i 1 ι 1 [ TCCACTCAAGGCTGGTTTATTGGACTGATGTGTGCGATTGCTCTTCTCAC 3279 v.l 3601 actactattattaactqtttqctttgtgaaqaqgaatagaggtggaaagt ! HI 1 I 1 I ' I 1 1 I N I II 1 ill II lllll U Π I I I I II lllll 11 1 ill 3650 v.4 3280 ! 1 1 1 1 I 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1- 1 1 1 1 1 1 ACTACTATTATTAACTGTTTGCTTTGTGAAGAGGAATAGAGGTGGAAAGT 3329 v.l 3651 actcagttaaagaaaaggaagatttgcatccagacccagaaattcagtca I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 3700 v.4 3330· 1 N ι N 1 1 ll &amp;#943; &amp;#943; ι &amp;#943; &amp;#943; i 1 1 ι I &amp;#943; 1 1 &amp;#943; I ι &amp;#943; &amp;#943; I ! 1 &amp;#943; ι ι Η 1 ι 1 &amp;#943; &amp;#943; 1 &amp;#943; 1 ι ι &amp;#943; &amp;#943; &amp;#943; &amp;#943; ACTCAGTTAAAGAAAAGGAAGATTTGCATCCAGACCCAGAAATTCAGTCA 3379 v.l 3701 qtaaaaaatqaaacctttggtgaatacagtgacagtgatgaaaagcctct 1 1 I I 1 111 II 1 1 1 I I 1 1 IN ! ill HI I III Η I ill I II ! I 1 II 1 1 1 I 1 3750 v.4 3380 1 1 I 1 1 1 1 1 I I 1 1 1 1 I 1 1 1 1 I I I I 1 I ι t 1 I ι I 1 1 &amp;#943; I 1 1 1 I 1 ι 1 1 I l 1 1 1 1 1 GTAAAAGATGAAACCTTTGGTGAATACAGTGACAGTGATGAAAAGCCTCT 3429 v.l 3751 caaagqaagccttcggtcccttaatagggatatgcagcctactgaaagtg i| in mi μ ι | | Min 11 1 1 1 II II II 1 1 111 II II Π 1 Π Π 1 II II 3800 v.4 3430 1 I i 1 1 1 1 &amp;#943; 1 1 I i &amp;#943; i 1 I I 1 1 i t t &amp;#943; I 1 ι I 1 I 1 I 1 1 i 1 1 I i 1 I ι 1 I I ! I i I E I CAAAGGAAGCCTTCGGTCCCTTAATAGGGATATGCAGCCTACTGAAAGTG 3479 v.l 3801 ctgacagcttagtcgaatacggagagggagaccatggtctcttcagtgaa II I II 1 1 |] 11 1 1 1 1 1 II 1 II II 1 II 11 1 1' II 1 II II II II II II 11 | | 1 3850 v.4 3480 1 I ( Μ 1 I Π 1 I 1 N II 1 ! 1 I 1 I I Μ 1 J Μ M 1 1 1 1 I 1 1 1 1 1 1 1 1 Μ 1 i.l S CTGACAGCTTAGTCGAATACGGAGAGGGAGACCATGGTCTCTTCAGTGAA 3529 v.l 3851 gatggatcatttattggtgcctacgctggatctaaggagaagggatctgt 11 1llII 1 1 1 1 1 1 1 1 1 1 1 1 II I 1 1 I 1) 1 H 1 II111 1 1111 II H 11 H 1 3900 v.4 3530 1 1 1 I 1 1 11II1 1 l I I 1 1 1 1 I 1 1 1 1 1 I 1 I 11 I I 1 I 1 I 1 1II 1 1 1 1 1 1 1 1 1 I GATGGATCATTTATTGGTGCCTACGCTGGATCTAAGGAGAAGGGATCTGT· 3579 v.l 3901 tgaaagcaatggaagttctacagcaacttttccccttcgggcataaacac Η 1 II Η Η Η Η Η 1 1 Η 1 I Π 1 Η Η Γ1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 3950 v.4 3580 1111111111111111111111)111111111111111111111111111 TGAAAGCAATGGAAGTTCTACAGCAACTTTTCCCCTTCGGGCATAAACAC 3629 V.l 3951 aacatatgtaagcaacgctactggttcaccccaaccttccatatttatct |l |l Π 1 II 11 II 1 1 II II 1 1 II 1 II Π Π I II II H 1 II 1 Π II 11 II 1 4000 v.4 3630 1 I 1 I I 1 1 1 1 I 1 1 1 I 1 I 1 1 1 1 1 I 1 1 1 1 I I 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 AACATATGTAAGCAACGCTACTGGTTCACCCCAACCTTCCATATTTATCT 3679 v.l 4001 gttcaaaggagcaagaactttcatataggaatagaaacatgctggccgaa II I II II II 1 1 II II | I I I 1 II 11 | | II | | I II II II II II II II 11 11 1 4050 v.4 3680 1 1 II 1 II 1 II I 1 1 1 1 1 1 1 1 1 j 1 1 1 I 1 I 1 1 1 I 1 j 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 I GTTCAAAGGAGCAAGAACTTTCATATAGGAATAG.AAACATGCTGGCCGAA 3729 V.l 4051 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac II111Ι&amp;#906;&amp;#906; 111 Π Π 11IIII Η 1111! Π 11II111111111II11! 11 GATTTCATCCAGAAGTCAACATCCTGCAATTATGTTGAAAAGAGTAGTAC. 4100 v.4 3730 3779 v.l 4101 tttcttcaaaatataaaatgccaagcacttcaggcctatgttttgcttat | II 1 1 II II II II II II II II II II II 1 II 1 II II II 1 1 1 I II 11 1 II II 4150 v.4 3780 1 I 1 1 1 1 1 1 1 1 1 I ! 1 1 1 ! 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 Π 1 I I 1 I II 1 1 1 1 1 1 1 ! TTTCTTCAAAATATA4AATGCCAAGCACTTCAGGCCTATGTTTTGCTTAT 3829 v.l 4151 attgttttcaggtgctcaaaatgcaaaacacaaaacaaatcctgcattta I Π II11H1111111111111II11 1 1 1 1 1 1 1 Π 11 1 1 1 1 1 1 1 1 I 1 1 1 1 4200 v.4 3830 1 1 1 1 1 1 1 1 1 1 1 I 1 I I I | I | 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I | 1 I | | | | | { | , 1 | I ATTGTTTTCAGGTGCTCAAAATGCAAAACACAAAACAAATCCTGCATTTA 3879 V.l 4201 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg | π 1 1 1 1 H 1 1 1 1 1 1 1 1 I 1 II II Π 1 1 II II 11II1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 4250 v.4 3880 I Η Η Π Π Π 1 1 II II II II II Π 1 1 1 II 1 H II II II 1 1 H II ! Η Π GATACACCTCAACTAAATCCAAAGTCCCCATTCAGTATATTCCATATTTG 3929 V.l 4251 cctgattttactattcggtgtgtttgcatagatgttgctacttggtggqt 1 1 1 &amp;#943; H I II1 1 II 1 1 I 1 1II 1 1 II 1 1 11 I H 1 1 1 I 1 1 1 1 1 1II1 1 I H H 4300 V.4 3930 1 1 1 1 1 I I | I I | I | | | | | I I I 1 1 1 1 1 1 1 II 1 1 1 1 I | | I I | | 1 1 | I I | | | H. CCTGATTTTACTATTCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGT 3979 v.l 4301 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga 1 II 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 H II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 f 1 1 1 1 4350 v.4 3980 1 II 1 1 I I | 1 | I | I | | | | | | | 1 1 1 I 1 1 I 1 1 1 1 1 I 1 1 | | | | 1 1 | | | | | | | | | TTTTCTCCGTATGCACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGA 4029 273 v.l 4351 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa II I 1 I I 11 II I I I I I 1 I (I II I 1 1 II 1 1 1 II 1 II I I I II II I II I 1 I I I 1 4400 1 1 i I 1 1 I. H 1 1 1 11 1 1 1 1 1 II 1 1 I 1 ι 11 1 I 1 I 1 1 1 1 t 1 1 ι Η 1 H 1 ι U 1 v.4 4030 CTTTGCTTCACTACAGGTTAAAAGACGATAAGCAAACTGGTTATTTAAAA 4079 v.l 4401 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac ι 1 I i ii 1 i &amp;#943; &amp;#943; ι &amp;#943; i i 1 i i &amp;#943; &amp;#970; i I i &amp;#943; 1 &amp;#943; i &amp;#943; &amp;#943; i i &amp;#943; I i 11 i &amp;#943; &amp;#943; 1 &amp;#943; I 1 &amp;#943; ! i 1 ! &amp;#943; &amp;#943; &amp;#943; 4450 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 V.4 4080 TGTAAAAAGGAATATGAAAGTCTTATTAAAACACTTCATTGAAAATATAC 4129 v.l 4451 agtctaaatttattatttaaattttactagcaaaagtcttaggtgaacaa 1 I I l I 1 I I I I 1 I 1 1 I II I 1 I II II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 4500 J i 1 1 1 1 II J i 1 1 1 11 It 1 H1 I 1 1 j 1 H 1 11 J ) 1 1 1 1 1 I 1 1 1 1 I I 1 11 1 s v.4 4130 AGTCTAAATTTATTATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAA 4179 v.l 4501 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa | II 1 1 1 II 1 II 1 1 1 1 1 1 1 II II 1 1 II 1 1 1 1 II 1 11 1 1 1 1 1 1 1 1! 1 II 1 1 1 4550 i 1 1 1 11 1 1 1 1 (I 1 1 1 H I 1 1 1 I 1 ι 1 1 1 1 I 1 1 1 U 1 I 1 1 1 1 1 1 1 1 1 i ι ι π v.4 418 0 TCAACTAGTATTTGTTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAA 4229 v.l 4551 acagaagtatacgtttttcagtttcaacatgaattttfcttatttctgtca | 1 1 1 j 1 1 I II 1 I 1 1 II 1 1 I I 1 1 I II I 1 1 II II II 1 1 1 1 1 1 1 1 1 II 1 11 1 ] 4600 I 1 I 1 1 I 1 1 1 1 I 1 1 1 i 1 1 1 I ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i I 1 1 1 1 1 1 1 I 1 1 H 1 I v.4 4230 ACAGAAGTATACGTTTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCA 4279 v.l 4601 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 H 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4650 1 1 1 &amp;#943; 1 1 i 1 1 I 1 1 H 1 &amp;#943; 1 1 &amp;#943; Π 1 1 11 1 I 1 I 1 1 1 1 I 1 1 i 1 1 1 &amp;#943; 1 I 1 1 ι &amp;#943; 1 1 1 4329 v.l 4651 tggactaaattcaactgcatggaagcggtggtcagaaggttgttttatac 1II 1 11 1 1 1 1 1 1 11 1 II 1 1 II 111IIII II II 1 II 1 II II 1 1 1 1 1 1 i 1 1 1 4700 1 1 &amp;#943; 11 1 1i II j I 1 1 I It II 1 } I 1 11) 1 1 1 1 1 &amp;#943; 1 1 1 1 I I 1 &amp;#943; 1 1 1 1 1 1 ι 1 1 1 v.4 4330 TGGACTAAATTCAACTGCATGGAAGCGGTGGTCAGAAGGTTGTTTTATAC 4379 v.l 47 01 gagaacaggcagaaagtgcccattgttcaggattctaatagctacatcta 111 111 1! II1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 III 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4750 1 1 I 1 1 ! 1 11 1 1 1 I 1 I 1 Η II &amp;#943; 1 1 U 1 It ι ι 1 ι 1 1 U 1 1 Η 1 Η 11 1 1 1 1 1 v.4 4380 GAGAACAGGCAGAAAGTGCCCATTGTTCAGGATTCTAATAGCTACATCTA 4429 v.l 4751 cttaatatcttcatttctaaattgactgcttttacctttttctcatgttt I 1 1 1 1 1 I 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 II 1 1 1 1 1 1 1 1 1 4800 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.4 4430 CTTAATATCTTCATTTCTAAATTGACTGCTTTTACCTTTTTCTCATGTTT 4479 v.l 4801 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg 1 1 1 1 1 I 1 1 1 I 1 I 1 1 1 Ι&amp;#938;I 1 1 1 1 I 1 1 | 1 I 1 1 I 1 1 | 1 1 I 1 1 I i 1 I I I 1 I 1 I i 4850 ι 1 ι &amp;#943; &amp;#943; Ι Ι Ι ι 1 ι i I I I 1 ι I I i 1 ! 1 &amp;#943; Ι ι 1 1 S 1 II I j 1 1 1 1 1 I ι ι 1 1 1 1 ! 1 ι 1 v.4 4480 ATATAATGGTATGCTTGCATATATTTCATGAATACATTGTACATATTATG 4529 v.l 4851 ttaateftttacacaatttaaaatatagatgtgttttattttgaagtgaga 11111111111111111111111111111111111111111111111111 4900 1 ι 1 i 1 1 &amp;#943; 1 I I I 1 ι i 1 ι &amp;#943; 1 &amp;#943; 1 1 1 1 I 1 1 &amp;#943; I &amp;#943; 1 1 &amp;#943; &amp;#943; 1 ι 1 1 &amp;#943; ! ι 1 ) ι 1 1 1 &amp;#943; 1 1 1 ν. 4 4 5 3 0 TTAATATTTACACAATTTARAATATAGATGTGTTTTATTTTGAAGTGAGA 4579 ν.1 4901 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat I I I I 1 1 .1 1 I I I I I 1 I I 1 1 I I I I I I I 1 I 11 1 I 1 I I I I I I I 1 I 1 I I I I II ι | 4950 1 1 II 1 Π 1 1 1 1 1 Μ 1 1 1 1 1 1 1 1 &amp;#943; 1 1 1 1 1 1 1 Η 1 Η 1 1 &amp;#943; 1 &amp;#943; &amp;#943; 1 1 11 &amp;#943; &amp;#943; &amp;#943; 1 1 V.4 45 8 0 AAATGAACATTAACAGGCATGTTTGTACAGCTAGAATATATTAGTAAGAT 4629 v.l 4951 actgtttttcgtcattccagagctacaactaataacacgaggttccaaag 1 1 1 1 1 1 1 1 11IIII1111111 1 1 1 1 1 I 111 I 11111 I 1 1 1 1 1 1 1 1 1 1 1 1 1 5000 1 I 1 1 1 1 1 1 11 1 111 1 1l 11 1 1 11 1 1 1 11 t 1 ι ι1 ιII Η 1 ι ι ι 1 ι i 1 11 1 1 v.4 4630 ACTGTTTTTCGTCATTCCAGAGCTACAACTAATAACACGAGGTTCCAAAG 4679 v.l 5001 ctgaagactttgtataaagtatttgggttttgttcttgtattgctttctt I 1 1 1 1 1 1 1 ! 1 1 1 1 1 ι 1 1 1 1 1 11&amp;#906; 1 1 1 1 I 1 t 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5050 I 1 1 1 1 1 1 1 1 1 1 1 1 I ι I I 1 I 1 1 I J 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I 1 1 1 1 1 1 1 1 v.4 4 58 0 CTGAAGACTTTGTATAAAGTATTTGGGTTTTGTTCTTGTATTGCTTTCTT 4729 v.l 5051 tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc 1 H j 1 I ! I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 I I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 Γ1 5100 Η &amp;#943; 1 hi Η &amp;#943; &amp;#943; ι u ι 1 u N i Ν &amp;#943; Π &amp;#943; &amp;#943; Π h'l &amp;#943; ! 1 1 1 &amp;#943;! ι &amp;#943; ! U ! 1 &amp;#943; ! ! v.4 4730 TCAACAGTTTCAAAATAAAATATCATAcAAATATTGAGGGAAATGTTTTC 4779 v.l 5101 atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc 5150 274

v.4 47 8 0 ATATTTTTCAAAATAGGTTTTTATTGTTGAATGTACATCTACCCCAGCCC v.1 5151 ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta ! 111111 U 1! i I H 1! I! I! 1111 Η ! I! 11! i 1 i 11 H I! 11! 111 i 1

v.4 4 83 0 CTCAAAAGAAAAACTGTTTACA.TAGAAATTCCTACACATACGTTTGCGTA v.1 5201 tatgttattttaaacatctttgtggtgagaattttttccccgatattctc I! 11 li I! i! 11!I 11 i 11 If I iTTlT Hi II Η II! II &amp;#943; &amp;#943; II !! III &amp;#943;!

v.4 4880 TATGTTATTTTAAACATCTTTGTGGTGAGAATTTTTTCCCCGATATTCTC v.1 5251 cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt

IIΠ II1111Π 11111II11IIIII!IIi1111111II11i11111! II

v.4 4930 CTTCTGTCAAAGTCAGAACAAATTCAGGGAATTTATTTTCTGGCAGTTGT v.1 5301 gctccagtccttttaaaattgtacatgaacatgttttagaaacaatatgg

HHH HI HHH I ΗΗΠΗΠΠΠΗΙ! III III! I 111 Π III

v.4 4980 GCTCCAGTCCTTTTAAAATTGTACATGAACATGTTTTAGAAACAATATGG v.1 5351 aggatgatgcatacatgtcggtcaagttcagcgctcgacattttatggaa ΗΠΗΙΗΗΗΙΠΗΙΙΠΠΗΠΗΠΠΗΠΠΠΙΠΠΗΙ

v.4 5 03 0 AGGATGATGCATACATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAA v.1 5401 agatttttttaaccttaccacgaaatacttaactactgtttaagtgaatt

Π I Η Η IIIIIIIIIIII Π Η II Η ΗI ΗII &amp;#943; Η I Π III. Η IIIII

v.4 5 080 AGATTTTTTTAACCTTACCACGAAATACTTAACTACTGTTTAAGTGAATT v.1 5451 gacttatttcactttagtttttgaactgtgattattggtatactgttata

111111II11 IH 111111111111IIIIΠ II111II11II111111II

v.4 5130 GACTTATTTCACTTTAGTTTTTGAACTGTGATTATTGGTATACTGTTATA v.1 5501 tcctcaacttggatttatggtaaccccttttagttcatggagaccaaaat ΠΗΠΠΗΠΠΠΗΗΠΠΠΠΗΠΠ1ΠΠΠΗΠΠΙΠ

v.4 5180 TCCTCAACTTGGATTTATGGTAACCCCTTtTAGTTCATGGAGACCAAAAT v.1 5551 ttggggtatttataatagtcagcgcaggaatgcacatggaatatctactt ΗΠΗΗΠΠΗΗΠΠΗΠΗΗΗΠΗ1ΗΗΗΗΗΗΗ!

v.4 5230 TTGGGGTATTTATAATAGTCAGCGCAGGAATGCACATGGAATATCTACTT v.1 5601 gtccttttgaacctcacqagtcatccagaatgtatagacaggaaaagcat 11IIII1111II Π 11 HI IIIΠIIII1111II1111IIΙ&amp;#938;Ι1111111

v.4 5280 GTCCTTTTGAACCTCACGAGTCATCCAGAATGTATAGACAGGAAAAGCAT v.1 5651 gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg II Π H 111III HI 111111II11 Π 111111II11II11IIIII1111

v.4 5330 GTCTTATTTAAAACTGTAATTTATGGGCTCAGGATCTGACCGCAGTCCCG v.1 5701 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga ΠΗΠΗΠΠΠΙΙΙΗΙΗΠΗΠΠΠΠΙΠΗΠΗΙΠΠΠ

v.4 5380 GGAGTAAGCATTTCAAAGGGGGAAGGCAGTGTGGTCCCTACCCTGTGTGA v.l 5751 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc

11i i 11!III11 Η 11{11111111&amp;#943;1111111i I Π 1 Π II111Η Π I

v.4 543 0 ATGTGAGGATGTAGACATCCATCAGTGCAACTCGAGCTCCATCCTCCTCC v.l 5 8 01 gatttctaaggctccagttttctggagggacagtcatcatgttttgattt ΗΠΝΠΠΗΠΙΙΠΗΗΠΠΠΠΗΠΙΠΠΗΠΙΠΗΝ

v.4 5480 GATTTCTAAGGcTCCAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTT v.l 5851 atctgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga ΗΠΠΠΠΠΗΗΗΗΗΗΗΠΠΠΠΙΠΠΠΗΗΠΠ!

v.4 5530 ATCTGGGAGAAAACTGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGA v.l 5901 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcag 4829 5200 4879 5250 4929 5300 4979 5350 5029 5400 5079 5450 5129 5500 5179 5550 5229 5600 5279 5650 5329 5700 5379 5750 5429 5800 5479 5850 5529 5900 5579 5950 275 '&amp;#905;τ» "L£uv-r, 3. v.4 5580 CGTTGGAGCTTAGTTCTGGTGTTATTCTGTCTCCTCTTCTTTGTCATCAG 5629 v.l 5951 ccaaaacgtggtttttaaagagagtcatgcaggttagaaataatgtcaaa II Η Iii111 I! Η 1II111IIIII!1!1fil11ilΗ Η 1II1 i 1II 1) 6000 v. 4 5530 CCAAAACGTGGTTTTTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAA 5679 v.l 6001 aatatttaggaatttaataacctttaagtcagaaactaaaacaaatactg ! I I 1 11 1 II 1 1 1 II II 1 II i 1 1 1 I 1 l| II 1 1 II i 1 1 I 1 1 II 1 I 1 II 1 1 1 1 6050 v. 4 5680 I i I t ! 1 I it Η Η ι 1 I 1 1 i 1 If 1 Η I 1 J J ! 1 i 1 1 I I 1 Η I I 1 I ) I 1 1 1 1 1 AATATTTAGGAATTTAATAACCTTTTkAGTCAGAAACTAAAACAAATACTG 5729 v.l 6051 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat | 1 I 1 |] l| 1 II 1 j 1 1 1 SI 1 I 1 1 II 1 |( 1 II 1 1 1 1 1 1 1 11 1 1 1 1 1 1 I 1 1 1 I 6100 v . 4 5730 1 U 1 1 1 i 1 t 1 il J Η 1 1 1 l ! Π ! N 1 i Η 1 l ! 1 N I 11 1 j i I 1 1 1 1 I I ll aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat 5779 v. 1 6101 caagattgctcctactcagatcttctgagtggctaaaacttatggatatg 1 ! 1 1 I ) I i 1 i i I I 1 I I 1 1 I f I 1 N 1 Nil II 11 1 1 1 1 II 1 11 i | II ) I it 6150 v . 4 5780 1 1 1 1 1 II 11 11 1 &amp;#943;1 I 1 1 1 II 1 1 1 11 111 I 1 1 ! 1 1 1 1 II 1 1 1 1 &amp;#943; 1 I 1 1 1 1 I CAAGATTGC'TCCTaCTCAGATCTTCTGAGTGGCTAAAACTTATGGATATG 5829 v. 1 6151 aaaaatgagattgaatgatgactatgctttgctatcattgttacctttcc II 1 1 1 1 1 II 1 1 1 II 1 II II 1 i 1 j II II 1 1 II 1 1 II II ] II 1 1 1 1 1 1 j 1 j j 6200 v. 4 5830 1 1 II II! 1 1 1 1 i 11 1 1 1 I 1 II I I I I 1 I 1 I I I 1 ! 1 1 1 1 N 1 1 1 I 1 1 I 1 l I &amp;#943; AAAAATGAGATTGAATGATGACTATGCTTTGCTATCATTGTTACCTTTCC 5879 v.l 6201 tcaatactatttggcaactactgggactcttcagcacaaaaggaatagat | II I I II |l j| I II I I II I I 1 II 1 1 1 1 1 II 11 || 1 II 1 1 1 1 1 1 1 1 II 1 1 I 6250 V.4 5880 II ! I 1 Μ 1 1 1 1 I 1 1 1 1 I i I 1 1 1 i I I 1 I t 11' I &amp;#943; ι 1 I 1 U ι ι l ι 1 1 1 ( Π 1 I TCAATACTATTTGGCAACTACTGGGACTCTTCAGCACAAAAGGAATAGAT 5929 v.l 6251 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt II 1 II I 1 1 1 II 1 ( | | 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 6300 V.4 5930 1 I t 1 ! 1 i ) ι 1 1 1 ι t ι ι ι i &lt; · I &lt; ! t *· I i ι 1 1 &amp;#943; ι ! 1 1 ι &amp;#943; I ι I 1 I l· 1 1 I I I CTATGATTGACCCTGATTTTAATTGTGAAATTATATGATTCATATATTTT 5979 v. 1 6301 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg II II Π II 1 II 1 II 1 1 I 1 I II 1 II 1 II 1 I 1 j 1 1 II 1 1 II 1 1 II 1 |] 1 1 1 1 6350 v.4 5980 I 1 1 1 I Π ! 1 1 I 1 II 1 1 ι II I U It 1 1 ι 1 1 I 1 i 1 1 1 I 1 I 1 1 1 1 l 1 1 1 II II ATGAATCAGAATAACCTTCAAATAAAATAAATCTAAGTCGGTTAAAATGG 6029 V.l 6351 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa II II II II 1 II 1 1 1 1 1 II 1 1 1 1 1 II 1 1 1 |I 1 1 II |1 1 1 11 II 1 1 1 II 1 II 6400 v.4 6030 ! I 11 It 1 ! [ 1 1 I i ι Μ 1 1 i I 1 H 1 1 1 ι II I II 1 I 1 Η 1 1 1 I I 1 1 I 1 I 1 II ATTTC'ATGATTTTCCCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAA 6079 v.l 6401 tggtaattataaattggtgatgcttgtttgcaaattgcccactcgtgata 1 I 11 1 1 II 1 I il 1 1 1 ! 1 1 1 1 1 1 ! 1 1 II 1 1 1 1 1 1 1 1 1 1 ! 1 1 II 1 1 1 1 1 II 1 6450 v, 4 6080 I 1 1 I L11111 I I 11 I I 1 1 11 II 1 II 1 1 1 1 II 1 1111 1 1 1 II 1 I 1 1 1 1 1 1 1 tggtaXttataaattggtgatgcttgtttgcaaattgcccactcgtga.ta 6129 v.l 6451 agtcaacagccaatatttaaaactttgttcgttactggctttaccctaac | j 1 II 1 ) 1 I IS 1 1 j 1 1 II 1 j| 1 I 1 II II II 1 1 II 1 1 j j II 1 1 J I II 1 1 6500 v. 4 6130 I U ! I i ll ( I I i I I IIt &amp;#943; Η &amp;#943;1 &amp;#943; 11 I 1 if 1 i t 1 11 I 11 I I S I 1 ! 1 I 1 1 ! J AGTCAACAGCCAATATTTAAAACTTTGTrCGTTACTGGCTTTACCCTAAC 6179 v.l 6501 tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag II j I j 1 | 1 1 1 1 1 1 1 1 II II II 1 l| 1 II 1 1 II 1 1 1 1 II 1 1 II II U 1 II 1 1 6550 v.4 6180 1 &amp;#943; ι ι ι &amp;#943; ι &amp;#943; 1 i 1 1 ι &amp;#943; ι I 1 &amp;#943; 1 I I 1 I 1 1 1 1 I 1 1 1 1 ) 1 1 I j J 1 I 1 1 1 1 1 1 1 1 I t TTTCTCTAGTCTACTGTCAATATCATTTTAATGTAATTGATTGTATATAG 6229 v.l 6551 tctcaagaatggttggtgggcatgagttcctagagaactgtccaagggtt | II 1 1 I II 1 1 1 II I j 1 1 I I 11 II 1 II j 1 1 1 II 1 II 1 II | 1 1 1 1 1 11 1 1 1 1 6600 v.4 6230 ι 1 1 ι 1 1 1 i1 I II I 1 I 11111111111111 1 1111111 I 1 1 111 1 Η 1111 TCTCAAGAATGGTTGGTGGGCATGAGTTCCTAGAGAACTGTCCAAGGGTT 6279 v.l 6601 gggaaaatccaaafctctcttcctggctccagcactgattttgtacataaa ! i 1 1 1 1 1 1 1 1 1 1 1 S J S 1 1 &amp;#938; ! 1 1 i t 1 1 i 1 1 t i f 1 1 I 1 i i 1 &amp;#943; i ! 1 ! i I 1 1 M 6650 v.4 6280 ι Η I ! 1 &amp;#943; Η 1 II 1 Η 1 I } i 11 I I Η 1 ) 1 | ι 11 1 I I I 1 I II 1 I I H I U II GGGAAAATCCAAATTCTCTTCCTGGcTCCAGGACTGATTTTGTACATAAA 6329 v.l 6651 cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa I 1 1 II 1 1 1 1 1 1 11 1 II 1 i I II 1 1 II 1 II 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 II I 1 11 6700 v.4 6330 1 &amp;#970; ι 1 U it 1 1 1 1 11 1 1 I 1 I I I I 11 1 1 11 I I II I } I 1 I 1 J I 1 I l I 1 1 1 I 11 CA.TTAGGCAGGTTGCTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAA 6379 276 v.l 6701 gtgctaataataatctcagttaccttatctttgtcacagggtgttctttt ιιιιιιιιιιιιιιιιιιι 11ιιιιιιι ii ι ι ι ι ι ι ι ι ( j ( &amp;#943; ι | ι ι ι ι &amp;#943; ι 6750 ι 1 1 ι t ι 1 ι N ι ι ι Π ι ι ι Μ l ι ι ι ι I ι l ι ι t 1 1 1 I 1 N Η ι ι t ι ι Π I ι I v.4 63 8 0 GTGCTAATAATAATCTCAGTTACCTTATCTTTGTCACAGGGTGTTCTTTT 6429 v.l 6751 ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc 1 1 1 1 I I 1 1 I 1 1 1 I I 1 1 1 1 1 1 Η 1 1 I I 1 I 1 1 1 I 1 1 1 i I 1 I I I I 1 1 1 ! 1 I 1 1 6800 I i Η II I l N I l &amp;#943; Η 1 1 Η 1 ι 1 ) i 1 1 1 J ι Η I 1 1 1 1 1 i !1 ι t1 1 11 1 I 1 1 V.4 6430 TTATGAAGAAAAATTTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTC: 6479 v.l 6801 ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc I 1 I i 1 I 1 III j II 1 1 I I 1 I 1 1 1 1 1 1 I 1 1 l-l 1 1 1 1 1 | I |’l 1 1 1 1 1 1 1 1 I 1 1 6850 { 1 S I I I 1 I 1 t I l ι I 1 I 1 I 1 I i 1 1 t 1 t i t 1 1 i 1 i i 1 1 I 1 t ( I t I i 1 1 I 1 1 1 v.4 64 8 0 ATAAGCAAACCTTTAACTAATTATGTATCTGAAAGTCACCCCCACATACC 6529 v.l 6851 aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca 1 1 1 I 1 1 I 1 I II 1 1 I 1 j 1 1 1 1 II 1 1 II 1 1 II j II 1 I 1 1 11 II 1 II I ! 1 ) II 6900 I 1 1 ! 1 1 11 f 1 1 [ 1 I 1 1 1 1 1 1 ! 1 1 1 U 1 i 1 1 &amp;#970; 1 I 1 1 1 I 1 ! 1 1 I I I I &amp;#943; 1 1 1 l 6579 v.l 6901 aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat 1 1 1 1 I 1 II 1 I II 1 1 1 II 1 11 1 1 1 | 1 I I | | I 1 1 II I I 1 1 1 II 1 1 1 1 1 II tl 6950 ι 1 1 1 U I U u I I U 1 1 11 U 1 I I U ι ι I U 1 I 1 11 U U 1 1 11 I u 1 I 1 v.4 6580 AATCTACATAAAATAAATCTACTGTTTAGTGAGCAGTATGAcTTGTACAT 6629 v.l 6951 gccattgaaaattattaatcagaagaaaattaagcagggtctttgctata 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ) 1 ) 1 ] 1 1 I 1 1 1 1 1 1 7000 1 1 H 1 11 &amp;#943; Π 1 1 H1 H ) H1 II1 1 I 1 ) I J 1 1 1 1 1 1 I II 1 1 i I 1 1 1 1 I 1 1 v.4 6 6 3 0 GCCATTGAAAATTATTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATA 6679 v.l 7001 caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga II I 1 | II 1 II II II 1 1 1 1 I (I ) 1 i 1 1 II 1 I 1 1 1 I II 1 1 II 1 1 1 1 1 II , 1 I 7050 1 l 1 I 1 1 1 I 1 1 &amp;#943; I &amp;#943; I 1 11 1 1 I 1 { ( ) 1 1 Η H 1 1 ι ι 1 Η 1 1 U U I 1 I 1 1 1 1 v.4 668 0 CAAAAGTGTTTTCCACTAATTTTGCATGCGTATTTATAAGAAAAATGTGA 6729 v.l 7051 atttggtggttttattctatcggtataaaggcatcgatattttagatgca | 1 1 1 II 1 II II 1 |j (I 1 1 1 1 1 1 1 j 1 1 j II 1 1 1 1 II 1 1 1 II j II j II 1 II I 7100 Η 1 1 1 1 I M i I 1 I 1 I 1 I 1 I 11 1 5 1 1 &amp;#943; I 1 I 1 I 1 1 ! 1 1 I 1 1 I I 1 1 &amp;#943; ι ι 1 1 f l V.4 6730 ATTTGGTGGTTTTATTCTATCGGTATAAAGGCATc GATATTTTAGATGCA 6779 v.l 7101 cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca | 1 j 1 1 II II 1 1 II II !| I II 1 II 1 1 1 II 1 1 1 II 11 Vl 1 1 1 1 1 1 II II 1 1 1 7150 I 1 1 1 1 1 1 1 1 1 1 I I I 1 ! I ! ι 1 I I 1 { I I 1 1 1 1 I 1 1 1 I 1 1 1 1 I 1 1 1 ι &amp;#943; 1 ι 1 l· 1 V.4 678 0 CCCGTGTTTGTAAAAATGTAGAGCACAATGGAATTATGCTGGAAGTCTCA 6829 v.l 7151 aataatatfcfcttttcctattttatactcatggaagagataagctaaagag 1 1 J 1 I 1 1 ! II 1 1 1 I I 1 1 11 1 SI t SI I 1 1 t| 1 1 1 1 1 1 U i 1 II II 1 1 1 II 1 7200 1 Η I I Η Η 1 1 Η II 1 1 I ι I 1 1 Π ) 1 1 1) 1 ι 1 IS ι 1 1 is 1 1 i Π Η I 1 II v.4 683 0 AATAATATTTTTTTCCTATTTTATACTCATGGAAGAGATAAGCTAAAGAG 6879 v.l 7201 gggacaataatgagaaatgttggtgtgcttttctaagcatttaaaacata | II I I I M I II I I , II I j 1 I 1 j I I || 1 || I 1 J I 1 I I I 1 1 1 I 1 1 1 1 I 1 1 1 1 7250 I 1 ! 1 1 1 1 LI 1 1 1 11 &amp;#943; i I I 1 1 IIl I 1 11 1 1 1 1 I I 1 I ι ι ι 1 ι i ι 1 1 ι ι 1 ι ι 1 692 9 v.l 7251 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc | 1 1 1 1 1 1 1 1 j 1 1 II 1 1 1 1 1 1 II II II 1 II 1 II 1 1 II II 1 I II II 1 I I II 1 7300 1 ll 1 1 ι 1 1 i 1 I 1 i 1 1 1 1 1 1 I 1 I l &amp;#943; I 1 ll I 1 1 1 I 1 11 1 I 1 1 1 U 1 I 1 i &amp;#943; 1 I V.4 6930 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc 6979 v.l 7301 atgtaacaatgttaaattaattataatgggattgggtttgttatctgtgg | || 1 II I 1 1 1 1 1 ! 1 1 I 1 1 1 1 1 I 1 1 11 1 1 1 1 II 1 ! II 1 1 1 1 I] 1 1 1 1 I 1 1 1 7350 1 1 1 1 1 1 1 1 1 ι 1 ι 1 1 ι 1 1 1 ι 1 I 1 1 1 1 1 1 1 ι 1 1 1 1 ι ι 1 ι 1 1 l 1 I l 1 1 1 i 1 1 1 v.4 6980 ATGTAACAATGTTAAATTAATTATAATGGGATTGGGTTTGTTATCTGTGG 7029 v.l 7351 tagtatatatcctagtgttcctatagtgaaataagtagggttcagccaaa 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 II I 111 111 11 1 1 I I 1 I 1 1 1 ! 1 1 1 7400 Π { 1 1 π 1 ΠI I 11 1 1 1 1 1 1 1 N I Η ι Π I 1 1 1 I II I 1 I I 1 11 II 1 1 11 1 v.4 7030 tagtatatatcctagtgttcctatagtgaaataagtagggttcagccaaa 7079 v.l 7401 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga II 1 H ! 1 Μ 1 i 1 I 1 1 1 1 Μ 1 I 1 1 &amp;#943; ! I! ii I 1 1 1 Μ 11 1 11II )1 1 1 ! I i 1 7450 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 V.4 7 08 0 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga 7129 v.l 7451 tgaaaggtatgtagaacaggttcacgtgattacctttttcttttggcttg | 1 1 1 1 1 1 1 j 1 1 II 1 1 1 I 1 j 1 1 I 1 1 1 1 II 1 1 1 1 1 1 1 1 1 j 1 1 1 J 1 1 1 1 1 11 j 7500 1 1 i 1 1 1 1 I 1 1 ! ι Ι ι 1 1 I I 1 1 I 1 II 1 1 1 I I 1 1 1 1 1 1 1 1 1 [ I { | ι [ I I ι ι 1 I V.4 7X3 0 TGAAAGGTATGTAGAACAGGTTCACGTGATTACCTTTTTCTTTTGGCTTG 7179 277 &amp;#970;. v.1 7501 V . 4 7180 v.i 7551 v.4 7230 v.1 7601 V.4 7280 gattaatattcatagtagaactttataaaacgtgtttgtattgtaggtgg

II11! II II! 111II I! (IIIIII i 11 Μ Ii I! II Η 111 i II11 &amp;#943; IIII

GATTAATATTCATAGTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGG tgtttgcattatgcttafcgactatgtatggtttgaaaatattttcattat

11 Π! 11II Η 111! 111! 111II11 HI 11! IIIII11 III! 11II III

TGTTTGTATTATGCTTATGACTATGTATGGTTTGAAAATATTTTCATTAT acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa

II11! I f 11!11IIIII! II Η I &amp;#943;! II I!11 Η II I!111II III 111II

ACATGAAATTCAACTTTCCAAATAAAAGTTCTACTTCATGTAATCCAAAA 7550 7229 7600 7279 7650 7329

Table LIVc. Peptide sequences of protein coded by 282P1G03 v.4 (SEQ ID NO: 166)

MEPLLLGRGL IVYLMFLLLK GNPEPTFSWT KDGNPFYFTD EEIEFIVPSV PKLPKEKIDP YMSQKGDLYF ANVEEKDSRN SKANSIKQRK PKLLLPPTES RETKENYGKT LKIENVSYQD GSNGILLCEA EGEPQPTIKW NVHGTILANA NIDWDVRPL PLEGRRYHIY ENGTLQINRT RIPKLHMLEL HCESKCDSHL DQGIYCCSAH TALDSAADIT YIVEFEGNKE EPGRWEELTR ETPPAAPDRN PQNIRVQASQ VTNHTLRVMT PAVYAPYDVK ATLSWGLPKK LNGNLTGYLL YLRACTSQGC GKPITEESST WGDNDSIFQD VIETRGREYA SVKEKEDLHP DPEIQSVKDE HGLFSEDGSF IGAYAGSKEK

FSKAIEIPSS VQQVPTIIKQ HRIIPSNNSG TFRIPNEGHI LEVEEGDPIV LPCNPPKGLP DYCCFAAFPR LRTIVQKMPM GSESSITILK GEILLLECFA KGNYRCTASN FLGTATHDFH RVNGSPVDNH PFAGDWFPR IQTKDGENYA TWGYSAFLH TEEDAGSYSC WVENAIGKTA KHSLKLSWSK DGEAFEINGT QVTVLDVPDP PENLHLSERQ VQGKKTTVIL PLAPFVRYQF PKEMIIKWEP LKSMEQNGPG VQAINQLGSG PDPQSVTLYS QYQIINDTYE IGELND ΙΝΙΤ LGEGSKGIGK ISGVNLTQKT GLYDDISTQG WFIGLMCAIA TFGEYSDSDE KPLKGSLRSL GSVESNGSST ATFPLRA

SKVQVAFPFD EYFQIECEAK SHFQGKYRCF ASNKLGIAMS PLHIYWMNIE LEHIEQDERV KLTVNSLKHA NDSSSSTEIG EGLPTPQVDW NKIGGDLPKG VIVEEPPRWT KKPQSAVYST EISFTNLQPN HTAVYQCEAS CEFFASPEAV VSWQKVEEVK VTANLDIRNA TKLRVSPKNP EDGRIIIDGA NLTISNVTLE NRSVRLTWEA GADHNSNISE RVIAVNEVGR SQPSQPSDHH LEYRVTWKPQ GAPVEWEEET GEDLPEQPTF LKVIKVDKDT TPSKPSWHLS NLNATTKYKF HPIEVFEPGA EHIVRLMTKN LLTLLLLTVC FVKRNRGGKY NRDMQPTESA DSLVEYGEGD 60 12 0 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1117

Table LVc. Amino acid sequence alignment of 282P1G03 v,1 (SEQ ID NO: 167) and 282P1G03 v.4 (SEQ ID NO: 168) v.1 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD II 1 II II 1 II I 1 I I 1 1 1 1 1 It I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 II 1 1 1 1 II 1 1 1 1 50 v.4 1 1 1 1 1 1 ι &#943; 1 II 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 i 1 I 1 1 1 1 1 II 1 1 1 1 1 1 1 1 MEPLLLGRGLIVYLMFLLLKFS KAIE IPS Ξ VQQVPTIIKQS KVQ VAFPFD 50 v.1 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 1 1 I II Π 1 II I II 11 I 1 l| I I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 II 1 1 1 1 100 v,4 51 1 1 II I II ! I I I II 1 I 1 1 I II I 1 1 1 1 1 I I 1 I I 1 1 1 1 II 1 1 1 1 1 1 II I 1 1 1 1 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI ' 100 v.1 101 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV I 1 1 1 1 1 1 i H 1 1 II II 1 I II 1 I 1 1 1 j 1 1 I 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 II 1 1 II 150 v . 4 101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 t 1 1 1 1 1 1 1 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV 150 v.1 151 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN 1 I I I I I 1 I 1 I 1 I I I I I I I I I I I I 1 I ! I I I I I I I I I I I I I I 1 I I I 1 I I I I ] 200 v . 4 151 11 1 1 ] 1 11 1 11 1 11111111 11 i 11 1 1 I 1 1 1 1 1 1 1 11 11 1 11 11111111 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN 200 v.1 201 dyccfaafprlrtivqkmpmkltvnslkhandssssteigskansikqrk 1 1 I I II 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 250 v.4 201 I 1 1 1 1 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 1 1 1 II1 111 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 dyccfaafprlrtivqkmpmkltvnslkhandssssteigskansikqrk 250 v.1 251 pklllpptesgsessitilkgeilllecfaeglptpqvdwnkiggdlpkg 1 1 1 1 II 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 300 v. 4 251 1 I 1111 I 1 1 1 1 1 1 i11111111IIII11II1111II 1 1 1 1 1 1 II 1 1 1 1 I 1 pklllpptesgsessitilkgeilllecfaeglptpqvdwnkiggdlpkg 300 v. 1 3 01 Retkenygktlkienvsyqdkgnyrctasnflgtathdfhviveepprwt 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 350 v.4 301 11 I II 1 II 1 1 1 11 111II111II1II11 111 1 1III 1 1 1 1 1 I 11111 1 i I Retkenygktlkienvsyqdkgnyrctasnflgtathdfhviveepprwt 350 278 V. 1 351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDHHPFAGDWFPR I I 1 I I I II I I I I II II 1 1 1 I I I 1 1 1 1 I 1 1 1 I 1 II II I I I I I I 1 I 1 I i I 1 I 400 ν. 4 351 1 I 1 I 1 I 1 I II 1 1 1 1 1 1 1 II 1 1 1 1 1 11 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 II 1 1 1 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDWHPFAGDWFPR 400 v.l 401 EXSFTNLQPNHTAVYQCEASNVHGTILARANIDWDIZRPLIQTKDGEHYA I I I ! I 1 I II II 1 1 || I II 1 I ! 1 1 1 It 1 1 1 I 1 I 1 1 1 I 1 1 1 I 1 1 II 1 I I 1 1 1 45 0 V.4 401 1 1 ! 1 1 I I ι ι ι ι ι ι 1 1 1 1 I ι ι I 1 1 ι ι 1 ι 1 ι I ι ι 1 1 1 i 1 ι I 1 ι ι 1 1 ι 1 ι 1 1 I EISFTNLQPNHTAVYQCEASNVHGTILANANIDWDVRPLIQTKDGENYA 450 v.l 451 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQIMRT 1 I !| 1 1 1 1 I I II 11 1 1 1 1 1 1 1 II 1 1 II 1 H 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 I 1 500 v.4 451 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 I 1 1 1 I ! 1 1 1 1 1 1 1 1 1 1 i 1 1 1 I I I 1 I 1 1 1 ! 1 1 I 1 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT 500 v.l 501 TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPmPRIPKLHMLEL | 1 1 II 1 1 1 II 1 II 1 II 1 1 I 1 1 1 1 1 1 1 II II 1 1 1 1 1 1 1 1 j 1 11 1 II 1 1 1 1 1 550 v.4 501 1 1 1 1 1 II 1 1 1 1 ι 1 1 i 1 1 1 1 1 1 1 1 1 1 11 I 1 I 1 1 I ι 1 1 1 1 1 I II 1 1 I 1 1 I 1 1 TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPKNPRIPKLHMLEL 550 v.l 551 HCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 600 v . 4 551 ! 1 1 1 1 1 ! 1 I 1 1 i 1 1 i 1 I 1 1 1 1 1 1 1 1 I ι 1 I i i i i 1 1 I 1 1 1 1 N I 1 1 Γιιι&#943; HCESKCDSHL KHSLKLSWSKDGEAFEINGTEDGRIIIDGAWLTISNVTLE 600 v.l 601 DQGIYCCSAHTAJLDSAADITQVTVLDVPDPPENLHLSERQEJRSVRLTWEA. 1 1 1 11111111 I 11&#943;111II11111111 11111111 1 11 II 1 1 1 1 1 1 111 650 v.4 601 1 1 l ι i 1 ι ι 1 ι ι ι ι 1 1 I 1 Η I I 1 N t I I 1 11 1 1 1 ι ι 1 I 1 1 ι 11 1 1 1 ι ι 1 1 1 DQGIYCCSAHTALiDSAMITQVTVLDVPDPPENLHLSERQNRSVRLTWEA 65 0 v. 1 651 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 ! 700 v.4 651 1 1 1 1 1 1 1111 1 11 1 I 1 1 1 1 1 1 I 1 1 1111 I 1 1 1 1 II1 1 1 1 1 1 1 11 1 1 1 II 1 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 700 v.l 701 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1II 1 1 1 1 1 1 1 1 1 1 1 11 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 750 v.4 701 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 750 v.l 751 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK I 1 1 1 1 1 1 1 1 1 1 1 1 1 , 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 800 v. 4 751 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 11 1111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 I 1 II 1 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 800 v. 1 801 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDV1KSTLVKVTWSTVP 1 1 Π Μ 1 1 1 &#943; 1 1 i 1 1 ! 1 1 i i ! 1 1 850 v.4 801 11 1 1 ι 1 111 11 i 1 1 11 11I1111 VQAINQLGSG£%>PQSVTLYSGED--------------------------- 823 v.l 851 KDRATHGRLKGYQXNWWKTKSLLDGRTHPKEVNILRFSGQRNSGMVPSLDA 900 v . 4 824 823 v.l 901 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL . I 1 I I II I I 1 I 1 I 1 I 1 1 1 1 I 950 v.4 824 1 1 1 II II II 1 1 1 1 11 1 1 1 1 ------------------------------LPEQPTFLKVIKVDKDTATL 843 v.l - 951 SWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDIWITTPSKPSi'JHLSNLN . II 1 1 II 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 ! 1 1 1 1 1 I 1 1 I 1 11 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1000 v.4 844 1 1 1 1 1 1 1 1 1 I 1 I 1 I 1 1 1 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 I 1 1 1 I I 1 1 I 1 1 1 1 SWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITTPSKPSWHLSNLN 893 v.l 1001 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNLTQKTHPI | II 1 1 1 1 I I I 1 ! I 1 I 1 I 1 I 1 I I 1 I 1 1 1 1 1 1 1 II 1 1 1 II ! 1 1 1 1 1 1 1 1 I 1 |. 1050 v„ 4 894 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNLTQKTHPI 943 v.l 1051 EVFEPGAEHIVRLMTKNWGDNDSIFQDVIETRGREYAGLYDDISTQGWFI 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1- 1 1100 V. 4 944 1 I ι π 1 1 1 1 1 I 111 1 11111111 1 II 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 EVFEPGAEHIVRLMTKNWGDNDSIFQDVIETRGREYAGLYOTISTQGWFI 993 v.l 1101 GLMCAIALLTLLLLTVCFVKRHRGGKYSVKEKEDLHPDPEIQSVKDETFG 1150 279 y-4 994 v.l 1151 v.4 1044 v.l 1201 v.4 1094

GLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPDPEIQSVKDETFG

EYSDSDE.KPEKGSLRSLNRDMQPTESADSLVEYG'EGDHGLFSEDGSFIGA

I Η 111111! il 11 N 11! III HI 111111 Ml I 111 11! Η 11! 11 i I

EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA YAGSKEKGSVESNGSSTATFPLRA 1224 I N I i 111 Ii Iii I i i i 11 i I i 11 YAGSKEKGSVESNGSSTATFPLRA 1117 1043 1200 1093

Table LHd. Nucleotide sequence of transcript variant 282P1G03 v.5 (SEQ ID NO: 169) cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg aatcgtatat agttcaacag tgagtatttt taaggatggc aacattc.agg tgcttcaaat tccaaaactc cctcccatgc attagaacac cgcaaacgtg attaaggact caagcaaaga taccatcctc acaggttgat ttatggcaag cacagccagc tcctcgctgg gttatgtgag agttgacaat ccttcaacca ccttgccaat agaaaattac acctgaggca gtatcatatc gtcttactca tattagaaat tatgcttgaa gtcctggagt tattgatgga ctgttcagct tgttccggat gacctgggaa aggaaacaaa cacagttatc cgaagtaggg fcccagatagg aaagtgggag ctggaagcca gcgggtgatg actaggatct tacagctcca gtcaacagtt gaaaacaaaa ttcaggacaa aacagtctta aacaccagaa gcgcccccgt acagatcgcg atactgcaaa taaggtctca ttgtcttctt ctaatgttcc gttccaacaa caaattgaat aacccttttt atcccaaacg aaactgggaa ccaaaagaaa aatcctccca atcgaacaag gaagaaaagg attgtacaga aaacccaaac aaaggggaaa tggaacaaaa actttgaaga aatttcttgg acaaagaagc gctgaaggag catccatttg. aatcatactg gccaatattg gctacagtgg gtcgtgtcct tatgaaaatg tgtfcgggtag gctacaaaac ttacattgtg aaagatggag gctaatttga catactgctc ccaccagaaa gctggagctg gaagagcctg ttacctttgg agaagtcagc aatccacaaa cctttgaaat cagggagccc acgcctgctg gggcctgacc gtgatccatg ccaaaggaca agtctgttgg agaaactctg gcctataact ggagtacctg cccggctccc tttcggaggc caaatcatag gctgtaaacc cctgaagagc tcctgttaaa tcataaaaca gtgaagctaa atttcactga aggggcacat tcgctatgtc aaattgaccc aaggcctccc atgaaagagt acagtcgcaa aaatgccaat tgctgttgcc tcttgctgct ttggtggtga tagagaatgt gaacagccac ctcagagtgc aacctcaacc ctggtgatgt ctgtgtacca atgttgtgga ttgggtacag ggcagaaggt gcacattgca aaaatgctat ttagagtttc aaagcaaatg aagcctttga ccatatctaa tagacagtgc accttcactt accacaacag gaaggtggga ctccatttgt ctagccagcc acataagggt ccatggagca cagtggagtg tctatgcccc ctcagtcagt gggtggacgt gagtacatgg atggaagaac gaatggttcc ctaaaggagc aacagccaac ggccggctcg ggcgcaggtg tggaactaag aaaagtgaga aatggagccg attctcaaaa gtcaaaagtc aggaaatcca ccatcggata atctcacttt agaagaaata tcttgaagtg acctttacac atacatgagc tgactactgt gaaactaaca tcccactgag tgagtgtttt cttaccaaag ctcctaccag tcacgatttt .tgtgtatagc cacaatcaag tgtcttcccc gtgtgaagcc tgtccgtcca tgctttctta ggaagaagtg gatcaacaga aggaaaaact tcctaagaat tgactcacat aattaatggc tgtaacttta tgccgatata gtctgaaaga caatattagc ggaactgacc gagataccag gtcagaccat tcaagcctct gaatggacca ggaagaagaa ttatgatgtc gactctctat tataaacagt acgtctgaaa acatcccaaa ttccttagat tggtcctgaa ttttctaaag ggggagaagg ctgtaaactg gggaacttaa ggagacatta cttttacttg gcaattgaaa caagttgcct gaaccaacat attccatcga caagggaaat gaatttatag gaggagggag atttattgga caaaagggag tgctttgctg gttaacagtt agtggcagtg gctgaaggct gggagagaaa gacaaaggaa cacgttatag accggaagca tggagagtca agggaaatca tcaaatgtcc ttqatacaaa cattgcgagt aaaCccctgg accaccgaag gcagtcacag cctcgtatcc ttgaaacaca acagaagatg gaggaccaag actcaagtaa cagaacagga gagtatattg agagtccaag ttcagggtca catgaaacac caacccaagg ggcctagagt acagtcacaa aaggtccagg tctggagaag acattagtta ggctatcaga gaagtgaaca gcctttagtg agtgagcctt gtcatcaaag cgcccgaggg caaaccataa tttactgttt agattttcat gaagaggact taccatcttc ttcccttcga tttcgtggac acaattcagg accgctgctt ttccaagtgt atccaattgt tgaatattga atctatactt catttccaag caaattccat agtcttcaat tgccaactcc caaaagaaaa attatcgctg tagaagagcc atggcatctt atggctcccc gttttaccaa atggaactat ccaaagatgg tctttgcttc agggcaggcg aagatgctgg ccaatttgga ccaaattgca gtttgaagtt gcaggataat, gtatttactg ctgttcttga gtgttcggct ttgaatttga gaaagaaaac tagccgtgaa caccagcagc aaatgattat acagagtgac accacacatt ctatcaatca actatcctga aagttacctg taaattggtg ttctaagatt aatttcattt atatatttca ttgataaaga

SO 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 280 y./qactgccact ttatcttggg gactacctaa gaaattaaat ggaaacttaa ctggctatct 3120 tttgcaatat cagataataa atgacaccta cgagattgga gaattaaatg atattaacat 3180 tacaactcca tcaaagccca gctggcacct ctcaaacctg aatgcaacta ccaagtacaa 3240 attctacttg agggcttgca cttcacaggg ctgtggaaaa ccgatcacgg aggaaagctc 3300 caccttagga gaagggagta aaggtatcgg gaagatatca ggagtaaatc ttactcaaaa 3360 gactcaccca atagaggtat ttgagccggg agctgaacat atagttcgcc taatgactaa 3420 gaattggggc gataacgata gcatttttca agatgtaatt gagacaagag ggagagaata 3480 tgctggttta tatgatgaca tctccactca aggctggttt attggactga tgtgtgcgat· 3540 tgctcttctc acactactat tattaactgt ttgctttgtg aagaggaata gaggtggaaa 3600 gtactcagtt aaagaaaagg aagatttgca tccagaccca gaaattcagt cagtaaaaga 3660 tgaaaccttt ggtgaataca gtgacagtga tgaaaagcct ctcaaaggaa gccttcggtc 3720 ccttaatagg gatatgcagc ctactgaaag tgctgacagc ttagtcgaat acggagaggg 3780 agaccatggt ctcttcagtg aagatggatc atttattggt gcctacgctg gatctaagga 3840 gaagggatct gttgaaagca atggaagttc tacagcaact tttccccttc gggcataaac 3900 acaacatatg taagcaacgc tactggttca ccccaacctt ccatatttat ctgttcaaag 3960 gagcaagaac tttcatatag gaatagaaac atgctggccg aagatttcat ccagaagtca 4020 acatcctgca attatgttga aaagagtagt actttcttca aaatataaaa tgccaagcac 4080 ttcaggccta tgttttgctt atattgtttt caggtgctca aaatgcaaaa cacaaaacaa 4140 atcctgcatt tagatacacc tcaactaaat ccaaagtccc cattcagtat attccatatt 4200 tgcctgattt tactattcgg tgtgtttgca tagatgttgc tacttggtgg gtttttctcc 4260 gtatgcacat tggtatacag tctctgagaa ctggcttggt gactttgctt cactacaggt 4320 taaaagacca taagcaaact ggttatttaa .aatgtaaaaa ggaatatgaa agtcttatta 4380 aaacacttca ttgaaaatat acagtctaaa tttattattt aaattttact agcaaaagtc 4440 ttaggtgaac a'atcaactag tatttgttga gctcctattt gcccagagat ggtcatattt 4500 aaacagaagt atacgttttt cagtttcaac atgaattttt ttatttctgt cagttatgac 4560 atccacgagc atcacttttt gtgtctgttt tttttttttt cttggactaa attcaactgc 4620 . atggaagcgg tggtcagaag gttgttttat acgagaacag gcagaaagtg cccattgttc 4680 aggattctaa tagctacatc tacttaatat cttcatttct aaattgactg cttttacctt 4740 tttctcatgt ttatataatg gtatgcttgc atatatttca tgaatacatt gtacatatta 4800 tgttaatatt tacacaattt aaaatataga tgtgttttat tttgaagtga gaaaatgaac 4860 attaacaggc. atgtttgtac agctagaata tattagtaag atactgtttt tcgtcattcc 4920 agagctacaa ctaataacac gaggttccaa agctgaagac tttgtataaa gtatttgggt 4980 tttgttcttg tattgctttc tttcaacagt ttcaaaataa aatatcatac aaatattgag 5040 ggaaatgttt tcatattttt caaaataggt ttttattgtt gaatgtacat ctaccccagc 5100 ccctcaaaag aaaaactgtt tacatagaaa ttcctacaca tacgtttgcg tatatgttat 5160 tttaaacatc tttgtggtga gaattttttc cccgatattc tccttctgtc aaagtcagaa 5220 caaattcagg gaatttattt tctggcagtt gtgctccagt ccttttaaaa ttgtacatga 5280 acatgtttta gaaacaatat ggaggatgat gcatacatgt cggtcaagtt cagcgctcga 5340 cattttatgg aaagattttt ttaaccttac cacgaaatac ttaactactg tttaagtgaa 5400 ttgacttatt tcactttagt ttttgaactg tgattattgg tatactgtta tatcctcaac 5460 ttggatttat ggtaacccct tttagttcat ggagaccaaa atttggggta tttataatag 5520 tcagcgcagg aatgcacatg gaatatctac ttgtcctttt gaacctcacg agtcatccag 5580 aatgtataga caggaaaagc atgtcttatt taaaactgta atttatgggc tcaggatctg 5640 accgcagtcc cgggagtaag catttcaaag ggggaaggca gtgtggtccc taccctgtgt 5700 gaatgtgagg atgtagacat ccatcagtgc aactcgagct ccatcctcct ccgatttcta 5760 aggctccagt tttctggagg gacagtcatc atgttttgat ttatctggga gaaaactgtg 5820 gtgcacagct tgtgaggagg gcaaggttgt gacgttcgag cttagttctg gtgttattct 5880 gtctcctctt ctttgtcatc agccaaaacg tggtttttaa agagagtcat gcaggttaga 5940 aataatgtca aaaatattta ggaatttaat aacctttaag tcagaaacta aaacaaatac 6000 tgaaatatta gctcttccta cacttcgtgt tcccctttag ctgcctgaaa atcaagattg 6060 ctcctactca gatcttctga gtggctaaaa cttatggata tgaaaaatga gattgaatga 6120 tgactatgct ttgctatcat tgttaccttt cctcaatact atttggcaac tactgggact 6180 cttcagcaca aaaggaatag atctatgatt gaccctgatt ttaattgtga aattatatga 6240 ttcatatatt ttatgaatca gaataacctt caaataaaat aaatctaagt cggttaaaat 6300 ggatttcatg attttccctc agaaaatgag taacggagtc cacggcgtgc aatggtaatt .6360 ataaattggt gatgcttgtt tgcaaattgc ccactcgtga taagtcaaca gccaatattt 6420 aaaactttgt tcgttactgg ctttacccta actttctcta gtctactgtc aatatcattt 6480 taatgtaatt gattgtatat agtctcaaga atggttggtg ggcatgagtt cctagagaac 6540 tgtccaaggg ttgggaaaat ccaaattctc ttcctggctc cagcactgat tttgtacata 6600 aacattaggc aggttgctta acctttttat ttcaaactct ctcaactcta aagtgctaat 6660 aataatctca gttaccttat ctttgtcaca gggtgttctt ttttatgaag aaaaatttga 6720 aaatgataaa agctaagatg ccttctaact tcataagcaa acctttaact aattatgtat 6780 ctgaaagtca cccccacata ccaactcaac ttttttcctg tgaacacata aatatatttt 6840 281 A . rtatagaaaaa caaatctaca taaaataaat ctactgttta gtgagcagta tgacttgtac 6900 atgccattga aaattattaa tcagaagaaa attaagcagg gtctttgcta tacaaaagtg 6960 ttttccacta attttgcatg cgtatttata agaaaaatgt gaatttggtg gttttattct 7020 atcggtataa aggcatcgat attttagatg cacccgtgtt tgtaaaaatg tagagcacaa 7080 tggaattatg ctggaagtct caaataatat ttttttccta ttttatactc atggaagaga 7140 taagctaaag aggggacaat aatgagaaat gttggtgtgc ttttctaagc atttaaaaca 7200 taattgccaa ttgaaaccct aaatatgttt acataccatt aagatatgat tcatgtaaca 7260 atgttaaatt aattataatg ggattgggtt tgttatctgt ggtagtatat atcctagtgt 7320 tcctatagtg aaataagtag ggttcagcca aagctttctt tgttttgtac cttaaattgt 7380 tcgattacgt catcaaaaga gatgaaaggt atgtagaaca ggttcacgtg attacctttt 7440 tcttttggct tggattaata ttcatagtag aactttataa aacgtgtttg tattgtaggt 7500 ggtgtttgta ttatgcttat gactatgtat ggtttgaaaa tattttcatt atacatgaaa 7560 ttcaactttc caaataaaag ttctacttca tgtaatccaa aa 7602

Table LIHd. Nucleotide sequence alignment of 282P1G03 v.1 (SEQ ID NO: 170) and 282P1G03 v.5 (SEQ ID NO: 171) iaccctqcqcqcccccqtcccqgctcccqqccgqctcqgqqqaqaaqq 50 v.l 1 v.5 1 v.l 51 v.5 51 v.l 101 v.5 101 v.l 151 v.5 151 v.l 201 v.5 201 v.l 251 v.5 251 v.l 301 v.5 301 v. 1 351 v.5 351 v.l 401 v. 5 401 v. 1 451 v.5 451 v.l 501 v.5 501 v.l 551 v.5 551 v.l 301 aatcgtatatctaatqttcctcctgttaaaattctcaaaagcaattgaaa

11 WII111 i li 111 I ill 11111li11111!II!i11111 i I i IIII 50 100 100 150 150 200 200 250 250 300 300 350 350 400 400 450 450 500 500 550 550 600 600 282 ,Αν -1 601 tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag I 1 1 1 1 1 1 1 1 1 1 1 I 1 II I 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 I 1 I II 1 11 I II 1 II 650 v. 5 601 1 1 I 1 H 1 1 1 1 1 I &#943; 1 ι 1 1 1 1 1 ! 1 1 I 11 ! 1 I I ! I &#943; I 1 1 1 1 I I 1 I &#943; I I ! N ! ! TGCTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650 v.l 651 tfcccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg I 1 I I I I 1 I 1 I 1 I 1 j ! I I I I 1 1 I I I 1 ! I I 1 1 1 1 1 1 |l 1 I 1 ! 1 1 1 1 i 1 1 1 II 700 v.5 651 &#943; ι i ι ι I 1 &#943; ι ι &#943; ii f N i ! I i 1 1 I 1 1 f 1 1 1 &#943; ι &#943; &#943; 1 1 ι 1 i 1 1 1 I i &#943; 11 1 1 i &#943; TTCCAAGTGTTCCAAAAcTCCCAAAAGAAAAAATTGACCCTCTTGAAGTG 700 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 1 1 1 1 1 1 1 11 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 750 V. 5 701 1 1 ! 1 1 II 1 1 1 11 1 ι ι &#943; I 1 i 1 1 1 1 1 1 11 j 1 1 1 1 H ! 1 I 1 11 H 1 1 1 1 1 1 1 I GAGGAGGGAGATCCAATTGTCCTCCCATGCAATCCTCCCAAAGGCCTCCC 750 v.l 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag II 1 1 1 I 1 l| 1 1 1 II 1 1 II 1 1 1 II 1 11 1 II 1 1 1 II 1 1 1 II II II 1 1 1 1 1 11 800 v.5 751 1 1 1 I ι &#943; 1 j 1 1 1 1 S I 1 1 I ! 1 1 1 1 1 If 1 1 ! 1 I 1 1 1 H I 1 1 1 i 1 1 1 1 I 1 if 1 I ACCTTTACACATTTATTGGATGAATATTGAATTAGAACACATCGAACAAG 80&#908; v.l 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg | 1 1 1 1 I 1 ! 1 &#943; i 1 &#943; I i &#943; i I 1 1 1 1 i 1 1 I I 1 1 1 1 1 I 1 1 1 1 II I 1 i| 1 11 1 1 i I 850 v.5 801 1 1 1 1 1 j 1 1 1 l 1 1 1 1 Η 1 1 ! ! 1 I 1 1 1 I 1 I t 1 1 1 I 1 1 1 &#943; I I 1 1 1 I 1 ! Il 1 1 1 ATGAAAGAGTATACATGAGCCAAAAGGGAGATCTATACTTCGCAAACGTG 850 v.l 851 gaagaaaaqgacagtcgcaatgactactgttgctttgctgcatttccaag 1 1 111 1 1 11II111II 111 1II 1111111111111 II 11 11 1 1 11 1 1 1 11 900 V.5 851 1 J 1 I 1 1 1 ι 1 1 I 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 i I 1 I 1 1 1 1 I I I 1 1 1 1 1 I 1 1 1 1 I i GAAGAAAAGGACAGTCGCAATGACTACTGTTGCTTTGCTGCATTTCCAAG 900 v.l 901 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt | 1 1 1 II I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II II 1 1 II II 1 1 1 1 1 1 ] 1 1 1 1 1 1 1 1 1 950 V.5 901 1 1 I 1 i I ! I 1 i I 1 1 I 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1. I 1 1 1 1 1 1 1 ι 1 1 I i 1 1 1 1 1 ATTAAGGACTATTGTACAGAAAATGCCAATGAAACTAACAGTTAACAGTT 950 V.l 951 taaagcatgctaatgaetcaagttcatccacagaaattggttccaaggca | 1 1000 v.5 951 ------------------------------------------------CA 952 v. 1 1001 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag | 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 II 1 1 1 1 j 1 1 1 1 1 1 1 1 1 1 1 1 1 1 |] 1 1 1 11 1050 V.5 953 i 1 ι 1 1 1 1 1 1 1 1 I l 1 I 1 1 1 ! 1 1 1 1 1 1 f I 1 1 1 1 1 1 I 1 1 1 ! I 1 1 1 1 1 1 i 1 1 1 1 AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG 1002 v.l 1051 tggcagtqaqtcttcaattaccatcctcaaaggggaaatcttgctqct-tg ill! H ill 111 i i i 1111 I i 1 I 1 I i 1 I!1 Η 111 &#943; I 1 i 1 1 1 1 1 1 1 1 i 1 1 1100 v.5 1003 ll 1 1 1 I I 1 1 I I 1 ! 1 1 1 1 u i 1 11 I 1 1 1 J I 1 11 1 1 II 1 1 1 i I 1 1 1 I 1 I ι &#943; 1 TGGCAGTGAGTGTTCAATTACCATCCTCAAAGGGGAAATCTTGCTGCTTG 1052 v. 1 1101 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt 1 1 1 1 ! T I II 1 11 I I | II ! | I I 1 I l| I | II || I I ! I 1 I 1 1 1 I ! ! ! I 1 ! 1 1 &#943; 1150 v.5 1053 ι ιι I 111 i &#943; 1 &#943; l II &#943; &#943; 1 11 1 1 1ι 1 1 1 1 1ι1 I 11 1i 11 ι ι 1 1 1 1 ! 1 1 ι ι ι ι AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGGAACAAAATT 1102 v. 1 1151 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac II 1 1 II 1 1 II I II 1 1 1 1 1 1 1 1 1 111 1 1 1 1 1 II 1 1 1 1 I |l 1 II II 1 l| 1 1 1 1200 . v.5 1103 ι I ι i ι 1 ι 1 1 1 1 1 1 ι 1 I ι 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι ! 1 1 I 1 1 1 1 1 I 1 1 1 GGTGGTGACTTACCAAAGGGGAGAGAAACAAAAGAAAATTATGGCAAGAC 1152 v.l 1201 tttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca i I || I || I IN || I I || 1 | I I I I I I HI || 1 I I || 11 I I I 1 I 1 III I || 1 1250 V.5 1153 1 1 1 1 1 ! 1 I 1 1 1 ! 1 1 ι 1 1 1 1 1 1 1 I j I 1 I 1 1 1 I 1 1 i ! I t S 1 1 ι ι 1 ι 1 1 1 1 I I TTTGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA 1202 V.l 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta 1 I 1 1 1 1 1 1 1 1 1 1 1 ) 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 II 1 1 1 t 1 1 1 1 1 I 1 1 1 1 1 1 1· 1300 v.5 1203 ι ι 1 I ! 1 1 1 S I 1 1 1 1 I 1 ι 1 1 1 ! 1 1 1 1 I I 1 I i i 1 1 ! 1 ι 1 ι ! 1 1 1 1 1 i ! 1 1 1 ! CAGCCAGCAATTTCTTGGGAACAGCCACTCACGATTTTCACGTTATAGTA 1252 v.l 1301 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtatagcac I 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1350 v. 5 1253 Η 1 i 1 1 ! i 1 i 1 1 Η 1 1 1 1 I 1 1 1 1 l 1 1 1 1 1 ι 1 i 1 1 1 I 1 1 1 1 1 1 i 1 ι i 1 H .1 GAAGAGCCTCCTCGCTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCAC 1302 v. 1 1351 cggaagcaatggcatcttgttatgtgaggctgaaggagaacctcaaccca 1 I II II 1 1 1 II II 1 1 II II 1IIIIIIIIII1 I 1IIII II 1 1 1 1 1 III 1 I 1 1400 v.5 1303 1 1 I 1 1 1 II 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 CGGAAGCAATGGCATCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCA 1352 283 v.l 1401 caatcaagtggagagtcaatggctccccagttgacaatcatccatttgct η η ι ι (ι ιιιιιιι| ι ι ι ι ι ι ι 11 ι η ι ι ι ι ι ι ι ι ι ι ι ιιιlι||if 1 j 1450 v.5 1353 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I CAATCAAGTGGAGAGTCAATGGCTCCCCAGTTGACAATCATCCATTTGCT 1402 v.l 1451 ggtgatgttgtcttccccagggaaatcagttttaccaaccttcaaccaaa Η Π II Π Π Π 1 I II Π Η Η 1 1 1 1 Π Η Η 1 1 1 1 1 1 11 1 1 1 Η 1 1 1 II 1500 v.5 1403 1 1 1 1 1 1 1 I Π Π Η 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 II 1 1 1 1 1 1 1 .1 1 1 1 1 1 1 1 1 1 1 GGTGATGTTGTCTTCCCCAGGGAAATCAGTTTTACCAACCTTCAACCAAA 1452 v.l 1501 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc I Η 1 II II 1 Η 1 II Η Η Η II1 Η Η Π 1 II II 11 1 1 1 I! 1 Π Π II 11 1550 v.5 1453 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TCATACTGCTGTGTACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCC 1502 v.l 1551 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc II1 II 1111111 1 1 1 1 Π 1 1 I 11 Π 1 Η II111II111 Η 1 1 II 1 1 1 1 1 1 1600 v.5 15 03 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 TTGCCAATGCCAATATTGATGTTGTGGATGTCCGTCCATTGATACAAACC 1552 v.l 1601 aaagatggagaaaattacgctacagtggttgggtacagtgctttcttaca 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1650 v.5 1553 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AAAGATGGAGAAAATTACGCTACAGTGGTTGGGTACAGTGCTTTCTTACA 1602 v.l 1651 ttgcgaqttctttgcttcacctgaggcagtcgtgtcctggcagaaggtgg 11IIII II II1 1 II III 1 Hill IIII Nil IIII11 III 1 III II I 1 II 1700. v.5 1603 II ι π II 1 1 II 1 II 1 H II 1 1 1 1 1 1 II 1 1 II 1 1 1 1 1 I 1 1 1 1 1 II1 1 1 1 1 1 ttGcgagttctttgcttcacctgaggcagtcgtgtcctggcagaaggtgg 1652 v.l 1701 aagaagtgaaacccctggagggcaggcggtatcatatctatgaaaatggc ι [III |I III 11 II | Η || || Η I | 1 II 1 I) ! II II 1 1 II 1 1 II II Nil 1750 v.5 1653 II 1 I 1 1 II II 1 If IIH II 1 I 1 1 1 II 1 1 1 II 1 II 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 AAGAAGTGAAACCCCTGGAGGGCAGGCGGTATCATATCTATGAAAATGGC 1702 v.l 1751 acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg IIII1 II 1 1 II 1 1 II 11 1 II 1 1 1 H II H 1 1 II 1IIIIII 1 1 1 1 1 1 II II 1800 v.5 1703 1 1 1 II 1 1 II II 1 11 1 I 1 1 1 11 1 1 1 1 1 1 II 1 1 II 1 1 II II II II 1 1 1 1 1 II ACATTGCAGATCAACAGAACCACCGAAGAAGATGCTGGGTCTTACTCATG 1752 v.l 1801 ttgggtagaaaatgctataggaaaaactgcagtcacagccaatttggata I II I 1 II 111 Π II Η Η II1 i 1 1 Η Η 1 Π 1 1 II Η 1 Π Η Η II II II 1850 v.5 1753 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TTGGGTAGAAAATGCTATAGGAAAAACTGCAGTCACAGCCAATTTGGATA 1802 v.l 1851 ttagaaatgctacaaaacttagagtttctcctaagaatcctcgtatcccc II1 II I 1 1 11 1 H H II 1 1! 1 1 1 II 1 1 1 1 1 1 1 II I 1 1 I II 1 II 1 11 II 11 1300 v.5 1803 1 1 1 I 1 1 1 I 1 1 1 1 1 1 II 11 II 1 II 1 II 1 1 II 1 II 11 1 1 1 II 1 II II 1 1 1 II TTAGAAATGCTACAAAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCC 1852 v.l 1901 aaattgcatatgcttgaattacattgtgaaagcaaatgtgactcacattt Il || I Η II II 1 Π Η II II 1 Π 1 Π Η II 1 II Η II Η 1 1 1 II 1 1 II 1 1 1950 v.5 1853 1 1 1 1 1 1 1 H 11 II 11 1 1 II 11II1 II II 1 1 I II 1 1 1 1 11 11 1 1 I 1 II 1 11 AAATTOCATATGCTTGAATTACATTGTGAAAGCAAA.TGTGACTCACATTT 1902 v.l 19 51 gaaacacagtttgaagttgtcctggagtaaagatggagaagcctttgaaa Η II 1 Η Η II 1 1 11 1 1 1 1 1 1 Η 1 Η II Η II II 1 1 II 1 Η 1 Π 1 1 1 I Π . 2000 v.5 1903 11 1 II II II II 1II II II 1 1 1 1 1 II II II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 II II 11 GAAACACAGTTTGAAGTTGTCCTGGAGTAAAGATGGAGAAGCCTTTGAAA 1952 v.l 2001 ttaatggcacagaagatggcaggataattattgatggagctaatttgacc H 1 Η Η Π 1 ι ι I H | | | I I | | | , )lI 1 Η 1 II 11 1 II 1 1 II 1 Π 1 II 1 1 2050 v.5 1953 1 1 1 ι ι ιιιι ι ι ι 1 ι 1 II II 1 I 1 Η Η I I! I I I II 1 1 Η II II II II II II TTAATGGCACAGAAGATGGCAGGATAATTATTGATGGAGCTAATTTGACC 2002 v.l 2051 atatctaatgtaactttagaggaccaaggtatttactgctgttcagctca I l| Π 1 Η II 1 Π II Η II 1 1 1 II Π Η 1 Π Η Π II 1 II I 1 1 Η II 1 1! 2100 v.5 2003 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 II I I 1 1 Ii II 1 H ATATCTAATGTAACTTTAGAGGACCAAGGTATTTACTGCTGTTCAGCTCA 2052 v.l 2101 tactgctctagacagtgctgccgatataactcaagtaactgttcttgatg Π I Π Η II Η II Π Π Η I 1 1 II Η 1 Η N 1 H 1 Η II II Π 1 II II II 2150 v.5 2053 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 I 1 1 1 1 I 1 I 1 1! 1 TACTGCTCTAGACAGTGCTGCCGATATAACTCAAGTAACTGTTCTTGATG 2102 v.l 2151 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt 2200 284 <v. 5 2103 TTCCGGATCCACCAGAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGT 2152 v.l 2201 gttcggctgacctgggaagctggagctgaccacaacagcaatattagcga II1IIII11II11III I I 11IIIIII111 I 111 I!1II1 1 I III 1 1 1 1 1 1 2250 v.5 2153 1 1 ! I I I I 1 ! ! 1 ! ι II i 11 1 II 1i 1 II1 II1 1 1 1 1 I 1 1 1 ! 1 ! 1 i ! ! 1 i &#943; 1 ! GTTCGGCTGACCTGGGAAGCTGGAGCTGACCACAACAGCAATATTAGCGA 2202 v.l 2251 gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg ι ι η ι i ι ι ηiιιjι ii ι ι ι ι η π ι ι ι ιη ιιιι|ιιιιι|&#943; ι ι &#943; | ι ι ι 2300 v.5 2203 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GTATATTGTTGAATTTGAAGGAAACAAAGAAGAGCCTGGAAGGTGGGAGG 2252 v.l 2301 aactgaccagagtccaaggaaagaaaaccacagttatcttacctttggct 1 1 II 1 111 Η 1 1 Η 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 II 1 1 II 1 1 Η 1 Η 1 1 1 1 II 1 2350 v.5 2253 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 II 1 I 1 1 1 I ι AACTGACCAGAGTCCAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCT 2302 v.l 2351 ccatttgtgagataccagttcagggtcatagccgtgaacgaagtagggag 111 1111II1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 111 II 1 1 1 Ν 1 2400 v.5 2303 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 ! 1 1 1 1 1 1 1 &#943; 1 1 1 1 1 1 I CCATTTGTGAGATACCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAG 2352 v.l 2401 aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 &#943; 1 1 1 I 1 1 1 1 1 ) 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 Η Η 2450 v.5 2353 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AAGTCAGCCTAGCCAGCCGTCAGACCATCATGAAACACCACCAGCAGCTC 2402 v.l 2451 cagataggaatccacaaaacataagggttcaagcctctcaacccaaggaa 11 ΠII111!IIII11111II11II11II1II111II11II11II11111 CAGATAGGAATCCACAAAACATAAGGGTTCAAGCCTCTCAACCCAAGGAA 2500 v.5 2403 2452 v.l 1 2501 atgattataaagtgggagcctttgaaatccatggagcagaatggaccagg 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2550 v.5 2453 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ATGATTATAAAGTGGGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGG 2502 v.l 2551 cctagagtacagagtgacctggaagccacagggagccccagtggagtggg 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 11 I 111 1 1 111 1 1 1 1 1 1 1 I II 1 1 1 1 2600 v.5 2503 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 CCTAGAGTACAGAGTGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGG 2552 v.l 2601 aagaagaaacagtcacaaaccacacattgcgggtgatgacgcctgctgtc 1 III II 1 1 I I II 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I II ill II 1 II II III 1 III III 1 2650 v.5 2553 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AAGAAGAAACAGTCACAAACCACACATTGCGGGTGATGACGCCTGCTGTC 2602 v.l 2651 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg | I 1 I 1 I I 1 I I I I 1 I I I I I I I I I 1 I I I I I I I 1 I I 1 I I II I 1 ! 1 1 I I 1 1 I i I 2700 v. 5 2603 1 I ! 1 1 ι ι 1 ! I 1 1 1 I 1 1 1 1 i ! 1 1 1 I 1 1 I 1 ι I 1 1 1 I 1 ι ι I 1 l ι ! i 1 1 1 ! 1 I I TATGCCCCTTATGATGTCAAGGTCCAGGCTATCAATCAACTAGGATCTGG 2652 v.l 2701 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata . I 1 1 III i 1 1 1 1 II 1 1 III II 1 1 11111111IIIIII III 1 1 1 II II II 1 1 2750 v.5 2653 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I I 1 I 1 1 I 1 1 I 1 1 1 1 &#943; 1 t 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GCCTGACCCTCAGTCAGTGACTCTCTATTCTGGAGAAGACTATCCTGATA 2702 v.l 2751 cagctccagtgatccatggggtggacgttataaacagtacattagttaaa 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 11 I 1 1 1 1 1 1 II 1 1 1 1 1 1 1 2800 v.5 2703 1 t > 1 1 1 ι 1 ! i 1 ι ι &#943; &#943; 1 I 1 1 I I ! t 1 &#943; &#943; ι I 1 1 ι ι ι I ι ι &#943; ι I ι i I 1 1 ! 1 ι I 1 1 CAGCTCCAGTGATCCATGGGGTGGACGTTATAAACAGTACATTAGTTAAA 2752 v.l 2801 gttacctggtcaacagttccaaaggacagagtacatggacgtctgaaagg 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2850 v.5 2753 1 1 1 11 1 1 I 1 11 1II1 1 1 111 1 1 1 1 1 1 1 II 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 I GTTACCTGGTCAACAGTTCCAAAGGACAGAGTACATGGACGTCTGAAAGG 2802 v.l 2851 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac I 1 I 1 1 I 1 1 1 1 I 1 I 1 1 I 1 I 1 1 I 1 1 1 1 1 1 ! I II 1 1 1 1 1 I II 1 1 1 ! 1 I II I 1 1 2900 v.5 2803 1 I I 1 1 i 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι 1 1 1 ι ι 1 1 1 1 1 1 1 1 1 1 ι CTATCAGATAAATTGGTGGAAAACAAAAAGTCTGTTGGATGGAAGAACAC 2852 v.l 2901 atcccaaagaagtgaacattctaagattttcaggacaaagaaactctgga I I I 1 1 1 I 1 1 1 1 1 1 T II 1 1 I 1 1 1 1 II 1 1 I 1 1 1 1 I 1 I 1 I 1 1 I 1 1 1 1 1 1 II 1 1 2950 v.5 2853 1 ! 1 1 ! I I 1 I 1 1 1 I } 1 1 &#943; ( 1 1 i &#943; 1 1 I 1 I 1 1 ( 1 1 1 1 1 1 1 L 1 ! ι 1 1 1 ! t ( 1 1 1 ATCCCAAAGAAGTGAACATTCTAAGATTTTCAGGACAAAGAAACTCTGGA 2902 v.l 2951 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc 3000 285 v.5 2903 ATGGTTCCTTCCTTAGATGCCTTTAGTGAATTTCATTTAACAGTCTTAGC 2952 v.l 3001 ctataactctaaaggagctggtcctgaaagtgagccttatatatttcaaa ! I I I 1 I I I 1 I I I &#943; II [ ! I &#943; II 1 1 &#943; ! 1 &#943; I I 1 II 1 ii i 1 1 I 1 1 1 1 i 1 t i 1 II 3050 v. 5 2953 J I &#943; 1 1 I 1 ι 1 1 1 i I ι &#943; i &#943; 1 ι i &#943; I 1 1 1 i I 1 ι I 1 1 ι I 1 I I i I I i 1 1 1 1 I 1 1 I 1 CTAT.AACTCTAAAGGAGCTGGTCCTGAAAGTGAGCCTTATATATTTCAAA 3002 v.l 3051 caccagaaggagtacctgaacagccaacttttctaaaggteatcaaagtt I 1 1 1 1 1 1 1 1 1 1 1 1 1 II It I 1 1 1 II 1 1 1 II II 1 II 1 II 1 II 1 1 1 1 II 1 11 1 3100 v.5 3003 I 1 1 1 I i 1 I 1 1 I j I 1 1 i ! 1 1 ! I I I i 1 I 1 ! 1 I 1 1 I i I I I I i i I 1 I ι 1 I j 1 1 1 CACCAGAAGGAGTACCTGAACAGCCAACTTTTCTAAAGGTCATCAAAGTT 3052 v.l 3101 gataaagacactgccactttatcttggggactacctaagaaattaaatgg II I I I III 1 I 1 111 1 1 I I II 1 1 11 II Hill 1 1 1 III || 1 1 III 1 I 1 Ml 3150 v.5 3053 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 GATAAAGACACTGCCACTTTATCTTGGGGACTACCTAAGAAATTAAATGG 3102 v.l 3151 aaacttaactggctatcttttgcaatatcagataataaatgacacctacg | 1 1 1 1 1 1 1 II 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 II 1 1 1 1 1 1 1 1 1 ] 1 1 1 1 1 1 1 1 1 1 1 1 1 3200 v . 5 3103 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 AAACTTAACTGGCTAT'CTTTTGCAATATCAGATAATAAATGACACCTACG '3152 v.l 3201 agattggagaattaaatgatattaacattacaactccatcaaagcccagc | 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 j II I II 1 1 1 1 1 II 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 3250 v.5 3153 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AGATTGGAGAATTAAATGATATTAACATTACAACTCCATCAAAGCCCAGC 3202 v.l 3251 tggcac'ctctcaaacctgaatgcaactaccaagtacaaattctacttgag | I I II II I I 1 1 II 1 1 |l 1 ] 1 1 1 1 1 1 1 1 II 1 1 1 1 1 |l 1 I- 1 1 1 1 I 1 1 1 1 1 3300 v.5 3203 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 TGGCACCTCTCAAACCTGAATGCAACTACCAAGTACAAATTCTACTTGAG 3252 v . 1 3301 ggcttgcacttcacagggctgtggaaaaccgatcacggaggaaagctcca 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3350 v.5 3253 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 GGCTTGCACTTCACAGGGCTGTGGAAAACCGATCACGGAGGAAAGCTCCA 3302 v.l 3351 ccttaggagaagggagtaaaggtatcgggaagatatcaggagtaaatctt II II 1 1 I 1 1 1 1 1 1 II I 1 1 1 1 II II 1 1 II 1 I 1 1 |l 1 II 1 II 1 II 1 1 1 1 II 1 3400 v.5 3303 1 I 1 1 1 I 1 l 1 1 1 1 1 1 &#943; I I 1 1 1 i 1 } 1 ) 1 1 ι 1 I I 1 1 i 1 1 1 1 I 1 1 t 1 I I 1 i i ι 1 CCTTAGGAGAAGGGAGTAAAGGTATCGGGAAGATATCAGGAGTAAATCTT 3352 v . 1 3401 actcaaaagactcacccaatagaggtatttqagccqqqagctqaacatat ι1111||1 I||111||11111|I|||1 I I 1 II II II II II | II 1I I | | | | 3450 v.5 3353 N I 1 1 ι 1 1 1 1 1 1 1 1 1 I ι ι 1 H 1 I 1 1 1 i t I 1 i 1 ι 1 1 1 1 1 ι I &#912; ! 1 1 1 Ι&#906; I I 1 ACTCAAAAGACTCACCCAATAGAGGTATTTGAGCCGGGAGCTGAACATAT 3402 v . 1 3451 agttcgcctaatgactaagaattggggcgataacgataqcatttttcaaq ι11 I III 111 I||1 I 11 III||IIIIIIII 1 1 1 II11II 1 1 1 1 1 1 1 1 1 II 3500 v.5 3403 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AGTTCGCCTAATGACTAAGAATTGGGGCGATAAcGATAGCATTTTTCAAG 3452 v . 1 3501 atgtaattgagacaagagggagagaatatgctggtttatatgatgacatc | II II 1 1 1 1 1 i 1 1 1 1 1 II II 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 3550 v.5 3453 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 ATGTAATTGAGACAAGAGGGAGAGAATATGCTGGTTTATATGATGACATC 3502 v . 1 3551 tccactcaaggctggtttattggactgatgtgtgcgattgctcttctcac | 1 1 II 1 1 I 1 1 1 1 1 1 1 1 l| 1 1 1 1 II 1 1 1 1 11 I 1 1 1 II 1 1 1 1 1 1 1 1 1 I 1 1 1 1 3600 v.5 3503 I i HI 1111 II &#943; 1 1 1 1 1 1 1 1 1 1 I ! 1 1 1 1 1 11 1 11111111 I 11 I 1 1 1 1 1 1 TCCACTCAAGGCTGGTTTATTGGACTGATGTGTGCGATTGCTCTTCTCAC 3552 v.l 3601 actactattattaactgtttgctttgtgaagaggaatagaggtggaaagt | 1 1 I 1 I 1 1 1 1 l| 1 1 1 1 1 1 II 1 1 1 II 1 1 I I I 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3650 v.5 3553 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 | | | 11 ι ι 1 1 1 1 1 1 1 1 1 1 1 1 ACTACTATTATTAACTGTTTGCTTTGTGAAGAGGAATAGAGGTGGAAAGT 3602 v.l 3651 actcagttaaagaaaaggaagatttgcatccagacccagaaattcagtca |l I II I 11 I I I I i j II 1 1 I 1 1 1 1 1 I 1 l| I II 1 1 1 I I I I I 1 1 1 I 1 1 11 |1 I 3700 v.5 3603 Il 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 i ι ι ι 111 11 | 1 j 1 1 1 1 ι ι ι 111 1 ACTCAGTTAAAGAAAAGGAAGATTTGCATCCAGACCCAGAAATTCAGTCA 3652 v.l 3701 gtaaaagatgaaacctttggtgaatacagtgacagtgatgaaaagcctct | 1 II 1 |l 1 I 1 1 II 1 1 1 1 1 1 I 1 11 II II 1 II 1 1 1 1 1 1 II 1 1 1 1 1 1 I 1 1 1 1 I 3750 v.5 3653 1 I 1 1 1 I 1 1 I 1 1 1 &#943; I 1 1 1 1 1 l 1 I I 1 j 1 I 1 111 1111111 I 1 1 1 I 1 1 I 1 I 1 1 GTAAAAGATGAAACCTTTGGTGAATACAGTGACAGTGATGAAAAGCCTCT 3702 286 •;V. 1 3751 caaaggaagccttcggtcccttaatagggatatgcagcctactgaaagtg 1111111II1111111 li 11111111111111II11111111II111111

v.5 3703 CAAAGGAAGCCTTCGGTCCCTTAATAGGGATATGCAGCCTACTGAAAGTG v.l 3801 ctgacagcttagtcgaatacggagagggagaccatggtctcttcagtgaa III IΙΙΙΙΙ1Ι&amp;#906;ΙΙΙ Illlllllll II11 mi III 11 III 1111 lllll

v.5 3753 CTGACAGCTTAGTCGAATACGGAGAGGGAGACCATGGTCTCTTCAGTGAA v.l 3851 gatggatcatttattggtgcctacgctggatctaaggagaagggatctgt

III U I III I ill 11 Η II111111 MS il Η I III III HI II51 ΗII

v.5 3803 GATGGATCATTTATTGGTGCCTACGCTGGATCTAAGGAGAAGGGATCTGT v.l 3901 tgaaagcaatggaagttctacagcaacttttccccttcgggcataaacac ΠΠΠΙΠΠΗΗΠΙΙΠΙΠΠΗΠΠΠΠΗΙΙΠΠΠΠΠ

v.5 3 853 TGAAAGCAATGGAAGTTCTACAGCAACTTTTCCCCTTCGGGCATAAACAC v.l 3 951 aacatatgtaagcaacgctactggttcaccccaaccttccatatttatct 111111II11II1111II11II1111!1111II Π 111II11111II111

v.5 3903 AACATATGTAAGCAACGCTACTGGTTCACCCCAACCTTCCATATTTATCT v.l 4001 gttcaaaggagcaagaactttcatataqqaatagaaacatgctggccgaa .· ππιπηπιιηηπιιππππππιηπιππηιππ

v.5 3953 GTTCAAAGGAGCAAGAACTTTCATATAGGAATAGAAACATGCTGGCCGAA v.l 4051 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac ηπππππππιηηπππππιπππιιπππππ

v.5 4003 GATTTCATCCAGAAGTCAACATCCTGCAATTATGTTGAAAAGAGTAGTAC v.l 4101 tttcttcaaaatataaaatgccaaacacttcaggcctatgttttgcttat ΠΠΠΙΠΠΙΙΠΠΠΠΠΠΙΗΠΠΠΠΠΙΠΠΠΙΠΠ

v.5 4 053 TTTCTTCAAAATATAAAATGCCAAGCACTTCAGGCCTATGTTTTGCTTAT v.l 4151 attgttttcaggtgctcaaaatgcaaaacacaaaacaaatcctgcattta 11111111111111111111111111111111111111111111111111

V.5 4103 ATTGTTTTCAGGTGCTCAAAATGCAAAACACAAAACAAATCCTGCATTTA v.l 4201 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg 1111 i 111II11 '1111111111111111111I11111111 i m 111111

v.5 4153 GATACACCTCAACTAAATCCAAAGTCCCCATTCAGTATATTCCATATTTG v.l 4251 cctgattttactattcggtgtgtttgcatagatgttgctacttggtgggt I ll! Hill! lllll III lllll I lllll Ilium 11! HI II lllll

v.5 4203 CCTGATTTTACTATTCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGT v.l 4301 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga ! II Π 11! 11111II11111IIIII111II111IIII111IIIII I!111

v.5 4253 TTTTCTCCGTATGCACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGA v.l 4351 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa

11111111111111111111111111111111111111111IIIIIIIII

v.5 4303 CTTTGCTTCACTACAGGTTAAAAGACCATAAGCAAACTGGTTATTTAAAA v.l 4401 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac

111IIIIIIIII11! IIIIIIIIII1111! 1IIIII111III Π 111H I

v.5 4353 TGTAAAAAGGAATATGAAAGTCTTATTAAAACACTTCATTGAAAATATAC v.l 4451 agtctaaatttattatttaaattttactagcaaaagtcttaggtgaacaa ΠΠΠΠΠΠΠΗΠΙΠΠΙΠΗΙΠΠΠΠΙΙΠΠΙΠΠΗ

v.5 4403 AGTCTAAATTTATTATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAA v.l 4501 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa

III1111II111111IIIIIIIIIIII111111II1111IIIΠIIIIII

v.5 4453 TCAACTAGTATTTGTTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAA 3800 3752 3850 3802 3900 3852 3950 3902 4000 3952 4050 4002 4100 4052 4150 4102 4200 4152 4250 4202 4300 4252 4350 4302 4400 4352 4450 4402 4500 4452 4550 4502 287 v.l 4551 acagaagtatacgtttttcagtttcaacatgaatttttttatttctgtca

! 1111111! 1111 il III1111Ii i111111111111 H IIII tl! 11 II

v.5 4503 ACAGAAGTATACGTTTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCA v.l 4601 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct IIII!IIIIIIIII! &amp;#943; I!!!!III &amp;#943;!IIIII!!!!! I Η ! 11! III!!! t

v.5 4553 GTTATGACATCCACgAGCATCACTTTTTGTGTCTGTTTTTTTTTTTTTCT v.l 4651 tggactaaattcaactgcatggaagcggtggtcagaaggttgttttatac 11111IIil11111! 11 i!IIIii Ili II111III il IIIII1111 Ii 11

v.5 4 603 TGGACTAAATTCAACTGCATGGAAGCGGTGGTCAGAAGGTTGTTTTATAC v.l 4701 gagaacaggcagaaagtgcccattgttcaggattctaatagctacatcta I! 11111111 ii 1111111IIIIIII i III111111111111111! 1111

v.5 4653 GAGAACAGGCAGAAAGTGCCCATTGTTCAGGATTCTAATAGCTACATCTA v.l 4751 cttaatatcttcatttctaaattqactqctttfcacctttttctcatgttt 1III II I iII!liII! 11111ΙΙ&amp;#938;ΙΙill 11!!111111111111 ll! 11 v.5 4703 CTTAATATCTTCATTTCTAAATTGACTGCTTTTACCTTTTTCTCATGTTT . v.l 4801 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg

11111111111111111111111111111111111111111111111111 v.5 4753 ATATAATGGTATGCTTGCATATATTTCATGAATACATTGTACATATTATG v.l 4851 ttaatatttacacaatttaaaatatagatgtgttttattttgaagtgaga

IlllllllllllllllillllllllllllllllllllllllllllllUI

v.5 4803 TTAATATTTAGACAATTTAAAATATAGATGTGTTTTATTTTGAAGTGAGA v.l 4901 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat IIIIIIIIHIlllllllllllillllllllllllimilllllllill

v.5 4 853 AAATGAACATTAACAGGCATGTTTGTACAGCTAGAATATATTAGTAAGAT v.l 4951 actgtttttcgtcattccagagctacaactaataacacgaggttccaaag

1111111111 ill lllllllllllllllllllim II! lillllll III

v.5 4 903 ACTGTTTTTCGTCATTCCAGAGCTACAACTAATAACACGAGGTTCCAAAG v.l 5001 ctgaagactttgtataaagtatttgggttttgttcttgtattgctttctt ΙΙ&amp;#938;ΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙ&amp;#938;ΙΙΙΙΙΙ&amp;#938;ΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙ

v.5 4953 CTGAAGACTTTGTATAAAGTATTTGGGTTTTGTTCTTGTATTGCTTTCTT v.l 5051 tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc nn π ι η mi η i m m in i r ru π 11 ι&amp;#970; 111 m η η ι hj

v.5 5003 TCAACAGTTTCAAAATAAAATATCATAcAAATATTGAGGGAAATGTTTTC v.l 5101 atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc

11111111111111111111111111111111111111111111111111 v.5 5053 ATATTTTTCAAAATAGGTTTTTATTGTTGAATGTACATCTACCCCAGCCC v.l 5151 ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta 11111111111111111111111111111111111111111 i 11111111

v.5 5103 CTCAAAAGAAAAACTGTTTACATAGAAATTCCTACACATACGTTTGCGTA v.l 5201 tatgttattttaaacatctttgtggtgagaattttttccccgatattctc imiimmiiiimmiiiiiiiiiiiniiHmiiiiiiii

v.5 5153 TATGTTATTTTAAACATCTTTGTGGTGAGAATTTTTTCCCCGATATTCTC v.l 5251 cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt

111!111II111111111 ill 11111111111111111111111111Ι&amp;#906;I

v.5 52 03 CTTCTGTCAAAGTCAGAACAAATTCAGGGAATTTATTTTCTGGCAGTTGT v.l 5301 gctccagtccttttaaaattgtacatgaacatgttttagaaacaatatgg 4600 4552 4650 4602 4700 4652 4750 4702 4800 4752 4850 4802 4900 4852 4950 4902 5000 4952 5050 5002 5100 5052 5150 5102 5200 5152 5250 5202 5300 5252 5350 288 5302 v.l 5351 aggatgatgcatacatgtcggtcaagttcagcgctcgacattttatggaa .11111111! 1! 1! 1! ! Μ Η 111111I! 1111111111111) 11II1111

v.5 5303 AGGATGATGCATACATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAA v.l 5401 agatttttttaaccttaccacgaaatacttaactactgtttaagtgaatt. IMMIIHNIMliNHHHNIlHIllHINllllHlllUl v.5 5353 AGATTTTTTTAACCTTACCACGAAATACTTAACTACTGTTTAAGTGAATT . v.l 5451 gacttatttcactttagtttttgaactgtgattattggtatactgttata

11II111 SI 1111 i 11111! 11II11111II111II11 li 11! 11111! I

v.5 54 03 GACTTATTTCACTTTAGTTTTTGAACTGTGATTATTGGTATACTGTTATA v.l 5501 tcctcaacttggatttatgataaccccttttagttcatggagaccaaaat

1111111111IIIII11II1111111IIII11II I! 11111IIIIIIIII

v.5 5453 TCCTCAACTTGGATTTATGGTAACCCCTTtTAGTTCATGGAGACCAAAAT v.l 5551 ttggqqtatttataatagtcaqcgcaggaatgcacatggaatatctact't 111III III 11111111 111 1111II111111III i I i Ii II11! 11 i 11

v.5 5503 TTGGGGTATTTATAATAGTCAGCGCAGGAATGCACATGGAATATCTACTT v.l 5601 gtccttttgaacctcacgagtcatccagaatgtatagacaggaaaagcat 111111111111II1111111111111111111111111IIIII111111

v.5 5553 GTCCTTTTGAACCTCACGAGTCATCCAGAATGTATAGACAGGAAAAGCAT v.l 5651 gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg 11111111111111111111111111111111111111111II111II11

v.5 5603 GTCTTATTTAAAACTGTAATTTATGGGCTCAGGATCTGACCGCAGTCCCG v.l 5701 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga iiiiiiimmiiiiiiiiimiiiiiimiimiiiimmi

v.5 5 653 GGAGTAAGCATTTCAAAGGGGGAAGGCAGTGTGGTCCCTACCCTGTGTGA v.l 5751 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc 1111IIII1111111111II111111111111111II111111II11111

v.5 5703 ATGTGAGGATGTAGACATCCATCAGTGCAACTCGAGCTCCATCCTCCTCC v.l 5801 gatttctaaggctccagttttctggagggacagtcatcatgttttgattt III1111111111111111111111111111111111111111II11111

v.5 5753 GATTTGTAAGGcTCCAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTT v.l 5851 atctgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga

11111111 Η 111111111111111111II111111111IIIII H 11II

v.5 5 8 03 ATCTGGGAGAAAACTGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGA v.l 5901 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcag ' III111IIIIIII1111111 H 11) 11 Id III 11! I 111 111111 U 111

v.5 5853 CGTTCGAGCTTAGTTCTGGTGTTATTCTGTCTCCTCTTCTTTGTCATCAG v.l 5951 ccaaaacgtggtttttaaagagagtcatgcaggttagaaataatgtcaaa 111111111 i 11 i 11111 i 111111111 i 11 i i 111 i 111! 111 i i i I i 1

v.5 5903 CCAAAACGTGGTTTTTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAA v.l 6001 aatatttaggaatttaataacctttaagtcagaaactaaaacaaatactg 11111111111.111111111111! Ill 111111IIII1111) II111111

V.5 5953 AATATTTAGGAATTTAATAACCTTTAAGTCAGAAACTAAAACAAATACTG v.l 6051 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat 11 H 11111II111111111111111111111111111 Ii 11! 1111111

v.5 6003 AAATATTAGCTCTTCCTACACTTCGTGTTCCCCTTTAGCTGCCTGAAAAT v.l 6101 caagattgctcctactcagatcttctgagtggctaaaacttatggatatg 5400 5352 5450 5402 5500 5452 5550 5502 5600 5552 5650 5602 5700 5652 5750 5702 5800 5752 5850 5802 5900 5852 5950 5902 6000 5952 6050 6002 6100 6052 6150 289

v.5 6 053 CAAGATTGCTCCTaCTCAGATCTTCTGAGTGGCTAAAACTTATGGATATG v.l 6151 aaaaatgaaattaaatgatgactatgctttgctatcattgttacctttcc

1111111111 Η 111II11111 &amp;#943; I Η I H 11 Π 11111 Π Η Η I! I Η I

v.5 6103 AAAAATGAGATTGAATGATGACTATGCTTTGCTATCATTGTTACCTTTCC v.l 6201 tcaatactatttggcaactactgggactcttcagcacaaaaggaatagat

IiII11II!111II1111!III111!I il11 III IIIII1II11IIII11

v.5 6153 TCAATACTATTTGGCAACTACTGGGACTCTTCAGCACAAAAGGAATAGAT v.l 6251 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt 1111111II11111111111111111111111111111111111111111

v.5 6203 CTATGATTGACCCTGATTTTAATTGTGAAATTATATGATTCATATATTTT v.l 6301 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg

Illlllllllllllllllllllillllllllillllllllllllllllll

v.5 6253 ATGAATCAGAATAACCTTCAAATAAAATAAATCTAAGTCGGTTAAAATGG v.l 6351 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa llllllllllllllllllllllllllllllllllilllllilllllllll

v.5 6-3 03 ATTTCATGATTTTCCCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAA v.l 6401 tggtaattataaattggtgatgcttgtttgcaaattgcccactcgtgata llllllllllllllllllllllllllllllllllllllllllllllllll

v.5 6353 TGGTAATTATAAATTGGTGATGCTTGTTTGCAAATTGCCCACTCGTGATA v.l 6451 agtcaacagccaatatttaaaactttgttcgttactggctttaccctaac I i 111111111111111111111111111111111111111111111111

v.5 6403 AGTCAACAGCCAATATTTAAAACTTTGTTCGTTACTGGCTTTACCCTAAC v.l 6501 tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag illilllllllilllliillllllllililllillilllllliiilllll

v.5 6453 TTTCTCTAGTCTACTGTCAATATCATTTTAATGTAATTGATTGTATATAG v.l 6551 tctcaagaatggttggtgggcatgagttcctagagaactgtccaagggtt ΙΙΙ&amp;#906;IIIIIII llllllll III llll I llllllll! 11111 INI III 11

v.5 6503 TCTCAAGAATGGTTGGTGGGCATGAGTTCCTAGAGAACTGTCCAAGGGTT v.l 6601 gggaaaatccaaattctcttcctgactccagcactgattttgtacataaa ι&amp;#970;ιιιιιιιιιιιιιιιιιιιιιι&amp;#912;ιιιιιιιιιιιιιιιιιιιιιιι&amp;#912;&amp;#943;

v.5 6553 GGGARAATCCAAATTCTCTTCCTGGcTCCAGCACTGATTTTGTACATAAA v.l 6651 cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa 11111111111111111111111111111111111111111111111111

v.5 6603 CATTAGGCAGGTTGCTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAA v.l 6701 gtgctaataataatctcagttaccttatctttgtcacagggtgttctttt 11111111111111111111111111111111111111111111111111

v.5 6653 GTGCTAATAATAATCTCAGTTACCTTATCTTTGTCACAGGGTGTTCTTTT v.l 6751 ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc lllllilllllllllllllllllllllllllllllllillllllllllll

V.5 6703 TTATGAAGAAAAATTTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTC v.l 6801 ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc 11111111111111111111111111111111111111111111111111

v.5 6753 ATAAGCAAACCTTTAACTAATTATGTATCTGAAAGTCACCCCCACATACC v.l 6851 aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca

I! 111111111111! 11IIIII11111IIIIII11IIIIII1111111II

v.5 6803 AACTCAACTTTTTTCCTGTGAACACATAAATATATTTTTATAGAAAAACA 6102 6200 6152 6250 6202 6300 6252 6350 63 02 6400 6352 6450 6402 6500 6452 6550 65 02 6600 6552 6650 6602 6700 6652 6750 6702 6800 6752 6850 6802 6900 6852 290 rv.l 6901 aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat 6950 1111111111111111111111i111111 III 111111111!11111111 v.5 6853 AATCTACATAAAATAAATCTACTGTTTAGTGAGCAGTATGAcTTGTACAT 6902 v.1 6951 gccattgaaaattattaatcagaagaaaattaagcagggtctttgctata 7 000 11111111111111111111111111111111111111111111111111 v.5 6903 GCCATTGAAAATTATTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATA 6952 v.1 7001 caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga 7050 I III I III 111 III 11111 III 11 III 111 III 11111111111111111 v.5 6953 CAAAAGTGTTTTCCACTAATTTTGCATGCGTATTTATAAGAAAAATGTGA 7002 v.1 7051 atttggtggttttattctatcggtataaaggcatcgatattttagatgca 7100

&amp;#943; IIII!111II I!Η 11 ΗIIII ΠII Ηi 11IIII1 Η III I!N &amp;#943; III v.5 7 0 03 ATTTGGTGGTTTTATTCTATCGGTATAAAGGCATcGATATTTTAGATGCA 7052 v.1 7101 cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca 7150 1111111111111111111II11111111111111111111111111111 v.5 7 053 CCCGTGTTTGTAAAAATGTAGAGCACAATGGAATTATGCTGGAAGTCTCA 7102 v.1 7151 aataatatttttttcctattttatactcatggaagagataagctaaagag 7200 - 11111! 111!111II111II1111II111II11111II11II11111111 v.5 7103 AATAATATTTTTTTCCTATTTTATACTCATGGAAGAGATAAGCTAAAGAG 7152 v.1 7201 gggacaataatgagaaatgttggtgtgcttttctaagcatttaaaacata 7250

i11II11II I!IIIIIIIII1111IIIIIIIIIII111IIII111111II v.5 7153 GGGACAATAATGAGAAATGTTGGTGTGCTTTTCTAAGCATTTAAAACATA 72 02 v.1 7251 attaceaattgaaaccctaaatatgtttacataccattaaqatatgattc 7300 ΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙΙ&amp;#938;ΙΙΙΗΙΙΙΙ v.5 72 03 ATTGCCAATTGAAACCCTAAATATGTTTACATACCATTAAGATATGATTC 7252 v.1 73 01 atgtaacaatgttaaattaattataatgggattqggtttgttatctgtgg 7350

1111111 III III 11 III I III 1111 III III 111111111111111 III v.5 7253 ATGTAACAATGTTAAATTAATTATAATGGGATTGGGTTTGTTATCTGTGG 73 02 v.1 73 51 tagtatatatcctagtgttcctatagtgaaataagtaaggttcagccaaa 7400

1111III i III11111111111111111111111111! 1111111111 H v.5 73 03 TAGTATATATCCTAGTGTTCCTATAGTGAAATAAGTAGGGTTCAGCCAAA 7352 v.1 7401 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga 7450

lllll hllllilll 1ΙΙΙΙΙΙΙ ΝΙΝΙ II llll lllflll I III I III v.5 73 53 GCTTTCTTTGTTTTGTACCTTAAATTGTTCGATTACGTCATCAAAAGAGA 74-02 v.1 7451 tgaaaggtatgtagaacaggttcacgtgattacctttttcttttggcttg 7500 mimimimmmimmmmmmmunm v.5 7403 TGAAAGGTATGTAGAACAGGTTCACGTGATTACCTTTTTCTTTTGGCTTG 7452 v.1 7501 gattaatattcatagtagaactttataaaacgtgtttgtattgtaggtgg 7550 mimmmmmmmmmimmmminm v.5 7453 GATTAATATTCATAGTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGG 7502 v.1 7551 tgtttgtattatgcttatgactatgtatggtttgaaaatattttcattat 7600 immmmmmmmmmmimmmmm v.5 7503 TGTTTGTATTATGCTTATGACTATGTATGGTTTGAAAATATTTTCATTAT 7552 v.1 7601 acatgaaattcaactttccaaafcaaaagttctacttcatgtaatccaaaa 7650 immmmmmmmmmmimmmmm v.5 7553 ACATGAAATTCAACTTTCCAAATAAAAGTTCTACTTCATGTAATCCAAAA 7602

Table LlVd. Peptide sequences of protein coded by 282P1G03 v.5 (SEQ ID NO: 172)

MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 60 291.GNPEPTFSWT KDGNPFYFTD HRIIPSNHSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 12 0 r EElEFiVPSV PKLPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV 18 0 YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSSNSI KQRKPKLLLP 24 0 PTESGSESSI TILKGEILLL ECFAEGLPTP QVDWNKIGGD LPKGRETKEN YGKTLKIENV 300 SYQDKGNYRC TA-SNFLGTAT HDFHVIVEEP PRWTKKPQSA VYSTGSNGIL LCEAEGEPQP 360 TIKWRVNGSP VDNHPFAGDV VFPREISFTN LQPNHTAVYQ CEASNVHGTI LANANIDWD 42 0 VRPLIQTKDG ENYATWGYS AFLHCEFFAS PEAWSWQKV EEVKPLEGRR YHIYENGTLQ 48 0 INRTTEEDAG SYSCWVENAI GKTAVTANLD IRNATKLRVS PKNPRIPKLH MLELHCESKC 54 0 DSHLKHSLKL SWSKDGEAFE INGTEDGRII IDGANLTISN VTLEDQGIYC CSAHTALDSA 60 0 ADITQVTVLD VPDPPENLHL SERQNRSVRL TWEAGADHNS NISEYIVEFE GNKEEPGRWE 660 ELTRVQGKKT TVILPLAPFV RYQFRVIAVN EVGRSQPSQP SDHHBTPPAA PDRNPQNIRV 72 0 QASQPKEMII KWEPLKSMEQ NGPGLEYRVT WKPQGAPVEW EEETVTNHTL RVMTPAVYAP 78 0 YDVKVQAINQ LGSGPDPQSV TLYSGEDYPD TAPVIHGVDV INSTLVKVTW STVPKDRVHG 84 0 RLKGYQINWW KTKSLLDGRT HPKEVNILRF SGQRNSGMVP SLDAFSEFHL TVLAYNSKGA 900 GPESEPYIFQ TPEGVPEQPT FLKVIKVDKD TATLSWGLPK KLNGNLTGYL LQYQIINDTY 960 EIGELNDINI TTPSKPSWHL SNLNATTKYK FYLRACTSQG CGKPITEESS TLGEGSKGIG 1020 KISGVNLTQK THPIEVFEPG AEHIVRLMTK NWGDNDSIFQ DVIETRGREY AGLYDDISTQ 10 8 0 GWFIGLMCAI ALLTLLLLTV CFVKRNRGGK YSVKEKEDLH PDPEIOSVKD ETFGEYSDSD 114 0 EKPLKGSLRS LNRDMQPTES ADSLVEYGEG DHGLFSEDGS FIGAYAGSKE KGSVESNGSS 12 0 0 TATFPLRA 12 08

Table LVd. Amino acid sequence alignment of 282P1G03 v.1 (SEQ ID NO: 173) and 282P1G03 v.5 (SEQ ID NO: 174) v.l 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD i I 1 1 1 1 1 I 1 ! II 1 1 I II 1 1 1 II 1 1 1 1 1 II 1 II II 1 1 II 1 1 ( I 1 1 II 1 1 II 50 v.5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I II 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD 50 v.l 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI | 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 100 v.5 51 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 v.l 101 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV | 1 1 1 1 I I 1 1 1 I 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 I 1 1 1 1 1 1 1 II 1 150 v.5 101 1 1111111II11 1111 1 1 1 I 1 1 1 1 1 1 II11II11IjI 11) 1 1 1 1 1 1 I II l SHFQGKYRCF ASNKLGIAMS EEIEFI VP SVPKLPKEKIDPLEVEEGDPIV 150 v.l 151 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN i 1 1 I || 1 1 1 I 1 I I 1 1 1 1 I 1 1 1 1 II 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 200 v.5 151 111II I 1II11 1 1 1 1 I 1II111II 111 1 1 I 1 1 1 1 1 1 1 11 1 1 1 1 1 I 1 1 1 1 1 LPCNPPKGLPPLHIYWNIELEHIEQDERVYMSQKGDLYFANVEEKDSKN 2 00 v.l 201 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDS S S STEIGSKAN SIKQRK | 1 1 1 1 1 I 1 j ι 1 II II 1 1 II 1 Η 1 1 1 1 -1111111 250 v.5 201 1 1 1 1 l.l 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1-1 1 1 1 - 1 1 1 1 1 1 1 DYCCFAAFPRLRTIVQKMPMKLTVNS----------------SNSIKQRK 234 v.l 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKI GGDLPKG | 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 11 1 1 1 1 1 1 1 I 1 I 1 1 | 1 1 1 1 1 1 1 1 1 II 1 I 1 1 II 1 300 v.5 235 i ! I I H ! I 1 1 1 I 1 1 1 i I I 1 1 I I 1 ! 1 J 1 1 1 1 I I 1 1 1 I 1 1 1 1 1 1 i I 1 1 1 1 1 1 PKLLLPPTES GSE S SITILKGEILLLE CFAEGLPTPQVDWNKIGGDLPKG 284 v.l 301 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 ! 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 II 350 v.5 235 N 1 1 1 1 1 1 1 1 1 1 1 1 1 1 111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT 334 v.l 351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR 1 I I I I I H 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 400 v.5 335 1 1 1 1 1 1 I I 1 1 1 I 11 1 l I l 1 1 11 1 1 1 1 1 II 1 II II 1 1 111 I 1 1 1 1 1 1 (I I I KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR 384· V.l 401 EISFTNLQPNHTAVYQCEASNVHGTILANANIDWD'VRPLIQTKDGENYA I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 If 1 1 1 1 1 1 450 v.5 385 1 111 I 1 111 1 1 1 11111111 111 1 1 I 1 1 1 11 1 1111111 1 1 I 11111111 EIS FTNLQPNHTAVYQCEAS nvhgt ilananid WD VRPLIQTKDGENYA 434 v.l 451 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT 1 1 1 1 I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 I 1 500 v.5 435 1 1 1 1 1 1 1 11 ! 1 I 1 1 1 111111 1 I N II I 1 I 1 I 1 1 1 1 I 1 1 1 I 1 11 1 I i 1 1 1 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT 484 292 ;V.l 501 TEEDAGSYS CWVENAIGKTAVTANLDIRNATKLRVS PKNPRIPKLHMLEL 1 i ! I 1 I 1 I 11 1 I ! 1 1 1 I I I I I I I 1 I 1 1 I 1 I 1 I 1 1 I 1 I ) 1 1 I 1 1 1 I ) I I 1 ) 550 v.5 485 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TEEDAGSYSCWVENAIGKTAVTANLDXRNATKLRVSPKNPRIPKLHMLEL 534 v.l 551 HCESKCDSHLKHSLKLSWSKDGEAFEXNGTEDGRIXXDGANLTISWTLE I I 1 II 1 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 II 1 1 1 II 1 I 1 1 1 1 1 1 II 1 I I 1 I 1 1 [ ! 1 1 600 v.5 535 1 1 I 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 ι I 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 1 1 1 1 I 1 ! i 1 1 1 1 1 HCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE 584 v.l 601 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA 1 1 1 1 1 1 1 1 1 I 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 I 1 1 1 1 ! 1 1 1 1 1 650 v.5 585 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 t 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA 634 v.l 651 gadhnsniseyivefegnkeepgrweeltrvqgkkttvilplapfvryqf ! 1 1 1 1 1 1 ! 1 1 I 1 ! 1 1 1 1 1 ! 1 ! 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 ! 1 I I 700 v.5 635 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 I ! 1 1 1 ! 1 1 I 1 1 1 1 1 1 1 ! 1 1 1 1 t ! 1 1 1 1 1 1 1 1 1 gadhnsniseyivefegnkeepgrweeltrvqgkkttvilplapfvryqf 684 v.l 701 rviavnevgrsqpsqpsdkhetppaapdrnpqnirvqasqpkemiikwep I I 1 I I 1 1 1 1 I I 1 1 I 1 1 1 I I 1 I 1 I 1 1 I 1 1 1 1 1 | | | | | | | | I 1 I I 11 I 1 1 ! 1 750 v.5 685 1 I ! 1 1 1 11 : 1 i !! 1 ! 1 1 1 !!! 1 ! ! 1 1 1 !!11 1 1 1 1 1 1 1 1 1 1 1 1 ι ι 1 ι 1 ι i RVIAVNEVGRSQPSQPSDHHETPPAAPDRirPQNIRVQASQPKEMXIKWEP 734 v.l 751 lksmeqngpgleyrvtwkpqgapveweeetvtnhtlrvmtpavyapydvk I II 1 ! 1 I I 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 I 1 1 II 1 !| 1 1 1 I 1 1 1 1 1 1 I 1 1 I 1 1 1 800 v.5 735 1 1 II II 1 1 1 1 1 II 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1&amp;#906; 1 1 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 784 v.l 801 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLVKVTWSTVP 1 I 1 1 ! 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I !! 1 1 I ! 1 1 1 1 1 I 1 1 1 1 1 1 1 1 850 v.5 785 1 1 1 1 ! 1 1 1 1 1 1 1 11 1 1 1 111 1 1 1 1 1 1 1 1 1 1 1 1 1 I 11 1 1 1 1 1 1 1 1 1 11 1 1 I VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLVKVTWSTVP 834 v.l 851 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILiRFSGQRNSGMVPSLDA 1 1 ! 1 1 1 I 1 ! li 1 II 1 1 ! 1 1 1 11 1 II 1 I 1 1 1 1 ! 1 li ! ! 1 ! ! 1 i 1 1 1 1 i II i 900 v.5 835 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSGQRNSGMVPSLDA 884 v.l 901 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVPKDTATL I I I I I I 1 I I I I 1 I I 1 I 1 I I 1 1 I I I I 1 I I 1 I 1 I I I I I 1 I 1 1 1 I 1 II I I I 1 1 950 v.5 885 1 1 1111 I 11 I 1 11111 1 1 1 1 I 11111II1 I 1 I 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL 934 v.l 951 SWGLPKKLNGNLTGYLLQYQIXNDTYEIGELNDINITTPSKPSWHLSNLN 1 II II 1 1 I 1 I I I 1 1 1 1 1 II I 1 I 1 1 i II 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1000 v.5 935 ι 1 1 1 1 1 ι 1 ι 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 1 1 SWGLPKKLNGNLTGYLLQYQIXNBTYEIGELNDINITTPSKPSWHLSNLN 984 v.l 1001 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNLTQKTHPI 1 1 1 1 1 M 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1050 v.5 985 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 ! 1 ! II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGWLTQKTHPI 1034 v.l 1051 EVFEPG AEHX VRLMTKNWGDNDS XFQDVIETRGREYAGLYDDISTQGWFI I I 1 I I I I 1 I I I I I 1 1 I 1 1 1 I I 1 I tl I 1 I I I I II I I 1 I I 1 I 1 I I 1 I 1 I I I 1 1100 v.5 1035 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 1 EVFEPGAEHIVRLMTKNWGDNDSIFQDVIETRGREYAGLYDDISTQGWFI 1084 v.l 1101 GLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPDPEIQSVKDETFG 1 1 1 1 i 1 1 i 1 1 1 1 i 1 1 i i 1 1 1 I 1 i 1 1 I 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1150 v.5 1085 1 1111 11II11 1 1111 111 1 1 1 1 1 1 1 1 ! 1 1 1 1 i ! 1 1 1 1 1 1 1 11 1 1 II 1 1 1 GLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPDPEIQSVKDETFG 1134 v.l 1151 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1 i !-l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ) 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1200 v.S 1135 II1 1 1 1 1 11 1 1 1 1 1 1 1 11111 1 1 1 1 1 1 1 11111111 1 1 1 1 1 111 I 11 1 1 1 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1184 v.l 12 01 YAGSKEKGSVESNGSSTATFPLRA 1224 1 1 ! I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.5 1185 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 111 1 YAGSKEKGSVESNGSSTATFPLRA 1208

Table LHe. Nucleotide sequence of transcript variant 282P1G03 v.6 (SEQ ID NO: 175) cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 293 60 120 .s'" ·'. tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540

aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt SOO tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaaaatt £60 agaacacatc gaacaagatg aaagagtata catgagccaa aagggagatc tafcacfctcgc, 720 aaacgtggaa gaaaaggaca gtcgcaatga ctactgttgc tttgctgcat ttccaagatt 780 aaggactatt gtacagaaaa tgccaatgaa actaacagtt aacagtttaa agcatgctaa 340 tgactcaagt tcatccacag aaattggttc caaggcaaat tccatcaagc aaagaaaacc 900 caaactgctg ttgcctccca ctgagagtgg cagtgagtct tcaattacca tcctcaaagg 960 ggaaatcttg ctgcttgagt gttttgctga aggcttgcca actccacagg ttgattggaa 1020 caaaattggt ggtgacttac caaaggggag agaaacaaaa gaaaattatg gcaagacttt 1080 gaagatagag aatgtctcct accaggacaa aggaaattat cgctgcacag ccagcaattt 1140 cttgggaaca gccactcacg attttcacgt tatagtagaa gagcctcctc gctggacaaa 1200 gaagcctcag agtgctgtgt atagcaccgg aagcaatggc atcttgttat gtgaggctga 1250 aggagaacct caacccacaa tcaagtggag agtcaatggc tccccagttg acaatcatcc 1320 atttgctggt gatgttgtct tccccaggga aatcagtttt accaaccttc aaccaaatca 1380 tactgctgtg taccagtgtg aagcctcaaa tgtccatgga actatccttg ccaatgccaa 1440 tattgatgtt gtggatgtcc gtccattgat acaaaccaaa gatggagaaa attacgctac 1500 aRtggttggg tacagtgctt tcttacattg cgagttcttt gcttcacctg aggcagtcgt 1560 gtcctggcag aaggtggaag aagtgaaacc cctggagggc aggcggtatc atatctatga 1620 aaatggcaca ttgcagatca acagaaccac cgaagaagat gctgggtctt actcatgttg 1680 ggtagaaaat gctataggaa aaactgcagt cacagccaat ttggatatta gaaatgctac 1740 aaaacttaga gtttctccta agaatcctcg tatccccaaa ttgcatatgc ttgaattaca 1800 ttgtgaaagc aaatgtgact cacatttgaa acacagtttg aagttgtcct ggagtaaaga 1860 tggagaagcc tttgaaatta atggcacaga agatggcagg ataattattg atggagctaa 1920 tttgaccata tctaatgtaa ctttagagga ccaaggtatt tactgctgtt cagctca.tac 1980 tgctctagac agtgctgccg atataactca agtaactgtt cttgatgttc cggatccacc 2040 agaaaacctt cacttgtctg aaagacagaa caggagtgtt cggctgacct gggaagctgg 2100 agctgaccac aacagcaata ttagcgagta tattgttgaa tttgaaggaa acaaagaaga 2160 gcctggaagg tgggaggaac tgaccagagt ccaaggaaag aaaaccacag ttatcttacc 2220 tttggctcca tttgtgagat accagttcag ggtcatagcc gtgaacgaag tagggagaag 2280 tcagcctagc cagccgtcag accatcatga aacaccacca gcagctccag ataggaatcc 2340 acaaaacata agggttcaag cctctcaacc caaggaaatg attataaagt gggagccttt 2400 gaaatccatg gagcagaatg gaccaggcct agagtacaga gtgacctgga agccacaggg 2460 agccccagtg gagtgggaag aagaaacagt cacaaaccac acattgcggg tgatgacgcc 2520 tgctgtctat gccccttatg atgtcaaggt ccaggctatc aatcaactag gatctgggcc 2580 tgaccctcag tcagtgactc tctattctgg agaagactafc cctgatacag ctccagtgat 2640 ccatggggtg gacgttataa acagtacatt agttaaagtt acctggtcaa cagttccaaa 2700 ggacagagta catggacgtc tgaaaggcta tcagataaat tggtggaaaa caaaaagtct 2760 gttggatgga agaacacatc ccaaagaagt gaacattcta agattttcag gacaaagaaa 2820 ctctggaatg gttccttcct tagatgcctt tagtgaattt catttaacag tcttagccta 2880 taactctaaa ggagctggtc ctgaaagtga gccttatata tttcaaacac cagaaggagt 2940 acctgaacag ccaacttttc taaaggtcat caaagttgat aaagacactg ccactttatc 3000 ttggggacta cctaagaaat taaatggaaa cttaactggc tatcttttgc aatatcagat 3060 aataaatgac acctacgaga ttggagaatt aaatgatatt aacattacaa ctccatcaaa 3120 gcccagctgg cacctctcaa acctgaatgc aactaccaag tacaaattct acttgagggc 3180 .ttgcacttca cagggctgtg gaaaaccgat cacggaggaa agctccacct taggagaagg 3240 gagtaaaggt atcgggaaga tatcaggagt aaatcttact caaaagactc acccaataga 3300 ggtatttgag ccgggagctg aacatatagt tcgcctaatg actaagaatt ggggcgataa 3360 cgatagcatt tttcaagatg taattgagac aagagggaga gaatatgctg gtttatatga 3420 tgacatctcc actcaaggct ggtttattgg actgatgtgt gcgattgctc ttctcacact 3480 actattatta actgtttgct ttgtgaagag gaatagaggt ggaaagtact cagttaaaga 3540 aaaggaagat ttgcatccag acccagaaat tcagtcagta aaagatgaaa cctttggtga 3600 atacagtgac agtgatgaaa agcctctcaa aggaagcctt cggtccctta atagggatat 3660 gcagcctact gaaagtgctg acagcttagt cgaatacgga gagggagacc atggtctctt 3720 cagtgaagat ggatcattta ttggtgccta cgctggatct aaggagaagg gatctgttga 3780 aagcaatgga agttctacag caacttttcc ccttcgggca taaacacaac atatgtaagc 3840 aacgctactg gttcacccca accttccata tttatctgtt caaaggagca agaactttca 3900 294 ^t-ataggaata gaaacatgct ggccgaagat ttcatccaga agtcaacatc ctgcaattat 3960 gttgaaaaga gtagtacttt cttcaaaata taaaatgcca agcacttcag gcctatgttt 4020 tgcttatatt gttttcaggt gctcaaaatg caaaacacaa aacaaatcct gcatttagat 4080 acacctcaac taaatccaaa gtccccattc agtatattcc atatttgcct gattttacta 4140 ttcggtgtgt ttgcatagat gttgetactt ggtgggtttt tctccgtatg cacattggta 4200 tacagtctct gagaactggc ttggtgactt tgcttcacta caggt'taaaa gaccataagc 4260 aaactggtta tttaaaatgt aaaaaggaat atgaaagtct tattaaaaca cttcattgaa 4320 aatatacagt ctaaatttat tatttaaatt ttactagcaa aagtcttagg tgaacaatca 4380 actagtattt gttgagctcc tatttgccca gagatggtca tatttaaaca gaagtatacg 4440 tttttcagtt tcaacatgaa tttttttatt tctgtcagtt atgacatcca cgagcatcac 4500 tttttgtgtc tgtttttttt tttttcttgg actaaattca actgcatgga agcggtggtc 4560 agaaggttgt tttatacgag aacaggcaga aagtgcccat tgttcaggat tctaatagct 4620 acatctactt aatatcttca tttctaaatt gactgctttt acctttttct catgtttata 4680 taatggtatg cttgcatata tttcatgaat acattgtaca tattatgtta atatttacac 4740 aatttaaaat atagatgtgt tttattttga agtgagaaaa tgaacattaa caggcatgtt 4800 tgtacagcta gaatatatta gtaagatact gtttttcgtc attccagagc tacaactaat 4860 aacacgaggt tccaaagctg· aagactttgt ataaagtatt tgggttttgt tcttgtattg 4920 ctttctttca acagtttcaa aataaaatat catacaaata ttgagggaaa tgttttcata 4980 tttttcaaaa taggttttta ttgttgaatg tacatctacc ccagcccctc aaaagaaaaa 5040 ctgtttacat agaaattcct acacatacgt ttgcgtatat gttatttt-aa acatctttgt 510 0 ggtgagaatt ttttccccga tattctcctt ctgtcaaagt cagaacaaat tcagggaatt 5160 tattttctgg cagttgtgct ccagtccttt taaaattgta catgaacatg ttttagaaac 5220 aatatggagg atgatgcata catgtcggtc aagttcagcg ctcgacattt tatggaaaga 5280 tttttttaac c.ttaccacga -aatacttaac tactgtttaa gtgaattgac ttatttcact 5340 ttagtttttg aactgtgatt attggtatac tgttatatcc tcaacttgga tttatggtaa 5400 ccccttttag ttcatggaga ccaaaatttg gggtatttat aatagtcagc gcaggaatgc 5460 acatggaata tctacttgtc cttttgaacc tcacgagtca tccagaatgt atagacagga 5520 aaagcatgtc ttatttaaaa ctgtaattta tgggctcagg atctgaccgc agtcccggga 5580 gtaagcattt caaaggggga'aggcagtgtg gtccctaccc tgtgtgaatg tgaggatgta 5640 gacatccatc agtgcaactc gagctccatc ctcctccgat ttctaaggct ccagttttct 5700 ggagggacag tcatcatgtt ttgatttatc tgggagaaaa.ctgtggtgca cagcttgtga 5760 ggagggcaag gttgtgacgt tcgagcttag ttctggtgtt attctgtctc ctcttctttg 5820 tcatcagcca aaacgtggtt tttaaagaga gtcatgcagg ttagaaataa tgtcaaaaat 5880 atttaggaat ttaataacct ttaagtcaga aactaaaaca aatactgaaa tattagctct 5940 tcctacactt cgtgttcccc tttagctgcc tgaaaatcaa gattgctcct actcagatct 6000 tctgagtggc taaaacttat ggatatgaaa aatgagattg aatgatgact atgctttgct 6060 atcattgtta cctttcctca atactatttg gcaactactg ggactcttca gcacaaaagg 6120 aatagatcta tgattgaccc tgattttaat tgtgaaatta tatgattcat atattttatg 6180 aatcagaata accttcaaat aaaataaatc taagtcggtt aaaatggatt tcatgatttt 6240 cccfccagaaa atgagtaacg gagtccacgg cgtgcaatgg taattataaa ttggtgatgc 6300 ttgtttgcaa attgcccact cgtgataagt caacagccaa tatttaaaac tttgttcgtt 6360 actggcttta cccfe'aacttt ctctagtcta ctgtcaatat cattttaatg taattgattg 6420 tatatagtct caagaatggt tggtgggcat gagttcctag agaactgtcc aagggttggg 6480 aaaatccaaa ttctcttcct ggctccagca ctgattttgt acataaacat taggcaggtt 6540 gcttaacctt tttatttcaa actctctcaa ctctaaagtg ctaataataa tctcagttac 6600 cttatctttg tcacagggtg ttctttttta tgaagaaaaa tttgaaaatg ataaaagcta 6660 agatgccttc taacttcata agcaaacctt taactaatta tgtatctgaa agtcaccccc 6720 acataccaac tcaacttttt tcctgtgaac acataaatat atttttatag aaaaacaaat 6780 ctacataaaa taaatctact gtttagtgag cagtatgact tgtacatgcc attgaaaatt 6840 attaatcaga agaaaattaa gcagggtctt tgctatacaa aagtgttttc cactaatttt 6900 gcatgcgtat ttataagaaa aatgtgaatt tggtggtttt attctatcgg tataaaggca 6960 tcgatatttt agatgcaccc gtgtttgtaa aaatgtagag cacaatggaa ttatgctgga 7020 agtctcaaat aatatttttt tcctatttta tactcatgga agagataagc taaagagggg 7080 acaataatga gaaatgttgg tgtgcttttc taagcattta aaacataatt gccaattgaa 7140 accctaaata tgtttacata ccattaagat atgattcatg taacaatgtt aaattaatta 7200 taatgggatt gggtttgtta tctgtggtag tatatatcet agtgttccta tagtgaaata 7260 agtagggttc agccaaagct ttctttgttt tgtaccttaa attgttcgat tacgtcatca 7320 aaagagatga aaggtatgta gaacaggttc acgtgattac ctttttcttt tggcttggat 7380 taatattcat agtagaactt tataaaacgt gtttgtattg taggtggtgt ttgtattatg 7440 cttatgacta tgtatggttt gaaaatattt tcattataca tgaaattcaa ctttccaaat 7500 aaaagttcta cttcatgtaa tccaaaa 7527 295

Table Lille. Nucleotide sequence alignment of 282P1G03 v.1 {SEQ ID NQ: 176) and 282H1GD3 v.b (StQ ID NO: v.l 1 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg [ | Μ I I 1 1 I I I I | || t i I I I | I || 1 1 II 1 I I 1 I | | | 1 II 1 I I II I I I I 1 I 50 v . 6 1 1 ι ι ! 1 1 1 1 1 i &amp;#943; &amp;#943; i 1 t &amp;#943; &amp;#943; ι 1 i t ι 1 1 i I I I 1 I i 1 1 &amp;#943; i 1 I Ι &amp;#943; ! I ! 1 S I 1 1 1 I ! CGGACCCTGCGCGCCCCCGTCCCGGCTCCCGGCCGGCTCGGGGGAGAAGG 50 v.l 51 cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg 1 I 1 1 1 1 1 1 I 1 I i 1 1 1 1 1 1 1 1 1 I 1 1 1 1 11 1 1!1 1 11 111 i !I 1!!111 iI 1 100 v. 6 51 &amp;#943; &amp;#943; Η 111 &amp;#943; ι1 ! H ! 1 I 11 Η I I II I 1 I I &amp;#943; 11 i &amp;#943; H ! It ! 11 I 1 1 ! 1 l Π 1 CGCCCGAGGGGAGGCGCCGGACAGATCGCGTTTCGGAGGCGGCGCAGGTG 100 v.l 101 ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcatag 1 1 I 1 1 1 1 1 1 I 1 1 I I 1 1 1 I 1 1 1 1 1 I I I 1 1 I I 1 1 I II 11 II 1 1 1 1 1 1 1 1 j 1 1 150 v. 6 101 I 1 1 1 1 1 1 I 1 ! 1 1 ι 1 1 1 I 1 1 1 I 1 II I 1 1 1 1 1 1 f 1 1 1 1 1 1 1 I 1 1 1 I 1 I II 1 I CTGTAAACTGCAAACCATAATCCTGTCTTAATACTGCAAACAAATCATAG 150 v.l 151 tggaactaaggggaacttaatttactgtttccaggttaactaaggtctca | II I I 1 I 1 I [ I I I I I I I I I 1 I I I 1 I I I 1 1 it 1 1 I I 1 I II 1 1 1 1 1 1 I 1 II I 200 v. 6 151 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 11 111 1 1 1 1 1 1 1 1 11 1 1 1 1 11 I II 1 1 1 1 1 1 1 1 i 1 TGGAACTAAGGGGAACTTAATTTACTGTTTCCAGGTTAACTAAGGTCTCA 200 v.l 201 gctgtaaaccaaaagtgagaggagacattaagattttcattcttaccggg 1 1 1 1 1 1 1 i 1 1 1 1 i 111 1 1 1 ! 1 1 1 ! 1 II i1 i111111111 1 1 1 11 1 1 i f 1 1 250 v. 6 201 i 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 Η 1 1 &amp;#943; I 1 1 1 1 I 1 1 l 1 ι 1 I 1 1 t ι ι 1 1 I 1 l ι ι H GCTGTAAACCAAAAGTGAGAGGAGACATTAAGATTTTCATTCTTACCGGG. 250 v. 1 251 ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact 1 II 1 1 11 1 1 1 1 1 1 1 1 I 1 11 i1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1111 11 ! 1 300 v. 6 251 ι 1 ! 1 &amp;#943; 1 1 i 1 ι I 1 Η ! I ι I 1 ι &amp;#943; 1 i 1 1 1 l ι 1 I ! 1 1 1 I ! 1 1 I 1 1 1 ι 1 1 !t I ! 1 TTGTCTTCTTCCTGAAGAGCAATGGAGCCGCTTTTACTTGGAAGAGGACT 300 v.l 301 aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I 1 1 i 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 11 350 v.6 301 1 1 I I 1 1 I I I I I 11 1 I 1 1 1 1 1 1 1 I 1 1 1 I 1 I I 1 I I 1 1 1 1 I 1 1 1 &amp;#943; 1 I 1TiiTi AATCGTATATCTAATGTTCCTCCTGTTAAAATTCTCAAAAGCAATTGAAA 350 v. 1 351 taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc 1 I 1 II 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 I 1 I 1 1 1 1 II 1 1 1 1 I 1 ! 1 1 1 I 1 1 1 1 I 1 1 ! 1 400 v. 6 351 1 1 1 1 &amp;#943; 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 i 1 I 1 I i 1 1 I 1 1 1 1 l TACCATCTTCAGTTCAACAGGTTCCAACAATCATAAAACAGTCAAAAGTC 400 v.l 401 caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagctaa 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 ! 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 ! 1 ! 1 1 1 II 1 450 v . 6 401 ι 1 1 II 1 II 1 1 I I i 1 11 I Η 1 I 1 I 1 II 1 ι ι 1 1 1 1 i 1 I 1 I I I 1 I I I 1 I 1 I 1 1 CAAGTTGCCTTTCCCTTCGATGAGTATTTTCAAATTGAATGTGAAGCTAA 450 v.l 451 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 111IIII1II11111111!!1II11IIII11 i 1II11II11111IIIIII 500 v. 6 451 AGGAAATCCAGAACCAACATTTTCGTGGACTAAGGATGGCAACCCTTTTT 500 v.l 501 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg II 1 I I I I 1 I 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 ] 1 1 1 I 1 I 1 1 I 1 I I I 1 I 1 II I I 1 550 v. 6 501 I 1 1 1 II I 1 1 1 11 1 I 1 1 1 1 1 ι 1 1 1 1 1 N 1 1 1 1 1 1 l 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 ATTTCACTGACCATCGGATAATTCCATCGAACAATTCAGGAACATTCAGG 550 v.l 551 atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt I 1 1 II 1 I 1 1 1 1 1 1 1 1 1 II 1 1 II 1 1 1 1 1 1 II 1 1 II II 1 1 1 1 1 1 1 1 f 1 1 1 |l 600 v. 6 551 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 I II 1 11 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 I 1 1 ATCCCAAACGAGGGGCACATATCTCACTTTCAAGGGAAATACCGCTGCTT 600 v.l 501 tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag. I 1 1 I 11 1 1 1 I 1 I 1 I I 1 I 1 1 I I 1 1 I I 1 1 I 1 1 1 ! I I I 1 1 I 1 1 1 1 1 1 I 1 t I 1 I 650 v. 6 601 II 1! 1 1 1 1 1 i I 1 1 ! 1 1 1 1 I 1 II II I 1 I 1 i I J 1 U 1 1 I H U I Ii 1 1 I 1 1 I TGGTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650 v.l 651 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg 1 1 1 1 1 1 700 651 1 1 1 1 1 1 656 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 75 0 Vo 6 657 656 v. 1 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 800 296 v. 6 657 -----------------------------AATTAGAACACATCGAACAAG 677 v.l 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg j I 1 1 I I j I 1 I 1 I ] 1 I 1 I II 1 I I I I II 1 I I 1 I 1 I ! I j 1 II 1 II 1 I 1 I I 1 ! 850 v. 6 678 1 ! 1 I 1 11 1 I 1 1 1 1 1 i 1 H I I 1 1 111 1 1 1 1 I 1 1 1 I 1 1 1 11 1 I I I 1 I 11 1 11 ATGAAAGAGTATACATGAGCCAAAAGGGAGATCTATACTTCGCAAACGTG 727 v.l 851 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 &amp;#943; 1 1 1 1 1 1 i i 1 1 1 ι Γ1 1 1 I 1 1 1 ! 1 1 1 1 1 1 t I 1 1 1 900 V. 5 728 1 1 ! 1 1 1 1 I 1 i I I 1 I 1 1 1 1 I 11 ιI I 1 1 1 Η 1 J 1 1 1 &amp;#943;&amp;#943; I i 1 I i 1 I It1 ll it GAAGAAAAGGACAGTCGCAATGACTACTGTTGCTTTGCTGCATTTCCAAG 777 v.l 901 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt 1 I 1 1 I 1 I 1 1 I 1 1 I 1 1 I 1 I I 1 1 1 1 1 1 1 1 ! I ( I 1 1 1 1 II II | j 1 1 1 f I 1 1 f 1 950 v. 6 778 11 i i I 1 i &amp;#943; 1 U 1 1 I 1 1 t ι i 1 1 i i i I ι 1 I I ι I i it 1 i I ! 1 1 1 ) 111 i 1 i &amp;#943; I ATTAAGGACTATTGTACAGAAAATGCCAATGAAACTAACAGTTAACAGTT 827 v.l 951 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca I 1 1 I || 1 1 I 11 1 1 I 1 U | | | I 1 ! t 1 | | | | II I I 1 I I Π I 1 11 1 || I 1 1 I 1 1000 v - 6 . 828 1 1 1 1 1 ! 1 1 ) 1 1 1 i 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TAAAGCATGCTAATGACTCAAGTTCATCCACAGAAATTGGTTCCAAGGCA 877 v.l 1001 aafctccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag ! 1 1 1 I 1 1 1 1 ! 1 ! 1 &amp;#912; 1 1 ! 1 1 I ' Π 1 1 1 1 1 I 1 1 I 1 II 1 1 i I 1 I 1 1 1 1 i 1 1 ! ! 1050 v. 6 878 N 1 I I U 1 Η 11 11 II l 1 &amp;#943; N 1 1 11 Η 1 1 1 i 1 1 1 i 1 1 i 1 1 I i J 1 j i 1 1 Π AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG 927 v.l 1051 tqqca.qtqaqtct:tcaatta.ccatcctcaaaggggaaafccttgctgcfctg II 111 || III ll | II111 111II111i1 11II III II1 1 11 III 1 11 1 II 1100 v. 5 928 1 I 1 1 N U I 1 1 U ll I I 1 U l ll ι H 1 1 1 U 1 Η ι U ι Ι Π·Ι l 1 I 1 1 1 1 1 TGGCAGTGAGTCTTCAATTACCATCCTCAAAGGGGAAATCTTGCTGCTTG 977 v.l 1101 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt | 1 1 |] 1 1 1 1 1 1 1 1 1 1 II 1 1 1 I 1 1 1 1 II 1 1 1 1 II 1 1 II | | 1 | 1 1 | 1 I 1 I H 1150 v. 6 978 1 I 1 S I I 1 I f 1 1 1 I 1 i ! I l ι 1 1 1 1 I I 1 1 1 1 1 1 I 1 ι ι I I I 1 1 I I 1 1 t 1 I 1 I 1 AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGG'AACAAAATT 1027 v.l 1151 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac | 1 1 1 1 1 II I 1 1 II 1 1 1 1 1 1 1 1 l| 1 1 1 1 1 1 1 1 II 1 II I 1 1 1 1 1 I 1 I 1 |&amp;#906; I I 1200 v. 6 1028 1 I 1 i J 1 ) &amp;#943; 1 1 1 j 11 1 1 1 I f i 1 1 I I 1 1 1 I 1 1 1 1 1 1 Ii 1 I S 1 1 1 ι ι &amp;#943; 1 i ι ι i GGTGGTGACTTACCAAAGGGGAGAGAAACAAAAGAAAATTATGGCAAGAC 1077 v.l 1201 tttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca If I II I I I I I )| II 1 I ] I I 1 1 |l 1 II I j 1 II 1 1 1 |l 1 1 II 1 1 1 1 1 II 1 II 1250 V, 6 1078 1 ι 11 &amp;#943; 1 I 1 1 1 1 ι 1 1 1 1 1 1 1 1 1 1 1 11 1 11 I 1 1 Π Η 1 1 i 1 Η Η H 1 ! 1 H TT-TGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA 1127 v.l 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta | I j II II II 1 l| 1 II 1 N 1 II 1 II II 1 1 1 (I 1 II II 1 1 II I II 1 H I 1 13 00 v B 6 1128 I I I I 1 I 1 I I I l 1 1 1 1 1 S 1 1 1 i 1 1 I 1 1 1 I 1 I 1 i &amp;#943; &amp;#943; l &amp;#943; I 1 s 1.1 l ι ( I &amp;#943; I I II CAGCCA&amp;amp;CAATTTCTTGGGAAXAGCCACTCACGATTTTCACGTTATAGTA 1177 v.l 13 01 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtatagcac !11!H m 1 ill II 1 11 m 11 1 1 1 1 111 I 1 1 1 III III 1 1 1 i ! i III I 1350 v. 6 1178 11 111 I I 1 11 111 11111 1 1 1 11 1 1 I 1 1 II 1 ! 1 1 1 1 1 1 1 II 1 I 1 1 1 1 1 1 ! GAAGAGCCTCCTCGCTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCAC 1227 v.l 1351 cggaagcaatggcatcttgttatgtqaqgctgaaggagaacctcaaccca illlllllllllllllllllllllilllllllllillllllllilillll 1400 v. 6 1228 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! I 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 11 11 1! II II ! 1 1 1 ! 1 CGGAAGCAATGGCATCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCA 1277 v.l 1401 caatcaagtggagagtcaatggctccccagttgacaatcatccatttgct 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 I!! 1 ! 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1! 1 1 1 1 1 1450 v. 6 1278 11 1 11 1 1 1 11111 11111 11111Ι&amp;#943;1 1llI 1 111 11 I 1 1 1! 1 1 1 1 II 1 II CAATCAAGTGGAGAGTCAATGGCTCCCCAGTTGACAATCATCCATTTGCT 1327 v.l 1451 ggtgatgttgtcttccccagggaaatcagttttaccaaccttcaaccaaa | I I I I I I I I I I I I I II I I I I I I I I I I I I || I I I I II 1 1 1 I I I I || j || I) 1500 v. 6 1328 1 1 I 11 1 1 1 1 1 1 1 II1 111 1 1 1 1 1 1 1 ! 1 i 1 1 1 1 1 1 1 1 1 111 1 1 II 1 1 1 111 GGTGATGTTGTCTTCCCCAGGGAAATCAGTTTTACCAACCTTCAACCAAA 1377 v.l 1501 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 S ! 1 I i 1 1 1 i 1 ! 1 1550 v. 6 1378 1 ι 1 I 1 I II 1 1 1 1 1 1 1 1 I 1)11 11 1 1 1 1 I 1 I 1 1 I 1 IJ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TCATACTGCTGTGTACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCC 1427 297 - -V . 1 1551 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc I 1 I II 1 1 1 1 I I 1 1 II 1 1 11 1 1 1 II 1 1 I 1 1 1 1 1 1 II 1 1 II I 1 I 1 1 I 1 1 I 1 t 1600 v. 6 1428 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 TTGCCAATGCCAATATTGATGTTGTGGATGTCCGTCCATTGATACAAACC 1477 v.l 1601 aaagatggagaaaattacgctacagfcggttgggtacagtgctttcttaca I 1 1 I 1 I 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1650 v. 6 147 3 ι ι 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ) 1 1 1 1 1 1 ) 1 1 AAAGATGGAGAAAATTACGCTACAGTGGTTGGGTACAGTGCTTTCTTACA 1527 v.l 1651 ttgcgagttctttgcttcacctgaggcagtcgtgtcctggcagaaggtgg 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 ( 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1700 v. 6 1528 1 1 1 I 1 1 1 II 1 1 1 1 1 1 1 1 I I 1 1 1 t 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1. 1 1 1 TTGCGAGTTCTTTGCTTCACCTGAGGCAGTCGTGTCCTGGCAGAAGGTGG 1577 v.l 1701 aagaagtgaaacccctggagggcaggcggtatcatatctatgaaaatggc 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1750 v. 6 1578 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AAGAAGTGAAACCCCTGGAGGGCAGGCGGTATCATATCTATGAAAATGGC 1627 v.l 1751 acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg 1 I 1 1 1 1 1 1 1 1)1 1 1 ! 11 I 1 I 1 1 1 I I 1 1 1 1 I 1 I I 1 1 1 i 1 I 1 11 1 11 1 I 1 1 I 1800 v. 6 1628 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 ACATTGCAGATCAACAGAACCACCGAAGAAGATGCTGGGTCTTACTCATG 1677 v. 1 1801 ttgggtagaaaatgctafcaggaaaaactgcagtcacagccaatttggata ) 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1850 v. 6 1678 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TTGGGTAGAAAATGCTATAGGAAAAACTGCAGTCACAGCCAATTTGGATA 1727 v.l 1851 ttagaaatgctacaaaacttagagtttctcctaagaatcctcgtatcccc 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ) 1 1 1 1 1 1 II 1 1900 v. 6 1728 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 I I 1 1 1 1 1 1 1 1 1 1 TTAGAAATGCTACAAAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCC 1777 v.l 1901 aaattgcatatgcttgaafctacattgtgaaagcaaatgtgactcacattt 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1950 v. 6 1778 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AAATTGCATATGCTTGAATTACATTGTGAAAGCAAATGTGACTCACATTT 1827 v.l 1951 gaaacacagtttgaagttgtcctggagtaaagatggagaagcctttgaaa 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 2000 v. 6 1828 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 .1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GAAACACAGTTTGAAGTTGTCCTGGAGTAAAGATGGAGAAGCCTTTGAAA 1877 v.l 2001 ttaatggcacaqaagatgqcaggataattattgatgqaactaatttqacc 1 1 II 1 | | I 1 I 1 II l| I 1 ill i ill 1 i 1 1 1 1 1 II 1 ill HI 1 1 II 1 II I I 1 2050 v . 6 1878 II 1 1 1 1 1 1 1 1 II 1 1 1 II I N11 Η I Η II 1 1 II Π Η II II 1 I! I 1 1! 1 1 TTAATGGCACAGAAGATGGCAGGATAATTATTGATGGAGCTAATTTGACC 1927 v.l 2051 atatctaatgtaactttagaggaccaaggtatttactgctgttcagctca 1 II 1 Γ&amp;#912;'Ι I l 1 1 1 1 1 II 1 Η 1 1 N 1 1 ι 1 1 1 I 1 1 i Η 1 1 Η 1 Η 1 1 ! 1 Η H 2100 v. 6 1928 ι 1 5 ! &amp;#943; ι 1 t ι 1 ι ι ι I 1 1 1 ι ι ι I ι ι H i H i.t 1 H 1 1 ) U 1 1 1 i 1 1 ι ι Π II ATATCTAATGTAACTTTAGAGGACCAAOGTATTTACTGCTGTTCAGCTCA - 1977 v.l 2101 tactgctctagacagtgctgccgatataactcaagtaactgttcttgatg jl || II || Η || |i || I! 1 II 1 1 1 Η 1 II 1 1 II II 1111 1 II II II Η II 2150 v . 6 1978 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 II II 1 II 1 1 1 1 II II II 1 1 II II 1 II II TACTGCTCTAGACAGTGCTGCCGATATAACTCAAGTAACTGTTCTTGATG 2027 v. 1 2151 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt II II1 1 II 1II 1 I II 1 1 1 I 1 1 1 1 1 II 1 II II 1 1 1 1 II II 11 II H 1 1 I 1 1 2200 v . 6 2028 1 I II 1 1!I 111 1 II 1 1 II I 1 1 1 1 1 11 II II II II 1 1 II 1 1 11 II ι 1 II II TTCCGGATCCACCAGAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGT 2077 v.l 2201 gttcggctgacctgggaagctggagctgaccacaacagcaatattagcga Π 1 II 1 Η I Π 1! S Π Π 1 1 1 1 1 1 I 1 II 1 1 1 1 Π I 1 II ! 1 1 Η Π II 11 1 2250 v . 6 2078 1 II 1 1 1 1 1 I 1 1 1 II 1 1 1 II II 1 II H 1 1 H II II II 11 1 II l.l II II 1 N GTTCGGCTGACCTGGGAAGCTGGAGCTGACCACAACAGCAATATTAGCGA 2127 v.l 2251 gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg ( | | Η Π Η Η Η II Η II H 1 II 1 1 II II1 I II 1 11 II 1 1 II 1 1 1 I II 1 2300 v. 6 2128 1 1 1 1 1 1 I 1 1 ! ι I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 I 1 l.l GTATATTGTTGAATTTGAAGGAAACAAAGAAGAGCCTGGAAGGTGGGAGG 2177 v.l 2301 aactgaccagagtccaaggaaagaaaaccacagttatcttacctttggct π I 1 IN II II II II II II 11 1IIIIII I 11 1 I 1 I 1 II 1 1 1 II II I! 1 II 2350 v. 6 2178 1 I 1 1 1 I 1 1 11ι i 1 I U 1 I 1 I I 1II IN II I 1I Π I 1 I 1 1 U I 1 II H N 1 AACTGACCAGAGTCCAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCT 2227 298 v.l 2351 ccatttgtgagataccagttcagggtcatagccgtgaacgaagtagggag μιιι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ιι ι ι ι ι ι ιι η ιιιιιιιιιιιιι ι ι ι ι ι | 2400 ι 1 1 1 I &amp;#943; ! 1 ι Ι &amp;#943; 1 1 I 1 I &amp;#943; ! i 1 I 1 1 S &amp;#943; ι I i 1 ! i i i &amp;#943; 1 &amp;#943; &amp;#943; I &amp;#943; f ι I 1 I 1 ! 1 i I i v.6 2 22 8 CCATTTGTGAGATACCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAG 2277 v.1 2401 aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc | II 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 II 1 1 II 1 1 1 1 1 1 1 I 1 1 II 1 1 II II 1 1 II 1 I 2450 1 1 1 ! 1 1 II 1 II 1 1 !1 1 I 1 111 I 11 1 1 1 1 1 1 1 1 II I 1 1 i 1 I 11 1 1 1 1 I II 1 v.6 227 8 AAGTCAGCCTAGCCAGCCGTCAGACCATCATGAAACACCACCAGCAGCTC 2327 v.1 2451 cagataggaatccacaaaacataagggttcaagcctctcaacccaaggaa | 1 1 I 1 1 II 11 1 1 |l 1 1 1 II 1 1 1 II II 1 1 1 1 1 1 |l 1 1 1 1 1 1 |l 1 1 II 1 1 1 1 2500 1 ι &amp;#943; 1 I 1 I I j 1 1 1 &amp;#943; 1 1 1 &amp;#943; i I 1 1 I 1 1 I I 1 1 i ι 1 1 I 1 1 1 1 1 I 1 I 1 t i 1 I 1 1 I ! v.6 2328 CAGATAGGAATCCACAAAACATAAGGGTTCAAGCCTCTCAACCCAAGGAA 2377 v.1 2501 atgattataaagtgggagcctttgaaatccatggagcagaatggaccagg IIII11111II IIIIIIII111IIII111 11 Μ IIII II 1 1II II 11II1 2550 Μ 1 1 1 1 1 1 Μ 1 Μ 1 1 Μ 1 1 1 1 1 1 1 1 1 1 1 1 1 Μ 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 v.6 237 8 ATGATTATAAAGTGGGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGG 2427 v.1 2551 cctagagtacagagtgacctggaagccacagggagccccagtggagtggg Μ Μ I 1 1 I 1 1 M 1 T 1 Μ 1 1 1 II 1 II 1 1 1 1 Μ Μ Μ 1 1 II Μ II II 1 Μ 1 1 2600 (I 1 11 1 1 1 1 1 i 1 1 11 1 1 1 1 II I 1 II II 1 1 1 1 1 I 1111 11 1 II 1 1 1 II 1 1 I v.6 242 8 CCTAGAGTACAGAGTGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGG 2477 v.l 2601 aagaagaaacagtcacaaaccacacattgcgggtgatgacgcctgctgtc | I I I I I ) I I I I I I I 1 I I I I I I I I I I I I I I I I I 1 1 1 1 1 1 1 1 1 11 I 1 1 1 1 I 1 2650 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.6 247 8 AAGAAGAAACAGTCACAAACCACACATTGCGGGTGATGACGCCTGCTGTC 2527 v.1 2651 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 2700 II II 1 1 1 1 Μ II 1 1 1 1 1 1 1 II 1 1 1 I 1 1 1 1 I II 1 1 1 1 Μ 1 1 1 II 1 1 1 II 1 1 v.6 2528 TATGCCCCTTATGATGTCAAGGTCCAGGCTATCAATCAACTAGGATCTGG 2577 v.1 2701 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata | 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 2750 1 1 1 1 11 1 1 1 I 1 1 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.6 2578 GCCTGACCCTCAGTCAGTGACTCTGTATTCTGGAGAAGACTATCCTGATA 2627 v.1 2751 cagctccaqtqatccatqgggtggacgttataaacagtacattagttaaa 1 Ml 11 1 Mill II 1 1 1 11 II II II Mil II II1 1 II II 1 II 1 II 1 II II 2800 II 1 1 1 1 1 Μ 1 Μ Μ 1 II 1 II M 1 II 1 1 1 1 Μ II 1 1 1 Μ II Μ Μ II 1 Μ 1 v.6 2 62 8 CAGCTCCAGTGATCCATGGGGTGGACGTTATAAACAGTACATTAGTTAAA 2 677 v.1 2801 gttacctgqtcaacagttccaaaggacagagtacatggacgtctgaaagg III 1 1 1 II III II 1 II 1 II 1 II III II II III 1 II II IMI 1 II III II 1 2850 II 1 1 1 1 1 II 1 II II 1 M 1 1 1 II 1 II 1 1 1 II 1 II 1 1 1 I 1 M II 1 1 M 1 M 1 v.6 2 67 8 GTTACCTGGTCAACAGTTCCAAAGGACAGAGTACATGGACGTCTGAAAGG 2727. v.l 2851 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac Μ Μ 1 1 1 Μ Μ Μ Μ Μ Μ Μ II 1 I I II Μ 1 II Μ 1 1 Μ II Μ 1 &amp;#970; Μ Μ 1 2500 II MI 1 1 1 1 1 1 11 II M 1 II II 1 II II II II It M 1 1 II 11 1 II M 1 1 1 I v.6 2728 CTATCAGATAAATTGGTGGAAAACAAAAAGTCTGTTGGATGGAAGAACAC 2777 v.l 2901 atcccaaagaagtgaacattctaagattttcaggacaaagaaactctgga II II 1 1 1 1 Μ II 1 II II 1 Μ Μ Μ 1 1 1 Μ II II 11 1 Μ Μ 1 Μ Μ Μ Μ 1 2950 1 11 1 1 1 1 II II II II 1 1 1 1 1 II 1 1 1 1 1 1 II 11 1 1 1 1 II M M M II 1 II 1 v.6 2778 ATCCCAAAGAAGTGAACATTCTAAGATTTTCAGGACAAAGAAACTCTGGA 2827 v.l 2951 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc ιι Τ η ιι π η η ι ι Η | ιι η |i ι Η ιι i| ι ι | ι ι ι η μ II II 1 Μ II 3000 M II111II 1II111 II 1 If II 1 1 I 1 1 M II IIII1 M IIιι ι If ιι 111 v.6 2828 ATGGTTCCTTCCTTAGATGCCTTTAGTGAATTTCATTTAACAGTCTTAGC 2877 v.l 3 0 01 ctataactctaaaggagctggtcctgaaagtgagccttatatatttcaaa 1 Μ Μ I 1 Μ Μ Μ II 1 1 1 Μ Μ Μ 1 1 1 1 1 Μ Μ 1 Μ 1 Μ II Μ Μ Μ 1 II 3050 Μ 1 I 1 1 I ι Μ Μ ι Μ Μ Μ 1 II 1 1 Μ ! Μ Μ Μ I I 1 Μ I Μ M 1 I 1 1 Μ 1 v.6 2 87 8 CTATAACTCTAAAGGAGCTGGTCCTGAAAGTGAGCCTTATATATTTCAAA 2927 v.l 3051 caccagaaggagtacctgaacagccaacttttctaaaggtcatcaaagtt II ι | η | η Η ιι II IIII l-M II 1 Μ Μ II 1 1 1 II 1 Μ Μ II II Μ II 1 3100 1 1 1 1 1 1 1 II M 1 I I I I 1 I 1 l-l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 2977 v.l 3101 gataaagacactgccactttatcttggggactacctaagaaattaaatgg 3150 299 ;γ;. 6 297 8 GATAAAGACACTGCCACTTTATCTTGGGGACTACCTAAGAAATTAAATGG 3027 v.l 3151 aaacttaactggctatcttttgcaatatcagataataaatgacacctacg II!ιιιιι ι ι ιιιιιι ι ι ) ι ι ι ii ι ι ii &amp;#943; η j ι iiIi|j |||j Η η Η ι 3200 1 1 1 1 1 1 1 1 1 1 ! 1 I 1 I 1 1 1 I 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I I v.6 3028 AAACTTAACTGGCTATCTTTTGCAATATCAGATAATAAATGACACCTACO 3077 v.l 3201 agattggagaattaaatgatattaacattacaactccatcaaagcccagc I I 1 1 &amp;#943; 1 i 1 &amp;#943; 1 1 l &amp;#912; i 1 &amp;#943; 1 1 1 1 &amp;#912; 1 1 I 1 I t i &amp;#943; i 1 1 1 1 t 1 ! &amp;#943; i 1 1 &amp;#943; &amp;#943; 1 1 1 ! 1 i i 3250 1 1 1 1 1 1 1 &amp;#943; 1 ! 1 il 1 1 I 1 ! I 1 1 1 1 1 1 1 1 1 1 1 t I i I 1 1 1 1 1 1 1 I 1 1 1 l 1 1 H v.6 3078 AGATTGGAGAATTAAATGATATTAACATTACAACTCCATCAAAGCCCAGC 3127 v.l 3251 tggcaccfcctcaaacctgaatgcaactaccaagtacaaattctacttgag | 1 II 1 1 1 || II 1 1 1 1 II 1 1 1 1 1 I 1! 1 1 I 1 II 1 1 1 II 1 1 1 II 1 1 1 1 1 t I II 3300 IIH H 1 H 11 11 II S 1 1 I I i I 1 1 1 1 1 1 I J 1 1 J 1 J J i 1 1 1 1 11 1 1 1 i 1 1 1 v.6 3128 TGGCACCTCTCAAACCTGAATGCAACTACCAAGTACAAATTCTACTTGAG 3177 v.l 3301 ggcttgcacttcacagggctgtggaaaaccgatcacggaggaaagctcca 1 I I II j It II II II I| III 1| !|| I I 1 I I || ! || I || || || I I || H |l 1 3350 I 1 1 I 1 &amp;#943; 1 ( 1 1 1 1 I it It I 1 ι 1 I &amp;#943; 1 ι Η II Η ι ι 1 ι 1 1 Η H 1 1 Η 1 Η 11 v.6 3178 GGCTTGCACTTCACAGGGCTGTGGAAAACCGATCACGGAGGAAAGCTCCA 3227 v.l 3 351 ccttaggagaagggagtaaaggtatcgggaagatatcaggagtaaatctt II I I I I I || I II (I 1 Ii H I &amp;#943; j 1 1 1 |l 1 I 1 || || || || 1 I || 1 j || 11 H 3400 Il t 1 1 1 1 H ! 1 i 1 1 1 1 I ! 1 1 1 1 ι I ι I U 1 ! 1 1 1 1 I 1 1 1 l ι &amp;#943; I I 1 &amp;#943; I 1 1! 1 v.6 3228 CCTTAGGAGAAGGGAGTAAAGGTATCGGGAAGATATCAGGAGTAAATCTT 3277 v.l 3401 actcaaaagactcacccaatagaggtatttgagccgggagctgaacatat IIHIIIIIIIIIIIIIIillllllllllllllllllllllintllll 1 v.6 3278 ACTCAAAAGACTCACCCAATAGAGGTATTTGAGCCGGGAGCTGAACATAT 3450 3327 v.l 3451 agttcgcctaatgactaagaattggggcgataacgatagcatttttcaag | 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 I 1 1 11 1 II 1 1 11 1 1 II 1 1 1 1 t 1 II 1 1 1 1 1 1 1 1 1 3500 Η Π H 1 1 I Ν 1 1 Ν H i J 1 &amp;#943; 1 1 1 J J 1 1 1 1 1 ι 1 1 1 1 J Η 1 j J 1 I 5 1 I I I 1 v.6 332 8 AGTTCGCCTAATGACTAAGAATTGGGGCGATAAcGATAGCATTTTTCAAG 3377 v.l 3501 atgtaattgagacaagagggagagaatatgctggtttatatgatgacatc Nil 1 II II llll 1 1 II IIII II II ! 1 1 III II II 1 1 1 1 1 II 1 II 1 1 1 1 1 3550 1 I I I I 1 1 I I 1 I I 1 I fl I Η 1 &amp;#943; I I ι 1 1 ! I I 1 H 1 1 U 1 1 1 ! 1 1 1 1 1 1· 1 I II v.6 3378 ATGTAATTGAGACAAGAGGGAGAGAATATGCTGGTTTATATGATGACATC 3427 v.l 3551 tccactcaaggctggtttattggactgatgtgtgcgattgctcttctcac ! I |l I I I I II I l| II I I I I I II II II 1 1 II II I 1 I 1 1 1 II 1 II |l H I 1 1 3600 ilII1 I II 1 11 I 11 11!11111111111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 v.6 342 8 TCCACTCAAGGCTGGTTTATTGGACTGATGTGTGCGATIGCTCTTCTCAC 3477 v.l 3601 actactattattaactqtttgctttgtgaagaggaatagaggtggaaagt 1 11 1 1 1 1 11II Π 1 1 11 1 11 II1 1 III II II I IN 1 1 III II II 11 1 III 3650 S 1 1 1 1 I I 1 ! 1 1 1 1 1 1 11 1 I 1 1 1 1 1 1 1 1 1 1 I I l I 1 1 I 1 1 1 ! 1 I ! 1 I I I I 1 i v.6 347 8 ACTACTATTATTAACTGTTTGCTTTGTGAAGAGGAATAGAGGTGGAAAGT 3527 v.l 3651 actcagttaaagaaaaggaagatttgcatccagacccagaaattcagtca -1 1 1 1 II 1 ! 1 1 1 1&amp;#943;111 I 1 1 1 1 1 1 1 1 1 1 II I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3700 II I if II ι 1 1 II 1 1 1 1 II II 1 1 II Η Η ι 1 II 1 1 II 1 1 If U 1 H 1 1 1 1 I v.6 3528 ACTCAGTTAAAGAAAAGGAAGATTTGCATCCAGACCCAGAAATTCAGTCA 3577 v.l 3701 gtaaaagatgaaacctttggtgaatacagtgacagtgatgaaaagcctct | 1 1 1 1 II 1 I 1 1 1 1 1 1 1 1 1 1 II II 1 1 1 II II 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 II 3750 II 1 1 I I I 1 I I I I 1 1 I 1 I 1 I I 1 1 I I II 1 I I I I 1 1 I 1 1 1 I 1 1 I I II I I I 1 u v = 6 3578 GTAAAAGATGAAACCTTTGGTGAATACAGTGACAGTGATGAAAAGCCTCT . 3627 v.l 3751 caaaggaagccttcggtcccttaatagggatatgcagcctactgaaagtg 1 11 ! 1 1 1! II 1 1 1 1 II 1 1 11 11II11 1 1 1 1 !I 1 1 I 1 1 1 1111 1 1 1 1 1 1 1 1 3800 1 1 1 1 1 1 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 1 1 1 II 1 1 1 1 II 11 1 1 1 1 1 1 l.l 1 1 1 II 1 v.6 3628 CAAAGGAAGCCTTCGGTCCCTTAATAGGGATATGCAGCCTACTGAAAGTG 3677 v.l 3 8 01 ctgacagcttagtcgaatacggagagggagaccatggtctcttcagtgaa 1 I 111 1 1 1 1 1 1 1 1 1 11 11 11 II Γ1 1 1 1 1 1 1 1 1 1 1 i 1 1 II 1 1 1 1 1 1 1 1 1 I 1 3850 Η Ν &amp;#943; 1 j 1 i 1 1 Ν 1 ι ι ι Π H i I 1 U 1 1 1 S 1 i i ι ι 1 1 1 1 i Η N ! I ! 1 1 I v.6 3678 CTGACAGCTTAGTCGAATACGGAGAGGGAGACCATGGTCTCTTCAGTGAA 3727 v.l 3 851 gatgaatcatttattggtgcctacgctggatctaaggagaagggatctgt 111 III 1111 11IIII11II1111IIIIII1111II II I ! Ι&amp;#938;Ι II II 1 1 1 3900 II 1 1 II 1 1 II I 11 I 1II 1 II 1 I l11 I 1 II I 1 II 1 1 I 1 I 1 1 II 1 1 1 1 1 1 1 1 v.6 3728 GATGGATCATTTATTGGTGCCTACGCTGGATCTAAGGAGAAGGGATCTGT 3777 v.l 3 901 tgaaagcaatggaagttctacagcaacttttccccttcgggcataaacac 3950 300 v.6 3778 TGAAAGCAATGGAAGTTCTACAGCAACTTTTCCCCTTCGGGCATAAACAC 3827 v.l 3951 aacatatgtaagcaacgctactggttcaccccaaccttccatatttatct I j I 1 1 I | 1 I 1 1 I I I 1 1 I ! I I ] 1 1 I 1 1 I I I I 1 I t 1 I 1 1 I 1 I | j I 1 1 I 1 I I I 4000 v.6 3828 1 1 J 1 1 1 11 1 11 i I I 1 1 1 1 I I 1 I I I 1 I 1 J 1 I 1 1 I 1 I i I I l &amp;#943; I I 1 li I 11 II AACATATGTAAGCAACGCTACTGGTTCACCCCAACCTTCCATATTTATCT 3877 v.l 4001 gttcaaaggagcaagaactttcatataggaatagaaacatgctggccgaa 1 I I II II II I 1 I I I I I 1 I I II I 1 j 1 j I 1 1 I II I I II 11 I II I I ! 1 1 1 1 1 ! 4050 v.6 3878 1 1 I I 1 U 1 I ! I 1 1 i 1 i 1 Π ! I I 1 1 1 I t I I i 1 i 1 1 i I ! i i 1 I i I t 1 1 i 1 1 ! GTTCAAAGGAGCAAGAACTTTCATATAGGAATAGAAACATGCTGGCCGAA 3927 v.l 4051 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac I I 1 1 1 II 1 1 1 1 1 1 1 1 II 1 1 1 I 1 1 |l 1 1 1 1 1 1 II 1 I 1 1 II 1 II II 1 II 1 i 1 4100 v.6 3928 J I 1 I j ! ι 1 I 1 ι ι H 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 s Η 1 1 1 1 1 1 ι 1 1 1 I ι &amp;#943; 1 1 ι I 1 GATTTCATCCAGAAGTCAACATCCTGCAATTATGTTGAAAAGAGTAGTAC 3977 v.l 4101 tttcttcaaaatataaaatgccaagcactfccaggcctatgttttgcttat 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 4150 v.6 3978 ! ι ι I I ι I 1 ι ι I 1 t 1 I 1 I 1 1 1 1 I ! 1 I 1 1 I 1 1 1 ι i 1 I I 1 1 i ι I &amp;#943; &amp;#943; ι &amp;#943; ι I I I 1 TTTGTTCAAAATATAAAATGCCAAGCACTTCAGGCCTATGTTTTGCTTAT 4027 v.l 4151 attgttttcaggtgctcaaaatgcaaaacacaaaacaaatcctgcattta | II II ! 1 I I II 1 1 1 1 II II 1 j 1 1 ) 1 1 II 11 1 II II 1 II 1 1 II 1 1 1 II 1 1 1 4200 v.6 4028 I 1 I 1 1 1 li 1 1 ! 1 1 1 1 I i 1 I 1 I II 1 I 1 1 1 I 1 I 1 1 1 I I I 1 1 1 1 1 11 1 t l ι 1 I ATTGTTTTCAGGTGCTCAAAATGCAAAACACAAAACAAATCCTGCATTTA 4077 v.l 4201 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg I I I I I I 1 I 1 I I 1 1 1 1 II I I I I I 11 || I I I I I I II 1 1 II 1 III I I 1 I I I 1 I 4250 v.6 4078 I 1 1 ! 1 I I 1 &amp;#943; I 1 11 i I I 1 1 I 1 1 1 I 1 I 11 1 I I ! 11 I ι 1 I i 1 1 1 I I 1 1 1 iiii GATACACCTCAACTAAATCCAAAGTCCCCATTCAGTATATTCCATATTTG 4127 v.l 4251 cctqattttactattcggtgtgtttgcatagatgttgctacttggtgggt 1 1 II 1111! 11 111 1 II IIIIII Him III IIIIIII11 1 111 II ill 4300 v.6 4128 I 1 I 1 1 1 I 1 SI I I 1 1 1 1 I 1 I 1 1 j 1 1 1 1 1 1 1 I l 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 ι 1 1 1 CCTGATTTTACTATTCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGT 4177 V.l 4301 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga η ιι π ιιιιιιιιιiiιη ιιιii ι ii |i i| ι η ι ι | ι ι || |i ι | | ι ι | 4350 V.6 4178 I I I I I I ι 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 ! ι 1 I · i 1 I I I I 4 I 1 1 1 1 l &amp;#943; 1 1 1 1 1 ΤΤΤ&amp;#943; TTTTCTCCGTATGCACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGA 4227 v.l 4351 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa | 1 1 II 1 1 l| 1 1 11 I I 1 || I II 1) l| 1 1) II 1 I II 1 1 l| II 1 I II II 1 II 1 4400 v.6 4228 1 1 I j 1 I i ! I 1 1 } 1 1 1 1 1 1 1 1 1 I I 1 i 1 i I &amp;#943; i I &amp;#943; 1 1 I I ! 1 I t I i I 1 1 f l 1 i 1 CTTTGCTTCACTACAGGTTAAAAGACCATAAGCAAACTGGTTATTTAAAA 4277 v.l 4401 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac il lillillllll 11111111111 Mill II lilill Hill Hill III 4450 V.6 4278 TGTAAAAAGGAATATGAAAGTCTTATTAAAACACTTCATTGAAAATATAC 4327 V.l 4451 agtctaaatttattatttaaattttactagcaaaagtcttaggtgaacaa H II I I II II 1 |l I 1 II || 1 1 1 I I |l || II j I j| 11 II I || II |j 1 1 || 1 4500 v.6 4328 i ι i i 1 1 I I I { i I I 1 l Η ι ι ι &amp;#943; i ι Η ι ι ι ι ι H f i ι Η ι Η ι ι i ι ι ι I ι ι &amp;#943; AGTCTAAATTTATTATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAA 4377 v.l 4501 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa II I I I 1 1 I I 1 1 I 1 I 1 I I 1 I I II I ! I 1 1 1 1 I I 1 || l| || 1 i 1 | 1 II 1 II 11 4550 v.6 4378 1 i 1 ι 1 ι ι ι l ι ι h 1 t 1 1 &amp;#943; 1 1 ! 1 1 ι. 1 &amp;#943; ι ι i &amp;#943; 1 1 1 &amp;#912; I 1 &amp;#943; &amp;#943; 1 1 I 1 I It 1 I 1-1 1 TCAACTAGTATTTGTTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAA 4427 v.l 4551 acagaagtatacgtttttcagtttcaacatgaatttttttatttctgtca Μ 111111 Μ1II Μ 11!11111II1111II11111111111 Μ 11!Μ 1 4600 v.6 442 8 ACAGAAGTATACGTTTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCA 447.7 v.l 4601 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct 4650 11 i 11IIIII11!1111111 li I Η 1111 Η 11II i 11III1111!Ili 1 v.6 447 8 GTTATGACATCCACgAGCATCACTTTTTGTGTCTGTTTTTTTTTTTTTCT 4527 v.l 4651 tggactaaattcaactgcatggaagcggtggtcagaaggttgttttatac 4700 11II111111111 III 111111111II11111II111II1il1II11111 v.6 452 8 TGGACTAAATTCAACTGCATGGAAGCGGTGGTCAGAAGGTTGTTTTATAC 4577 301 1 &lt;5£.l 4701 gagaacaggcagaaagtgcccattgttcaggattctaatagctacatcta 1 1 I I I 1 1 I 1 I I 1 1 1 11 I 1 I I 1 II II II II I 1 I 1 I I || II I I II 1 I Η I || 4750 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I v. 6 457 8 GAGAACAGGCAGAAAGTGCCCATTG’TTCAGGATTCTAATAGCTACATCTA 4627 v.l 4751 cttaatatcttcatttctaaattgactgcttttaccttfcttctcatgttt | I I II 1! 1 1 I II 1 1 1 1 I 1 1 1 1 I I 1 I I 1 II 1 I 1 1 II 1 I I 1 1 1 1 j I I 1 I ! H 4800 1 1 1 I 1 1 1 1 1 1 l I 1 1 l l 1 1 1 1 ι ι ι 1 ι ι 1 ι I t ι ι ι 1 ι 1 i i 1.1 I I ι i ι ι I I II v.S 4 62 8 CTTAATATCTTCATTTCTAAATTGACTGCTTTTACCTTTTTCTCATGTTT 4677 v.l 4801 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg | I 1 II I II 1 1 1 1 1 II 1 1 1 I 1 1 1 1 1 1 1 l| 1 1 1 1 1 1 II 1 1 II 1 II 1 II 1 1 1 1 4850 1 i 1 11 1 1 1 II 1 1 1 1 t II 1 1 ! II 1 1 1 1 1 1 1 I 1 i 1 I 1 1 1 1 1 Π I L1 1 Π 1 I 1 v.S 467 8 ATATAATGGTATGCTTGCATATATTTCATGAATACATTGTACATATTATG 4727 v.l 4851 ttaatatttacacaatttaaaatatagatgtgttttattttgaagtgaga I I II I I I I I J I I l| I I II 1 II I I || I II II 1 1 I j j 1 II 1 1 1 1 j II II H 1 4900 I 1 1 1 1 1 I ! 1 1 1 1 1 I 1 1 &amp;#943; i 1 1 i 1 1 ! &amp;#943; 1 1 1 1 &amp;#943; 1 I i 1 I 1 1 1 1 I I t I S 1 I 1 I I I v.S 4728 TTAATATTTACACAATTTAAAATATAGATGTGTTTTATTTTGAAGTGAGA 4777 v.l 4901 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat i 1 1 i i Ii 1 i 1 I i i i i i i 1 i i 11i i i 1 I i i 1 1 i &amp;#943; &amp;#943; &amp;#943; &amp;#943; &amp;#943; i &amp;#943; &amp;#943; i i i i i i ii &amp;#943; &amp;#943; 4950 &amp;#943; 1 I 1 i I 1 I 1 1 &amp;#943; t I i 1 1 1 s l ι ι 1 &amp;#943; 1 i &amp;#943; 1 t ι ι 1 I I 1 ι I i 1 I 1 i i &amp;#943; 1 1 1 1 I 1 I v. 6 4 77 8 AAATGAACATTAACAGGCATGTTTGTACAGCTAGAATATATTAGTAAGAT 4827 v.l 4951 actgtttttcgtcattccagagctacaactaataacacgaggttccaaag | I I I I I I 1 I I I I 1 I I I I II I I I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ] j 1 1 1 1 1 5000 i &amp;#943; &amp;#943; &amp;#943; &amp;#943; &amp;#943; &amp;#943; Η &amp;#943; &amp;#943; ι 1 &amp;#943; &amp;#943; 1 &amp;#943; &amp;#943; &amp;#943; &amp;#943; 1 U 1 Η &amp;#943; i &amp;#943; 1 ( 1 1 1 &amp;#943; t i 1 I 1 1 1 &amp;#943; 1 1 &amp;#943; 1 1 H 4877 v.l 5.001 ctgaagactttgtataaagtatttgggttttgttcttgtattgctttctt | I I I I 1 I I I I I I II I I I I I I I I I I I I 1 I II I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 j| 1 5050 &amp;#943; 1 I 1 [ 1 1 j 1 1 1 1 1 I 1 I 1 1 1 1 i 1 I 1 i t 1 1 I l 1 1 I I 1 1 1 I I I I 1 1 1 1 1 1 1 I I v;S 4 87 8 CTGAAGACTTTGTATAAAGTATTTGGGTTTTGTTCTTGTATTGCTTTCTT 4927 v.l 5051 tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ) 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 . 5100 1 1 &amp;#943; J 1 j j 1 J I ! 1 1 1 1 i 1 1 1 &amp;#943; ι 1 1 1 1 &amp;#943; 1 1 ι ι 1 1 1 t ι 1 i 1 1 1 1 1 1 1 1 ' 1 I 1 1 v.S 492 8 TCAACAGTTTCAAAATAAAATATCATAcAAATATTGAGGGAAATGTTTTC 4977 v.l 5101 atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 , 1 1 1 1 ! 1 1 1 1 1 ! 1 i i 1 i 5150 ι I I 1 1 1 1 i 1 ! 1 i 1 I i 1 I 1 1 11 ι 1 1 1 1 i 1 I 1 1 1 I 1 1 1 I 1 1 1 1 1 1 I I 1 1 Ι&amp;#906; I v.S 4 97 8 ATATTTTTCAAAATAGGTTTTTATTGTTGAATGTACATCTACCCCAGCCC 5027 v.l 5151 ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta | j 1 1 j I I I 1 1 I 1 I I 1 I 1 1 1 1 1 I 1 1 1 1 I 1 II 1 1 1 1 1 I I 1 1 1 1 1 1 1 I 1 1 1 1 1 5200 ! ! I } j ; ! &amp;#943; ! ! 1 1 i 1 1 ! &amp;#943; 1 1 I Η I 1 t i I ι ι i t ι i ι &amp;#943; ι i &amp;#943; &amp;#943; I ! ! I i 1 I i ! 1 I v.S 502 8 CTCAAAAGAAAAACTGTTTACATAGAAATTCCTACACATACGTTTGCGTA 5077 v.l 5201 tatgttattttaaacatctttgtggtgagaattttttccccgatattctc 1 I 1 i ΓI 11 l1 ! 1 l 11 i 1I&amp;#943;1 1 i i I 1 1 i ! 1 1 i 1 1 1 I 1 | 1 | | | li 1 | | |1 1| 5250 i ι ι ι ι ι ι &amp;#906; i i I ι i I t I 5 1 -ι ι ι ι I i 1 i I ι 1 &amp;#943; 1 s ι ι ι i ’ &amp;#943; ι 1 i it 1 ι ι I ι } S v.S 507 8 TATGTTATTTTAAACATCTTTGTGGTGAGAATTTTTTCCCCGATA.TTCTC 5127 v.l 5251 cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt | 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 I 1 1 1 I 5300 i I I 1 1 I 1 i &amp;#943; 1 I 1 1 1 1 I 1 1 I 1 1 Η 1 1 1 ! 1 1 1 1 t i t 1 I I i 1 ! 1 I 1 ! 1 1 I i I 1 v.S 512 8 CTTCTGTCAAAGTCAGAACAAATTCAGGGAATTTATTTTCTGGCAGTTGT 5177 v.l 53 01 gctccagtccttttaaaattgtacatgaacatgttttagaaacaatatgg 1 1 i 1 1 i 1 I 1 i i 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 I 1 ! 1 i 1 ! 1 1 1 1 1 1 1 1 1 1 i 1 1 1 i 1 1 5350 ! 1 1 1 1 1 1 I 1 1 1 I ! 1 I 1 1 1 1 t 1 1 I 1 1 1 1 1 1 1 1 ! ! 1 1 1 I 1 ! 1 I 1 1 1 1 1 1 1 I 1 v. 6 517 8 GCTCCAGTCCTTTTAAAATTGTACATGAACATGTTTTAGAAACAATATGG 5227 v.l 5351 aggatgatgcatacatgtcggtcaagttcagcgctcgacattttatggaa ! 1 1 1 l-i i 1 1 1 i 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 i I 1 1 1 i 1 1 1 1 1 1 1 i 1 5400 ι ι I 1 I ! I 1 I I 1 1 1 I I 1 1 1 1 1 1 1 I 1 ! 1 I I 1 1 I 1 I I I 1 1 1 1 I 1 1 &amp;#943; I 1 1 1 ι 1 I v.S 522 8 AGGATGATGCATACATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAA 5277 v.l 5401 agatttttttaaccttaccacgaaatacttaactactgtttaagtgaatt 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 I 1 1 1 5450 i 1 1 1 1 1 1 I 1 I II 1 I I 1 I 1 1 I 1 1 1 I I ! 1 II I 1 I 1 1 1 1 1 1 II I I I 1 I 1 1 1 -I I 5327 v.l 5451 gacttatttcactttagtttttgaactgtgattattggtatactgttata 1 I ! 1 1 i I 1 &amp;#943; 1 1 1 ! 1 1 1 1 1 t 1 1 1 1 1 1 1 1 1 ! 1 1 i ! 1 1 Η 1 1 1 1 1 1 1 1 1 1 1 ! ! 5500 1 ι Η 1 i 1 1 i 1 I II i 1 1 i i 1 1 1 1 1 1 1 1 1 II I 1 1 1 I 1 1 1 1 i 1 1 1 1 i 1 1 1 1 1 I v.S 532 8 GACTTATTTCACTTTAGTTTTTGAACTGTGATTATTGGTATACTGTTATA 5377 302 v. 1 5501 tcctcaacttggatttatggtaaccccttttagttcatggagaccaaaat I 1 I 1 I I I 1 II II 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 I I I 1 1 1 1 I 1 1 i 1 1 1 1 II 1 1 II 5550 v. 6 5378 1 1 1 j 1 1 I 1 1 1 I 1 I 1 1 [ ι 1 1 l 1 1 1 1 1 1 ι I I l 1 j 1 1 I 1 1 1 &amp;#943; 1 1 ι 1 1 1 I l Η 1 TCCTCAACTTGGATTTATGGTAACCCCTTtTAGTTCATGGAGACCAAAAT 5427 v.l 5551 ttqqqgtatttataatagtcagcgcaggaatqcacatggaatatctactt '’&lt;’''11111111111111 111 11IIII1111111IIII 1 1 1 1 1 11 1 11 5600 v . 6 5428 ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι ι 1 I ι ι 1 I 1 I I 1 I 1 1 1 I I I I I 1 1 1 1 1 1 1 1 1 TTGGGGTATTTATAATAGTCAGCGCAGGAATGCACATGGAATATCTACTT 5477 v.l 5601 gtccttttgaacctcacgagtcatccagaatgtatagacaggaaaagcat 1111111II11111111111111111111111111II1111111111111 5650 V. δ 5478 GTCCTTTTGAACCTCACGAGTCATCCAGAATGTATAGACAGGAAAAGCAT 5527 v.l 5651 gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg | I I I I II I 11 I I I 1 1 1 1 1 1 1 1 I I 1 j 1 1 1 III 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 II 1 1 5700 V . δ 5528 1 I ) 1 I I i &amp;#943; I ι &amp;#943; j I i 1 I 1 1 ι 1 i i 1 1 1 1 1 1 ! i i I ! 1 i I 1 1 1 ( &amp;#943; 1 ! i ι 1 1 I 1 i GTCTTATTTAAAAOTGTAATTTATGGGCTCAGGATCTGACCGCAGTCCCG 5577 v.l 5701 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga 11 1 11 1 II 1 1 1 II II II 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 1 1 1 5750 v. 6 5578 1 I 1 &amp;#943; 1 1 1 1 1 1 I 1 i ! 1 i 1 1 1 1 1 1 ι ι &amp;#943; 1 1 I I 1 1 Ι ι 1 1 1 ι I 1 1 1 1 1 1 1 1 1 1 ! 1 GGAGTAAGCATTTCAAAGGGGGAAGGCAGTGTGGTCCCTACCCTOTGTGA 5627 v.l 5751 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc II I I I I II I II I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 5800 v . 6 5628 1 1 1 1 1 ι 1 ι 1 i ι 1 I 1 t 1 1 &amp;#943; it ι 1 I 1 1 1 I 1 ι ( I 1 f I ι 1 1 1 1 1 ι ι 1 &amp;#943; I f 1 i 1 1 ATqTGAGGATGTAGACATCCATCAGTGCAACTCGAGCTCCATCCTCCTCC 5677 v.l 5801 gatttctaaggctccagttttctggagggacagtcatcatgttttgattt | 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5850 V. δ 5678 1 1 I 1 1 I 1 1 I 1 · I 1 1 1 1 I 1 I 1 1 1 1 I 1 1 I 1 1 1 I 1 1 i 1 l I I 1 1 1 1 1 i 1 1 1 1 1 I &amp;#943; GATTTCTAAGGcTCCAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTT 5727 v. 1 5851 atctgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga | II II 1 1 1 II 1 1 1 1 II 1 I IS II II II 1 I 1 II 1 1 I 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 5900 V. δ 5728 ι ι ι ι &amp;#943; ι 1 1 ι I 1 1 1 1 1 1 1 ι ι i I 1 1 1 I 1 Π I 1 II 1 1 1 I &amp;#943; 1 ι II I 1 I I 1 I 1 ! ) ATCTGGGAGAAAACTGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGA 5777 v.l 5901 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcaq INI II II II 1 II 1 1 1 II II II1111IIII111111111 1 1 II 1 1 1 1 1 II 5950 v. δ 5778 I 1 I 1 1 1 1 I 1 f 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 I 1 111 1 1 II 1 1 1 1 1 I 1 1 I I 1 1 ι 1 1 CGTTCGAGCTTAGTTCTGGTGTTATTCTGTCTCCTCTTCTTTGTCATCAG 5827 v.l 5951 ccaaaacgtggtttttaaagagagtcatqcaggttagaaataatatcaaa 111111IIIIII111111IIIIII11ιι&amp;#912;ι ιι&amp;#912;ι1II111111Ι&amp;#938;Ι 1 1 11 6000 V. δ 5828 1 1 1 ι I &amp;#943; I 1 1 I I 1 1 1 1 1 1 I 1 1 It 1 I 1 1 I i I j 1 I 1 1 1 i 1 1 1 &amp;#943; &amp;#943; &amp;#943; i &amp;#943; 1 ι Η 1 i CCAAAACGTGGTTTTTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAA 5877 v.l 6001 aatatfctaggaatttaataacctttaagtcagaaactaaaacaaatactg 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 ι ι Γι 1 1 1 6050 v. δ 5878 1 1 1 I 1 1 1 1 1 1 1 1 1 I I I I I 1 1 1 1 1 1 I I I I 1 1 I 1 I I -I I I I I 1 1 1 1 I I I | | | | AATATTTAGGAATTTAATAACCTTTAAGTCAGAAACTAAAACAAATACTG 5927 v.l 6051 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat | I I I I I I I I I I I I I I I I I I I I I I II I I I I I I I I I I I I II I I 1 1 1 1 1 1 1 1 1 6100 V-δ 5928 1 1! II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 AAATATTAGCTCTTCCTACACTTCGTGTTCCCCTTTAGCTGCCTGAAAAT 5977 v.l 6101 caagattgctcctactcagatcttctgagtqgctaaaacttatgqatatq 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II II II II I 1 1 1 III I 1 II III 1 II 6150 V-_ 6 5978 i ! i U ! &amp;#943; 1 H I 1 1 1 1 1 I i 1 ! i 1 I 1 1 N ι Η 1 I I ! Η 1 i ! ! 1 I 1 I I I ! 1 1 1 CAAGATTGCTCCTaCTCAGATCTTGTGAGTGGCTAAAACTTATGGATATG 6027 v.l 6151 aaaaatgagattgaatgatgactatgctttgctatcattgttacctttcc 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 I 1 1 6200 v. 6 6028 1 1 1 ! 1 1 1 ! j 1 I 1 ι 1 I 1 1 1 I &amp;#943; 1 1 1 1 1 I 1 1 1 J I j 1 ι 1 j 1 t I I 1 &amp;#943; I I 1 Ι Ι ι 1 1 AAAAATGAGATTGAATGATGACTATGCTTTGCTATCATTGTTACCTTTCC 6077 v.l 6201 tcaatactatttggcaactactgggactcttcagcacaaaaggaatagat I HI 1 1 1 I 1 1 I II II 1 1 1 I 1 1 I 11II1 1 1 1 1 1 II 1 1 1 1 1 1 II II 1 1 1 III 6250 v. 6 6078 I I I 1 1 1 1 1 I &amp;#943; I 1 1 &amp;#943; I I 1 1 I 1 I i 1 &amp;#943; 1 1 I J 1 1 i 1 I i 1 I I 1 I 1 I &amp;#943; &amp;#943; 1 1 II I 1 1 TCAATACTATTTGGCAACTACTGGGACTCTTCAGCACAAAAGGAATAGAT 6127 v.l 6251 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt 6300 303 v. 6 6128 CTATGATTGACCCTGATTTTAATTGTGAAATTATATGATTCATATATTTT 6177 v.l 6301 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg I I I 1 I I II 1 I I 1 I II 1 I I 1 1 1 1 I II I 1 II 1 1 I j 1 i 1 II 1 II 1 1 1 II 1 II 1 6350 V . β 6178 I 1 1 1 1 1 ι 1 &amp;#943; 1 I I 1 I 1 1 Ι &amp;#943; 1 1 1 I 1 1 I I 1 1 1 I 1 ι I I 1 1 I 1 I I ! 1 ι I 1 i 1 1 I I ATGAATCAGAATAACCTTCAAATAAAATAAATCTAAGTCGGTTAAAATGG 6227 v.l 6351 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa | ! 1 1 1 1 1 II 1 I I 1 II 1 11 1 1 1 1 1 1 II 1 II 1 I 1 1 II I I 1 1 1 1 1 I 1 1 I 1 1 1 1 6400 v. 6 6228 ! I 1 ! I 1 II ! ι ι ! I ι ι&amp;#943;1 I1 i 1llI Ilι Η ι H !1 I 11 1 1 1 1 1 i 1 I 1 1 1 1 I ATTTCATGATTTTCCCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAA 6277 v.l 6401 tggt'aattataaattggtgatgcttgtttgcaaattgcccactcgtgata I 1 1 ] 1 1 I 1 I 1 1 1 1 II 1 1 1 1 1 11 1 , 1 I 1 ] |. 1 1 1 II 1 ] 1 II II 1 1 l| 1 1 1 I 1 6450 v. 6 6278 I I 1 1 1 1 1 i 1 1 1 1 1 i 1 I 1 1 1 1 Η 1 I 1 1 1 1 [1 1 1 1 1 &amp;#943; 1 I I Η I 1 I 1 1 1 1 1 1 I TGGTAATTATAAATTGGTGATGCTTGTTTGCAAATTGCCCACTCGTGATA 6327 v.l 6451 agtcaacagccaatatttaaaactttgttcgttactggctttaccctaac II 1 II 1 1 j 1 1 II 1 1 I 11 j II ] 1 II 1 1 1 1 II 1 1 1 1 II II 1 1 1 1 1 II 1 1 I II 6500 v „6 6328 ! 1 1 i i 1 I &amp;#943; I 1 1 I ! i 1 &amp;#943; 1 1 I 1 1 I 1 i 1 I 1 I I Π 1 1 I 1 1 I I I I &amp;#943; 1 i I i I I ! 1 1 AGTCAACAGCCAATATTTAAAACTTTGTTCGTTACTGGCTTTACCCTAAC 6377 v.l 6501 tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag | Ij 1 Η 1 1 J 11 1 Η II 1 1 1 1 III 1 I 1 1 1 II 1 1 1 1 1 II II II 1 1 II 1 1 II 1 6550 v. 6 6378 1 ι 1 ) ι i 1 1 1 I 1 1 I 1 I 1 1 i I 1 1 1 ι 1 1 1 1 I I 1 1 1 1 1 1 i &amp;#943; i 1 i 1 1 I 1 I I ! I 1 I TTTCTCTAGTCTACTGTCAATATCATTTTAATGTAATTGATTGTATATAG 6427 v.l 6551 tctcaagaatqqttggtgggcatqagttcctagagaactqtccaaggqtt 11)11)11)111)111 I I I I 11 I ill!1111111111) III 1 1 1 II II I 1 6600 V. β 6428 1 1 ·( 1 1 N ! 1 1 Η 1 1 Η ! Η 1 &amp;#943; If &amp;#943; &amp;#943; I ) &amp;#943; i 1 &amp;#943; &amp;#943; Π 1 I N 1 N I i &amp;#943; Η N I 1 TCTCAAGAATGGTTGGTGGGGATGAGTTCCTAGAGAACTGTCCAAGGGTT 6477 v.l 6601 gggaaaatccaaattctcttcctggctccagcactgattttgtacataaa | 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 II II 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 6650 v. 6 6478 I 1 1 1 I 1 I 1 1 1 I 1 1 t 1 ι I I 1 I t I i I 1 I 1 I 1 I 1 1 l 1 1 I 1 I I I i I 1 I 1 I 1 1 1 I GGGAAAATCCAAATTCTCTTCCTGGcTCCAGCACTGATTTTGTACATAAA 6527 v. 1 6651 cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa 11111111 i i 111111II1! 1111IIIIII 1.11111111111IIIIII11 6700 v. 6 bbzi b CATTAGGCAGGTTGCTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAA 6577 v.l 6701 gtgctaataataatctcagttaccttatctttgtcacagggtgttctttt | 1 1 1 ) 1 1 1 1 I 1 1 1 1 II 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 6750 v. 6 6578 i 1 1 1 1 1 II i 1 1 1 1 ! 1 I 1 1 1 1 1 I ! 1 i I I I 1 1 I 1 i 1 I 1 I 1 I 1 1 i 1 i I 1 1 1 I i GTGCTAATAATAATCTCAGTTACCTTATCTTTGTCACAGGGTGTTCTTTT 6627 v.l 6751 ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc 1 1 II 1 1 1 1 II 1 1 1 1 1! 1 1 I! 1 1 I! 1 1 II 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 6300 v.6 6628 ι ι 1 1 1 1 1 1 ! 1 1 i 1 1 ι &amp;#943; 1 &amp;#943; 1 1 I 1 1 I 1 1 1 i 1 I 1 1 I 1 ! 1 1 i &amp;#943; i 1 I I 1 1 I I i i I TTATGAAGAAAAATTTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTC 6677 v.l 68 01 ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc | I I I I 1 I I I 1 I I 1 I 1 II 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I I 1 1 1 1 II 1 1 II 1 1 1 6850 v. 6 6678 1 1 1 I i t I I I 1 I 1 &amp;#943; 1 1 1 i I I i 1 1 1 1 1 1 Ι·Η 1 I i H I 1 1 1 1 I 1 I 1 1 l ι i i I I ATAAGCAAACCTTTAACTAATTATGTATCTGAAAGTCACCCCCACATACC 6727 v.l 6851 aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca 11111111! 1IIII111II11111111II1111II1111II11IIII111 6900 v. 6 6728 AACTCAACTTTTTTCCTGTGAACACATAAATATATTTTTATAGAAAAACA 6777 v.l 6901 aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat II 1 II II II j II II || &amp;#943; || I II I) | | II | 11 || II 1 | II H | | | | j) 1 II 6950 v.6 6778 i j ι ι ι ι ι ι ι 1 I i 1 &amp;#943; I 1 1 1 1 I I 1 &amp;#943; 1 l &amp;#943; 1 1 I &amp;#943; &amp;#943; 1 1 I 1 1 I 1 1 I I &amp;#943; &amp;#943; 1 &amp;#943; ! I I i i AATCTACATAAAATAAATCTACTGTTTAGTGAGCAGTATGAcTTGTACAT 6827 v.l 6951 gccattgaaaattafctaatcagaagaaaattaagcagggtctttgctata | I I 1 I 1 1 1 II 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 II 1 1 II 1 1 jj II II II j 1 1 7000 v.6 6828 I 1 I i 1 I &amp;#943; 1 I i 1 I 1 I i i I 1 1 1 1 1 I I i 1 1 I 1 1 1 1 ι I 1 1 j 1 &amp;#943; 1 I J I I 1 I 1 I I I GCCATTGAAAATTATTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATA 6877 v.l 7001 caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 H 1 1 1 1 1 1 1 1 1 1 1 1 I 7050 v.6 6878 I 1 1 i I 1 1 I 1 I i 1 1 I I 1 I 1 i I 1 I 1 1 I I 1 I I 1 1 I 1 1 1 I 1 i i I 1 I it I l &amp;#943; 1 I 1 CAAAAGTGTTTTCCACTAATTTTGCATGCGTATTTATAAGAAAAATGTGA 6927 v.l 7051 atttggtggttttattctatcggtataaaggcatcgatattttagatgca 7100 304 v.6 692 8 ATTTGGTGGTTTTATTCTATCGGTATAAAGGCATcGATATTTTAGATGCA 6977 v.l 7101 cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca 7150 nm iiiimi minim mum mu mu mmiim v.6 697 8 CCCGTGTTTGTAAAAATGTAGAGCACAATGGAATTATGCTGGAAGTCTCA 7027 v.l 7151 aataatatttttttcctattttatactcatggaagagataagctaaagag 7200 MMMiMMmmmmmiimmimiM mm m v.6 7028 AATAATATTTTTTTCCTATTTTATACTCATGGAAGAGATAAGCTAAAGAG 7077 v.l 7201 gggacaataatgagaaatgtfcggtgtgcttttctaagcatttaaaacata 7250

I III Μ M 11 Ml Μ I 111 I Ml III I III III III I M Ml 11 Ml III v.6 7078 GGGACAATAATGAGAAATGTTGGTGTGCTTTTCTAAGCATTTAAAACATA 7127 v.l 7251 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc 7300 III! M II111 111 I ill I III 11 III III II III I M III 111 III 111 v.6 7128 ATTGCCAATTGAAACCCTAAATA.TGTTTACATACCATTAAGATATGATTC 7177 v.l 7301 atgtaacaatgttaaattaattataatgggattgggtttgttatctgtgq 7350

MiiiMMMMimmmimmimmmmmiiM v.6 7178 ATGTAACAATGTTAAATTAATTATAATGGGATTGGGTTTGTTATCTGTGG 7227 v.l 7 3 51 tagfcatatatcctagtgttcctatagtgaaataagtagggttcagccaaa 740 0

II III II I! III III III III III III III I M I MI IM III III I III v.6 7228 TAGTATATATCCTAGTGTTCCTATAGTGAAATAAGTAGGGTTCAGCCAAA 7277 , v.l 7401 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga 7450 mMMMmmmmmmmmimmmimm v.6 7278 GCTTTCTTTGTTTTGTACCTTAAATTGTTCGATTACGTCATCAAAAGAGA 7327 v.l 7451 tgaaaggtatgtagaacaggttcacgtgattacctttttcttttggcttg 7500 immMmmmmmmmmmmMmm m v.6 7328 TGAAAGGTATGTAGAACAGGTTCACGTGATTACCTTTTTCTTTTGGCTTG 7377 v.l 7501 gattaatattcatagtagaactttataaaacgtgtttgtattgtaggtgg 7550

I III Μ I Μ M I! Ml III III 11 111 HI III III I III HI Ml I III v.6 7 378 GATTAATATTCATAGTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGG 7427 v.l 7551 tgtttgtattatgcttatgactatgtatggtttgaaaatattttcattat 7600

Ml Μ Μ M Ml Ml III ill 111 III HI Ml I III III II! Ml I Ml v.6 742 8 TGTTTGTATTATGCTTATGACTATGTATGGTTTGAAAATATTTTCATTAT 7477 v.l 7601 acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa 7650 imiMHiiiiMimmimimimmmiimmii v.6 7478 ACATGAAATTCAACTTTCCAAATAAAAGTTCTACTTCATGTAATCCAAAA 7527

Table LIVe. Peptide sequences of MEPLLLGRGL IVYLMFLLLK GNPEPTFSWT KDGNPFYFTD EEIEFIVPKL EHIEQDERVY ' LTVNSLKHAN DSSSSTEIGS GLPTPQVDWN KIGGDLPKGR IVEEPPRWTK KPQSAVISTG ISFTNLQPNH TAVYQCEASN EFFASPEAW SWQKVEEVKP TANLDIRNAT KLRVSPKNPR DGRIIIDGAN LTISNVTLED RSVRLTWEAG ADHNSNISEY VIAVNEVGRS QPSQPSDHHE EYRVTWKPQG APVEWEEETV EDYPDTAPVI HGVDVINSTL

protein coded by 282P1G03 v.6 (SEQ ID NO: 178) FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF MSQKGDLYFA NVEEKDSRND YCCFAAFPRL KANSIKQRKP KLLLPPTESG SESSITILKG ETKENYGKTL KIENVSYQDK GNYRCTASNF SNGILLCEAE GEPQPTIKWR VNGSPVDNHP VHGTILANAN IDWDVRPLI QTKDGENYAT LEGRRYHIYE NGTLQINRTT EEDAGSYSCW IPKLHMLELH CESKCDSHLK HSLKLSWSKD QGIYCCSAHT ALDSAADITQ VTVLDVPDPP IVEFEGNKEE PGRWEELTRV QGKKTTVILP TPPAAPDRNP QNIRVQASQP KEMIIKWEPL TNHTLRVMTP AVYAPYDVKV QAINQLGSGP VKVTWSTVPK DRVHGRLKGY QINWWKTKSL

EYFQIECEAK ASNKLGIAMS RTIVQKMPMK EILLLECFAE LGTATHDFHV FAGDWFPRE WGYSAFLHC VENAIGKTAV GEAFEINGTE -ENLHLSERQN LAPFVRYQFR KSMEQNGPGL DPQSVTLYSG LDGRTHPKEV 60 120 180 240 300 360 420 480 540 600 660 720 780 840 305 HIL'EFSGQRN SGMVPSLDAF SEFHLTVLAY NSKGAGPESE PYIFQTPEGV PEQPTFLKVI 900 KVDKDTATLS WGLPKKLNGN LTGYLLQYQI INDTYEIGEL NDINITTPSK PSWHLSNLNA 960 TTKYKFYLRA CTSQGCGKPI TEESSTLGEG SKGIGKISGV NLTQKTHPIE VFEPGAEHIV 1020 RLMTKNWGDN DSIFQDVIET RGREYAGLYD DISTQGWFIG LMCAIALLTL LLLTVCFVKR 10 8 0 NRGGKYSVKE KEDLHPDPEI QSVKDETFGE YSDSDEKPLK GSLRSLNRDM QPTESADSLV 1140 EYGEGDHGLF SEDGSFIGAY AGSKEKGSVE SNGSSTATFP LRA 1183

Table LVe. Amino acid sequence alignment of 282P1G03 v.1 (SEQ iD NO: 179) and 282P1G03 v.6 (SEQ ID NO: 180) v.l 1 MEPLLLGRGLIVYLMFLLLKFSKAIEI PS S VQQVPTIIKQSKVQVAFPFD I 1 I H I 1 11 I 1 1 I II 1 1 1 1 1 II 1 I I 1 1 1 jl II II 1 1 1 1 1 ! 1 I II I 1 I I 1 1 50 v . 6 1 I ! 1 I 1 II 1 1 1 1 1 I 1 1 1 1 1 1 1 II 1 I 1 II 1 II II 11 111 11 l 1 1 1 1 i 1 1 1 1 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPS SVQQVPTIIKQSKVQVAFPFD 50 v.l SI EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 1 1 1 I I II 1 |l 1 II I II 1 1 1 1 1 1 1 1 1 t 1 1 II 1 1 1 1 1 I 1 II II I 1 1 1 1 1 1 1 1 100 v. 6 51 1 1 1 1 1 1 II II 1 i II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 v. 1 101 SHFQGKYRCFASNKLGIAMSEEIEFIVP SVPKLPKEKIDPLEVEEGDPIV 1 1 1 11 1 1 1 II ! 1 1 II I 1 1 1 1 II 1 1 I ! 1 1 150 v. 6 101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I SHFQGKYRCFASNKLGIAMSEEIEFIVP---------------------- 128 v.l 151 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN . 1 1 1 I 1 1 1 1 1 1 |I 1 I I 1 1 I II 1 I 1 1 1 1 1 1 1 1 200 v. 6 129 - 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 ----------------KLEHIEQDERVYMSQKGDLYFANVEEKDSRN 159 v.l 201 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK I 1 I I I II I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 250 v. 6 ISO 1 1 1 111 1 1 1 1 1 1 1 II 1 1 1 11 I 11 1 1 1 1 1 1 1 I 1111 1 1 1 1 1 1 1 1 I 1111 1 1 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK 209 V. 1 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 300 v. 6 210 1111111111111 I 11111 I 11111II 1 1 1 1 1 1 1 1 1 1 1 1 I II 1 II 1 1 1 1 1 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKI GGDLPKG 259 v.l 301 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT I 1 , 1 I I II 1 I 1 1 I I 1 II II 1 1 I I II I 1 i 1 1 1 1 1 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 1 1 350 v. 6 260 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 I 1 1 1 1 1 1 1 1 1 i 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT 309 v.l 351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR | I I I I I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ) 1 1 1 ) 1 1 1 I Μ 1 1 1 1 I 1 1 1 400 v.6 310 I 1 1 1 1111111II1 I 1 1 1 1 11 I 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR 359 v.l 401 EISFTNLQPNHTAVYQCEASNVHGTILANANIDWDVR.PLIQTKDGENYA 1 i 1 Π I 1 1 i 1 ! H ! ! 1 1 I 1 &#912; ! 1 1 I I 1 &#943; 1 Η ! Η II Η 1 1 1 1 1 i 1 ! 1 i i i i 450 v.6 360 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 II EIS FTNLQ PNHTAVYQCEASNVHGTILANANID WDVRPLIQTKDGENYA 409 v.l 451 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQIHRT 11 1 1 1 1 1 1 1 1 1 I 1 II I 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 I 1 1 1 500 v. 6 410 1 1 1 1 1111 1 I 1 11 It 11 1 1 1111 1 1 1 1 1 1 1111 1 1 1 1 1 1 1 1111II I 1 1 1 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT. 459 v. 1 501 TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPKNPRIPKLHMLEL 1 1 1 I 1 1 1 1 ! 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 , 1 11 1 ! 1 1 1 1 1 1 1 1 1 1 550 v. 6 460 I 1 I 11 I 11111 I 11III II1II1IIII II II11II I 1 1 1 l 1 1 1 1 11 1 1 II TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPKNPRIPKLHMLEL 509 v.l 551 hceskcdshlkhslklswskdgeafeingtedgriiidganltisnvtle Π I II ι | | 11 i Μ 1 Η 11 1 M I ! If 1 Π Η Η 1 1 1 1 1 1 I &#943; f 1 I I! 1 &#943; 1 1 &#943; 600 v. 6 510 111111 111 11 ι 11 Η 111111 I 11 ι 11111 1 Η 1 111 111 1111111 I I HCESKCDSHL KHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE 559 v.l 601 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA I 1 1 1 1 1 1 1 1 1 1 1 I 1 I I I ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 '1 I 650 v. 6 560 1 1 1 1 1 1 1 1 II I 11111 1 1 I 1 i I I II 1 H 11 I I 11 I 111 1 1 I 1 I 1 1 1 1 1 1 1 dqgiyccsahtaldsaaditqvtvldvpdppenlhlsbrqnrsvrltwea 609 v.l 651 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 7 00 306 .v-,'6 610 GADHNSNISEYIWFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF 659 v.l 701 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 750 v. 6 660 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 RVXAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 709 v.l 751 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK ι il I μ ι ι ι ι ι t ι t ι i ι ι ι ι ι | ι | ii ι ι ii t Μ t ι I I ! I 1 1 &#943; i ! 1 ! ’ ι 1 I 800 V . ζ 710 ι 1 1 1 1 i 1 1 1 i ι 1 I 1 ι I 1 ι &#943; ι 1 1 I I ι I ι ι ι ι ι 1 1 ι ι ι 1 i ι 1 LI II Η ι ι 1 1 LKSMEQNGPGLEYRVTWKPQGAPWWEEETVTNHTLRVMTPAVYAPYDVK 759 v. 1 801 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVD VINSTLVKVTWSTVP 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 850 v. 6 760 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLVKVTWSTVP 809 V.l 851 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSGQRNSGMVPSLDA 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 900 v. 6 810 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSGQRNSGMVPSLDA 859 v.l 901 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL 1 1 I 1 I 1 1 > 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι I 1 1 1 1 1 1 1 1 I 1 1 1 > I 1 1 1 1 1 950 v. 6 860 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 ι 1 1 1 1 I 1 1 1 1 1 1 1 1 ι 1 1 1 1 1 1 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL 909 v.l 951 SWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITTPSKPSWHLSNLN 1 1 I 1,. I 1 I I I I 1 1 1 1 1 I I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1000 v. 6 910 1 1 1 Γ 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1- 1 1 1 1 1 1 1 Ξ WGLPKKLNGMLTGYLLQYQIINDTYEIGELMDINITTPS KPSWHLSNLN 959 v.l 1001 ATTKYKF YLRACTS QGCGKP I TEES STLGEGSKG IGKI S GVNLTQKTHPI 1 1 I 1 1 1 I 1 1 I I 11 1 1 1 1 1 1 I 1 11 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 I I 1 1 1 1050 v.6 960 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNLTQKTHPI 1009 v.l 1051 EVFEPGAEHIVRLMTKNWGDMDSIFQDVIETRGREYAGLYLDISTQGWFI 1 1 I I I I I 1 I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1100 v. 6 1010 1 1 1 I 1 1 1 1 1 I II 1 1 1 111 1 111 1 1 1 1 1 1 1 1 1 1 111 111 11 1 1 1 1 1 1 1 1 1 I EVFEPGAEHIVRLMTKNWGDNBSIFQDVIETRGREYAGLYDDISTQGWFI 1059 v.l 1101 GLMCATAT,T,TT,T,T,T,TVGRVKRWGGKYGVKEKRnT.HPnPETn.9VKnFTFR 1150 v. 6 1060 II Η II111 Η 111II!11111111111111111 il1!11Ι&#938;Ι11!1111 GLMCAIALLTLLLLTVCFVKRKRGGKYSVKEKEDLHPDPEIQSVKDETFG 1109 v.l 1151 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA I I 1 I 1 I I I 1 1 1 1 1 I ! 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1' I 1 1 1 I 1 1 ! 1 1 1 1 1 1200 v. 6 1110 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 EYSDSIOEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1159 v.l 1201 YAGSKEKGSVESNGSSTATFPLRA 1224 ι I ! ι ι ι ι ι ι ι ι ι ι η ι ι ι ι ι ι ι ι i v. 6 1160 111 1 1 1 1 i 1 1 1 I II 1 II 1 1 1 1 1 1 1 YAGSKEKGSVESNGSSTATFPLRA 1183

Table Lllf. Nucleotide sequence of transcript variant 282P1G03 v.7 (SEQ ID NO: 181) cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg aatcgtatat agttcaacag tgagtatttt taaggatggc aacattcagg tgcttcaaat tccaaaactc cctcccatgc attagaacac gcgcccccgt acagatcgcg atactgcaaa taaggtctca ttgtcttctt ctaatgttcc gttccaacaa caaattgaat aacccttttt atcccaaacg aaactgggaa ccaaaagaaa aatcctccca atcgaacaag cccggctccc tttcggaggc caaatcatag gctgtaaacc cctgaagagc tcctgttaaa tcataaaaca gtgaagctaa atttcactga aggggcacat tcgctatgtc aaattgaccc aaggcctccc atgaaagagt ggccggctcg ggcgcaggtg tggaactaag aaaagtgaga aatggagccg attctcaaaa gtcaaaagtc aggaaatcca ccatcggata atctcacttt agaagaaata tcttgaagtg acctttacac atacatgagc ggggagaagg ctgtaaactg gggaacttaa ggagacatta cttttacttg gcaattgaaa caagttgcct gaaccaacat attccatcga caagggaaat gaatttatag gaggagggag atttattgga caaaagggag cgcccgaggg caaaccataa tttactgttt agattttcat gaagaggact taccatcttc ttcccttcga tttcgtggac acaattcagg accgctgctt ttccaagtgt atccaattgt tgaatattga atctatactt 60 120 180 240 300 360 420 480 540 600 660 720 780 840 307 i &amp;#906;cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagataaca tctctcatga 1320 gctcttcact ttacatccag agcctcctcg ctggacaaag aagcctcaga gtgctgtgta 1380 tagcaccgga agcaatggca tcttgttatg tgaggctgaa ggagaacctc aacccacaat 1440 caagtggaga gtcaatggct ccccagttga caatcatcca tttgctggtg atgttgtctt 1500 ccccagggaa atcagtttta ccaaccttca accaaatcat actgctgtgt accagtgtga 1560 agcctcaaat gtccatggaa ctatccttgc caatgccaat' attgatgttg tggatgtccg 1620 tccattgata caaaccaaag atggagaaaa ttacgctaca gtggttgggt acagtgcttt 1680 cttacattgc gagttctttg cttcacctga ggcagtcgtg tcctggcaga aggtggaaga 1740 agtgaaaccc ctggagggca ggcggtatca tatctatgaa aatggcacat tgcagatcaa 1800 cagaaccacc gaagaagatg ctgggtctta ctcatgttgg gtagaaaatg ctataggaaa 1860 aactgcagtc acagccaatt tggatattag aaatgctaca aaacttagag tttctcctaa 1920 gaatcctcgt atccccaaat tgcatatgct tgaattacat tgtgaaagca aatgtgactc 1980 acatttgaaa cacagtttga agttgtcctg gagtaaagat ggagaagcct ttgaaattaa 2040 tggcacagaa gatggcagga taattattga tggagctaat ttgaccatat ctaatgtaac 2100 tttagaggac caaggtattt actgctgttc agctcatact gctctagaca gtgctgccga 2160 tataactcaa gtaactgttc ttgatgttcc ggatccacca gaaaaccttc acttgtctga 2220 aagacagaac aggagtgttc ggctgacctg ggaagctgga gctgaccaca acagcaatat 2280 tagcgagtat attgttgaat ttgaaggaaa caaagaagag cctggaaggt gggaggaact 2340 gaccagagtc caaggaaaga aaaccacagt tatcttacct ttggctccat ttgtgagata 2400 ccagttcagg gtcatagccg tgaacgaagt agggagaagt cagcctagcc agccgtcaga 2460 ccatcatgaa acaccaccag cagctccaga taggaatcca caaaacataa gggttcaagc 2520 ctctcaaccc aaggaaatga ttataaagtg ggagcctttg aaatccatgg agcagaatgg 2580 accaggccta gagtacagag tgacctggaa gccacaggga gccccagtgg agtgggaaga 2640 agaaacagtc acaaaccaca cattgcgggt gatgacgcct gctgtctatg ccccttatga 2700 tgtcaaggtc caggctatca atcaactagg atctgggcct gaccctcagt cagtgactct 2760 ctattctgga gaagactatc ctgatacagc tccagtgatc catggggtgg acgttataaa 2820 cagtacatta gttaaagtta cctggtcaac agttccaaag gacagagtac atggacgtct .2880 gaaaggctat cagataaatt ggtggaaaac aaaaagtctg ttggatggaa gaacacatcc 2940 caaagaagtg aacattctaa gatt'ttcagg acaaagaaac tctggaatgg ttccttcctt 3000 agatgccttt agtgaatttc atttaacagt cttagcctat aactctaaag gagctggtcc 3060 tgaaagtgag ccttatatat ttcaaacacc agaaggagta cctgaacagc caacttttct 3120 aaaggtcatc aaagttgata aagacactgc cactttatct tggggactac ctaagaaatt 3180 aaatggaaac ttaactggct atcttttgca atatcagata ataaatgaca cctacgagat 3240 tggagaatta aatgatatta acattacaac tccatcaaag cccagctggc acctctcaaa 3300 cctgaatgca actaccaagt acaaattcta cttgagggct tgcacttcac agggctgtgg 3360 aaaaccgatc acggaggaaa gctccacctt aggagaaggg agtaaaggta tcgggaagat 3420 atcaggagta aatcttactc aaaagactca cccaatagag gtatttgagc cgggagctga 3.480 acatatagtt cgcctaatga ctaagaattg gggcgataac gatagcattt ttcaagatgt 3540 aattgagaca agagggagag aatatgctgg tttatatgat gacatctcca ctcaaggctg 3600 gtttattgga ctgatgtgtg cgattgctct tctcacacta ctattattaa ctgtttgctt 3660 tgtgaagagg aatagaggtg gaaagtactc agttaaagaa aaggaagatt tgcatccaga 3720 cccagaaatt cagtcagtaa aagatgaaac ctttggtgaa tacagtgaca gtgatgaaaa 3780 gcctctcaaa ggaagccttc ggtcccttaa tagggatatg cagcctactg aaagtgctga 3840 cagcttagtc gaatacggag agggagacca tggtctcttc agtgaagatg gatcatttat 3900 tggtgcctac gctggatcta aggagaaggg atctgttgaa agcaatggaa gttctacagc 3960 aacttttccc cttcgggcat aaacacaaca tatgtaagca acgctactgg ttcaccccaa 4020 ccttccatat ttatctgttc aaaggagcaa gaactttcat ataggaatag aaacatgctg 4080 gccgaagatt tcatccagaa gtcaacatcc tgcaattatg ttgaaaagag tagtactttc 4140 ttcaaaatat aaaatgccaa gcacttcagg cctatgtttt gcttatattg ttttcaggtg 4200 ctcaaaatgc aaaacacaaa acaaatcctg catttagata cacctcaact aaatccaaag 4260 tccccattca gtatattcca tatttgcctg attttactat tcggtgtgtt tgcatagatg 4320 ttgctacttg gtgggttttt ctccgtatgc acattggtat acagtctctg agaactggct 4380 fc9gtgacttt gcttcactac aggttaaaag accataagca aactggttat ttaaaatgta 4440 aaaaggaata tgaaagtctt attaaaacac ttcattgaaa atatacagtc taaatttatt 4500 atttaaattt tactagcaaa agtcttaggt gaacaatcaa ctagtatttg ttgagctcct 4560 atttgcccag agatggtcat atttaaacag aagtatacgt ttttcagttt caacatgaat 4620 308 ^ttttttattt ctgtcagtta tgacatccac gagcatcact ttttgtgtct gttttttttt 4680 ttttcttgga ctaaattcaa ctgcatggaa gcggtggtca gaaggttgtt ttatacgaga 4740 acaggcagaa agtgcccatt gttcaggatt ctaatagcta catctactta atatcttcat 4800 ttctaaattg actgctttta cctttttctc atgtttatat aatggtatgc ttgcatatat 4860 ttcatgaata cattgtacat attatgttaa tatttacaca atttaaaata tagatgtgtt 4920 ttattttgaa gtgagaaaat gaacattaac aggcatgttt gtacagctag aatatattag 4980 taagatactg tttttcgtca ttccagagct acaactaata acacgaggtt ccaaagctga 5040 agactttgta taaagtattt gggttttgtt cttgtattgc tttctttcaa cagtttcaaa 5100 ataaaatatc atacaaatat tgagggaaat gttttcatat ttttcaaaat aggtttttat 5160 tgttgaatgt acatctaccc cagcccctca aaagaaaaac tgttfcacata gaaattccta 5220 cacatacgtt tgcgtatatg ttattttaaa catctttgtg gtgagaattt tttccccgat 5280 attctccttc tgtcaaagtc agaacaaatt cagggaattt attttctggc agttgtgctc 5340 cagtcctttt aaaattgtac atgaacatgt tttagaaaca atatggagga tgatgcatac 5400 atgtcggtca agttcagcgc tcgacatttt atggaaagat ttttttaacc ttaccacgaa 5460 atacttaact actgtttaag tgaattgact tatttcactt tagtttttga actgtgatta 5520 ttggtatact gttatatcct caacttggat ttatggtaac cccttttagt tcatggagac 5580 caaaatttgg ggtatttata atagtcagcg caggaatgca catggaatat ctacttgtcc 5640 ttttgaacct cacgagtcat ccagaatgta tagacaggaa aagcatgtct tatttaaaac 5700 tgtaatttat gggctcagga tctgaccgca gtcccgggag taagcatttc aaagggggaa 5760 ggcagtgtgg tccctaccct gtgtgaatgt gaggatgtag acatccatca gtgcaactcg 5820 agctccatcc tcctccgatt tctaaggctc cagttttctg gagggacagt catcatgttt 5880 tgatttatct gggagaaaac tgtggtgcac agcttgtgag gagggcaagg ttgtgacgtt 5940 cgagcttagt tctggtgtta ttctgtctcc tcttctttgt catcagccaa aacgtggttt 6000 ttaaagagag tcatgcaggt tagaaataat gtcaaaaata tttaggaatt taataacctt 6060 taagtcagaa actaaaacaa atactgaaat attagctctt cctacacttc gtgttcccct 6120 ttagctgcct gaaaatcaag attgctccta ctcagatctt ctgagtggct aaaacttatg 6180 gatatgaaaa atgagattga atgatgacta tgctttgcta tcattgttac ctttcctcaa 6240 tactatttgg caactactgg gactcttcag cacaaaagga atagatctat gattgaccct 6300 gattttaatt gtgaaattat atgattcata tattttatga atcagaataa ccttcaaata 6360 aaataaatct aagtcggtta aaatggattt catgattttc cctcagaaaa tgagtaacgg 6420 agtccacggc gtgcaatggt aattataaat tggtgatgct tgtttgcaaa ttgcccactc 6480 gtgataagtc aacagccaat atttaaaact ttgttcgtta ctggctttac cctaactttc 6540 tctagtctac tgtcaatatc attttaatgt aattgattgt atatagtctc aagaatggtt 6600 ggtgggcatg agttcctaga gaactgtcca agggttggga aaatccaaat tctcttcctg 6660 gctccagcac tgattttgta cataaacatt aggcaggttg cttaaccttt ttatttcaaa 6720 ctctctcaac tctaaagtgc taataataat ctcagttacc ttatctttgt cacagggtgt 6780 tcttttttat gaagaaaaat ttgaaaatga taaaagctaa gatgccttct aacttcataa 6840 gcaaaccttt aactaattat gtatctgaaa gtcaccccca cataccaact caactttttt 6900 cctgtgaaca cataaatata tttttataga aaaacaaatc tacataaaat aaatctactg 6960 tttagtgagc agtatgactt gtacatgcca ttgaaaatta ttaatcagaa gaaaattaag 7020 cagggtcttt gctatacaaa agtgttttcc actaattttg catgcgtatt tataagaaaa 7080 atgtgaattt ggtggtttta ttctatcggt ataaaggcat- cgatatttta gatgcacccg 7140 tgtttgtaaa aatgtagagc acaatggaat tatgctggaa gtctcaaata atattttttt 7200 cctattttat actcatggaa gagataagct aaagagggga caataatgag aaatgttggt 7260 gtgcttttct aagcatttaa aacataattg ccaattgaaa ccctaaatat gtttacatac 7320 cattaagata tgattcatgt aacaatgtta aattaattat aatgggattg ggtttgttat 7380 ctgtggtagt atatatccta gtgttcctat agtgaaataa gtagggttca gccaaagctt 7440 tctttgtttt gtaccttaaa ttgttcgatt acgtcatcaa aagagatgaa aggtatgtag 7500 aacaggttca cgtgattacc tttttctttt ggcttggatt aatattcata gtagaacttt 7560 ataaaacgtg tttgtattgt aggtggtgtt tgtattatgc ttatgactat gtatggtttg 7620 aaaatatttt cattatacat gaaattcaac tttccaaata aaagttctac ttcatgtaat 7680 ccaaaa 7686

Table LHIf. Nucleotide sequence alignment of 282P1G03 v.1 (SEQ ID NO: 182) and 282P1G03 v.7 (SEQ ID NO: 183) v.l 1' cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg I 1 I I I I I II I I 1 1 1 I 1 II I 1 1 1 1 1 II 1 | 1 1 1 1 1 II 1 1 1 1 1 1 (I II I 1 I I 1 50 v.7 1 1 11 1 I 11 1 1 1 1 1 11 1 I 1 1 11 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II I 1 1 1 1 1 CGGACCCTGCGCGCCCCCGTCCCGGCTCCCGGCCGGCTCGGGGGAGAAGG 50 v.l 51 cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg 1 111111 1 1 1 1 1 1 1 1 1 1 I i 11111 1 1 1 1 1 1 1 111 i 11 I I 1 1 1 1 i 1 1 1 I I I 100 v.7 51 ! i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 CGCCCGAGGGGAGGCGCCGGACAGATCGCGTTTCGGAGGCGGCGCAGGTG 100 309 v.l 101 ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcatag I II 1 II I 1 II II I 1 II II I 1 II 1 1 I 1 1 I II I II 1 1 1 1 ] 1 1 1 1 i II 1 1 1 1 1 15 0 v.7 101 J ! Η H 11 1 1 1 I 1 ι I 1 ι II ι 1 &amp;#943; &amp;#943; ι i ι 1 1 U 1 ι 1 l Η &amp;#943; 1 ι I I Η Π 1 Η 1 1 CTGTAAACTGCAAACCATAATCCTGTCTTAATACTGCAAACAAATCATAG 15 0 v.l 151 tggaactaaggggaacttaatttactgtttccaggttaactaaggtctca 1 1 1 II ! 1 f 1 1 1 1 1 I | I j j 1 1 j 1 1 1 1 1 1 I I 1 I 1 I 1 j 1 I I I 1 | 1 I 1 1 1 1 1 1 I 200 v.7 151 1 1 1 1 1 1 1 l ι ι j s SI II S 1 ι I 1 Η Η 1 1 II I 1 ι ι ι ι 1 I ι II 1 I 1 { ! Η U 1 TGGAACTAAGGGGAACTTAATTTACTGTTTCCAGGTTAACTAAGGTCTCA 200 v.l 201 gctgtaaaccaaaagtgagaggagacattaagatttfccatfccttaccggg ι || i I 1 I [ ι Η Η 1 i Hi Hi! HI &amp;#943; llllillNHIIIIlllll II i I 250 v.7 201 1 1 1 1 II π π II II1 I II ι Π US I Π II 1 11 I Π 1 II 1 I ( i &amp;#943; H i 1 1 Π GCTGTAAACCAAAAGTGAGAGGAGACATTAAGATTTTCATTCTTACCGGG 250 v.l 251 ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact I I I jj Ii II 1 I I I 1 I I I ! I Η Π [ I 1 I 1 1 I H II 1 II II || 1 l| 1 II I ] 1 300 v.7 251 1 1 1 &amp;#943; II Η Η Η II 1 II Π 1 Π ι 1 I I ! 1 I 1 Π I Η Η Π Π Η 1 ι ι II 1 I TTGTCTTCTTCCTGAAGAGCAATGGAGCCGCTTTTACTTGGAAGAGGACT 300 v.l 301 aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa 1 ) 1 1 1 1 1 1 1 1 1 1 i 1 1 1 I 1 1 1 ! 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 I 1 1 1 350 v.7 301 I II 1 I Η I Π Π 1 i Η Η 1 1 1 I 1 II I II 1 1 1 1 1 1 1 Η ι I ι Π 1 1 I I 1 i u AATCGTATATCTAATGTTCCTCCTGTTAAAATTCTCAAAAGCAATTGAAA 350 v.l 3 51 taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc 1 1 1 1 1 1 1 1 1 1 1111 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 II 1 1 1 11111111 1 1 1 1 1 1 1 1 400 v. 7 351 &amp;#943; I &amp;#943; 1 Π 1 Π Π Η Π I 1 1 I 1 Π Π I I 1 1 1 1 1 1 1 1 1 1 1 1 1 Π Π I 1 I I 1 1 I TACCATCTTCAGTTCAACAGGTTCCAACAATCATAAAACAGTCAAAAGTC 400 v.l 401 caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagctaa 11111! 1111111!11!Ill 1!1 Η II 11! III!! 1111II11 il 11! I! CAAGTTGCCTTTCCCTTCGATGAGTATTTTCAAATTGAATGTGAAGCTAA 450 v.7 401 450 v.l 451 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 11111111111111! 111111111111111111111111 II 11111'l 111 500 v. 7 451 AGGAAATCCAGAACCAACATTTTCGTGGACTAAGGATGGCAACCCTTTTT 500 v.l 501 atttcactgaccatcggataattccatcgaaeaattcaggaacattcagg 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! I 1 550 v. 7 501 1 1 i ! 9 1 1 I ι H I 1 1 Η II ι ι ι U t I 1 1 i 1 1 i I 1 Η H i i Η Η I 1 1 1 1 1 1 ATTTCACTGACCATCGGATAATTCCATCGAACAATTCAGGAACATTCAGG 550 v. 1 551 atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt 11111 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1111i!S1 I 1 1 1 1 f 1 600 V.7 551 1 1 1 Π Π Π I 1 ι Η Π II H I Π 1 1 II 1 II &amp;#943; &amp;#943; II i ii H II Π 1 ι II I 1 1 ATCCCAAACGAGGGGCACATATCTCACTTTCAAGGGAAATACCGCTGCTT 600 v-1 SOI tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag 1 1 I 1 II t 1 I 1 I 1 1 1 1 1 I 1 1 1 1 1 1 I I 1 1 I 1 I 1111!|I|I! | | | ! | | | 1 1 | 650 v.7 601 1 1 1 1 1 1 1 1 1 1 1111 1 1 1 1 1 I 1 1 1 I 1 1 ι &amp;#943; ι 1 I ! 1ι 1 111 1 1 I 1 II 1 1 1 1 1 1 TGCTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650 v.l 651 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg 1111111111 I 1 1 1 1 1 IS 1 1111 I I 111111111HI 1II I 1 1 1 1 1 1 1 1 1 700 v.7 651 i I Ι ι I Π 1 I 1 1 H I I 1 1 1 1 1 1 1 I 1 1.1 1 1 1 1 1 1 1 I π I π 1 η π 1 I I 1 1 I TTCCAAGTGTTCCAAAAcTCCCAAAAGAAAAAATTGACCCTCTTGAAGTG 700 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 1 1 I 1 1 I I 1 I I 1 1 II 1 I 1 1 11 1 1 J 1 II 1 1 j| 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 I 1 1 750 v.7 701 1 1 1 1 1 1 1 1 1 1 1 1 1 ! II 1 1 I 1 1 1 1 1 &amp;#943; 1 I 1 1 I 1 1 1 I I I 1 1 ! 1 1 1 &amp;#943; 1 1 1 1 I I 1 GAGGAGGGAGATCCAATTGTCCTCCCATGCAATCCTCCCAAAGGCCTCCC 750 v. 1 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 1 1 1 1 1 1 1 I I I 1 1 I 1 1 1 I 1 1 1 1 I 1 I! 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 I 1 I 1 1 I 1 1 1 800 v. 7 751 I 1II11 11 1111 1 1 1 1 II I 1 I 1 ι 1 1 1 1 11 I 1 I 1 I 1 1 111 1 1 1 I 1 1 I 1 1 1 1 ACCTTTACACATTTATTGGATGAATATTGAATTAGAACACATCGAACAAG ' 800 v.l 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg 1 1 I II1 1 1 I I I I I 1 1 I 1 I 1 1 1 I 1 I I I ! 1 I 1 1 M 1 1 1 1 1 1 tI 11 I 1 I 1 1&amp;#906; 1 850 v.7 801 ! 1 ( 1 i 1 1 i U 1 hi 1 i &amp;#943; I 1 I 1 ' ! ! N ! ! 1 I I! 1 11 ι 1 1 1 1 &amp;#943; 1 1 1 I &amp;#943; 1 ! i ! ATGAAAGAGTATACATGAGCCAAAAGGGAGATCTATACTTCGCAAACGTG 850 v.l 851 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag 1 I I 1 1 1 1 II 1 1 1 I I 1 1 1 1 1 1 I 1 I 1 I I 11 I 1 j 1 j j 1 I 1 1 1 1 1 1 |l 1 1 1 i ! 1 900 v.7 851 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GAAGAAAAGGACAGTCGCAATGACTACTGTTGCTTTGCTGCATTTCCAAG 900 310 v.l 901 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt

IIIIIII 111 111111 III III 11111111111II111111111111 III

v.7 901 ATTAAGGACTATTGTACAGAAAATGCCAATGAAACTAACAGTTAACAGTT v.l 951 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca

III III I III II1111111 llll 111 l.l III 11111111 Η111111 III

v.7 951 TAAAGCATGCTAATGACTCAAGTTCATCCACAGAAATTGGTTCCAAGGCA v.l 1001 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag

111IIIIII111111II III 1111111111111IIII111111111 Hl I

v.7 1001 AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG v.l 1051 tqqcaqtqaqtcttcaattaccatcctcaaaggggaaatcttgctgcttg III llll Hill! I inimil! Ill Hill HI III llll I Illllll

v.7 1051 TGGCAGTGAGTCTTCAATTACCATCCTCAAAGGOGAAATCTTGCTGCTTG v.l 1101 aqtqttttqctaaagqcttqccaactccacaggttgattggaacaaaatt

1111111 III 111111 111 III 111111 III 1111111111111111 III

v.7 1101 AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGGAACAAAATT v.l 1151 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac 11111111111111111111111111111111111 H 1111111111111

v.7 1151 GGTGGTGACTTACCAAAGGGGAGAGAAACAAAAGAAAATTATGGCAAGAC v.l 1201 tttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca 111II111Ii 1111!11II1111111111111IIII1111II11111111

v.7 12 01 TTTGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA v.l 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta

-I111 III III 1111111 III 11111111 HI 111111111111111 III I

v.7 12 51 CAGCCAGCAATTTCTTGGGAACAGCCACTCACGATTTTCACGTTATAGTA v.l 1301 ga------------------------------------agagcctcctcg ii iimiiiiiii

v.7 1301 GAAGataacatctctcatgagctcttcactttacatccagAGCCTCCTCG v.l 1315 ctggacaaagaagcctcagagtgctgtgtatagcaccggaagcaatggca

1111 III HI 111111 III 111 111111 111 1111111111111111 III

v.7 13 51 CTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCACCGGAAGCAATGGCA v.l 1365 tcttgfetatgtgaggctgaaqgagaacctcaacccacaatcaaqtggaga 111IIII1111! U 11II1Ι&amp;#938;Π 1IIII11111111II111! I! III111

v.7 1401 TCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCACAATCAAGTGGAGA v.l 1415 gtcaatggctccccagttgacaatcatccatttgctagtgatgttgtctt II III 11 III 1111111 III III 111II HI 11111111! 1111111111

v.7 1451 GTCAATGGCTCCCCAGTTGACAATCATCCATTTGCTGGTGATGTTGTCTT v.l 1465 ccccagggaaatcagttttaccaaccttcaaccaaatcatactgctgtgt 111111111i IIIIIIIIII111111111111II i II I! I! 111111111

v.7 1501 CCCCAGGGAAATCAG TTTTACCAACCTTCAACCAAATCATACTGCTGTGT v.l 1515 accagtgtgaagcctcaaatgtccatggaactatccttgccaatgccaat

IIIIII11II1111111 III HI III11! 111111II1111! II11 III I

v.7 1551 ACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCCTTGCCAATGCCAAT v.l 1565 attgatgttgtggatgtccgtccattgatacaaaccaaagatggagaaaa

Hili π mu 11 iiimmin iimiiiiiii ι hi in nm v.7 1601 attgatgttgtggatgtccgtccattgatacaaaccaaagatggagaaaa v.l 1615 ttacgctacagtggttgggtacagtgctttcttacattgcgagttctttg 950 950 1000 1000 1050 1050 1100 1100 1150 1150 1200 1200 1250 1250 1300 1300 1314 1350 1364 1400 1414 1450 1464 1500 1514 1550 1564 1600 1614 1650 1664 311 . ν,.7 1651 TTACGCTACAGTGGTTGGGTACAGTGCTTTCTTACATTGCGAGTTCTTTG 1700 v.l 1665 cttcacctgaggcagtcgtgtcctggcagaaggtggaagaagtgaaaccc I I I 1 1 I I 1 1 I 1 1 1 II 1 I 1 !I I 1 1 II 1 I 1 1 1 1 1 I 1 II 1 1 I i II 1 1 II II 1714 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 v.7 17 01 CTTCACCTGAGGCAGTCGTGTCCTGGCAGAAGGTGGAAGAAGTGAAACCC 1750 v.l 1715 ctggagggcaggcggtatcatatctatgaaaatqqcacattgcagatcaa II 1 1 I 1 I 1 1 I 1 I 1 1 1 1 II I 1 1 1 1 j 1 I ι&#912; I I 1 1 1 1 ) j I 1 II II II I 1 1 1 1 I 1764 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 .v.7 1751 CTGGAGGGCAGGCGGTATCATATCTATGAAAATGGCACATTGCAGATCAA 1800 v.l 1765 cagaaccaccgaagaagatgctgggtcttactcatgttgggtagaaaatg | 1 I 1 1 I 1 i 1 II 1 II 1 l| II 1 ) II II I 1 1 I 1 11 1 II I II I 1 1 1 1 I 1 1 II I 1 1814 I 1Γ1 1 1 i 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 11111111 1 1 111 1 1 1 1 1 1 1 1 11 v.7 1801 CAG7\ACCACCGAAGAAGATGCTGGGTCTTACTCATGTTGGGTAGAAAATG 1850 v.l 1815 ctataggaaaaactgcagtcacagccaatttggatattagaaatgctaca 1 I I I I || 1 || 1 1 1 1 1 II 1 1 1 I 1 II 1 1 I 1 II 1 l| |l 1 1 II || I II 1 II I 11 1864 1 1 I II 1 1 1 1 1 1 1 1 1 1 1 I 1 1 II 1 1 I 1 1 1 I I 1 1 1 1 1 I 1 1 I I I 1 1 I 1 1 1 ι 1 1 1 v.7 1851 CTATAGGAAAAACTGCAGTCACAGCCAATTTGGATATTAGAAATGCTACA 1900 v.l 1865 aaacttagagtttctcctaagaatcctcgtatccccaaattgcatatgct 1 I II 1 I 1 1 1 1 1 1 I I I 1 l| 1 1 1 I 1 I 1 1 I I 1 1 I 1 1 j 1 1 1 1 II 1 1 1 II |l 1 I 1 1914 1 I 1 1 1 1 | 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 v.7 1901 AAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCCAAATTGCATATGCT 1950 v.l 1915 tgaattacattgtgaaagcaaatgtgactcacatttgaaacacagtttga I 1 II 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 I 1 1 1 1 1 1 1 1 1 1964 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 .1 1 1 1 1 1 1 I v.7 1951 TGAATTACATTGTGAAAGCAAATGTGACTCACATTTGAAACACAGTTTGA 2000 v.l 1965 agttgtcctggagtaaagatggagaagcctttgaaattaatggcacagaa 1 1 1 1 1 1 I 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2014 1 1 I 1 ι 1 &#943; ι ι ι I I 1 1 1 1 i 1 I 1 ! 1 1 1 1 1 1 I I 1 I I 1 1 1 1 1 I 1 1 I 1 I i I 1 I 1 &#943; > v.7 2 001 AGTTGTGCTGGAGTAAAGATGGAGAAGCCTTTGAAATTAATGGCACAGAA 2050 v.l 2015 gatggcaggataattattgatggagctaatttgaccatatctaatgtaac 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 I 1 2064 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 v.7 2051 GATGGCAGGATAATTATTGATGGAGCTAATTTGACCATATCTAATGTAAC 2100 v.l 2065 tttagaggaccaaggtatttactgctgttcagctcatactgctctagaca 1 1 1 1 1 1 1 1 1 1 111 1 I 1 1 1 1 1 1 li 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 II &#943; 2114 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.7 2101 TTTAGAGGACCAAGGTATTTACTGCTGTTCAGCTCATACTGCTCTAGACA 2150 v.l 2115 gtgctgccgatataactcaagtaactgttcttgatgttccggatccacca II 1 1 II 1 1 1 1 111 II 1 1 II 1 1 1 1 1 1 1 I! 1 1 1 1 1 1 1 1 I I 1 II 1 II 11 1 1 1 1 2164 1 1 1 1 1 I 1 I 1 I 1 1 1 1 1 1 ll 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I I 1 1 I 1 1 ! 1 1 1 1 1 1 v.7 2151 GTGCTGCCGATATAACTCAAGTAACTGTTCTTGATGTTCCGGATCCACCA *’ ) 2200 v.l 2165 gaaaaccttcacttqtctqaaaqacaqaacaggagtgttcggctgacctg ι I I ι ι π I I ι I 1 1 1 1 I J lillllll 111 1 I I III II II I lillllll 1 1 1 2214 1 1 II 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 II I v.7 2201 GAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGTGTTCGGCTGACCTG , 2250 v.l 2215 ggaagctggagctgaccacaacagcaatattagcgagtatattgttgaat 1 II II II II III II 1 1 1 1 1 1 1 1 II 1 11111111 II II 111 1 1 ill II 11 1 2264 1 II II 1 I 1 I 1 111 1 11 1 II II II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 II I 1 v.7 2251 GGAAGCTGGAGCTGACCACAACAGCAATATTAGCGAGTATATTGTTGAAT 2300 v.l 2265 ttgaaggaaacaaagaagagcctggaaggtgggaggaactgaccagagtc ! 1111! 1 ll! 1II1! ii 1! 111 U 1!!1!li!1!! 1!! 1 &#943;! II1IIII11 v.7 23 01 TTGAAGGAAACAAAGAAGAGCCTGGAAGGTGGGAGGAACTGACCAGAGTC 2314 2350 v.l 2315 caaggaaagaaaaccacagttatcttacctttggctccatttgtgagata 1 i 1 11 1 1 I j II 1 1 1 1 I II II 1 1 1 1 I 1 1 1 1 I 1 I 1 1 II II I 1 1 1 1 I 1 1 I II 1 2364 1 1 1 I 1 1 1 1 1 I I 1 1 1 1 i 1 I 1 1 1 1 ! 1 1 1 II 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 v.7 -2351 CAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCTCCATTTGTGAGATA 2400 v.l 23 65 ccagttcagggtcataqccgtgaacgaagtaqggagaagtcagcctag'cc mill! II II 1 1 I I I 1 I I 1 1 1 I I 111! II HI III I! Ill I II H HI 1 2414 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 V.7 2401 CCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAGAAGTCAGCCTAGCC 2450 v.l 2415 agccgtcagaccatcatgaaacaccaccagcagctccagataggaatcca 2464 312 v.7 2451 AGCCGTCAGACCATCATGAAACACCACCAGCAGCTCCAGATAGGAATCCA 2500 v.l 2465 caaaacataagggttcaaacctctcaacccaaggaaatgattataaagtg ! 1 I 1 t 1 I I 1 1 1 II I I 1 I I I I I I ! 1 I I 1 1 I I ! I I j 1 1 I I i i I I 1 II i j 1 1 1 2514 v.7 2501 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I l 1 1 1 I 1 CAAAACATAAGGGTTCAAGCCTCTCAACCCAAGGAAATGATTATAAAGTG 2550 v. 1 2515 ggagcctttgaaatccatggagcagaatggaccaggcctagagtacagag I i 1 1 I 1 1 1 1 1 1 II 1 1 1 I 1 1 1 1 1 I 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 II II II I 1 1 1 II 25 64 v.7 2551 I 1 I 1 1 i 1 i 1 ι [ 1 &#943; 1 i ι ! i i i I 1 ! 1 I I 1 1 S 1 1 I 1 1 1 1 ι 1 &#943; 1 } 1 1 1 I 1 1 1 1 1 GGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGGCCTAGAGTACAGAG 2600 v.l 2565 tgacctggaagccacagggagccccagtggagtgggaagaagaaacagtc I 1 1 1 I 1 1 I 1 1 I 1 1 1' 1 1 1 1 1 1 1 1 ! 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 l 1 1 1 ! 1 1 1 1 1 1 1 2614 v.7 2601 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i I 1 1 1 1 1 1 1 1 I 1 TGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGGAAGAAGAAACAGTC 2650 v.l 2615 acaaaccacacattgcgggtgatgacgcctgctgtctatgccccttatga | I I I I I I I I I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 j I I 1 I 1 1 1 1 1 1 I Il- 2664 v.7 2651 Il 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 ACAAACCACACATTGCGGGTGATGACGCCTGCTGTCTATGCCCCTTATGA 2700 v.l 2665 tgtcaaggtccaggctatcaatcaactaggatctgggcctgaccctcagt 1 1 I 1 1 II 1 1 1 1 11 1 1 j 1 II 1 1 1 1 1 1 1 1 ! [ 1 1 1 1 II 1 1 1 1 1 II 1 1 I 1 I II 1 2714 v.7 2701 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TGTCAAGGTCCAGGCTATCAATCAACTAGGATCTGGGCCTGACCCTCAGT 2750 v.l 2715 cagtgactctctattctggagaagactatcctgatacagctccagtgatc 1 III II1111111111IIII II II 1 11 1 1 1 1II11 1 1 II 1 I 1 11 II II 1 1 2764 v.7 2751 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 CAGTGACTCTCTATTCTGGAGAAGACTATCCTGATACAGCTCCAGTGATC 2800 v.l 2765 catggggtggacgttataaacagtacattagttaaagttacctggtcaac 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 2814 v.7 2801 11111111111111111111111111111111111111111111111111 CATGGGGTGGACGTTATAAACAGTACATTAGTTAAAGTTACCTGGTCAAC 2850 v.l 2815 agttccaaaggacagagtacatggacgtctgaaaggctatcagataaatt II 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 II 1 1 1 II 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2864 v.7 2851 I 1 1 I 1 II 1 1 1 1 1 1 1 ! 1 1 ii 1 1 I I 1 1 1 1 II 1 I 1 11 I 1 1 II 1 1 1 1 1 1 I 1 1 1 I AGTTCCAAAGGACAGAGTACATGGACGTCTGAAAGGCTATCAGATAAATT 2900 v.l 2865 ggtggaaaacaaaaagtctgttggatggaagaacacatcccaaagaagtg 1111III 1 1 1 1 1 1 ! 1 1 1 1 I! I 1 1 1 1 1 1 1 1 1II I 1 1 1 1 1 1 I 1 1 1 1 1 11 1 1 1 2914 v.7 2901 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 GGTGGAAAACAAAAAGTCTGTTGGATGGAAGAACACATCCCAAAGAAGTG 2950 v.l 2915 aacattctaagattttcaggacaaagaaactctggaatggttccttcctt 1 1 1 1 1 1 1 &#943; II 1 1 1 1 !! 1 1 1 I &#943; 1 1 1 1 1 1 &#943; 1) 1 1 1 ! 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 2964 v.7 2951 1 1 111J 1 1 1 I 1 1 1 1 1 1 &#943; 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 Μ 1 1 1 1 1 1 AACATiCTAAGATTTTCAGGACAAAGAAACTCTGGAATGGTTCCTTCCTT 3000 v.l 2965 agatgcctttagtgaatttcatttaacagtcttagcctataactctaaag 1 1 1 1 1 1 1 1 1 I 1 1 1 11 11 11 1 1 1 II 1 11 1 1 11 1 II1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3014 v.7 3001 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AGATGCCTTTAGTGAATTTCATTTAACAGTCTTAGCCTATAACTCTAAAG 3050 v.l 3015 gagctggtcctgaaagtgagccttatatatttcaaacaccagaaggagta 1 II1111 I 1 1 1 1 I 1 I 1111! 1 1 1111 1 1 1 11!11 1 1 I 1 1 1 1 1 1 1 1 111 I 1 3064 v.7 3051 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 GAGCTGGTCCTGAAAGTGAGCCTTATATATTTCAAACACCAGAAGGAGTA 3100 v.l 3065 cctgaacagccaacttttctaaaggtcatcaaagttgataaagacactgc 1 1 1 1 1 1 1 11 II 1 1 I 1 1 1 11 II1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 3114 v.7 3101 1 1 I 1 1 1 1 1 1 i 1 1 1 1 1 I I 1 i 1 1 ι 1 1 1 1 I I 1 I I J I j 1 I 1 1 &#943; 1 &#943; ι 1 1 1 J 1 1 1 I CCTGAACAGCCAACTTTTCTAAAGGTCATCAAAGTTGATAAAGACACTGC 3150 v.l 3115 cactttatcttggggactacctaagaaattaaatggaaacttaactggct 1 1 1 ! I 1 I 1 I 1 1 1 1 II i 111 ! 11 II1 I I 1 I 11 I 11 1 11 1 I I 1 I I 1 1 1 I lil 3164 v.7 3151 1 1 I I -I 1 i 1 1 i 1 I 1 < i 1 1 Ι &#906; I i 1 ! ι I ι I 1 1 1 i 1 I 1 1 1 I 1 1 <· I 1 1 1 1 1 1 i 1 CACTTTATCTTGGGGACTACCTAAGAAATTAAATGGAAACTTAACTGGCT 3200 v.l 3165 atcttttgcaatatcagataataaatgacacctacgagattggagaatta 1 1 I 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 3214 v.7 3201 1 1 1 11111 J 1 1 1 1 1 1 1 I II 1 1 1 1 IJ 1111 1 1 ) ) 1 1 1 1 J 11 1 1 1 1 1 1 1 1 11 ATCTTTTGCAATATCAGATAATAAATGACACCTACGAGATTGGAGAATTA 3250 313 "vr^z -Λ- v.r 3215 aatgatattaacattacaactccatcaaagcccagctggcacctctcaaa I I II | I I I I I I I | 1 I I II I | I I I II | I I 1 I I II I I 1 | I | I I I I || |i i 1 | 3264 v.7 3251 1 N ! i I 1 II 1 i 1 ι 1 1 I I i &#943; U &#943; &#943; I I i 1 1 ! 1!1 1 1 ! ! i I 1 i 1 ι1 i 11 U I I AATGATATTAACATTACAACTCCATCAAAGCCCAGCTGGCACCTCTCAAA 3300 v.l 3265 cctgaatgcaactaccaagtacaaattctacttgagggcttgcacttcac | I ! I I I 1 1 1 I 1 I | | 1 1 1 I I I I 1 1 1 1 j 1 1 1 1 1 I j 1 I 1 1 1 1 1 1 1 1 1 1 I) 1 1 i 3314 v.7 3301 1 1 1 1 ι ι ι ι ι 1 ι 1 1 1 1 I 1 1 1 |-1 1 it I I 1 ! ! 1 1 1 1 1 ι I ι I ι 1 ι 1 1 1 1 1 1 1 ! ! CCTGAATGCAACTACCAAGTACAAATTCTACTTGAGGGCTTGCACTTCAC 3350 v. 1 3315 agggctgtggaaaaccgatcacggaggaaagctccaccttaggagaaggg 1 1 1 1 II 1 1 1 1 I 1 |! II l| II If 1 1 1 II I 1 1 II II 1 II 11 II I 1 I l| 1 1 II 3364 v.7 3351 1 H H 1 1 U 1 it 1 1 1 1 Π 1 i 1 1 H 1 1 1 H i ι I 1 1 I I 1 I 1 I II 1 l &#943; 1 1 I 1 1. AGGGCTGTGGAAAACCGATCACGGAGGAAAGCTCCACCTTAGGAGAAGGG 3400 v.l 3365 agtaaaggtatcgggaagatatcaggagtaaatcttactcaaaagactca | 1 11 II 1 11 1 1 1 1 II j l 1 II II 1 1 1 1 1 1 II II 1 1 II 1 SI 1 1 III 1 1 I 1 1 1 3414 v.7 3401 I ι 1 I i t I ι ι &#943; 1 1 Η 1 &#943; 1 i 1 I I 1 ! &#943; II J 1 &#943; 1 1 Π 1 1 1 1 il 1 U 1 l H 1 I 1 1 AGTAAAGGTATCGGGAAGATATCAGGAGTAAATCTTACTCAAAAGACTCA 3450 v.l 3415 cccaataoaaqtatttgagccgggagctgaacatatagttcgcctaatga II ιι1 I 1&#970;ιΤ&#970;ι 1 1 I I II || II 111 Ii 1 I 11 Η 11 11 1 1 H ! ! 1 Η 1 1 1 I 3464 v.7 3451 1 H U 1 II II I I I 1 II I 1 ! 1 I 1 l ι &#943; 1 &#943; I 1 1 1 iΜ II 1 1 1 1 1 t II &#943; 1 &#943; i u CCCAATAGAGGTATTTGAGCCGGGAGCTGAACATATAGTTCGCCTAATGA 3500 v.l 3465 ctaagaattggggcgataacgatagcatttttcaagatgtaattgagaca. 1II11IIII11i111111IIiIIIIII &#943; 1 hl II&#943; IIili! 111II li 111 3514 v.7 3501 CTAAGAATTGGGGCGATAAcGATAGCATTTTTCAAGATGTAATTGAGACA v.l 3515 agagggagagaatatgctggtttatatgatgacatctccactcaaggctg II II II II 1 1 ] 1 1 1 1 1 1 1 1 1 1 1 II 11 1 1 II 1 1 1 I II 1 1 )| 11 II 1 1 1 I II 3564 v. 7 3551 I 1 1 1 I I 1 I I 1 1 I I I I I I I I 1 &#943; ι 1 &#943; 1 1 ι 1 it 1 1 1 1 1 I I 1 1 1 1 1 if f f 1 1 1 1 AGAGGGAGAGAATATGCTGGTTTATATGATGACATCTCCACTCAAGGCTG 3600 V.l 3565 gtttattggactgatgtgtgcgattgctcttctcacactactattattaa 11II 1 I 11 IS 11 1 1 1 1 II1 1 1II!1 &#943;1 1 1 II 1 1 1 1 II I, 1 1 1 1 1 1 1 1 II ! 3614 v.7 3601 &#943; 1 1 &#943; 1 I 1 ι I &#943; 1 Π J 1 1 1 1 1 1 H 1 I 1 I ! 1 1 1 1 i 1 l 1 I I 1 1 1 1 I ι t I 1 1 1 &#943; &#943; GTTTATTGGACTGATGTGTGCGATTGCTCTTCTCACACTACTATTATTAA 3650 v.l 3615 ctgtttgctttgtgaagaggaatagaggtggaaagtactcagttaaagaa 1 II1 1 II 11 IIIIIIIIIIII 1 1II II 11 III 1 II1 1 1 11 II 1 I 1 1 1 1 1 1 3664 v.7 3651 I 1 I 1 1 I 1 { 1 1 1 I 1 1 I II i I i 1 f )1 i f f t i f i 1 I f } f I 1 fI 1f 11 1 1 1 1 1 1 CTGTTTGCTTTGTGAAGAGGAATAGAGGTGGAAAGTACTCAGTTAAAGAA 3700 v.l 3665 aaggaagatttgcatccagacccagaaattcagtcagtaaaagatgaaac | j II I 1 II II II 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I II 1 1 1 1 1 1 1 1 I 1 1 I 1 I Π 1 1 3714 v.7 3701 1 1 1 1 1 J l ι 1 1 1 j iι ι 1 1 1II Η 1 1 I I l &#943; II 1 1 S 1 1 1 1 1 1 Η Π 1 l ι II ll AAGGAAGATTTGCATCCAGACCCAGAAATTCAGTCAGTAAAAGATGAAAC 3750 v.l 3715 ctttqgtgaatacagtgacagtgatgaaaagcctcfccaaaggaagccttc | I 1 j >j 1 j 1 1 1 I I 1 1 1 I 1 11 1 1 I I 1 11 1 1 H I 1 1 1 1 1 || H I I I 1 I I I 1 I 3764 v.7 3751 1 1 N ! i 1 1 N ! 1 1 I i 1 1 f &#943; &#943; N 1 1 I 1 N Π &#943; 1 if II &#912; ι 1 &#943; I 1 ι H ! I 1 Π CTTTGGTCAATACAGTGACAGTGATGAAAAGCCTCTCAAAGGAAGCCTTC 3800 v.l 3765 ggtcccttaatagqqatatgcagcctactgaaaqtqctqacagcttagtc 111 1 1 1 1 1 1 1 1 111 II 1 I III 11 II 1 1 1 || 1 1 1 II III II 1 III 1 I II |j 3814 v.7 3801 U 1 1 I I I 1 1 1 I I 1 ! I I I 1 I I t I t i I I 1 1 1 1 1 1 1 I | 1 I i 1 I I I il 1 if 1 II GGTCCCTTAATAGGGATATGCAGCCTACTGAAAGTGCTGACAGCTTAGTC 3850 v.l 3815 gaatacqqaqaqggagaccatggtcfccttcagtgaaqatqaatcatttat 11 11 1 1 III II III II1 11 1 III 1 1 II 1 1 1 II HI II 1 Nil 1 1 I 1 1 1 1 1 3864 V.'? 3351 1 I 1 ! 1 1 1 I 1 1 1 1 1 1 1 I 1 1 I 1 I i &#943; ι ! I i ι 1 1 1 1 1 I I I I I 1 I I ! I II U U 1 GAATACGGAGAGGGAGACCATGGTCTCTTCAGTGAAGATGGATCATTTAT 3900 v.l 3865 tggtgcctacgctggatctaaggagaagggatctgttgaaagcaatggaa 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 914 v.7 3901 I 1 ι I I 1 1 1 1 1 1 1 I 1 1 i l I i ι H i It I I f I i i | I | 1 || i 1 I J 1 1 II 1 ) 1 I i TGGTGCCTACGCTGGATCTAAGGAGAAGGGATCTGTTGAAAGGAATGGAA 3950 v.l 3915 gttctacagcaacttttccccttcgggcataaacacaacatatgtaagca 1 1 I 1 1 1 ! &#943; 1 I !11II 1 1 1 1 11 li1 1 1!1 111!I 11 I 1111 Η 11111 I 1! 3964 V.7 3951 1 11 1 1 1 I! 1 11111 I 1 1 1 1 1 I 1 I 1 1 1 I 1 1 1 I I 1 I 1 1 I I |I 1 I 1 1 I 1 1 1 1 I GTTCTACAGCAACTTTTCCCCTTCGGGCATAAACACAACATATGTAAGCA 4000 v.l 3965 acgctactggttcaccccaaccttccatatttatctgttcaaaggagcaa 1 ! 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 II 1 II ! 1 1 ! 1 1 4014 v. 7 4001 1 I II11 I 11111II111 H I 1 1 1 II 11 111111111111II I 11 li 1 1 1 1 ACGCTACTGGTTCACCCCAACCTTCCATATTTATCTGTTCAAAGGAGCAA 4050 314 &#970;, _i,rt v.l 4015 gaactttcatataggaatagaaacatgctggccgaagatttcatccagaa I I I I I 1 1 I II I I I I || I I 1 II 1 I I I I I I 1 I I I 1 1 1 1 1 1 I 1 1 1 I I 1 II II 1 4064 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I. 1 1 1 1 1 1 1 I v.7 4051 GAACTTTCATATAGGAATAGAAACATGCTGGCCGAAGATTTCATCCAGAA 4100 v.l 40 65 gtcaacatcctgcaattatgttgaaaagagtagtactttcttcaaaatat I I I II 1 || 1 I I I I I II I j 1 1 I 1 i 1 i j i i 1 1 I 1 i I i I I 1 1 I I 1 I i I I I I 1 1 4114 I I 1 1 ι I 1 ι Η 1 1 I 1 I 1 1 111 I 1 I 1 I 1 I 11 I II 1 1 1 I II 1 1 1 I 1 &#943; 1 1 1 I 1 1 v.7 4101 GTCAACATCCTGCAATTATGTTGAAAAGAGTAGTACTTTCTTCAAAATAT 4150 v.l 4115 aaaatgccaagcacttcaggcctatgttttgcttatattgttttcaggtg 111 ι 1111111π 11 ηιii11iiiiι ηι 11 ι η ι II11| ι ι) 111 li ι 4164 1 ι N 1 t 1 I II I 1 I ι 1 1 I 1 I 1 1 I 1 1 1 1 I 1 1 li It 1 1 I 1 1 I I t i I I 1 ι 1 1 II v.7 4151 AAAATGCCAAGCACTTCAGGCCTATGTTTTGCTTATATTGTTTTCAGGTG 4200 v.l 4165 ctcaaaatgcaaaacacaaaacaaatcctgcatttagatacacctcaact I I I 1 I 1 I I 1 1 I I 1 I II 1 1 I I 1 1 I 1 I I I 1 1 I 1 1 I I I II 1 tl 1 1 I I 1 I I I I I 4214 1 1 ! 1 I 1 1 1 I 1 1 ! 1 1 II 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I I I 1 I 1 1 1 I v.7 42 01 CTCAAAATGCAAAACACAAAACAAATCCTGCATTTAGATAGACCTCAACT 4250 v.l 4215 aaatccaaagtccccattcagtatattccatatttgcctgattttactat 11II111II1 if 11 Η&#943;11 Η Η&#943; 11!1&#943;1IIII &#943;m&#943; 11 i II1II111 v.7 4251 AAATCCAAAGTCCCCATTCAGTATATTCCATATTTGCCTGATTTTACTAT 4264 4300 v.l 4265 tcggtgtgtttgcatagatgttgctacttggtgggtttttctccgtatgc 1 II II II III III II llllIIII 1 1 II I 11 II II II 1 1 1 1 1 1 1 II 1 1 III 4314 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 U 1 1 I I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 v.7 43 01 TCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGTTTTTCTCCGTATGC 4350 v.l 4315 acattggtatacagtctctgagaactggcttggtgactttgcttcactac I 1 I I I 1 I I I 1 I I I 1 I 1 I 1 1 I 1 1 I I 1 1 I 1 I 1 1 1 1 1 1 1 l| I 1 1 I 1 1 I I 1 1 1 I 4364 1 1 I 1 I 1 1 1 I 1 1 1 1 I t I 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 I 1 1 I 1 1 1 1 1 1 1 I I v.7 4351 ACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGACTTTGCTTCACTAC 4400 v.l 4365 aggttaaaagaccataagcaaactggttatttaaaatgtaaaaaggaata - 1 I 1 1 II 1 1 1 1 1 1 &#943; 1 1 1 1 II 1 1 II i 1 1 I 1 1 1 II1111II II II 1 II II 1 1 1 4414 1 1 1 I 1 1 1 I 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 I 1 1 I t 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 V.7 4401 AGGTTAAAAGACCATAAGCAAACTGGTTATTTAAAATGTAAAAAGGAATA 4450 v.l 4415 tgaaagtcttattaaaacacttcattgaaaatatacagtctaaatttatt 1I 1 11 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 II 1 1 1 1 1 1 I 1 1 1 1 4464 1 1 I I 1 1 1 I I 1 1 I I 1 1 1 1 1 I I I 1 1 1 1 1 1 1 1 1 I t 1 1 1 1 I 1 1 I 1 I 1 1 1 I 1 1 1 1 v.7 4451 TGAAAGTCTTATTAAAACACTTCATTGAAAATATACAGTCTAAATTTATT 4500 v.l 4465 atttaaattttactagcaaaagtcttaggtgaacaatcaactagtatttg 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 i 1 1 1 1 ! 1 1 ! I 1 1 1 i i 1 1 1 1 1 i 1 1 4514 I 1 I 1 1 I 1 I I 1 i I t 1 1 I I 1 1 1 1 1 1 1 I I I 1 I 1 I I 1 1 1 1 1 1 I I 1 t I I 1 1 1 1 1 1 v.7 45 01 ATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAATCAACTAGTATTTG 4550 v.l 4515 ttgagctcctatttgcccagagatgqtcatatttaaacagaaqtatacgt 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 T 1 1 1 1 1 1 1 4564 I 1 I I 1 1 1 1 I I I I 1 I I 1 1 J I 1 1 1 1 I I 1 1 1 1 I 1 I I 1 1 1 1 I ! 1 1 1 I 1 1 1 i 1 I 1 v.7 4551 TTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAAACAGAAGTATACGT 4600 v.l 45 65 ttttcagtttcaacatgaatttttttatttctgtcagttatgacatccac 1 1 1 1 II 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 4614 1 1 1 I 1 I 1 1 i 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 I 1 1 1 1 1 1 ! 1 1 1 1 I I 1 1 1 1 1 1 v.7 4601 TTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCAGTTATGACATCCAC 4650 v.l 4615 gagcatcactttttgtgtctgtttttttttttttcttggactaaattcaa 1 1 1 1 1 1 1 ! Η 1 1 ! 1 1 1 : 1 1 ! 1 1 1 I 1 111111111 I 1 II I 1 1 1 1 1 1 1 ! Μ 1 4664 Π I i I N 1 If I 1 Η I &#943; Π &#943; H 1 Η 1 1 Η 1 Η &#943; II 1 t 1 1 i Π ι ι 1 il 1 1 Π 4700 v.l 4665 ctgcatggaagcggtggtcagaaggttgttttatacgagaacaggcagaa 1 I 1 1 1 1 1 1 II 1 1 1 I 1 1 1 111111 1 1 1 1 1 1 1 II II 1 1 1 II 1 1 1 1 I 1 1 1 1 1 1 4714 1 1 f S 1 1 1 i 1 1 1 I 1 1 I 1 1 i 1 1 1 1 1 I 1 1 I 1 I 1 1 1 I 1 1 ! 1 1 1 1 1 I 1 1 1 I ! I 1 1 v.7 4701 CTGCATGGAAGCGGTGGTCAGAAGGTTGTTTTATACGAGAACAGGCAGAA 4750 v.l 4715 agtgcccattgttcaggattctaatagctacatctacttaatatcttcat I I I 1 1 I 1 1 I 1 1 I 1 I I I I 1 I 1 1 I 1 1 1 1 1 1 II 1 I 1 1 j 1 H I II I 1 1 1 1 1 1 1 I 4764 Η II 1 i Η I 1 I I 1 I I i I 1 1 I ! 1 1 Η 1 1 1 Π 1 1 1 1 1 1 1 I 1 1 1 1 I i 1 I I i 1 i v.7 4 7 S1 ACTGCCCATTGTTCAGGATTCTAATAGCTACATCTACTTAATATCTTCAT 4800 v.l 4765 ttctaaattgactgcttttacctttttctcatgtttatataatggtatgc 4814 315 "·· —________ v l·]' "4 8 01 TTCTAAATTGACTGCTTTTACCTTTT'TCTCATGTTTATATAA.TGGTATGC v.l 4815 ttgcatatatttcatgaatacattgtacatattatgfctaatatttacaca ΗΗΙΗΙΗ&#943;ΗΗ&#943;ΗΠΗΗΗΙ&#943;ΗΙΗΗΗΗΙΗΗΙΗΙΗ

V-7 4 851 TTGCATATATTTCATGAATACATTGTACATATTATGTTAATATTTACACA v.l 4865 atfctaaaatatagatgtgttttattttgaagtgagaaaatgaacattaac I 11111IIIii 111! IIIIII I! IIIIIIIIII11 Ii 11 Η&amp;#943; 1111 if I &amp;#943;

V-7 4901 ATTTAAAATATAGATGTGTTTTATTTTGAAGTGAGAAAATGAACATTAAC v.l 4915 aggcatgtttgtacagctagaatatattagtaagatactgtttfctcgtca IIIIIIII11111111II11111IIIIIII111111111111 SI i 11! 1!

v-7 4951 AGGCATGTTTGTACAGCTAGAATATATTAGTAAGATACTGTTTTTCGTCA v.l 4965 ttccagagctacaactaataacacgaggttccaaagctgaagactttgta ΙΙΙΙ&amp;#906;ΙΙΙΙΙ II Illlllllll I llllllllllll 111111)1)111))1

v.7 50 01 TTCCAGAGCTACAACTAATAACACGAGGTTCCAAAGCTGAAGACTTTGTA v.l 5015 taaagtatttgggttttgttcttgtattgctttctttcaacagtttcaaa

11H 11II11111111111111111!111IIII11 Η II11II I! IIIII

v.7 5051 TAAAGTATTTGGGTTTTGTTCTTOTATTGCTTTCTTTCAACAGTTTCAAA v.l 5065 ataaaatatcatacaaatattgagggaaatgttttcatatttttcaaaat

II HI I! Ill 1111 llllll llllllll I III III HUH UH II HI

v.7 S101. ATAAAATATCATAcAAATATTGAGGGAAATGTTTTCATATTTTTCAAAAT v.l 5115 aggtttttattgttgaatgtacatctaccccagcccctcaaaagaaaaac

1111!! IIIIII111111IIIII11IIIII11!IIIIIIIII1111 IS II

v.7 5151 AGGTTTTTATTGTTGAATGTACATCTACCCCAGCCCCTCAAAAGAAAAAC v.l 5165 tgtttacatagaaattcctacacatacgtttgcgtatatgttattttaaa 111111111111II111111111111111111111111111111111111

v.7 52 01 TGTTTACATAGAAATT-CCTACACATACGTTTGCGTATATGTTATTTTAAA v.l 5215 catctttgtggtgagaattttttccccgatattctccttctgtcaaagtc ΙΙΗΙΗΙΙΗΙΙΗΗΗΙΗΙΗΗΙΙΗΙΗΗΙΗΙΙΗΗΠΠΙ

v.7 5251 CATCTTTGTGGTGAGAATTTTTTCCCCGATATTCTCCTTCTGTCAAAGTC v.l 5265 agaacaaattcagggaatttattttctggcagttgtgctccagtcctttt 111i11i11II11111m1111ll 11111!1111111111111 ll 111!

v.7 53 01 AGAACAAATTCAGGGAATTTATTTTCTGGCAGTTGTGCTCCAGTCCTTTT v.l 5315 aaaattgtacatgaacatgttttagaaacaatatggaggatgatgcatac IIII Η ΗII I! 11! IIII111II1! 11! Hl Η II11111111II il. 11

v.7 5351 AAAATTGTACATGAACATGTTTTAGAAACAATATGGAGGATGATGCATAC v.l 5365 atgtcggtcaagttcagcgctcgacattttatggaaagatttttttaacc 11IIII111111IIIIIIIII11II111II1111111IIII11IIII111

v.7 5401 ATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAAAGATTTTTTTAACC v.l 5415 ttaccacgaaatacttaactactg.tttaaqtgaattgacttatttcactt Π Π Π Π Π Π Π Π Η I U1111Π I Π Ι&amp;#938; I Η I ΠI Η Η Π I Η Π

v.7 5451 TTACCACGAAATACTTAACTACTGTTTAAGTGAATTGACTTATTTCACTT v.l 5455 tagtttttgaactgtgattattgcrtatactgttatatcctcaacttggat

UMiiliGiiUUiUUliGUMiUUUliiiUiMUlGGM v.l 5515 ttatggtaacccctttfcagttcatggagaccaaaatttggggtatttata IIIII11IIII111111IIIIIIIIII1111111II I!111111 II 1111

v.7 5551 TTATGGTAACCCCTTtTAGTTCATGGAGACCAAAATTTGGGGTATTTATA v.l 5565 atagtcagcgcaggaatgcacatggaatatctacttgtccttttgaacct 4850 4 8 64 4900 4914 4950 4964 5000 5014 5050 5064 5100 5114 5150 5164 5200 5214 5250 5264 5300 5314 5350 53 64 5400 5414 5450 5464 5500 5514 5550 5564 5600 5614 316 v.7 5 6 01 ATAGTCAGCGCAGGAATGCACATGGAATATCTACTTGTCCTTTTGAACCT 5650 v.l 5615 cacgagtcatccagaatgtatagacaggaaaagcatgtcttatttaaaac I I I | 1 | 1 1 1 1 I I 1 1 j I 1 I I 1 I I I I I ! &#912; 1 1 1 1 | [ If I I ( I i I | I i 1 I 1 ! I &#943; 5-664 1 1 I I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι 1 1 1 1 1 i t 1 1 1 I v.7 5 651 CACGAGTCATCCAGAATGTATAGACAGGAAAAGCATGTCTTATTTAAAAC 5700 v.l 5665 tgtaatttatgggctcaggatctgaccgcagtcccgggagtaagcatttc I 1 I I 1 I 1 1 I II I I 1 I I 1 I I I 1 II I I I I 1 I II II l| | 1 1 | II II !| I 11 I 1 5714 1 1 I j 1 1 l ι i 1 i 1 1 ! 1 1 r I 1 I 1 I L I 1 1 I 1 1 I i 1 ι 1 1 t ι ι 1 i 1 I 1 I ι ι i t 1 > v.7 5701 TGTAATTTA.TGGGCTCA.GGATCTGACCGCAGTCCCGGGAGTAAGCATTTC 5750 v.l 5715 aaagggggaaggcagtgtggtccctaccctgtgtgaatgtgaggatgtag 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i i 1 1 1 1 1 ! i 1 1 1 1 1 1 1 5764 ! ! 1 1 1 1 I i 1 1 1 j 1 ! i ! 1 1 I 1 i j 1 I 1 i ! I i l ! 1 ι 1 i I I ! 1 1 I 1 ι 1 I ι 1 i i I v.7 5751 AAAGGGGGAAGGCAGTGTGGTCCCTACCCTGTGTGAATGTGAGGATGTAG 5800 v.l 5765 acatccatcagtgcaactcgagctccatcctcctccgatttctaaggctc I II I I || I I I I I || II II 1 |l I 1 || 1 !| I I II || 1 1 II II II 1 II II II 1 5814 ι 1 ! ι 1 I i ι ι 1 ! 1 1 1 ι ι ! i &#943; ! 1 1 i 1 i 1 I i i ι 1 1 i 1 1 ! &#943; ! 1 i i 1 1 i i ι ι 1 1 I v.7 5 8 01 ACATCCATCAGTGCAACTCGAGCTCCATCCTCCTCCGATTTCTAAGGcTC 5850 v.l 5815 cagttttctggagggacagtcatcatgttttgatttatctgggagaaaac I I I i 1 1 1 1 I I 1 1 I I 1 1 1 1 1 1 1 1 1 II 1 1 1 I II 1 1 1 1 1 1 1 1 II 1 1 1 1 1 I II 1 5864 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 v.7 5851 CAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTTATCTGGGAGAAAAC 5900 v.l 5865 tgtcjgtgcacagcttgtgaggagggcaaggttgtgacgttcgagcttagt | I 1 1 I I 1 1 1 1 1 1 1 1 1 1 II 1 I 1 1 1 1 1 1 1 II 1 1 1 1 II II 1 1 II 1 1 1 1 1 II II 5914 1 1 1 1 1 1 1 I 1 1 II 1 1 1 1 I 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 Η v.7 5901 TGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGACGTTCGAGCTTAGT 5950 v.l 5915 tctggtgttattctgtctcctcttctttgtcatcagccaaaacgtggttt 1 &#943; 1 1 1 &#943; 1 1 1 1 &#943; 1 I 1 &#943; 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 &#943; 1 ! 1 I 1 1 5964 1 1 1111 ii I I 1 1 1 1 II 1 11 111 1 I 1 1 1 1 l Η ι 1 1 1 1 I I ι ι ι ι 1 ι 1 ι 1 ι 11 v.7 5951 TCTGGTGTTATTCTGTCTCCTCTTCTTTGTCATCAGCCAAAACGTGGTTT 6000 v.l 5965 ttaaagagagtcatgcaggttagaaataatgtcaaaaatatttaggaatt i I i i &#943; &#943; 1 i &#943; i ! 11 i &#943; 1 1 H ! i I &#943; ! 1II 111 ! 1 1 &#943; 1 1 &#912; 1 I 1 1 1 1 I 1 1 I I 1! 6014 1 1 II 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 t 1 1 1 1 1 1 1 v.7 6001 TTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAAAATATTTAGGAATT 6050 v.l 6015 taataacctttaagtcagaaactaaaacaaatactgaaatattagctctt 1 1 l| 1 11 I II I 1 I I 1 I 1 I I I I II 1 1 1 1 II 1 1 1 1 ]| 1 1 1 1 |l || 1 1 1 1 1 1 I 6064 I l &#943; 1 · I 1 1 I ! 1 ! 1 1 i 1 1 1 i 1 i 1 1 I ! t i i 1 &#943; 1 I i i 1 ! 1 ! &#943; 1 s I 1 1 ι 1 ! 1 1 1 v.7 6051 TAATAACCTTTAAGTCAGAAACTAAAACAAATACTGAAATATTAGCTCTT 6100 v.l 6065 cctacacttcgtgttcccctttagctgcctgaaaatcaagattgctccta 11 li 1 Ll! 1 i &#943; 1111! 11 Η II!! 1111111!! 111 If 1! 1111S! Η 11 v . 7 6101 CCTACACTTCGTGTTCCCCTTTAjGCTGCCTCAAAATCAAGATTGCTCCTa 6114 6150 v.l 6115 ctcagatcttctgagtggctaaaacttatggatatgaaaaatgagattga | I 1 I I I 1 I I I I I II 1 I I I 1 I 1 l| I 1 I I || I I I I 11 I I I I II II I I I I I l| 6164 1 ι i I ι 1 i I I ι 1 1 1 1 ι 1 I i 1 1 I i 1 1 ι ι &#943; I ι 1 ι 1 I i t 1 S 1 ! 1 1 ι 1 1 S ι i 1 1 1 v.7 6151 CTCAGATCTTCTGAGTGGCTAAAACTTATGGATATGAAAAATGAGATTGA 620Q v.l 6165 atgatgactatgctttgctafccattgttacctttcctcaatactatttgg II I II 1 1 1 1 I I I II 1 1 1 1 1 1 1 1 I 1 I 1 I 1 1 1 1 II 1 II 1 | 1 1 1 1 1 1 1 1 1 1 1 1 6214 1 1 I 1 1 ι 1 1 ι 1 ι 1 1 i ι 1 ι ι ι ι 1 1 1 1 i 1 1 1 1 1 1 1 i 1 I 1 1 1 I 1 1 1 1 I 1 1 I ! 1 ! v.7 6201 ATGATGACTATGCTTTGCTATCATTGTTACCTTTCCTCAATACTATTTGG 6250 v.l 6215 caactactgggactcttcagcacaaaaggaatagatctatgattgaccct 11 I I III 1 I I I I I I I I I I II II I I I I I I I I I ] I I I 1 ] I 1 1 1 1 I 1 1 1 1 1 1 1 6264 11 I 1 1 1 1 1 II 1 ! 1 !1 1 1 I 1 1 1 1 1 1 I I 1II 1 1II 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 v.7 6251 CAACTACTGGGACTCTTCAGCACAAAAGGAATAGATCTATGATTGACCCT 6300 v.l 6265 gattttaattgtgaaattatatgattcatatattttatgaatcagaataa ! II I II I I I j I I II 1 1 1 1 1 II I] 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 II 1 11 6314 1 1 1 1 1 I 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I i 1 1 ! 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I I v.7 6301 GATTTTAATTGTGAAATTATATGATTCATATATTTTATGAATCAGAATAA 6350 v.l 6315 ccttcaaataaaataaatctaagtcggttaaaatggatttcatgattttc | 1 1 1 1 1 II 1 1 II 1 1 1 1 1 1 II 1 1 1 1 1 1 1 II 1 1 1 1 II 1 1 1 1 II 1 II 1 j 1 1 1 1 6364 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.7 6351 CCTTCAAATAAAATAAATCTAAGTCGGTTAAAATGGATTTCATGATTTTC 6400 317 v.l" 6365 cctcagaaaatgagtaacggagtccacggcgtgcaatggtaattataaat | 1 11 1 I II |l II I I I I I 1 I I I II 1 1 II II 11 1 1 It I II II 1 1 1 1 1 1 I I II 6414 v. 7 6401 Η 11 1 I i 1 1 J j ) I 1 Η 1 J I I } I 1 ! I 1 I 1 I 1 II 1 1 1 I 1 l Η 1 I I I 1 1 1 1 I 1 CCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAATGGTAATTATAAAT 6450 v.l 6415 tggtgatgcttgtttgcaaattgcccactcgtgataagtcaacagccaat t 1 I | ι | 1 j I 1 1 1 1 1 1 1 I !| !| 1 I 1 1 1 j I 1 I 1 1 1 I 1 I I I ι 1 1 1 1 1 1 1 1 II 1 64(54 v.7 6451 ι 1 1 &#943; 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 ι 1 1 ι ι 1 ι 1 t 1 1 1 I 1 1 ι i 1 ! I I I 1 I TGGTGATGCTTGTTTGCAAATTGCCCACTCGTGATAAGTCAACAGCCAAT 6500 v.l 6465 atttaaaactttgttcgttactggctttaccctaactttctctagtctac 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 ! 1 ! 1 11 1 H 11 1 1 1 1 1 1 11 1 1 1 ! 1 1 1 I 1 1 1 1 1 6514 v.7 6501 I ( 1 1 1 f 1 1 I i It 1 &#943; I 1 I H f 1 U U 1 11 N i i 1 1 II I 1 J II 1 I 11 1 1 1 1 1 ATTTAAAACTTTGTTCGTTAOTGGCTTTACCCTAACTTTCTCTAGTCTAC 6550 v.l 6515 tgtcaatatcattttaatgtaattgattgtatatagtctcaagaatggtt | 1 1 1 1 I 11 1 II II II 1 II l| 1 1 II H 1 I j| 1 I 1 i 1 1 I 1 1 II l| II 1 II II 6564 v.7 6551 &#943; 1 I 11 ! 1 I 1 ! I 1 I I 1 1 1 ! i U I ! ) 1 U $ 1 i I ) I 1 1 ! I 1 i U i U 1 I I i i 1 TGTCAATATCATTTTAATGTAATTGATTGTATATAGTOTCAAGAATGGTT 6600 v.l 6565 aqtgqqcatqagttcctagagaactgt.ccaagggttgggaa.aatccaaat Hi Mil III i IIII111 II I I il H i il 1 i ii 1II If 1 i! &#943; &#943; 1II Μ &#943; 1 6614 v.7 6601 &#943; ) ) I 1 S 1 1 Ν I 1 Η Μ i 1 i 1 i I i 1 Η t i i i ι I i 1 i 1 ! ι I 1 t 1 i 1 I ι ι i i 1 GGTGGGCATGAGTTCCTAGAGAACTGTCCAAGGGTTGGGAAAATCCAAAT 6650 v. 1 6615 tctcttcctggctccagcactgattttgtacataaacattaggcaggttg II j I I I Η II I I I I I I || I II II 1 1 11 l| 1 1 II 11 1 II I II l| 11 11 11 I 6664 v.7 6651 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 f I 1 I 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 TCTCTTCCTGGcTCCAGCACTGATTTTGTACATAAACATTAGGCAGGTTG 6700 v.l 6665 cttaacctttttatttcaaactctctcaactctaaagtgctaataataat 11 i 11 li11111II11!111IIi11il1 i II11ii11IIili 1!111i 1i 6714 v. 7 6701 CTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAAGTGCTAATAATAAT 6750 v.l 6715 ctcagttaccttatctttgtcacagggtgttcttttttatgaagaaaaat II1111111!1111!11iIIi!1i11 iΜ 111II1 iII 1II1111II111 6764 v. 7 6751 CTCAGTTACCTTATCTTTGTCACAGGGTGTTCTTTTTTATGAAGAAZkAAT b 8OU v.l 6765 ttgaaaatgataaaagctaagatgccttctaacttcataagcaaaccttt 11 I 1 II 1 1 II 1 1 1 II 1 1 1 I II I 1 1 1 Π 1 11 1 )| 1 II 1 1 II II 1 II 11 1 II 6814 v.7 6801 ι 1 1 1 1 i i 1 1 ι 1 1 I ι ι ι II 1 1 1 I I ι ι ι ι 1 1 I I I 1 1 1 1 Ι ι ι i ι ι 1 1 ι 1 1 ! ! I TTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTCATAAGCAAACCTTT 6850 v.l 6815 aactaattatgtatctgaaagtcacccccacataccaactcaactttttt 1 1 1 I ] 1 1 1 1 I 1 1 1 1 1 1 1 1111111111U11 I Π1 1 1 i 1 1 i1 1i i IIH1 6864 v.7 6851 ι Η I I ! 11 Η H1 I Η I Iι Η IIII1 I N1 II ! 1 I 1 1 1 I 1 1 1 1ι&#943; li 1 ι 1 AACTAATTATGTATCTGAAAGTCACCCCCACATACCAACTCAACTTTTTT 6900 v.l 6865 cctgtgaacacataaatatatttttatagaaaaacaaatctacataaaat . 11II η 1111 Η 1 II 11 Η Η II11! 1111 Η II11111 Η Η Η 1II11 CCTGTGAACACATAAATATATTTTTATAGAAAAACAAATCTACATAAAAT 6914 v.7 6901 6950 v.l 6915 aaatctactgtttagtgagcagtatgacttgtacatgccattgaaaatta |( 1 I 1 1 1 1 1 II 1 j jl II II 11 1 I II II II II II Π II II 1 11 SI j 1 II II 6964 v.7 6951 j 1 I 1 1 1 1 1 I 1 1 1 1 1 I I I 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 ι 1 1 1 1 1 1 1 1 1 I Ι ι 1 1 1 1 1 AAATCTACTGTTTAGTGAGCAGTATGAcTTGTACATGCCATTGAAAATTA 7000 v.l 6965 ttaatcagaagaaaattaagcagggtctttgctatacaaaagtgttttcc Η 1 1 1 I 1 1 !! 1 1 1 I II 1 l H 1 !! II II 1 1 1 1 1 1 1 1 1 1 1 I 1 Π 1 II II Π 1 7014 v.7 7001 1 1 1 1 1 1 1 1 1 1 1 II i 1 I ι ι ι II 1 1 1 -1 1 I 1 1 1 1 II I I 1 1 1 I 1 1 II 1 1 1 1 1 1 1 TTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATACAAAAGTGTTTTCC 7050 v.l 7015 actaattttgcatgcgtatttataagaaaaatgtgaatttggtggtttta η | || | | η ι Η il lΗ Η 11||Η IIII Π II 1 I 1 I 1 1 1 II Η II II II 7064 v.7 7051 U 1 1 1 1 &#943; 1 1 Μ &#943; Π 1 1 1 1 1 Η 1 N 1 1 &#943; I 1 Η 1 1 Η 1 I 1 I 1 H i Η 1 1 1 U ACTAATTTTGCATGCGTATTTATAAGAAAAATGTGAATTTGGTGGTTTTA 7100 v.l 7065 ttctatcggtataaaggcatcgatattttagatgcacccgtgtttgtaaa ! I 1 1 1 It 1 1 1 Η 1 Η Π 1 Π 1 Η II 1 1 I 1 1 1 1 1 1 1 1 i 1 1 1 Π Π Π Π Π 7114 v.7 7101 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 | 1 1 I | I | | | I | | | | 1 1 1 1 1 1 1 1 1 1 TTCTATCGGTATAAAGGCATcGATATTTTAGATGCACCCGTGTTTGTAAA 7150 v.l 7115 aatgtagagcacaatggaattatgctggaagtctcaaataatattttttt I I I t I I I I I I I 1 |l II II II II 1 II I II II I I I I I I I I I I I I ]| 1 II 1 II 7154 V.7 7151 1111111IIII11 1 1 1 1 1 1 II 1 1 1 1 I 1 1 1 II111II11 1 1 1 1 1 1 1 ι1 1 I 1 AATGTAGAGCACAATGGAATTATGCTGGAAGTCTCAAATAATATTTTTTT 7200 318 v.l 7165 cctattttatactcatggaagagataagctaaagaggggacaataatgag I I I I 1 I 1 I 1 1 I I I 1 I II II 1 1 1 1 I I 1 1 1 1 I 1 1 I II 1 |! II I 1 I 1 1 II I 1 1 7214 V. 7 7201 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 CCTATTTTATACTCATGGAAGAGATAAGCTAAAGAGGGGACAATAATGAG 7250 v.l 7215 aaatgttggtgtgcttttctaagcatttaaaacataattgccaattgaaa 1 1 I 11 I 11 1 1 1 1 1 1 I 1 1 II II I 11 1 1 III i 1 1 i i i i 1 i 1 1 i 1 i i i 1 I i 1 i 7264 v.7 7251 1 1 1 I 1 1 1 1 1 1 .1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AAATGTTGGTGTGCTTTTCTAAGCATTTAAAACATAATTGCCAATTGAAA 7300 v.l 7265 ccctaaatatgtttacataccattaagatatgattcatgtaacaatgtta 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 I I 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 7314 v.7 7301 i 1 i &#943; I I 1 Ι &#943; &#943; ι I 1 i 1 i Ι ι &#943; 1 1 1 1 t 1 t I I I i ι 1 I ι i I i ! 1 ! I 1 I I i i 1 i i i CCCTAAATATGTTTACATACCATTAAGATATGATTCATGTAACAATGTTA 7350 v.l 7315 aattaattataatggqattggqtttgttatctgtggtagtatatatccta 1 1 1 1 1 1 1 1 1 1 I 1 IIIIII III IIIIIIII 1 1 I II I II 1 1 1 1 1 1 1 1 1 1 1 1 1 7364 v.7 7351 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 AATTAATTATAATGGGATTGGGTTTGTTATCTGTGGTAGTATATATCCTA 7400 v.l 7365 gtgttcctatagtgaaataagtagggttcagccaaagctttctttgtttt 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 7414 V.7 7401 I j I 1 ! &#943; { j i &#943; 1 1 i t ι ι I 1 1 I 1 1 ι 1 * I 1 i 1 I 1 &#943; &#943; ι &#943; < I ' &#943; ι 1 < * ι 1 i 1 I ι 1 GTGTTCCTATAGTGAAATAAGTAGGGTTCAGCCAAAGCTTTCTTTGTTTT 7450 V. 1 7415 gtaccttaaattgttcgattacgtcatcaaaagagatgaaaggtatgtag 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 7464 v.7 7451 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GTACCTTAAATTGTTCGATTACGTCATCAAAAGAGATGAAAGGTATGTAG 7500 v.l 7465 aacaggttcacgtgattacctttttcttttggcttggattaatattcata Iι111 I 111 I I 111111111 I 1 1 1 1 1 I 1 1 1 11 I 11 I 1 11 1 1 i 1 1 1 1 1 II 1 7514 v.7 7501 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 AACAGGTTCACGTGATTACCTTTTTCTTTTGGCTTGGATTAATATTCATA 7550 v.l 7515 qtagaactttataaaacgtgtttgtattgtaggtggtgtttgtattatgc 1 1 II1 1 I 1 II 1 111 II II II 1 1 II 1 1 1 III II II II INI 1 II1 I II II ! 7564 v.7 7551 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 GTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGGTGTTTGTATTATGC 7600 v.l 7565 ttatgactatgtatggtttgaaaatattttcattatacatgaaattcaac 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 I ! I 1 1 1 1 1 I 1 1 I 1 1 1 1 1 7614 v.7 7601 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 I 1 1 1 1 TTATGACTATGTATGGTTTGAAAATATTTTCATTATACATGAAATTCAAC 7650 v.l 7615 tttccaaataaaagttctacttcatgtaatccaaaa 7 650 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.7 7651 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TTTCCAAATAAAAGTTCTACTTCATGTAATCCAAAA 7686

Table LIVf. Peptide sequences of protein coded by 282P1G03 v.7 {SEQ ID NO: 184)

MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS EEIEFIVPSV PKLPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSLKHA NDSSSSTEIG SKANSIKQRK PKLLLPPTES GSESSITILK GEILLLECFA EGLPTPQVDW NKIGGDLPKG RETKENYGKT LKIENVSYQD KGNYRCTASN FLGTATHDFH VIVEDNISHE LFTLHPEPPR WTKKPQSAVY STGSNGILLC EAEGEPQPTl KWRVNGSPVD NHPFAGDWF PREISFTNLQ PNHTAVYQCE ASNVHGTILA NANIDWDVR PLIQTKDGEN YATWGYSAF LHCEFFASPE AVVSWQKVEE VKPLEGRRYH IYENGTLQIN RTTEEDAGSY SCWVENAIGK TAVTANLDIR NATKLRVSPK NPRIPKLHML ELHCESKCDS HLKHSLKLSW SKDGEAFEIN GTEDGRIIID GANLTISNVT LEDQGIYCCS AHTALDSAAD ITQVTVLDVP DPPENLHLSE RQNRSVRLTW EAGADHNSNI SEYIVEFEGN KEEPGRWEEL TRVQGKKTTV ILPLAPFVRY QFRVIAVNEV GRSQPSQPSD HHETPPAAPD RNPQNIRVQA SQPKEMIIKW EPLKSMEQNG PGLEYRVTWK PQGAPVEWEE ETVTNHTLRV MTPAVYAPYD VKVQAINQLG SGPDPQSVTL YSGEDYPDTA PVIHGVDVIN STLVKVTWST VPKDRVHGRL KGYQINWWKT KSLLDGRTHP KEVNILRFSG QRNSGMVPSL DAFSEFHLTV LAYNSKGAGP ESEPYIFQTP EGVPEQPTFL KVIKVDKDTA TLSWGLPKKL NGNLTGYLLQ YQIINDTYEI GELNDINITT PSKPSWHLSN LNATTKYKFY LRACTSQGCG KPITEESSTL GEGSKGIGKI SGVNLTQKTH PIEVFEPGAE HIVRLMTKNW GDNDSIFQDV IETRGREYAG LYDDISTQGW FIGLMCAIAL LTLLLLTVCF VKRNRGGKYS VKEKEDLHPD PEIQSVKDET FGEYSDSDEK PLKGSLRSLN RDMQPTESAD SLVEYGEGDH GLFSEDGSFI GAYAGSKEKG SVESNGSSTA TFPLRA

SO 120 180 240 300 360 420 480 540 600 660 720 780 340 900 960 1020 1080 1140 1200 1236 319

Table LVf. Amino acid sequence alignment of 282P1G03 v.1 (SEQ ID NO: 185) and 282P1G03 v.7 (SEQ ID NO: 186) v.l. 1 MEPLLLGRGLIVYLMFLLLKFSKAXEIPSSVQQVPTIIKQSKVQVAFPFD I 1 1 1 1 1 1 1 1 I 1 I 1 I I 1 1 1 II 1 1 1 II 1 1 I i I 1 1 1 1 1 1 ) II I I 1 1 I II I I 1 1 50 v.7 1 1 1 1 1 1 1 1 1 1&amp;#906; 1 ι 1 I I I I L1 1 1 I 1 1 1 1 1 1 1 1 1 J 1 I 1 J 1 1 1 1 I 1 1 I I » MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD 50 v.l 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 1 1 I I 1 I 11 I II I I 1 I I I II 1 1 I 1 1 i 1 i 1 1 1 1 1 1 ! 1 1 1 II 1 1 1 I 1 1 1 1 1 1 1 100 v.7 51 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 i 1 I 1 1 1 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 v.l 101 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV 1 1 I 11 11 I 111111 1 1 1 1 1 1 1 1 1 111111 I 1111 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 15 0 v.7 101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 11 1 1 1 1 1 1 1 1 1 1 1 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV 15 0 v. 1 151 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN 1 1 1 1 1 1 1 1 1 ! 1 1 i 1 1 1 II I 1 1 1 1 1 1 I 1 1 1 ! 1 I 1 I I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 200 V.7 151 ! 1 II 1 I I 1 ! 1 1 ι 1 ι 1 1 1 ! 1 ! ! 1 1 1 1 1 I 1 1 1 ! 1 1 1 I 1 ! 1 1 ! 1 1 I 1 ! 1 ! 1 1 1 LPCNPPKGLPPLHIYWMNIEIiEHIEQDERVYMSQKGDLiYF ANVEEKDSRN 200 v.l 201 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 250 v.7 201 1 1 1 1 1II 1 Ill111 1 1 1 1 1 1 I 1 1 1 I 1 111II111 I 1 11 1 1 1 1 1 1 1 1 1 1 I 1 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK 250 v.l 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG ι ι 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 300 v.7 251 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG 300 v.l 301 RETKENYGKTLKIENVS YQDKGNYRCTASNFLGTATHDFHVIVE------ I I 1 1 1 1 1 I I j I I I 1 I 1 I 1 1 1 1 1 I 1 1 1 1 1 11 1 1 I 1 1 1 1 1 1 1 1 1 1 1 344 v. 7 301 1 1 1 1 1 1 1 1 I 1 II 1 1 1 1 1 1 1 111111II11111111 1 1 1 1 1 1 1 1 1 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEDNISHE 350 v.l 345 ------EPPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVD 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 388 v.7 351 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I i 1 1 1 1 1 1 1 1 1 LFTLHPEPPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVD 400 v.l 389 NHPFAGD WFPREISFTNLQPNHTAVYQCEASNVHGTILANANIDWDVR 1 i I I t 1 1 1 I 1 1 1 I 1 I j 1 1 1 ! 1 1 1 I 1 1 1 1 1 1 I 1 j 1 I I 1 1 1 I I 1 ! I 1 1 1 1 1 1 438 v.7 401 1 1 1 1 i I 1 1 I 1 ! 1 1 I 1 1 1 1 1 1 1 I I! 1 1 1 1 11ι 1 I 1 1 1 1 1 ι i !ι 1 1 I 1 1 1 1 1 NHPFAGD WFPRE X S FTNLQPNHTAVYQCE ASNVHGTILANANIDWDVR 450 v.l 439 PLIQTKDGENYATWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYH llll T 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I I 1 1 1 1 II 1 1 1 1 1 1 I ! II 1 1 I I 1 1 1 1 1 1 I 488 v.7 451 1 1 1 I II1 1 1 !II1 ! I 1 1 1 1 1 1 I 1 1 1 1 1 1 11!1 1 1 I 1 1 1 1 1 1 1 1 I 1 I II 1 1 PLIQTKDGENYATWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRR.YH 500 v.l 489 IYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPK I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 538 v.7 501 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I 1 1 1 ! 1 ! 1 1 I I 1 IYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDIENATKLRVSPK 550 v.l 539 NPRIPKLHMLELHCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIID i 1 1 i 1 1 1 1 1 i ! 1 1 1 1 ! 1 1 i 1 1 1 1 i 1 1 1 1 i 1 i i i 1 i 1 I 1 1 i 1 1 1 i i 1 i 1 i I 588 v.7 551 1 111 i 111111 1 1 1 II11111111 1 I 1 1 1 1 1 1 1 1 1 1 11 1 11111111111 NPRIPKLHMLELHCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIID 600 v.l .589 GANLTISNVTLEDQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSE 1 I II I I 1 I I I 1 I I || 11 I 1 1 1 I J 1 1 I I I 1 1 1 I 1 1 1 1 I I I ) I 1 1 I 1 I 1 1 1 1 638 v.7 601 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 II 11 1 1 1 1 1 111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 111 GANLTISNVTLEDQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSE 650 v.l 639 RQNRSVRLTWEAGADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTV 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 688 v.7 651 1 I 1 I 1 II 1 1 II I 1 1 1 1 1 1 1111 1111 1 1 1 1 1 1 1 I 1 ) 1 1 1 1 I 1 1 1 1 1 1 1 I 1 RQNRSVRLTWEAGADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTV 700 v.l 689 ILPLAPFVRYQFRVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQA 1 1 ! 1 1 1 1 1 i 1 I 1 1 1 1 1 1 I 1 1 1 1 I 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 I 1 1 1 1 738 v.7 701 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 ILPL APFVRYQFRVIAVNEVGRS QP S QP SDHHETP PAAPDRNPQNIRVQA 750 320 v. 1 739 SQPKEMIIKWEPLKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRV I I 1 I 1 I 1 1 1 1 I II I 1 I II I I l' 1 I 1 1 1 I 1 1 I I 1 I 1 II I I 1 1 1 1 1 1 1 I 1 I I I 788 v. 7 751 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 SQPKEMIIKWEPLKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRV 800 v. 1 789 MTPAVYAPYDVKVQAINQLGSGPDPQSVTLYSGEDYPDTARVIHGVDVIN I 1 I I II 1 I 1 I I 1 1 1 i 1 I 1 t 1 i i j I 1 j I I | 1 1 I 1 I I I 1 I 1 1 I 1 II ] 1 1 11 I 838 v. 7 801 H 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l 1 ι ι 1 ι ι ι 1 MTPAVYAPYDVKVQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVIN 850 v.l 839 STLVKVTWSTVPKDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSG 1 I 1 I I I I I || I 1 I 1 I I I I I I I I I 1 1 1 1 ! 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 j 1 1 1 S88 v, 7 851 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 STLVKVTWSTVPKDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSG 900 v.l 889 QRNSGMVPSLDAFSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFL I | I j j II I I II I I I I I I 1 1 |! 1 1 1 I 1 1 1 || 1 II 1 l| 1 1 I 1 1 j I 1 1 1 1 I 93 8 v. 7 901 1 1 1 1 1 1 1 I 1 1 1 II11 1 I 1 1 1 1 1 111111 I 1 1 1 1 II II i 11 1 I 1 1 I 1 II 1 1 QKNSGMVPSLDAFSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFL 950 v.l 939 KVI KVDKDTATLS WGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITT I I I I I I 1 I I I 1 1 II I I 1 I I 1 It I I I 1 II I 1 1 1 1 1 II 1 II 1 1 1 1 II 1 1 1 1 1 988 v.7 951 1 11 1 11 111|II11 11 1111 I 1 1 1 II 11 1 11 1 11 1 1 1 I II 1 1 1 1 1 1 1 1 1 1 KVIKVDKDTATLSWGLPKKLNGNLTGYLLQYQIINDTYEIGELND INITT 1000 v.l 989 PSKPSWHLSNLNATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKI i 1 I 1 1 I H 1 1 1 1 I I 1 1 I I 1 1 1 1 1 1 1 1 i 1 1 1 1 1 I 1 1 &amp;#943; 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1038 v.7 1001 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I-1 1 1 1 1 1 1 1 1 1 1 1 PSKPSWHLSNLNATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKI 1050 v.l 1039 SGVNLTQKTHPIEVFEPGAEHIVRLMTKNWGDNDSIFQDVIETRGREYAG 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1088 v.7 1051 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 II SGVNLTQKTHPIEVFEPGAEHIVRLMTKNWGDNDSIFQDVIETRGREYAG 1100 v.l 1089 LYDDI STQGWFI GLMCAIALLTLLLLTVCFVKRNRGGKYS VKEKEDLHPD 1 1 1 1 1 1 1 1 1 1 1 1 111 11 1 11 11II I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 113 8 v.7 1101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 LYDDISTQGWFIGLMCAIALLTLLLLTVCFVKKNRGGKYSVKEKEDLHPD 1150 v.l 1139 PEIQSVKDETFGEYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDH 1 1 1 1 1 1 1 1 1 1 ! 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1188 v.7 1151 111 II 1 1 II 1 1 1 i 1 1 1 1 1 II 1 II11111111111 1111 II 1 1 1 1 1 1 I 1 1 1 PBIQSVKDETFGEYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDH 1200 v.l 1189 GLFSEDGSFIGAYAGSKEKGSVESNGSSTATFPLRA. 1224 1! 1 1 1 1 1 ! 1 1 1 1 I 1 1 1 1 I 1 1 i 1 ! 1 1 1 1 1 I 1 I I 1 1 1 1 v.7 1201 II111 II 1 1 1 1 1 1 1 1 11 I 1 II I 1 1 IIII1 1 1 1 1 1 1 1 GLFSEDGSFIGAYAGSKEKGSVESNGSSTATFPLRA 123 6

Table Lllg. Nucleotide sequence of transcript variant 282P1G03 v.8 (SEQ ID NO: 187) cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact aatcgtatat ctaatattcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaaaatt agaacacatc gaacaagatg aaagagtata catgagccaa aagggagatc tatacttcgc aaacgtggaa gaaaaggaca gtcgcaatga ctactgttgc tttgctgcat ttccaagatt aaggactatt gtacagaaaa tgccaatgaa actaacagtt aacagtttaa agcatgctaa tgactcaagt tcatccacag aaattggttc caaggcaaat tccatcaagc aaagaaaacc caaactgctg ttgcctccca ctgagagtgg cagtgagtct tcaattacca tcctcaaagg ggaaatcttg ctgcttgagt gttttgctga aggcttgcca actccacagg ttgattggaa caaaattggt ggtgacttac caaaggggag agaaacaaaa gaaaattatg gcaagacttt gaagatagag aatgtctcct accaggacaa aggaaattat cgctgcacag ccagcaattt cttgggaaca gccactcacg attttcacgt tatagtagaa gataacatct ctcatgagct 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 12 0 0 321 I efctcacttta catccagagc ctcctcgctg gacaaagaag cctcagagtg ctgtgtatag 1260 caccggaagc aatggcatct tgttatgtga ggctgaagga gaacctcaac ccacaatcaa 1320 gtggagagtc aatggctccc cagttgacaa tcatccattt gctggtgatg ttgtcttccc 1380 cagggaaatc agttttacca accttcaacc aaatcatact gctgtgtacc agtgtgaagc 1440 ctcaaatgtc catggaacta tccttgccaa tgccaatatt gatgttgtgg atgtccgtcc 1500 attgatacaa accaaagatg gagaaaatta cgctacagtg gttgggtaca gtgctttctt 1560 acattgcgag ttctttgctt cacctgaggc agtcgtgtcc tggcagaagg tggaagaagt 1620 gaaacccctg gagggcaggc ggtatcatat ctatgaaaat ggcacattgc agatcaacag 1680 aaccaccgaa gaagatgctg ggtcttactc atgttgggta gaaaatgcta taggaaaaac 1740 tgcagtcaca gccaatttgg atattagaaa tgctacaaaa cttagagttt ctcctaagaa 1800 tcctcgtatc cccaaattgc atatgcttga attacattgt gaaagcaaat gtgactcaca 1860 tttgaaacac agtttgaagt tgtcctggag taaagatgga gaagcctttg aaattaatgg 1920 cacagaagat ggcaggataa ttattgatgg agctaatttg accatatcta atgtaacttt 1980 agaggaccaa ggtatttact gctgttcagc tcatactgct ctagacagtg ctgccgatat 2040 aactcaagta actgttcttg atgttccgga tccaccagaa aaccttcact tgtctgaaag 2100 acagaacagg agtgttcggc tgacctggga agctggagct gaccacaaca gcaatattag 2160 cgagtatatt gttgaatttg aaggaaacaa agaagagcct ggaaggtggg aggaactgac 2220 cagagtccaa ggaaagaaaa ccacagttat cttacctttg gctccatttg tgagatacca 2280 gttcagggtc atagccgtga acgaagtagg gagaagtcag cctagccagc cgtcagacca 2340 tcatgaaaca ccaccagcag ctccagatag gaatccacaa aacataaggg ttcaagcctc 2400 tcaacccaag gaaatgatta taaagtggga gcctttgaaa tccatggagc agaatggacc 2460 aggcctagag tacagagtga cctggaagcc acagggagcc ccagtggagt gggaagaaga 2520 aacagtcaca aaccacacat tgcgggtgat gacgcctgct gtctatgccc cttatgatgt 2580 caaggtccag gctatcaatc aactaggatc tgggcctgac cctcagtcag tgactctcta 2640 ttctggagaa gactatcctg atacagctcc agtgatccat ggggtggacg ttataaacag 2700 tacattagtt aaagttacct ggtcaacagt tccaaaggac agagtacatg gacgtctgaa 2760 aggctatcag ataaattggt ggaaaacaaa aagtctgttg gatggaagaa cacatcccaa 2820 agaagtgaac attctaagat tttcaggaca aagaaactct ggaatggttc cttccttaga 2880 tgcctttagt gaatttcatt taacagtctt agcctataac tctaaaggag ctggtcctga 2940 aagtgagcct tatatatttc aaacaccaga aggagtacct gaacagccaa cttttctaaa 3000 ggtcatcaaa gttgataaag acactgccac tttatcttgg ggactaccta agaaattaaa 3060 tggaaactta actggctatc ttttgcaata fccagataata aatgacacct acgagattgg 3120 agaattaaat gatattaaca ttacaactcc atcaaagccc agctggcacc tctcaaacct 3180 gaatgcaact accaagtaca aattctactt gagggcttgc acttcacagg gctgtggaaa 3240 accgatcacg gaggaaagct ccaccttagg agaagggagt aaaggtatcg ggaagatatc 3300 aggagtaaat cttactcaaa agactcaccc aatagaggta tttgagccgg gagctgaaca 33 60 tatagttcgc ctaatgacta agaattgggg cgataacgat agcatttttc aagatgtaat 3420 tgagacaaga gggagagaat atgctggttt atatgatgac atctccactc aaggctggtt 3480 tattggactg atgtgtgcga ttgctcttct cacactacta ttattaactg tttgctttgt 3540 gaagaggaat agaggtggaa agtactcagt taaagaaaag gaagatttgc atccagaccc 3600 agaaattcag tcagtaaaag atgaaacctt tggtgaatac agtgacagtg atgaaaagcc 3660 tctcaaagga agcctfccggt cccttaatag ggatatgcag cctactgaaa gtgctgacag 3720 cttagtcgaa tacggagagg gagaccatgg tctcttcagt gaagatggat catttattgg 3780 tgcctacgct ggatctaagg agaagggatc tgttgaaagc aatggaagtt ctacagcaac 3840 ttttcccctt cgggcataaa cacaacatat gtaagcaacg ctactggttc accccaacct 3900 tccatattta tctgttcaaa ggagcaagaa ctttcatata ggaatagaaa catgctggcc 3960 gaagatttca tccagaagtc aacatcctgc aattatgttg aaaagagtag tactttcttc 4020 aaaatataaa atgccaagca cttcaggcct atgttttgct tatattgttt tcaggtgctc 4080 aaaatgcaaa acacaaaaca aatcctqcat ttagatacac ctcaactaaa tccaaagtcc 4140 ccattcagta tattccatat ttgcctgatt ttactattcg gtgtgtttgc atagatgttg 4200 ctacttggtg ggtttttctc cgtatgcaca ttggtataca gtctctgaga actggcttgg 4260 tgactttgct tcactacagg ttaaaagacc ataagcaaac tggttattta aaatgtaaaa 4320 aggaatatga aagtcttatt aaaacacttc attgaaaata tacagtctaa atttattatt 4380 taaattttac tagcaaaagt cttaggtgaa caatcaacta gtatttgttg agctcctatt 4440 tgcccagaga tggtcatatt taaacagaag tatacgtttt tcagtttcaa catgaatttt 4500 tttatttctg tcagttatga catccacgag catcactttt tgtgtctgtt tttttttttt 4560 tcttggacta aattcaactg catggaagcg gtggtcagaa ggttgtttta tacgagaaca 4620 ggcagaaagt gcccattgtt caggattcta atagctacat ctacttaata tcttcatttc 4680 taaattgact gcttttacct ttttctcatg tttatataat ggtatgcttg catatatttc 4740 atgaatacat tgtacatatt atgttaatat ttacacaatt taaaatatag atgtgtttta 4800 ttttgaagtg agaaaatgaa cattaacagg catgtttgta cagctagaat atattagtaa 4860 gatactgttt ttcgtcattc cagagctaca actaataaca cgaggttcca aagctgaaga 4920 ctttgtataa agtatttggg ttttgttctt gtattgcttt ctttcaacag tttcaaaata 4980 322 i a-iatatcata caaatattga gggaaatgtt ttcatatttt tcaaaatagg tttttattgt 5040 tgaatgtaca tctaccccag cccctcaaaa gaaaaactgt ttacatagaa attcctacac 5100 atacgtttgc gtatatgtta ttttaaacat ctttgtggtg agaatttttt ccccgatatt 5160 ctccttctgt caaagtcaga acaaattcag ggaatttatt ttctggcagt tgtgctccag 5220 tccttttaaa attgtacatg aacatgtttt agaaacaata tggaggatga tgcatacatg 5280 tcggtcaagt tcagcgctcg acattttatg gaaagatttt tttaacctta ccacgaaata 5340 cttaactact gtttaagtga attgacttat ttcactttag tttttgaact gtgattattg 5400 gtatactgtt atatcctcaa cttggattta tggtaacccc ttttagttca tggagaccaa 5460 aatttggggt atttataata gtcagcgcag gaatgcacat ggaatatcta cttgtccttt 5520 tgaacctcac gagtcatcca gaatgtatag acaggaaaag catgtcttat ttaaaactgt 5580 aatttatggg ctcaggatct gaccgcagtc ccgggagtaa gcatttcaaa gggggaaggc 5640 agtgtggtcc ctaccctgtg tgaatgtgag gatgtagaca tccatcagtg caactcgagc 5700 tccatcctcc tccgatttct aaggctcca'g ttttctggag ggacagtcat catgttttga 5760 tttatctggg agaaaactgt ggtgcacagc ttgtgaggag ggcaaggttg tgacgttcga 5820 gcttagttct ggtgttattc tgtctcctct tctttgtcat cagccaaaac gtggttttta 5880 aagagagtca tgcaggttag aaataatgtc aaaaatattt aggaatttaa taacctttaa 5940 gtcagaaact aaaacaaata ctgaaatatt agctcttcct acacttcgtg ttccccttta 6000 gctgcctgaa aatcaagatt gctcctactc agatcttctg agtggctaaa acttatggat 6060 atgaaaaatg agattgaatg atgactatgc tttgctatca ttgttacctt tcctcaatac 6120 tatttggcaa ctactgggac tcttcagcac aaaaggaata gatctatgat tgaccctgat 6180 tttaattgtg aaattatatg attcatatat tttatgaatc agaataacct tcaaataaaa 6240 taaatct-aag tcggttaaaa tggatttcat gattttccct cagaaaatga gtaacggagt 6300 ccacggcgtg caatggtaat tataaattgg tgatgcttgt ttgcaaattg cccactcgtg 6360 ataagtcaac agccaatatt taaaactttg ttcgttactg gctttaccct aactttctct 6420 agtctactgt caatatcatt ttaatgtaat tgattgtata tagtctcaag aatggttggt 6480 gggcatgagt tcctagagaa ctgtccaagg gttgggaaaa tccaaattct cttcctggct 6540 ccagcactga ttttgtacat aaacattagg caggttgctt aaccttttta tttcaaactc 6600 tctcaactct aaagtgctaa taataatctc agttacctta tctttgtcac agggtgttct 6660 tttttatgaa gaaaaatttg aaaatgataa aagctaagat gccttctaac ttcataagca 6720 aacctttaac taattatgta tctgaaagtc acccccacat accaactcaa cttttttcct 6780 gtgaacacat aaatatattt ttatagaaaa acaaatctac ataaaataaa tctactgttt 6840 agtgagcagt atgacttgta catgccattg aaaattatta atcagaagaa aattaagcag 6900 ggtctttgct atacaaaagt gttttccact aattttgcat gcgtatttat aagaaaaatg 6960 tgaatttggt ggttttattc tatcggtata aaggcatcga- tattttagat gcacccgtgt 7020 ttgtaaaaat gtagagcaca atggaattat gctggaagtc tcaaataata tttttttcct 7080 attttatact catggaagag ataagctaaa gaggggacaa taatgagaaa tgttggtgtg 7140 cttttctaag catttaaaac ataattgcca attgaaaccc taaatatgtt tacataccat 7200 taagatatga ttcatgtaac aatgttaaat taattataat gggattgggt ttgttatctg 7260 tggtagtata tatcctagtg ttcctatagt gaaataagta gggtfccagcc aaagctttct 7320 ttgttttgta ccttaaattg ttcgattacg tcatcaaaag agatgaaagg tatgtagaac 7380 aggttcacgt gattaccttt ttcttttggc ttggattaat attcatagta gaactttata 7440 aaacgtgttt gtattgtagg tggtgtttgt attatgctta tgactatgta tggtttgaaa 7500 atattttcat tatacatgaa attcaacttt ccaaataaaa gttctacttc atgtaatcca 7560 aaa 7563

Table Llllg. Nucleotide sequence alignment of 282P1G03 v.1 (SEQ ID NO: 188) and 282P1G03 v.8 (SEQ ID NO: 189) v.l 1 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg I 1 II 1 1 11 II 1 1 I 1 1 I 1 1 I II I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 II 1 1 II 1 II 1 1 1 1 1 50 v. 8 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 I 1 1 CGGACCCTGCGCGCCCCCGTCCCGGCTCCCGGCCGGCTCGGGGGAGAAGG 50 v. 1 51 cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg ! 1 ! &#943; II ! 1 1 Η 1 &#943; 1 1 1 i &#943; &#943; i i &#943; i i &#943; i i I i 1 i i 1 1 1 H i 1 &#943; &#943; 1 i &#943; i ! 1 1 1 &#943; 100 V. 8 51 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 I 1 1 I 1 1 1 1 1 I 1 II 1 1 CGCCCGAGGGGAGGCGCCGGACAGATCGCGTTTCGGAGGCGGCGCAGGTG 100 V.l 101 ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcataq 1U 1 1 I 1 1 Η I 1 I 1 I 1 1 1 II M ! 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 ! Η I &#943; II 150 v.8 101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 CTGTAAACTGCAAACCATAATCCTGTCTTAATACTGCAAACAAATCATAG 150 v.l 151 tggaactaaggggaacttaatttactqtttccaggttaactaaggtctca 1111111II1! 11111111111111IIII111 ill il 11 il 111111111 TGGAACTAAGGGGAACTTAATTTACTGTTTCCAGGTTAACTAAGGTCTCA . 200 v. 8 151 200 V. 1 201 gctgtaaaccaaaagtgagaggagacattaagattttca-ttcttaccggg 250 323 v. 8 201 GCTGTAAACCAAAAGTGAGAGGAGACATTAAGATTTTCATTCTTACCGGG 250 v.l 251 ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact 11 il il li I Π I! 1 HI 11 Η Η &#943; Π i! II111 II Η Π 1 Η II! II! 11 300 ν.8 251 TTGTCTTCTTCCTGAAGAGCAATGGAGCCGCTTTTACTTGGAAGAGGACT 3 00 v.l 301 aatcgtatatctaatgttcctcctgttaaaatfcc.tcaaaaqcaattgaaa 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 i 1 &#943; 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ill I 1 11 1 1 1 1 350 ν.8 301 ' 1 I 1 1 1 1 1 1 1 1 I I II 1 ι I 1 I I 1 ! ι &#943; II 11 ! I I Η ι 1 1 1 ι 1 ι I 1 I I II l 1 1 I AATCGTATATCTAATGTTCCTCGTGTTAAAATTCTCAAAAGCAATTGAAA 350 v.l 351 taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc 1 1 1 t 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 &#943; 1 1 1 &#943; 1 1 1 1 1 1 1 1 I 400 ν.8 351 1 I 1 t 1 1 ι i 1 1 1 1 I N N I 1 1 1 1 1 1 H 1 1 1 1 I 1 1 I I 1 1 1 1 1 1 1 1 1 I 1 ι 1 1 i TACCATCTTCAGTTCAACAGGTTCCAACAATCATAAAACAGTCAAAAGTC 400 v.l 401 caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagctaa ι ι ι ι ι &#943; η ι ι ι ι ) ii ι ι ηlliiii||ιιιι ii ι ιι |i ι ι ι ι ι ι ιiiIll 450 ν.8 401 ) 1 j I I j I 1 t 1 1 i i I E i 1 N i- 1 1 1 { 1 i E 1 1 1 i H 1 H ( I 1 1 1 H 1 1 1 I > 1 i CAAGTTGCCTTTCCCTTCGATGAGTATTTTCAAATTGAATGTGAAGCTAA 450 v.l 451 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt !11 1 i 1 ! 1 I 1 1 1 Η 1 1 1 I 1 1 I 1 1 ! 1 1 1 1 &#943; 1 ! II I 1 1 1 1 1 1 I 1 I Η 1 1 1 I ! 500 ν.8 451 &#943; { I ι i INI I 1 1 ι1 I I 11 II &#943;It 1 1 11 f I J 1 1 I 1 1 1 1 11 1 J 1 Η 1 1 ι i 1 i AGGAAATCCAGAACCAACATTTTCGTGGACTAAGGATGGCAACCCTTTTT 500 v.l 501 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg | I I 1 II 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 II 1 1 1 || 1 1 1 I 1 1 1 . 550 ν.8 501 1 11 11111111 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I II I 1 11 I 11 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTTCACTGACCATCGGATAATTCCATCGAACAATTCAGGAACATTCAGG 550 v.l 551 atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt | 1 1 1 1 1 1 1 1 |.| 1 II 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 1 1 1 1 1 II 1 1 II II 1 II 600 ν.8 551 I 1 1 i 1 1 1 ι &#943; I l 1 1 j &#943; 1 1 1 I 1 1 1 1 I 1 I I I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 ATCCCAAACGAGGGGCACA'rATCTCACTTTCAAGGGAAATACCGCTGCTT 600 v.l SOI tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag 1 1 1 1 11 I 11 I 1 1 1 1! I I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 li 1 I I 1 1 1 I 1 1 1 1 I 1 1 1 650 ν.8 SOI 1 J 1 1 II 1 1 1 1 1 1 1 1 j 1 I 1 1 t I ! 1 1 1 1 1 1 I 1 1 I 1 ι I I 1 I 1 1 1 ! 1 1 1 1 I I I 1 TGCTTCAAATAAACTGGGAATCGCTATGTCAGAAGAAATAGAATTTATAG 650’ v.l 651 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcfctgaagtg llllll 700 •ζ- R £ R &#906; ι &#943; &#943; &#943; I i 656 v.l 701 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 750 v. 8 657 656 v.l 751 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 800 v. 8 657 1 1 1 1 1 1 II 1 1 1 1 1 1 I 1 1 1 1 1 1 -----------------------------AATTAGAACACATCGAACAAG 677 v. 1 801 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg &#943; !1 11 111 I 1 1 1II i!11111 1 1 1 1 I I 1 1 1 i I 1 1 1 1 1 I 1 I I 11111 1 1 I 1 850 v. 8 678 1 1 I 1 I 1 II 1 1 I 1 I I 1 1 I I 1 I ! 1 1 1 I 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I ATGAAAGAGTATACATGAGCCAAAAGGGAGATCTATACTTCGCAAACGTG 727 v.l 851 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II j 1 1 1 1 1 II 1 j 1 | 1 1 1 I 1 I ) 1 1 1 1 1 1 1 1 1 1 | | 900 v. 8 728 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag 777 v.l 901 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt 1 1 1 1 1 1 1 II 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 II I 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 I 950 v. 8 778 1 ! 1 I 1 11 1 i 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 II 1 1 I 1 1 1 1 1 1 1 1 ATTAAGGACTATTGTACAGAAAATGCCAATGAAACTAACAGTTAACAGTT 827 v. 1 951 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca 1 1 1 1 1 1 i li 1 I II 1 1 1 1 1 I I 1 1 I 1 1 t II 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1000 v. 8 828 1 1 1 1 i 1 1 i ι 1 1 I 1 I I 1 1 1 1 i ll I ! 11 i 1 1 &#943; 1 1 1 1 1 1 1 1 1 1 I 1 l ! 1 ι 1 1 1 1 TAAAGCATGCTAATGACTCAAGTTCATCCACAGAAATTGGTTCCAAGGCA 877 324 ! νν&#970; 1001 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag I I 1 I 1 I 1 I II 1 1 1 I I 1 1 1 I I 1 I I I 1 1 I I I II I I I I I I I I I 1 I I 1 I I 1 I 1 I 1050 Il 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! I 1 I II 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 v.8 87 8 AATTCCATCAAGCAAAGAAAACCCAAACTGCTGTTGCCTCCCACTGAGAG 927 v.l 1051 tggcagtgagtcttcaattaccatcctcaaaggggaaatcttgctgcttg 1 1 1 Π 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 111 I 1111111111II11 S11111 111 I 11 110 0 1 ι ι 1 ι ι ι i i 1 1 I i | 1 i I 1 1 I 1 &#943; &#912; » 1 1 I 1 1 I I J 1 I 1 1 1 1 s 1 1 I I l ι I I I I 1 v.8 928 TGGCAGTGAGTCTTCAATTACCATCCTCAAAGGGGAAATCTTGCTGCTTG 977 v.l 1101 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt I I 1 1 1 II 1 1 11 111 i1 1 1 1 1 1llll111 1 1 I 1 111 I 11 1 1 1 1 1 I 1 III 1 1 1150 ! ι 1 1 1 Η 1 1 1 I 1 1 I I &#943; 1 ι ι I i 1 I 1 1 t ! 1 ι Η 1 ! 1 1 I 1 S ! ι I t 1 I 1 1 1 ι ι &#943; v.8 978 AGTGTTTTGCTGAAGGCTTGCCAACTCCACAGGTTGATTGGAACAAAATT 1027 v.l 1151 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac 1 I 1 III 11 II1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 III 1 I 1200 1 1 I I I 1 1 I 1 1 I 1 1 I 1 1 1 I 1 1 1 I I 1 1 ! I 1 1 I H 1 1 1 1 I ! 1 I I I I I 1 1 1 1 1 I v.8 102 8 GGTGGTGACTTACCAAAGGGGAGAGAAACAAAAGAAAATTATGGCAAGAC 1077 v.l 1201 tttqaaqatagagaatqtctcctaccaggacaaaggaaattatcgctgca 1 1 nil! I I II 11 | 111!! | II11! II 1 1 II I 1 Hill 111 1 1 II 1 III 1 1250 ι S ! I 1 &#943; &#943; 1 I 1 1 S i i I i ι I l l &#912; i &#943; &#943; ι &#912; i i ι i &#943; ι &#943; ι ι i ι i ι ι s ι ι ι ι ι i 1 ι ι v._,8 107 8 TTTGAAGATAGAGAATGTCTCCTACCAGGACAAAGGAAATTATCGCTGCA 1127 v.l 1251 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta I I I 1 1 I 1 1 1 1 1 1 1 I 1 1 I I I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 I 1 1 I I I 1 I I 1 I 1 1 1 1300 1 ! 1 1 1 I 1 1 1 1 1 1 1 1 1 ! 1 1 I I 1 I 1 1 II I 1 1 1 1 I 1 I 1 1 1 II I 1 I 1 1 1 II 1 I 1 v.8 112 8 CAGCCAGCAATTTCTTGGGAACAGCCACTCACGATTTTCACGTTATAGTA 1177 v.l 1301 ga------------------------------------agagcctcctcg 1 ! I!11 I I 1 I I 1 1 1 1314 I $ 1 I ! 1 l ι &#943; i i I I I v.8 1178 GAAGataacatctctcatgagctcttcactttacatccagAGCCTCCTCG 1227 v.l 1315 ctggacaaagaagcctcagagtgctgtgtataqcaccqgaagcaatggca I 1 I 1 I I 1 I 1 I 1 1 I 1 I I I I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1364 I 1 1 1 I 1 J 1 1 1 I 1 ι ι 1 I 1 i I 1 1 1 1 I 1 1 1 1 I 1 I I 1 1 I I 1 1 1 It 1 I I ! 1 1 1 I I v.8 1228 CTGGACAAAGAAGCCTCAGAGTGCTGTGTATAGCACCGGAAGCAATGGCA 1277 v.l 1365 tcttgttatgtgaggctgaaggagaacctcaacccacaatcaagtggaqa 1 1 1 1 1 I 1 1 1 I 1 111111 I 111111111111 I I 1 1 1 1 I 1 1 II 1 1 11 I 1111 1414 I ! I 1 f 1 I 1 1 I 1 1 1 II ! 1 U 1 I 1 I 1 1 1 1 1 1 1 1 l 1 1 1 1 1 1 1 ι 1 I 1 1 II II I 1 v.8 1278 TCTTGTTATGTGAGGCTGAAGGAGAACCTCAACCCACAATCAAGTGGAGA 1327 v.l 1415 gtcaatggctccccagttgacaatcatccatttgctggtgatgttgtctt 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 ι π 1 | | | 1 | II I I I 1 1 | | | I I I ι | II | | | | 1 I 14 64 I I 1 1 I ll 1 i 1 1 I 1 II l 1 Γ ι t ι 1 1 1 I 1 IS I II 1 1 I 1 1 1 1 1 I I 1 I 1 I &#943; 1 I 1 1 v.8 132 8 GTCAATGGCTCCCCAGTTGACAATCATCCATTTGCTGGTGATGTTGTCTT 1377 v.l 1465 ccccagggaaatcagttttaccaaccttcaaccaaatcatactgctgtgt Hill M 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 | 1 1514 N Η I ! i I 1 i 1 l·! ! N 1 I s ι i 1 1 I S I ι &#943; ι 1 S N I 1 II 1 I II I 1 I I 1 1 I I I v.8 13 78 CCCCAGGGAAATCAGTTTTACCAACCTTCAACCAAATCATACTGCTGTGT 1427 v.l 1515 accagtgtgaagcctcaaatgtccatggaactatccttgccaatgccaat 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1564 I 1 I I I I I I 1 1 I I I 1 I 1 1 1 I I 1 I 1 I 1 I I I I I II 1 I 1 t II I 1 I I I 1 II I I 1 I v.8 1428 ACCAGTGTGAAGCCTCAAATGTCCATGGAACTATCC?TTGCCAATGCCAAT 1477 v.l 1565 attgatgttgtggatgtccgtccattgatacaaaceaaagatggagaaaa 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 I 1 I I 1 1 I 1 1 1 1 1 1 1614 1 1 1 1 1 1 1 1 1 1 I 1 II I 1 I I 1 1 I 1 I 1 I I 1 1 1 I 1! 1 1 1 1 1 I I I I I 1 1 1 1 II 1 1 v.8 14 78 ATTGATGTTGTGGATGTCCGTCCATTGATACAAACCAAAGATGGAGAAAA 1527 v.l 1615 ttacgctacagtggttqggtacagtgctttcttacattgcgaqttctttg Η 1II! i Iiil N I Η 11 H 111!11 It 1111II1 Η 111! 1111 11 111 v.8 1528 TTACGCTAGAGTGGTTGGGTACAGTGCTTTCTTACATTGCGAGTTCTTTG 1664 1577 v.l 1665 cttcacctgaggcagtcgtgtcctggcagaaggtggaagaagtgaaaccc I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I I 1 1714 γττ&#943; I I I I 1 I I I I I 1 1 I 1 I I I 1 E 1 1 I I I I 1 I I I 1 I < I 1 I 1 l &#943; 1 1 1 I I I I 1 v.8 157 8 CTTCACCTGAGGCAGTCGTGTCCTGGCAGAAGGTGGAAGAAGTGAAACCC 1627 v.l 1715 ctggagggcaggcggtatcatatctatgaaaatggcacattgcagatcaa I 1 1 1 1 1 1 i I I I I 1 I 1 1 I I 1 1 1 1 1 1 1 I I 1 I 1 1 1 II 1 1 1 I 1 I ! I 1 1 1 I 1 1 1 I 1764 1 1 1 I ! 1 1 1 1 1 1 I 1 I I | I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 i 1 I 1 I II I 1 1 I I I I v.8 162 8 CTGGAGGGCAGGCGGTATCATATCTATGAAAATGGCACATTGCAGATCAA 1677 325 v.l 1765 cagaaccaccgaagaagatgctgggtcttactcatgttgggtagaaaatg II 1 II 1 II 1 II 1 I j 1 1 II 1 1 1 I 1 I 1 j I 1 1 1 I I It It 1 1 1 II II II II II 1 1814 1 1 1 I l &#943; 1 ι 1 t { I 1 i ! i i f i i I I ( i i ! ) ! ! I 1 ι 1 i i ι I i I 1 I ) i i 1 I ι I I 1 v.8 1678 CAGAACCACCGAAGAAGATGCTGGGTCTTACTCATGTTGGGTAGAAAATG 1727 v.l 1815 ctataggaaaaactgcagtcacagccaatttggatattagaaatgctaca 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 i 1 1 1 1 1 1 1 1 1 I I I 1 1 1864 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι ι 1 ι 1 v.8 172 8 CTATAGGAAAAACTGCAGTCACAGCCAATTTGGATATTAGAAATGCTACA 1777 v.l 1865 aaacttagagtttctcctaagaatcctcgtatccccaaattgcatatgct 1 1 I 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1914 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 v.8 1778 AAACTTAGAGTTTCTCCTAAGAATCCTCGTATCCCCAAATTGCATATGCT 1827 v.l 1915 tgaattacattgtgaaagcaaatgtgactcaeatttgaaacacagtttga I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1964 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 v. 8 1828 TGAATTACATTGTGAAAGCAAATGTGACTCACATTTGAAACACAGTTTGA 1877 v.l 1965 agttgtcctqgagtaaagatggagaagcctttgaaattaatggcacagaa II 1 III 1 1 I II II 1 I 1 III II II II II 1 1 I 1 II 1 1 1 1 1 I I Ι&#906;Π 1 1 H II 2014 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 V.8 187 8 AGTTGTCCTGGAGTAAAGATGGAGAAGCCTTTGAAATTAATGGCACAGAA 1927 v.l 2015 gatggcaggataattattgatggagctaatttgaccatatetaatgtaac 1 I I I I 1 || 11 1 1111 11II11111 11 1111 | II | I | | | 1 | | | | 1 II I 1 1 1 2064 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.8 192 8 GATGGCAGGATAATTATTGATGGAGCTAATTTGACCATATCTAATGTAAC 1977 v.l 2065 tttagaggaccaaggtatttactgctgttcagctcatactgctctagaca 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 ! 1 1 1 I 1 1 1 1 I 1 I I I 1 1 1 1 1 1 ! 1 1 2114 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 v.8 1978 TTTAGAGGACCAAGGTATTTACTGCTGTTCAGCTCATACTGCTCTAGACA 2027 v.l 2115 gtgctgccgatataactcaagtaactgttcttgatgttccggatccacca 1II111111 I I 1 1 11 1 1 1 1 1 1 H 1 1 1 1 1 1111 1 11 1 1 1 1 1 I 1 1 1 II 1 1 1 1 2164 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.8 2028 GTGCTGCCGATATAACTCAAGTAACTGTTCTTGATGTTCCGGATCCACCA 2077 v.l 2165 gaaaaccttcacttgtctgaaagacagaacaggagtgttcggctgacctg I I'l 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 2214 I 1 1 1 1 I 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 v.8 207 8 GAAAACCTTCACTTGTCTGAAAGACAGAACAGGAGTGTTCGGCTGACCTG 2127 v.l 2215 ggaagctggagctgaccacaacagcaatattagcgagtatattgttgaat 1111111111 Ii 111 il 11111 i HU11 i 11111II11II11111! 1II V.8 212 8 GGAAGCTGGAGCTGACCACAACAGCAATATTAGCGAGTATATTGTTGAAT 2264 2177 v.l 2265 ttgaaggaaacaaagaagagcctggaaggtgggaggaactgaccagagtc 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 T 1 I 2 314 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 v.8 2178 TTGAAGGAAACAAAGAAGAGCCTGGAAGGTGGGAGGAACTGACCAGAGTC 2227 v.l 2315 caaggaaagaaaaccacagttatcttacctttggctccatttgtgagata 1 1 1 1 II 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 H 1 1 1 1 1 1 I 1 1 1 I I 1 1 I 1 1 1 I 1 1 1 2364 I i i i 1 I < I 1 ! 1 i 1 1 ! 1 i i I i 1 ι 1 &#943; 1 1 ι I &#943; 1 1 1 i i ι ι I I i i ι 1 ι Ι ι ι 1 ! i 1 v.8 2228 CAAGGAAAGAAAACCACAGTTATCTTACCTTTGGCTCCATTTGTGAGATA 2277 v.l 2365 ccagttcagggtcataqccgtqaacqaaqtaqqqagaagtcagcctagcc 1 1 l|l! ι &#943; 11II1II II1 IIII1 1 II INI 11II IIIIII 1 III 11 Nil 2414 1 I 1 1 1 1 I I I 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 v.8 2278 CCAGTTCAGGGTCATAGCCGTGAACGAAGTAGGGAGAAGTCAGCCTAGCC 2327 v.l 2415 agccgtcagaceatcatgaaacaccaccagcagctccagataggaatcca 1 I 11 H 1 H 1 ΓΠ I 1 I 1 1 1 I!1 I 1 I I 1111 I 1111111 I 1 1 1 1 1 I 1 II 1 1 2464 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I I 1 1 I 1 1 1 I I 1 I I 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 v.8 2328 AGCCGTCAGACCATCATGAAACACCACCAGCAGCTCCAGATAGGAATCCA 2377 v.l 2465 caaaacataagggttcaagcctctcaacccaaggaaatgattataaagtg I 1 1 I 1 1 1 1 1 1 1! 1 1 1 1 I 1 1 1 I 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 I I I'l 1 2514 I 1 1 1 I 1 1 II 1 1 I 1 I I 1 I I 1 I I I I I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I II I 1 1 1 1 1 1 1 I v.8 2378 CAAAACATAAGGGTTCAAGCCTCTCAACCCAAGGAAATGATTATAAAGTG 2427 v.l 2515 ggagcctttgaaatccatggagcagaatggaccaggcctagagtacagag 2564 326 I . Via 2428 GGAGCCTTTGAAATCCATGGAGCAGAATGGACCAGGCCTAGAGTACAGAG 2477 v.l 2565 tgacctggaagccacagggagccccagtggagtgggaagaagaaacagtc &#943; 1 Η 1 1 1 &#943; 1 1 1 &#943; i II 1 1 N 1 &#943; &#943; ! I 11 Π!1II!11111 I 111 11 1 1 1 1 ! 1 2614 I 1 1 ! 1 1 I I 1 ! 1 1 1 1 1 1 1 II 1 1 1 1 1 1 I 1 I 1 1 1 1 I 1 1 1 1 1 1 I I 1 1 1 I 1 1 I I I v. 8 24 7 8 TGACCTGGAAGCCACAGGGAGCCCCAGTGGAGTGGGAAGAAGAAACAGTC 2527 v.l 2615 acaaaccacacattgcgggtgatgacgcctgctgtctatgccccttatga 1 I II 1 I 1 II I I II 1 I I I i 1 1! 1 1 1 ! I I I I I II !| I I II 1 ) 11 1 I 1 1 1 1 1 2664 1 1 1 1 1 I I i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ,1 1 1 1 1 i I 1 1 1 I I I ι 1 I ι 1 1 ι 1 1 ι v.8 252 8 ACAAACCACACATTGCGGGTGATGACGCCTGCTGTCTATGCCCCTTATGA 2577 v.l 2665 tgtcaaggtccaggctatcaatcaactaggatctgggcctgaccctcagt I I 1 1 I I 1 I 1 II 1 I I 1 I 1 I 1 1 1 I 1 I II I 1 1 1 1 I II II II It 1 1 II I I 1 1 I 1 2714 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I H 1 1 1 1 1 1 1 1 v.S 2578 TGTCAAGGTCCAGOCTATCAATCAACTAGGATCTGGGCCTGACCCTCAGT 2627 v.l 2715 cagtgactctctattctggagaagactatcctgatacagctccagtgatc I 1 I 1 1 II I 1 1 1 I 1 1 1 1 1 I II 1 I 1 ] I I 1 II 11 1 1 1 II II II 1 I 1 1 1 I I 1 I 1 2764 II 1 I 1 I 1 II 1 1 II 1 1 1 1 1 1 I I I I I I I I 1 I I I I I I I I I 1 1 I 1 1 1 1 II 1 II 1 v.8 2 62 8 CAGTGACTCTCTATTCTGGAGAAGACTATCCTGATACAGCTCCAGTGATC • 2677 v.l 2765 catggggtggacgttataaacagtacattagttaaagttacctggtcaac 11 1 I I I 1 I 1 1 I 1 I I 1 1 ! I 1 I 1 I I II I 1 I 1 1 II I II I I I II 1 I I 1 I I 1 1 I I 2814 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1111111111ι 11II I 1 1 1 1 1 II! 1 11 1 1 v.8 2 678 CATGGGGTGGACGTTATAAACAGTACATTAGTTAAAGTTACCTGGTCAAC 2727 v.l 2815 agttccaaaggacagagtacatggacgtctgaaaggctatcagataaatt II111II1111!II111II11 il II11li II1li II1 If 11 H III11II v. 8 2728 AGTTCCAAAGGACAGAGTACATGGACGTCTGAAAGGCTATCAGATAAATT 2864 2777 v.l 2865 ggtggaaaacaaaaagtctgttggatggaagaacacatcccaaagaagtg II 111 II1|| 1 I 1 I ll ll III II ll ll ll 1||||||||||| | I II | II II 2914 1 1 1 1 II 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 11 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 v.8 277 8 GGTGGAAAACAAAAAGTCTGTTGGATGGAAGAACACATCCCAAAGAAGTG 2827 v.l 2915 aacattctaagattttcaggacaaagaaactctggaatggttccttcctt lllllllllllllill Hill Hill lillllll MINI II Hili III v.8 2 82 8 AACATTCTAAGATTTTCAGGACAAAGAAACTCTGGAATGGTTCCTTCCTT 2964 2877 v.l 2965 agatgcctttagtgaatttcatttaacagtcttagcctataactctaaag II 11 I II 1 l| 1 II 1 1 1 1 II II II II 1 1 II 1 1 1 II II 1 II II II II l| II 1 3014 1 1 1 I 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 v.S 2 87 8 AGATGCCTTTAGTGAATTTCATTTAACAGTCTTAGCCTATAACTCTAAAG 2927 v.l 3015 gagctggtcctgaaagtgagccttatatatttcaaacaccagaaggagta 1! 11111111 Η1 i 1II111 Η111111!111111111111111111111 v.S 2 92 8 GAGCTGGTCCTGAAAGTGAGCCTTATATATTTCAAACACCAGAAGGAGTA 3064 2977 v.l 3065 cctgaacagccaacttttctaaaggtcatcaaagttgataaagacactgc II II 1 I II II 1 II 1 II II (I II j 1 1 II j 1 1 1 i j 1 II 1 1 II 1! 1 II II II j 3114 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.8 297 8 CCTGAACAGCCAACTTTTCTAAAGGTCATCAAAGTTGATAAAGACACTGC 3027 v.l 3115 cactttatcttggggactacctaagaaattaaatggaaacttaactggct 11 ι ι ι ηι η ι i| || |i || || i| || ii π II Η IIII111 Π 1 II II Π 1 3164 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 1 1 1 1 1 1 1 1 i 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 v.S 3 02 8 CACTTTATCTTGGGGACTACCTAAGAAATTAAATGGAAACTTAACTGGCT 3077 v.l 3165 atcttttgcaatatcagataataaatgacacctacgagattggagaatta 1 Π 1 1 1 II 1 1 I II1 Π i H i i i Π Π Η 1 I 111 I 11 i I 11 ! 1 1 II ! I Π ! 3214 1 1 1111II II II1 1 1 111 11 1 1 1 1 1 I 1 11 II II II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 v.8 3078 ATCTTTTGCAATATCAGATAATAAATGACACCTACGAGATTGGAGAATTA 3127 v.l 3215 aatgatattaacattacaactccatcaaagcccagctgqcacctctcaaa II II j 1 , 1 ) 1 1 |l 11 II |l || II II j j 1 | | 1 || 1 II 1 II II 1 1 l| II 1 || 3264 11 1 II 1 1 1 1 1 I 1 1 I I 1 1 1 1 1 111111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι11 v.S 312 8 AATGATATTAACATTACAACTCCATCAAAGCCCAGCTGGCACCTCTCAAA 3177 v.l 3265 ccfcgaatgcaactaccaagtacaaattctacttgagggcttgcacttcac II II II II 1 1 1 1 II 1 1 1 II 1 II II II 1 11 1 1 1 1 1 1 1 1 1 | | 1 II l| II 1 II 3314 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 1 I 1 1 1 1 1 1 1 1 1 1 v.8 3178 CCTGAATGCAACTACCAAGTACAAATTCTACTTGAGGGCTTGCACTTCAC 3227 v.l 3315 agggctgtggaaaaccgatcacggaggaaagctccaccttaggagaaggg 3364 327 v.8 3228 AGGGCTGTGGAAAACCGATCACGGAGGAAAGCTCCACCTTAGGAGAAGGG 3277 v.l 3365 aqtaaaqqtatcqggaaqatafecaggagtaaatcttactcaaaagactca III Hi III 1 1 Hill 1 1 I HI 1 il 1 1 I I 1 ! Η I I H HI ! Η Η ! II H 3414 v.8 3278 i i II i 1 1 1 1 l 1 1 II II 1 i II Η 1 I I i Ν ι 1 t i N 11 1 II 1 i ι Η 1 II Η I AGTAAAGGTATCGGGAAGATATCAGGAGTAAATCTTACTCAAAAGACTCA 3327 v. 1 3415 cccaatagaggtatttgagccgggagctgaacatatagttcgcctaatga 1 1 1 II 1 1 I 111 1 1 1 1 I 1 III 1 1 1 i 1 II 1 1 1 1 1 1 1 1 1 i 1 I 1111111 1 111 3464 v. 8 3328 1 I I 1 1 1 1 1 1 II 1 1 1 1 1 1 I 1 1 1 I 1 1 II 1 1 1 I 1 I 1 1 I II 1 1 II 1 1 1 1 1 1 1 1 J CCCAATAGAGGTATTTGAGCCGGGAGCTGAACATATAGTTCGCCTAATGA 3377 v. 1 3465 ctaagaattggggcgataacgatagcatttttcaagatgtaattgagaca 11II11111 Hil 11111!1!1! 1111!11111111!IIII1) i 1111II 3514 v.8 3378 CTAAGAATTGGGGCGATAAcGATAGCATTTTTCAAGATGTAATTGAGACA 3427 v.l 3515 agaqqqaqaqaatatgctggtttatatgatgacatctccactcaaggctg III III II ill 1 1 1 III II III 1 1 1 1 II 1 II 1 I II 1 1 1 1 1 I 1 1 II II 1 1 1 3564 v. 8 3428 1 II II 11II II II1 1 1 1 II 1 1 1 1 I I 1 I 1 1 1 111111II 1! I I 1 1 1 II II 1 AGAGGGAGAGAATATGCTGGTTTATATGATGACATCTCCACTCAAGGCTG 3477 v.l 3565 gtttattggactgatg.tgtgcgattgctcttctcacactactattattaa 1 It II I t II 1 1 II I I II II j II II 1 I II N II 1 II 1 II j II I! II 1 II II 3614 v. 8 34-78 I 1 1 11 1 1 1 1 1 1 1 1 I I 1 1 I 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 I 1 1 1 I 1 1 1 1 11 II H 1 1 GTTTATTGGACTGATGTGTGCGATTGCTCTTCTCACACTACTATTATTAA 3527 v.l 3615 ctqtttgctttgtqaagaggaatagaggtggaaagtactcagttaaagaa 1 l| || || I 1 I III || -II || 11 I I || III || || f I I I 1 I I I I II I I 1 II 1 1 3664 v. 8 3528 II1 It 1 1 1 1 1 1 1 1 I 1 1 I II11111 1111 1 1 1 1 1 1 1 1 111 11 1 1 1 1 1 I 1 i 1 CTGTTTGCTTTGTGAAGAGGAATAGAGGTGGAAAGTACTCAGTTAAAGAA 3577 v.l 3665 aaggaagatttgcatccagacccagaaattcagtcagtaaaagatgaaac ι ι ι ii ιι ι ι ι | i| ι ιι | | ι ι ii ι ||| ι | ι | | ι ιι ι | | | | || ι 11 ι ι ι|ι | 3714 v. 8 3578 1 1 ι ι 1 1 ι 1 1 I 1 Η 1 1 1 1 1 1 1 1 1 I 1 ! 1 1 1 I I 1 ! 1 1 1 1 ! 1 1 1 1 1 Η i 1 1 1 1 1 AAGGAAGATTTGCATCCAGACCCAGAAATTCAGTCAGTAAAAGATGAAAC 3627 v.l 3 715 ctttggtq'aatacagtgacagtgatgaaaagcctctcaaaggaagccttc I 1 1 ΠΙΙ II 1 1 II II 1111 II II 1 IIII 1 II 1 1 1 11 1 1 1 II II II 1 1 1 H 3764 v. 8 3628 Il II I 1 II 1 i || 1 i1 1 I11 Ν1 1 II J 1 I J 1 1 1 1 1 J ι 1 1 1 I 1 1 1 1 1 1 ! 1 1 1 CTTTGGTGAATACAGTGACAGTGATGAAAAGCCTCTCAAAGGAAGCCTTC 3677 v.l 3765 ggtcccttaatagggatatgcagcctactgaaagtgctgacagcttagtc II I 1 J II 1 1 1 I II 1 I I 1 1 1 II 1 1 1 II II 1 1 1 1 1 1 1 i I I 1 1 I 1 1 I 1 1 1 1 1 1 3814 v.8 3 67 8 1 1 1 { ι I J 1 ! I 1 j 1 1 H 1 I 1 II I 1 1 1 I I 1 1 1 I 1 1 I 1 I 1 ! 1 I I 1 1 1 1 I 1 1 1 I GGTCCCTTAATAGGGATATGCAGCCTACTGAAAGTGCTGACAGCTTAGTC 3727 v.l 3815 gaatacqqaqaqqqagaccatggtctcttcagtgaagatggatcatttat IIι π II III III II III 11 III 1 I!1II III IIιIIII II II Η 1 1 1 1 1 3864 xm 8 3728 1 ι &#943; 1 t I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 i 1 1 1 1 1 ι 1 1 I I 1 f 1 Η ! &#943; I I 1 i gaatAcggagagggagaccatggtctcttcagtgaagatggatcatttat 3777 v.l 3865 tggtqcctacqctggatctaaggagaagggatctgttgaaagcaatggaa III II II 1 1 II III III II II HI II III IN 1 I II II III II 1 HI II 1 3914 v.8 3778 1 1 1 I I 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 t I 1 I 1 II 1 I I 1 1 I I 1 1 1 1 TGGTGCCTACGCTGGATCTAAGGAGAAGGGATCTGTTGAAAGCAATGGAA 3827 v.l 3915 gttctacagcaacttttccccttcgggcataaacacaacatatgtaagca II 1 t I I I 1 1 1 1 1 1 1 I 1 || I I I 1 II 1 I l| II i || 1 1 1 I I 1 |l 11 II I 1! I 1 3964 v.8 3828 1 1 1 1 I 1 ! 1 1 I 1 I I 1 ! I! I II 1111 1 II 1 1 1 1 1 1 1 1 1 11 1 I 1 1 1 1 I 1 1 1 1 1 GTTCTACAGCAACTTTTCCCCTTCGGGCATAAACACAACATATGTAAGCA 3877 v.l 3965 acgctactggttcaccccaaccttccatatttafcctgttcaaaggagcaa | I | 1 | 1 | I I | 1 | I |l | I | ι 11 Η | | | | 1 1 I I I 1 | || | I | I | || || l| l| | 4014 v.8 3878 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 11 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ACGCTACTGGTTCACCCCAACCTTCCATATTTATCTGTTCAAAGGAGCAA 3927 v.l 4015 gaactttcatataggaatagaaacatgctggccgaagatttcatccagaa || | ι ι ιiiι η || ii ι ι ι ι i| ||il || | t η ι ) ι ιιι ι ι ι ι ι ι ιιι| i | | 4064 v.8 3928 I ι I H t U 1 U I I i ι ι &#943; Η 1 ι I i r i ι Η I U 1 U 1 i S 1 1 II 1 I 1 Η 1 Η 1 GAACTTTCATATAGGAATAGAAACATGCTGGCCGAAGATTTCATCCAGAA· 3977 v.l 4065 gtcaacatcctgcaattatgttgaaaagagtagtactttcttcaaaatat II 1 1 1 1 1 II 1 II 1 II 1 II I ( 1 I II II II I 1 I 1 1 1 1 1 1 I I |l 1 I II 1 1 II 1 4114 v.8 3978 II111 1 1 11 1 1 1 1 1 11 II 1 II 1 11 I 1 11i 1 1 1 11 1 11 1 1 1 1 1 1 1 1 1 1 1 II GTCAACATCCTGCAATTATGTTGAAAAGAGTAGTACTTTCTTCAAAATAT 4027 328 γ.&#912;.1 4115 aaaatgccaagcacttcaggcctatgfctttgcttatattgttttcaggtg 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 t 1 1 1 11i11111111!1i11111111111 I 11 4164 v.8 4028 1 I 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I ι 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 AAAATGCCAAGCACTTCAGGCCTATGTTTTGCTTATATTGTTTTCAGGTG 4077 v.l 4165 ctcaaaatgcaaaacacaaaacaaatcctgcatttagatacacctcaact 1 11 I 1 1 I I I ! I I 1 I ) 1 ) ) 11 I ! 1 I I 1 I I 1 I 1 1 1 i I 1 1 J 1 1 1 1 1 1 1 1 i 1 1 &#938; 4214 v.8 4078 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 ι 1 I I 1 1 1 1 I 1 f I 1 1 1 1 1 1 1 1 1 f I 1 1 I 1 i 1 1 1 CTCAAAATGCAAAACACAAAACAAATCCTGCATTTAGATACACCTCAACT 4127 v.l 4215 aaatccaaagtccccattcagtatattccatafcttgcctgattttactat 11 i 1 I I I I 1 1 I 1 I I 1 II II 1 1 II 1 1 I I II I I II 1 II I I 1 I 1 1 I II 1 1 I ] I 4264 v.8 4128 1 1 I 1 ι 1 1 I i ! ! I 1 ! : i ι ! 1 I t &#943; I i 1 1 1 1 1 1 1 I ι 1 I 1 1 1 i ι i ι I I i H i H AAATCCAAAGTCCCCATTCAGTATATTCCATATTTGCCTGATTTTACTAT 4177 v.l 4265 tcggtgtgtttgcatagatgttgctacttggtgggtttttctccgtatgc 1 1 1 III 1 1 1 1 1 1 ! 1 1 I! ! 1 I 1 1 1 lit I 1 1 &#943; 11! &#943; HI ( Η!1 &#943; 1 i I 1 I 1 1 4314 v.8 4178 111 1 1 II 1 I1 I 1 I 1 1 I l ι 1 1 I U H 1 I 1 SI 1 It I II I l l 1 M 1 I 1 1 1 1 I I TCGGTGTGTTTGCATAGATGTTGCTACTTGGTGGGTTTTTCTCCGTA’TGC 4227 v.l 4315 acattggtatacagtctctgagaactggcttggtgactttgcttcactac 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 t 1 4364 v.8 4228 Η 1 &#943; ι 1 &#943; Η I &#943; &#943; Η Η Π &#943; &#943; I I &#943; ! 1 1 I 1 1 Π 1 1 Η 1 1 1 Η 1 1 1 1 1 1 Π 1 1 ACATTGGTATACAGTCTCTGAGAACTGGCTTGGTGACTTTGCTTCACTAC 4277 v.l 4365 aggttaaaagaccataagcaaactggttatttaaaatgtaaaaaggaata 1 U i n 1 1 1 I ! 1 1 II I 1 1 1 ! ! 1 1 i 1 1 I 1 1 1 1 1 1 1 ! 1 1 f 1 1 ! i 1 1 I i 1 ! &#943; &#943; 4414 v.8 4278 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 II 1 1 1 1 AGGTTAAAAGACCATAAGCAAACTGGTTATTTAAAATGTATIAAAGGAATA 4327 v.l 4415 tgaaagtcttattaaaacactteattgaaaatatacagtctaaatttatt II 1 I II 1 1 H I 1 1 1 1 1' II 1 1 1 1 1 1 1 1 1 I II 1 1 1 H II 1 1 j II H II 1 1 1 1 4464 v.8 4328 1 I I 1 j I 1 I l 1 1 1 I i 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 U 1 I 1 1 1 I I I U I I 1 I TGAAAGTCTTATTAAAACACTTCATTGAAAATATACAGTCTAAATTTATT 4377 v.l 4465 atttaaattttactagcaaaagtcttaggtgaacaatcaactagtatttg 1 1 1 I 1 1 11 11 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 Ii 1 I 1 1 1 1 1 i 1 i 111 I i 1 I 1 I 11 I 1 4514 v.8 4378 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 ATTTAAATTTTACTAGCAAAAGTCTTAGGTGAACAATCAACTAGTATTTG 4427 v.l 4515 ttgagctc'ctatttgcccagagatggtcatatttaaacagaagtatacgt 1 1 1 1 t 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 11 i 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 I 4564 v.8 4428 I I 1 1 1 1 I 1 I 1 1 1 I I 1 1 1 I I I J I 1 I 1 1 1 1 1 1 1 1 I 1 ι 1 1 I 1 1 1 1 1 1 I I I 1 1 1 TTGAGCTCCTATTTGCCCAGAGATGGTCATATTTAAACAGAAGTATACGT 4477 v.l 4565 ttttcagtttcaacatgaatttttttatttctgtcagttatgacatccac Η&#943;ΜΗΗΗΙΝΗΗΗΗΗΗΙΗΜΗΙΗΜΗΠ ΜΗΝΗ 4614 v.3 4478 TTTTCAGTTTCAACATGAATTTTTTTATTTCTGTCAGTTATGACATCCAC 4527 v.l 4615 gagcatcactttttgtgtctgtttttttttttttcttggactaaattcaa 1 1 1 1 I l- l 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 ! 1 1 1 1 I 4664 V.8 4528 1 ll 1 ! N I 1 1 1 1 1 I I 1 1&#906; II ! 11 I i 11 I 1 1 ι I 1 1 I IIU lll·ItI 1 U 1 I gAGCATCACTTTTTGTGTCTGTTTTTTTTTTTTTCTTGGACTAAATTCAA 4577 v.l 4665 ctgcatggaagcggtggtcagaaggttgttttatacgagaacaggcagaa I 1 1 1 1 1 1 I II l| 1 1 H 1 1 I 1 II 1 II 1 II 1 ( 1 j 1 I II 1 1 I 1 1 1 1 1 1 1 I 1 1 1 4714 v.8 4578 I I I I I 1 ι Π N 1 I 1 1 1 1 1 1 1 1 1 II 1 ι l ι Π 1 ι I I l ι i 1 1 1 1 1 1 1 I I 1 1 1 1 CTGGATGGAAGCGGTGGTCAGAAGGTTGTTTTATACGAGAACAGGCAGAA 4627 v.l 4715 agtgcccattgttcaggattctaatagctacatctacttaatatcttcat 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4764 v.8 4628 1 1 i 1 Η H ! I N hi 1 ) &#943; &#943; 1 &#943; &#943; 1 1 1 1 1 N 1 il ! N 1 1 1! 1 &#943; J N ! 1 J i i! AGTGCCCATTGTTCAGGATTCTAATAGCTAGATCTACTTAATATCTTCAT 4677 v.l 4755 ttctaaattgactgcttttacctttttctcatgtttatataatggtatgc | I 1 II 1 1 1 I 1 I II 1 1 1 I 1 1 l| II 1 1 1 1 1 1 1 1 II j 1 1 1 1 1 1 1 1 1 1 1 II j 1 1 4814 v.8 4678 1 II 1 I I I ! 1 1 1 If 1 1 I 1 1 ! 111 1 1 ! 1 1 1 1 I 1 I 1 I i I 1 1 I 1 I i 1 I f 1 I 1 1 1 Τ&#906;&#908;τΑΑΑτταΑοτοαττττΑΟοτττττοτοΑτατττΑΤΑΤΑΑΤβατΑτΘΟ 4727 v.l 4815 ttgcatatatttcatgaatacattgtacatattatgttaatatttacaca I I |l I II j 1 II I I 1 I II II 1 H 1 ! I II )| j I jl 1 I 1 | | I 1 i I J I l| I I I I 4864 v.8 4728 1 1 1 1 1 | | |1 | 1 I 11 1 1 1 1 1 1 1 1 1 11 1i H 1 iI 1 I ! 1 1 1 1 ! 1 | 1 1 1 1 1 !1 1 TTGCATATATTTCATGAATACATTGTACATATTATGTTAATATTTACACA 4777 v.l 4865 atttaaaatatagatgtgttttattttgaagtgagaaaatgaacattaac 11 I 111111111 1 1 I 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1111111111 1 1 111 4914 V.8 4778 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 111 1 1 1 t 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ATTTAAAATATAGATGTGTTTTATTTTGAAGTGAGAAAATGAACATTAAC 4827 329 &#943;. v.l 4915 v.8 4828 v.l 4965 v. 8 4878 v.l 5015 v. 8 4928 v.l 5065 v.8 4978 v.l 5115 v.8 5028 v.l 5165 v. 8 5078 v.l 5215 V.8 5128 V.l 5265 v. 8 5178 v.l 5315 v. 8 5228 v.l 5365 V. 8 5278 v.l 5415 V. 8 5328 v.l 5465 v.8 5378 v.l 5515 v.8 5428 v.l 5565 v.8 5478 v.l 5615 v.8 5528 v.l 5665 aggcatgtttgtacagctagaatatattagtaagatactgtttttcgtca

iGGiiUiUUiUcUiiiMUUUiCTMUUUUUUiU ttccagagctacaactaataacacqaggttccaaagcfcgaagactttgta

111111 m I Π U f I III! 111Ι&amp;#938;Π 11111! S111111 U &amp;#943; 11 111 i I

TTCCAGAGCTACAACTAATAACACGAGGTTCCAAAGCTGAAGACTTTGTA taaagtatttgggttttgttcttgtattgctttctttcaacagtttcaaa IIII 11II Ii 11II111IIIII ilII1!I ilI)II11!1IIIIIII1111

TAAAGTATTTGGGTTTTGTTCTTGTATTGCTTTCTTTCAACAGTTTCAAA ataaaatatcatacaaatattgagggaaatgttttcatatttttcaaaat 1111! IIIII111il1II!111111II111111II1111111111II111

ATAAAATATCATAcAAATATTGAGGGAAATGTTTTCATATTTTTCAAAAT aggtttttattgttgaatgtacatctaccccagcccctcaaaaaaaaaac II11II1111111111II111111 III 1111111II SI 111111111111

AGGTTTTTATTGTTGAATGTACATCTACCCCAGCCCCTCAAAAGAAAAAC tgtttacatagaaattcctacacatacgtttgcgtatatgttattttaaa

1II11! 11II1II1111!II11111!II111111II11II H IIII11II

TGTTTACATAGAAATTCCTACACATACGTTTGCGTATATGTTATTTTAAA catctttgtggtgagaattttttccccgatattctccttctgtcaaagt c IIIIIIIII11II111IIII11IIIII11!IIIIIII111IIIIII111!

CATCTTTGTGGTGAGAATTTTTTCCCCGATATTCTCCTTCTGTCAAAGTC agaacaaattcagggaatttattttctggcagttgtgctccagtcctttt 111111IIII I!1111111111111IIII111II111111111II11111

AGAACAAATTCAGGGAATTTATTTTCTGGCAGTTGTGCTCCAGTCCTTTT aaaattgtacatgaacatgttttagaaacaatatggaggatgatgcatac

111111111 ill 1111111111111111111111111111111II111II

AAAATTOTACATGAACATGTTTTAGAAACAATATGGAGGATGATGCATAC atgtcggtcaagttcagcgctcgacattttatggaaagatttttttaacc

111II Η 111111II II II1111ΗI Η II11111II11II11 II&amp;#943; 11 II

ATGTCGGTCAAGTTCAGCGCTCGACATTTTATGGAAAGATTTTTTTAACC ttaccacgaaatacttaactactgtttaagtgaattgacttatttcactt uiiiiiiiii.iiiiiiiiiiiiimiiiiiiiiiiuiiiiiiiim

TTACCACGAAATACTTAACTACTGTTTAAGTGAATTGACTTATTTCACTT tagtttttgaactgtgattattggtatactgttatatcctcaacttggat lllllllllllllllllllllltlllllllllilllllllltllllllll

TAGTTTTTGAACTGTGATTATTGGTATACTGTTATATCCTCAACTTGGAT ttatggtaaccccttttagttcatggagaccaaaatttggggtatttata iiHiiiiiiiiiiiimiiiiiiiiiiiiiiiiiiiimiiiiiiii

TTATGGTAACCCCTTtTAGTTCATGGAGACCAAAATTTGGGGTATTTATA atagtcagcgcaggaatgcacatggaatatctacttgtccttttgaacct

11111111111111111111111111111111111111111111111111 ATAGTCAGCGCAGGAATGCACATGGAATATCTACTTGTCCTTTTGAACCT cacgagtcatccagaatgtatagacaggaaaagcatgtcttatttaaaac

11111111111111111111111111111111111111111111111 Μ I

CACGAGTCATCCAGAATGTATAGACAGGAAAAGCATGTCTTATTTAAAAC tgtaatttatgggctcaggatctgaccgcagtcccgggagtaagcatttc 4964 4377 5014 4927 5064 4977 5114 5027 5164 5077 5214 5127 5264 5177 5314 5227 5364 5277 5414 5327 5464 5377 5514 5427 5564 5477 5614 5527 5664 5577 5714 330

vt'8 5578 TGTAATTTATGGGCTCAGGATCTGACCGCAGTCCCGGGAGTAAGCATTTC v.l 5715 aaagggggaaggcagtgtggtcectaccctgtgtgaatgtgaggatgtag

111 II 11II H ! i Hl 1111!! Ill 1 HI 11 &amp;#943; 1I I 11 II III HI 111II

v.8 562 8 AAAGGGGGAAGGCAGTGTGGTCCCTACCCTGTGTGAATGTGAGGATGTAG v.l 5765 acatccatcagtgcaactcgagctccatcctcctccgatttctaaggctc

ΗΠΗΠΠΠΠΗΙΗ1ΗΗ IHHHIHHIHIUHHIHI

v.8 5678 ACATCCATCAGTGCAACTCGAGCTCCATCCTCCTCCGATTTCTAAGGcTC v.l 5815 cagttttctggagggacagtcatcatgttttgatttatctgggagaaaac III1111II1111! 111111111111111 i 11111111111111111111

v.8 5728 CAGTTTTCTGGAGGGACAGTCATCATGTTTTGATTTATCTGGGAGAAAAC v.l 5865 tgtggtgcacagcttgtgaggagggcaaggttgtgacgttcgagcttagt 11IIII1111111111111111111111II11 Η ΠIIIII11II11111

v.8 5778 TGTGGTGCACAGCTTGTGAGGAGGGCAAGGTTGTGACGTTCGAGCTTAGT v.l 5915 tctggtgttattctgtctcctcttcfcttgtcatcagccaaaacgtggttt 1111111!II11III III III111111111111111II111111! 1II11

v.8 5828 TCTGGTGTTATTCTGTCTCCTCTTCTTTGTCATCAGCCAAAACGTGGTTT v.l 5965 ttaaagagagtcatgcaggttagaaataatgtcaaaaatatttaggaatt 111H111111IIIII1111II11111II11111 π II I! II11! 11111

v.8 5878 TTAAAGAGAGTCATGCAGGTTAGAAATAATGTCAAAAATATTTAGGAATT v.l 6015 taataacctttaagtcagaaactaaaacaaatactgaaatattagctctt Π IIII111 Π 11111II1111! 111II111IIIIII Π 111II111111

v.8 592 8 TAATAACCTTTAAGTCAGAAACTAAAACAAATACTGAAATATTAGCTCTT v.l 6065 cctacacttcgtgttcccctttagctgcctgaaaatcaagattgctccta 1111111111111111111111111111111111IIII11111II11111 v.8 5978 CCTACACTTCGTGTTCCCCTTTAGCTGCCTGAAAATCAAGATTGCTCCTa v.l 6115 ctcagatcttctgagtggctaaaacttatggatatgaaaaatgagattga Π ΠIIIIII11)1111II11! II111IIIII11111! I! 111111 SI 11

v.8 6028 CTCAGATCTTCTGAGTGGCTAAAACTTATGGATATGAAAAATGAGATTGA v.l 6165 atgatgactatgctttgctatcattgttacctttcctcaatactatttgg 1111111111111111 Η II II I! 111111111 SI 111111111111111

v. 8 607 8 ATGATGACTATGCTTTGCTATCATTGTTACCTTTCCTCAATACTATTTGG v.l 6215 caactactgggactcttcagcacaaaaggaatagatctatgattgaccct

111IIII11111! π 111IIII11IIIII11IIIII11IIIIII111 III

v.8 '6128 CAACTACTGGGACTCTTCAGCACAAAAGGAATAGATCTATGATTGACCCT v.l 6265 gattttaattgtgaaattatatgattcatatattttatgaatcagaataa 1111S1111111 H 11111111111111111111111111111111 ll 11

v.8 617 8 GATTTTAATTGTGAAATTATATGATTCATATATTTTATGAATCAGAATAA v.l 6315 ccttcaaataaaataaatctaagtcggttaaaatggatttcatgattttc

III11111IIIIIII H 11 π III11IIIIIIIIIIIIII Ii iii Ii III

v.8 6228 CCTTCAAATAAAATAAATCTAAGTCGGTTAAAATGGATTTCATGATTTTC v.l 6365 cctcagaaaatgagtaacggagtccacggcgtgcaatggtaattataaat 11111.1 II111 IS 111111 π III I! 111II111111II11111111111

v.8 6278 CCTCAGAAAATGAGTAACgGAGTCCACGGCGTGCAATGGTAATTATAAAT v.l 6415 tggtgatgcttgtttgcaaattgcccactcgtgataagtcaacagccaat 11111IIII11111II11II11111111IIIII Π 11IIIIIIIII1111

v.8 6328 TGGTGATGCTTGTTTGCAAATTGCCCACTCGTGATAAGTCAACAGCCAAT v.l 6465 atttaaaactttgttcgttactggctttaccctaactttctctagtctac 5627 5764 5677 5 814 5727 5864 5777 5914 5827 5964 5877 6014 5927 6064 5977 6114 6027 6164 6077 6214 6127 62 64 6177 6314 6227 6364 6277 6414 6327 6464 6377 6514 331 v. 8 6378 ν. 1 6515 v.8 6428 v. 1 6565 v.8 6478 v. 1 6615 v. 8 6528 v.l 6665 v. 8 6578 v. 1 6715 v.8 66-2 8 v.l 6765 v.8 6678 v.l 6815 v.8 6728 v.l 6865 v.8 6778 v.l 6915 v.8 6828 v.l 6965 v.3 6878 v.l 7015 v. 8 6928 v.l 7 065 v.8 6978 v.l 7115 v.8 7028 v.l 7165 V. 8 7078 V.l 7215 y. 8 7128

ATTTAAAACTTTGTTCGTTACTGGCTTTACCCTAACTTTCTCTAGTCTAC tgtcaatatcattttaatgtaattgattgtatatagtctcaagaatggtt

TGTCAATATCATTTTAATGTAATTGATTGTATATAGTCTCAAGAATGGTT ggtgggcatgagttcctagagaactgtccaagggttgggaaaatccaaat li I Η 11 Η 11II Π 11 i 11 IH 111II11! I!! I &amp;#943; 111 il 11III! 111

GGTGGGCATGAGTTCCTAGAGAACTOTCCAAGGGTTGGGAAAATCCAAAT tctcttcctggctccagcactgattttgtacataaacattaggcaggttg IIIIIilIIIIIIIII I!IIIII111H II111111!111II11111111

TCTCTTCCTGGcTCCAGCACTGATTTTGTACATAAACATTAGGCAGGTTG cttaacctttttatttcaaactctctcaactctaaagtgctaataataat 1111111111111111111111 Η 11111111111111!11111111111

CTTAACCTTTTTATTTCAAACTCTCTCAACTCTAAAGTGCTAATAATAAT ctcagttaccttatctttgtcacagggtgttcttttttatgaagaaaaat I i 111111111!111 liIII11111111SIIII!I!1111111II11111 -

CTCAGTTACCTTATCTTTGTCACAGGGTGTTCTTTTTTATGAAGAAAAAT ttgaaaatgataaaagctaagatgccttctaacttcataagcaaaccttt miiiiiimiiiiiiimiiimiimimimiiimm

TTGAAAATGATAAAAGCTAAGATGCCTTCTAACTTCATAAGCAAACCTTT aactaattatgtatctgaaagtcacccccacataccaactcaactttttt

III1111111II1111IIIIIIIIIIIII11! IIIIII I! 11111 Ml! I

AACTAATTATGTATCTGAAAGTCACCCCCACATACCAACTCAACTTTTTT cctgtgaacacataaatatatttttatagaaaaacaaatctacataaaat

II11111II1111II1111111111111II111111II11! II11111! I

CCTGTGAACACATAAATATATTTTTATAGAAAAACAAATCTACATAAAAT aaatctactgtttagtgagcagtatgacttgtacatgccattgaaaatta 111111111111111111111111111111111111 III 11111111111

AAATCTACTGTTTAGTGAGCAGTATGAcTTGTACATGCCATTGAAAATTA ttaatcagaagaaaattaagcagggtctttgctatacaaaagtgttttcc

11! I IJ 111111111111111II111111111IIIII111! 1111! 11! I

TTAATCAGAAGAAAATTAAGCAGGGTCTTTGCTATACAAAAGTGTTTTCC actaattttgcatgcgtatttataagaaaaatgtgaatttggtggtttta 1111! III11111!11111II1111! 1111IIIII1111111IIII I! 11

ACTAATTTTGCATGCGTATTTATAAGAAAAATGTGAATTTGGTGGTTTTA ttctatcggtataaaggcatcgatattttagatgcacccgtgtttgtaaa II111111111111111111111111! 11111111111111111111111

TTCTATCGGTATAAAGGCATcGATATTTTAGATGCACCCGTGTTTGTAAA aatgtagagcacaatggaattatgctggaagtctcaaataatattttttt I!111111111111! 11111111111111!! 111111111) 111111II1

AATGTAGAGCACAATGGAATTATGCTGGAAGTCTCAAATAATATTTTTTT cctattttatactcatggaagagataagctaaagaggggacaataatgag H HIII11111111II I!II111II11II11111 IT 1111111! 11111

CCTATTTTATACTCATGGAAGAGATAAGCTAAAGAGGGGACAATAATGAG aaatgttggtgtgcttttctaagcatttaaaacataattgccaattgaaa 11IIIIIIII1111111II111111111111111 HU II111! II li 11

AAATGTTGGTGTGCTTTTCTAAGCATTTAAAACATAATTGCCAATTGAAA 6427 6564 6477 6614 6527 6664 6577 6714 6627 6764 6677 6814 6727 6864 6777 6914 6827 6964 6877 7014 6927 7 064 6977 7114 7027 7164 7077 7214 7127 7264 7177 332 V-Ll 7265 ccctaaatatgtttacataccattaagatatgattcatgtaacaatgtta I I I 1 I II I 1 I 1 1 I 1 1 I 1 II II 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 I 1 I 1 1 1 1 I I 1 If ! I 7314 v. 8 7178 11i1 1 1 111 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 i 1111i111111 II 1 1 1 1 1 i 1 1 1 1 1 CCCTAAATATGTTTACATACCATTAAGATATGATTCATGTAACAATGTTA 7227 v.l 7315 aattaattataatgggattgggtttgttatctgtggtagtatatatccta 1 1 1 ι 1 I ι ι 1 ι ι 1 I ι 1 | 11 | ι | 1 1 | | | | ι 1 I | I l I I 1 ! | | | 1 | 1 1 | | 1 1 | | 7364 V.8 7228 1 1 1 ι 1 &amp;#943; ι ι 1ii i Iι 111ιιι1 I i 1 I I 1ι ι i 1 i ι ι 1 ι 1 1 i I ι 1 ι ι 1i ιιι1 AATTAATTATAATGGGATTGGGTTTGTTATCTGTGGTAGTATATATCCTA 7277 v.l 7365 gtgttcctatagtgaaataagtagggttcagccaaagctttctttgtttt 1 || I I 1 I I 1 I || 11 I 1 I 1 1 l| 1 I l| || 1 I || II II ] I I I 1 1 I II I 1 111 1 7414 V. 8 72 7 8 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 I 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 GTGTTCCTATAGTGAAATAAGTAGGGTTCAGCCAAAGCTTTCTTTGTTTT 7327 v.l 7415 gtaccttaaattgttcgattacgtcatcaaaagagatgaaaggtatgtag t 1 11 I 1 1 1111111111 1 1 ! I 1 1 1 i 1 I 1 1 1 H 1 1 1 1 II 1 1 1 1 1 1 t 1 1 1 ! 1 7464 v.8 7328 ! 1 1 1 1 1 1 1 i 1 1 1 1 t 1 1 1 1 ! 1 1 1 1 1 1 1 i 1 1 i 1 1 1 1 1 1 1 1 I 1 1 i t I 1 1 1 1 1 1 GTACCTTAAATTGTTCGATTACGTCATCAAAAGAGATGAAAGGTATGTAG 7377 v.l 7465 aacaggttcacgtgattacctttttcttttggcttggattaatattcata 1 1 1 1 1 i 1 1 1 1 i i 1 1 1 1 1 1 1 1 1 1 1 1 Ι&amp;#906; I 1 1 1 1 1 1 i 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 7514 v.8 7378 I 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 1 1 1 AACAGGTTCACGTGATTACCTTTTT.CTTTTGGCTTGGATTAATATTCATA 7427 V.l 7515 gtagaactttataaaacgtgtttgtattgtaggtggtgtttgtattatgc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 11 1 i 1 1 &amp;#943;I 1 I 1 111 111 1 1 1 11 1 1 1 1 7564 v.8 7428 11i 1 1 1 II 1 1 1 1 i 1 1 1 1 1 11 1 1 1 1 111II 11 I II 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 t GTAGAACTTTATAAAACGTGTTTGTATTGTAGGTGGTGTTTGTATTATGC 7477 v.l 7565 ttatgactatgtatggtttgaaaatattttcattatacatgaaattcaac 1 1 | I | I I Μ | I 1 | | | I | 1 1 I | | 1 II l| | | | | | j | | I j | | | | ) | | | | | | | 1 7614 v.8 7478 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 TTATGACTATGTATGGTTTGAAAATATTTTCATTATACATGAAATTCAAC 7527 v.l 7615 tttccaaataaaagttctacttcatgtaatccaaaa 7650 1111 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 il 11 1 1 1 1 1 1 1 1 v.8 7528 1 I I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 I 1 1 I 1 1 ! 1 1 1 TTTCCAAATAAAAGTTCTACTTCATGTAATCCAAAA 7563

Table LIVg. Peptide sequences of protein coded by 282P1G03 v.8 (SEQ ID NO: 190) MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 60 GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 120 EEIEFIVPKL EHIEQDERVY MSQKGDLYFA NVEEKDSRND YCCFAAFPRL RTIVQKMPMK 180 LTVNSLKHAN DSSSSTEIGS KANSIKQRKP.KLLLPPTESG SESSITILKG EILLLECFAE 240 GLPTPQVDWN KIGGDLPKGR ETKENYGKTL KIENVSYQDK GNYRCTASNF LGTATHDFHV '300 IVEDNISHEL FTLHPEPPRW TKKPQSAVYS TGSNGILLCE AEGEPQPTIK WRVNGSPVDN 360 HPFAGDVVFP REISFTNLQP NHTAVYQCEA SNVHGTILAN ANIDWDVRP LIQTKDGENY 42 0 ATWGYSAFL HCEFFASPEA WSWQKVEEV KPLEGRRYHI YENGTLQINR TTEEDAGSYS 48 0 CWVENAIGKT AVTANLDIRN ATKLRVSPKN PRIPKLHMLE LHCESKCDSH LKHSLKLSWS 54 0 KDGEAFEING TEDGRIIIDG ANLTISNVTL EDQGIYCCSA HTALDSAADI TQVTVLDVPD 600 PPENLHLSER QNRSVRLTWE AGADHNSNIS EYIVEFEGNK EEPGRWEELT RVQGKKTTVl 66 0 LPLAPFVRYQ FRVIAVNEVG RSQPSQPSDH HETPPAAPDR NPQNIRVQAS QPKEMIIKWE 720 PLKSMEQNGP GLEYRVTWKP QGAPVEWEEE TVTNHTLRVM TPAVYAPYDV KVQAINQLGS 780 GPDPQSVTLY SGEDYPDTAP VIHGVDVINS TLVKVTWSTV PKDRVHGRLK GYQINWWKTK 84 0 SLLDGRTHPK EVNILRFSGQ RNSGMVPSLD AFSEFHLTVL AYNSKGAGPE SEPYIFQTPE 900 GVPEQPTFLK VIKVDKDTAT LSWGLPKKLN GNLTGYLLQY QIINDTYEIG ELNDINITTP 960 SKPSWHLSNL NATTKYKFYL RACTSQGCGK PITEESSTLG EGSKGIGKIS GVNLTQKTHP 1020 IEVFEPGAEH IVRLMTKNWG DNDSIFQDVI ETRGREYAGL YDDISTQGWF IGLMCAIALL 1080 TLLLLTVCFV KRNRGGKYSV KEKEDLHPDP EIQSVKDETF GEYSDSDEKP LKGSLRSLNR 1140 DMQPTESADS LVEYGEGDHG LFSEDGSFIG AYAGSKEKGS VESNGSSTAT FPLRA 1195

Table LVg. Amino acid sequence alignment of 282P1G03 v.1 (SEQ ID NO: 191) and 282P1G03 v.8 (SEQ ID NO: 192) V.l 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD | II I I I I I I I I I I I I I ! II 1 1 1 1 II l| 1 j 1 1 1 1 1 1 1 1 1 I 1 1 1 1 j 1 1 1 1 ' 50 v. 8 1 !! 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I I 1 1 1 1 1 1 1 1 ! 1 1 1 t 1 ! 1 1 1 11 1 1 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD 50 v.l 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 333 ΛΛ, 8 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 v.l 101 shfqgkyrcfasnklgiamseeiefiypsvpklpkekidpleveegdpiv 1 1 1 1 1 1 1 1 1 ! 1 I 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 150 V.8 101 1 1 I 1 1 1 1 1 1 1 11 II 1 1 1 1 1 I 1 1 1 1 1 I 1 1 SHFQGKYRCFASNKLGIAMSEEIEFIVP----------------------- 123 v.l 151 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQkGDLYFANVEEKDSRN . I | | | ι i 1 II II 1 1 I I I 1 ! I II II II I 1 1 200 v.8 129 - 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 -------------------KLEHIEQDERVYMSQKGDLYFANVEEKDSRN 159 v.l 201 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHANDSSSSTEIGSKANSIKQRK I 1 I I I I I II I 1 I 1 i| 1 1 | 1 I I 1 II 1 1 II 1 1 1 j II 1 1 1 1 j II 1 1 II 1 1 1 1 1 250 v.8 160 1 1 1 1 1 1 || 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1111 I 1111111 1 1 1 1 I 1 1 1 1 1 1 DYCCFAAFPRLRT WQKMPMKLIWSLKHANDS SS STEIG SKANS IKQRK 209 v.l 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG 1 II I I I 1 II 1 I 1 1 I 1 1 1 1 ! 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 j 1 I 1 II 1 I 1 1 1 1 1 1 300 v. 8 210 111111 I 1111111II 1 1 II 1 I 1 I 111 II 1 1 11 1 1 1 1 1 I 1 I II 1 1 1 1 1 1 1 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG 259 v.l 301 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVE------ 1 1 1 I II 1 1 ! 1 1 1 1 1 II 1 1 1 1 1 11 1 II 1 1 1 II I 1 I 1 1 1 1 1 1 1 1 I 1 344 v. 8 260 1II ill 1 I I II1IIII 1 1 1 1 II 1 I 111 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 I RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEDNISHE 309 v.l 345 ------EPPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVD 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 388 v.8 310 ' 1 I 1 1 1 1 1 1 1 1 1 1 1 1 J 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 LFTLHPEPPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVD 359 v.l 389 NHPFAGDWFPREISFTNLQPNHTAVYQCEASNVHGTILANANIDWDVR 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 438 v.8 360 1 ! 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 NHPFAGDWFPREISFTNLQPNHTAVYQCEASNVHGTILANAiriDWDVR 409 v.l 439 PLIQTKDGENYATWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYH I 1 I I I I 1 i 1 I 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 488 v.8 410 II1 11111111111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 PLIQTKDGENYATWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYH 459 v.l 489 IYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPK I I I I I I II I I 1 I I &amp;#943; 1 II |! II H l| II 1 1 I 1 1 1 I 1 1 1 1 1 1 1 I 1 It || I 538 v. 8 460 1 1 1 1 1 1 1 I I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 IYENGTLQINRTTEEDAGS ΥΞ CWVENAIGKTAVTANLDIRNATKLRVS P K 509 v.l 53 9 NPRIPKLHMLELHCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIID 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 588 v.8 510 1 I 111IIII I II111 I 1 I 1l11111 I 1111111II1111 1 1 I II 1 1 i I 1 1 NPRIPKLHMLELHCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIID V 559 v.l 589 GANLTISNVTLEDQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSE | 1 I I I 1 I 1 I I 1 I 1 I I I I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 S38 V.8 560 1 1 1 1 II 1 1 II 11!1111111111111 I 111111II111 1 1 1 1 1 1 I 1 1 1 1 1 GANLTISNVTLEDQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSE 609 v.l 63 9 RQNRSVRLTWEAGADHNSNISEYIVEFBGNKEEPGRWEELTRVQGKKTTV 1 I 1 1 1 1 I 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 688 V. 8 610 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 RQNRSVRLTWEAGADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTV 659 v.l 689 ILPLAPFVRYQFRVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQA 1 111 I i 1 1 1 1 i II i 1 1 1 I i 1 I I 1 1 1 1 I 11 1 I 1 1!1 1 1 I 1 1 1 1 I 1 1 1 1 ι ι ι 738 v.8 660 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 h I 1 ι ι ι ILPLAPFVRYQFRVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQA 709 v.l 739 SQPKEMIIKWEPLKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRV 1 1 1 1 1 1 11 1 1 1 11 1 1 1 1 1 1 1 111111 1 1t11 1 1 1 1 111 1 1 II 1 1 1 1 1 1 1 1 788 v.8 710 111 1 1 1 1 II 1 1 111 I I 1111 I I 1 1 I 1 1 1111111 1 1 1 1 1 1 1 11II 1 1 1 1 1 SQPKEMIIKWEPLKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRV 759 v.l 789 MTPAVYAPYDVKVQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVIN 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 i 838 V.8 760 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 I 1 I 1 1 1 1 1 1 MTPAVYAPYDVKVQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVIN 809 v.l 839 STLVKVTWSTVPKDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSG 888 334 v. 8 810 STL VKWWSTVPKDRVHGRLKGYQINWWKT KSLLDGRTHP KEVNILRFSG 859 v.l 889 QRNSGMVPSIjDAFSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFL ! 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 93 8 v.8 860 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I I 1 1 1 1 1 1 1 1 QRNSGMVPSLDAFSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFL 909 v.l 939 KVIKVDKDTATLSWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITT 1 I 1 1 I 1 1 I I I 1 1 1 I 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 I 1 1 I 1 1 1 I 1 1 988 v.8 910 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1. 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 KVIKVDKDTATLSWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITT 959 v.l 989 PSKPSWHLSNLNATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKI I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1038 v.8 960 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 PSKPSWHLSNLNATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKI 1009 v.l 1039 SGVNLTQKTHPIEVFEPGAEHIVRLMTKNWGDNDSIFQD VIETRGREYAG 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1088 v.8 1010 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 SGVNLTQKTHP IEVFEPGAEHIVRLMTKNWGDND SIFQDVIETRGREYAG 1059 v. 1 1089 LYDDISTQGWFIGLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPD 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1138 v. 8 1060 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 LYDDISTQGWFIGLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPD 1109 v. 1 1139 PEIQSVKDETFGEYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDH I I 11 II I 1 II 1 II 1 1 1 1 II 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I I I 1 1 1 ) 1 1 1 I 1 1 I 1188 v.8 1110 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 PEIQSVKDETFGEYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDH 1159 v.l 1189 GLFSEDGSFIGAYAGSKEKGSVESNGSSTATFPLRA 1224 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 I I I I 1 I 1 v. 8 1160 1 1 I 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 i 1 1 111 1 1 1 1 GLFSEDGSFIGAYAGSKEKGSVESNGSSTATFPLRA 1195

Table Ll!h. Nucleotide sequence of 282P1G03v.28 (SEQ ID NO: 193) cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggcgccgg acagatcgcg tttcggaggc ggcgcagttt ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt atttcactga c-cat’cggata attccatcga acaattcagg aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa acccaaactg ctgttgcctc ' ccactgagag tggcagtgag tcttcaatta ccatcctcaa aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca' cagccagcaa tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg ttgggtagaa aatgctatag 60 12 0 180' 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 114 0 12 00 1260 1320 1380 144 0 1500 1560 1620 1680 1740 335 _gaaaaactgc agtcacagcc aatttggata ttagaaatgc tacaaaactt agagtttctc 1800 ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt acattgtgaa agcaaatgtg 1860 actcacattt gaaacacagt ttgaagttgt cctggagtaa agatggagaa gcctttgaaa 1920 ttaatggcac agaagatggc aggataatta ttgatggagc taatttgacc atatctaatg 1980 taactttaga ggaccaaggt atttactgct gttcagctca tactgctcta gacagtgctg 2040 ccgatataac tcaagtaact gttcttgatg ttccggatcc accagaaaac cttcacttgt 2100 ctgaaagaca gaacaggagt gttcggctga cctgggaagc tggagctgac cacaacagca 2160 atattagcga gtatattgtt gaatttgaag gaaacaaaga agagcctgga aggtgggagg 2220 aactgaccag agtccaagga aagaaaacca cagttatctt acctttggct ccatttgtga 2280 gataccagtt cagggtcata gccgtgaacg aagtagggag aagtcagcct agccagccgt 2340 cagaccatca tgaaacacca ccagcagctc cagataggaa tccacaaaac ataagggttc 2400 aagcctctca acccaaggaa atgattataa agtgggagcc tttgaaatcc atggagcaga 2460 atggaccagg cctagagtac agagtgacct ggaagccaca gggagcccca gtggagtggg 2520 aagaagaaac agtcacaaac cacacattgc gggtgatgac gcctgctgtc tatgcccctt 2580 atgatgtcaa ggtccaggct atcaatcaac taggatctgg gcctgaccct cagtcagtga 2640 ctctctattc tggagaagac tatcctgata cagctccagt gatccatggg gtggacgtta 2700 taaacagtac attagttaaa gttacctggt caacagttcc aaaggacaga gtacatggac 2760 gtctgaaagg ctatcagata aattggtgga aaacaaaaag tctgttggat ggaagaacac 2820 atcccaaaga agtgaacatt ctaagatttt caggacaaag aaactctgga atggttcctt 2880 ccttagatgc ctttagtgaa tttcatttaa cagtcttagc ctataactct aaaggagctg 2940 gtcctgaaag tgagccttat atatttcaaa caccagaagg agtacctgaa cagccaactt 3000 ttctaaaggt catcaaagtt gataaagaca ctgccacttt atcttgggga ctacctaaga 3060 aattaaatgg aaacttaact ggctatcttt tgcaatatca gataataaat gacacctacg 3120 agattggaga attaaatgat attaacatta caactccatc aaagcccagc tggcacctct 3180 caaacctgaa tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct 3240 gtggaaaacc gatcacggag gaaagctcca ccttaggaga agggagtaaa ggtatcggga 3300 agatatcagg agtaaatctt actcaaaaga ctcacccaat agaggtattt gagccgggag 3360 ctgaacatat agttcgccta atgactaaga attggggcga taacgatagc atttttcaag 3420 atgtaattga gacaagaggg agagaatatg ctggtttata tgatgacatc tccactcaag 3480 gctggtttat tggactgatg tgtgcgattg ctc-ttctcac actactatta ttaactgttt 3540 gctttgtgaa gaggaataga ggtggaaagt actcagttaa agaaaaggaa gatttgcatc 3600 cagacccaga aattcagtca gtaaaagatg aaacctttgg tgaatacagt gacagtgatg 3660 aaaagcctct caaaggaagc cttcggtccc ttaataggga tatgcagcct actgaaagtg 3720 ctgacagctt agtcgaatac ggagagggag accatggtct cttcagtgaa gatggatcat 3780 ttattggtgc ctacgctgga tctaaggaga agggatctgt tgaaagcaat ggaagttcta 3840 cagcaacttt tccccttcgg gcataaacac aacatatgta agcaacgcta ctggttcacc 3900 ccaaccttcc atatttatct gttcaaagga gcaagaactt tcatatagga atagaaacat 3960 gctggccgaa gatttcatcc agaagtcaac atcctgcaat tatgttgaaa agagtagtac 4020 tttcttcaaa atataaaatg ccaagcactt caggcctatg ttttgcttat attgttttca 4080 ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta gatacacctc aactaaatcc 4140 aaagtcccca ttcagtatat tccatatttg cctgatttta ctattcggtg tgtttgcata 4200 gatgttgcta ctt'ggtgggt ttttctccgt atgcacattg gtatacagtc tctgagaact 42 60 ggcttggtga ctttgcttca ctacaggtta aaagaccata agcaaactgg ttatttaaaa 4320 tgtaaaaagg aatatgaaag tcttattaaa acacttcatt gaaaatatac agtctaaatt 4380 tattatttaa attttactag caaaagtctt aggtgaacaa tcaactagta tttgttgagc 4440 tcctatttgc ccagagatgg tcatatttaa acagaagtat acgtttttca gtttcaacat 4500 gaattttttt atttctgtca gttatgacat ccacgagcat cactttttgt g'tctgttttt 4560 ttttttttct tggactaaat tcaactgcat ggaagcggtg gtcagaaggt tgttttatac 4620 gagaacaggc agaaagtgcc cattgttcag gattctaata gctacatcta cttaatatct 4680 tcatttctaa attgactgct tttacctttt tctcatgttt atataatggt atgcttgcat 4740 atatttcatg aatacattgt acatattatg ttaatattta cacaatttaa aatatagatg 4800 tgttttattt tgaagtgaga aaatgaacat taacaggcat gtttgtacag ctagaatata 4860 ttagtaagat actgtttttc gtcattccag agctacaact aataacacga ggttccaaag 4920 ctgaagactt tgtataaagt atttgggttt tgttcttgta ttgctttctt tcaacagttt 4980 caaaataaaa tatcatacaa atattgaggg aaatgttttc atatttttca aaataggttt 5040 ttattgttga atgtacatct accccagccc ctcaaaagaa aaactgttta catagaaatt 5100 cctacacata cgtttgcgta tatgttattt taaacatctt tgtggtgaga attttttccc 5160 cgatattctc cttctgtcaa agtcagaaca aattcaggga atttattttc tggcagttgt 5220 gctccagtcc ttttaaaatt gtacatgaac.atgttttaga aacaatatgg aggatgatgc 5280 atacatgtcg gtcaagttca gcgctcgaca ttttatggaa agattttttt aaccttacca 5340 cgaaatactt aactactgtt taagtgaatt gacttatttc actttagttt ttgaactgtg 5400 attattggta tactgttata tcctcaactt ggatttatgg taaccccttt tagttcatgg 5460 agaccaaaat ttggggtatt tataatagtc agcgca.ggaa tgcacatgga atatctactt 5520 336 gfcccttttga acctcacgag tcatccagaa tgtatagaca ggaaaagcat gtcttattta 5580 aaactgtaat ttatgggctc aggatctgac cgcagtcccg ggagtaagca tttcaaaggg 5640 ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat gtagacatcc atcagtgcaa 5700 ctcgagctcc atcctcctcc gatttctaag gctccagttt tctggaggga cagtcatcat 5760 gttttgattt atctgggaga aaactgtggt gcacagcttg tgaggagggc aaggttgtga 5820 cgttcgagct tagttctggt gttattctgt ctcctcttct ttgtcatcag ccaaaacgtg 5880 gtttttaaag agagtcatgc aggttagaaa taatgtcaaa aatatttagg aatttaataa 5940 cctttaagtc agaaactaaa acaaatactg aaatattagc tcttcctaca cttcgtgttc 6000 ccctttagct gcctgaaaat caagattgct cctactcaga tcttctgagt ggctaaaact 6060 tatggatatg aaaaatgaga ttgaatgatg actatgcttt gctatcattg ttacctfctcc 6120 tcaatactat ttggcaacta ctgggactct tcagcacaaa aggaatagat ctatgattga 6180 ccctgatttt aattgtgaaa ttatatgatt catatatttt atgaatcaga ataaccttca 6240 aataaaataa atctaagtcg gttaaaatgg atttcatgat tttccctcag aaaatgagta 6300 acggagtcca cggcgtgcaa tggtaattat aaattggtga tgcttgtttg caaattgccc 6360 actcgtgata agtcaacagc caatatttaa aactttgttc gttactggct ttaccctaac 6420 tttctctagt ctactgtcaa tatcatttta atgtaattga ttgtatatag tctcaagaat 6480 ggttggtggg catgagttcc tagagaactg tccaagggtt gggaaaatcc aaattctctt 6540 cctggctcca gcactgattt tgtacataaa cattaggcag gttgcttaac ctttttattt 6600 caaactctct caactctaaa gtgctaataa taatctcagt taccttatct ttgtcacagg 6660 gtgttctttt ttatgaagaa aaatttgaaa atgataaaag ctaagatgcc ttctaacttc 6720 ataagcaaac ctttaactaa ttatgtatct gaaagtcacc cccacatacc aactcaactt 6780 ttttcctgtg aacacataaa tatattttta tagaaaaaca aatctacata aaataaatct 6840 actgtttagt gagcagtatg acttgtacat gccattgaaa attattaatc agaagaaaat 6900 taagcagggt ctttgctata caaaagtgtt ttccactaat tttgcatgcg tatttataag .6960 aaaaatgtga atttggtggt tttattctat cggtataaag gcatcgatat tttagatgca 7020 cccgtgtttg taaaaatgta gagcacaatg gaattatgct ggaagtctca aataatattt 7080 ttttcctatt ttatactcat ggaagagata agctaaagag gggacaataa tgagaaatgt 7140 tggtgtgctt ttctaagcat ttaaaacata attgccaatt gaaaccctaa atatgtttac 7200 ataccattaa gatatgattc atgtaacaat gttaaattaa ttataatggg attgggtttg 7260 ttatctgtgg tagtatatat cctagtgttc ctatagtgaa ataagtaggg ttcagccaaa 7320 gctttctttg ttttgtacct taaattgttc gattacgtca tcaaaagaga tgaaaggtat 7380 gtagaacagg ttcacgtgat tacctttttc ttttggcttg gattaatatt catagtagaa 7440 ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt atgcttatga ctatgtatgg 7500 tttgaaaata ttttcattat acatgaaatt caactttcca aataaaagtt ctacttcatg 7560 taatccaaaa 7570

Table LIHh. v. 2 8 v.l v.2 8 v. 1 v. 28 v.l v.28 v. 1 v.28 v.l v.28 v.l v.28

Nucleotide sequence alignment of 2S2P1G03 v.1 (SEQ ID NO: 194) and 282P1G03 v.28 (SEQ ID NO: 1 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg 1 51 51 97 101 97 151 121 201 171 251 221 cggaccctgcgcgcccccgtcccggctcccggccggctcgggggagaagg cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgca-----

II1111II I! 11111! il! 11 Η IIII11 III 1 Hi 11) II11II cgcccgaggggaggcgccggacagatcgcgtttcggaggcggcgcaggtg ctgtaaactgcaaaccataatcctgtcttaatactgcaaacaaatcatag --------------------------gtttccaggttaactaaggtctca

11! II111111111.1IIII11II tggaactaaggggaacttaatttactgtttccaggttaactaaggtctca gctgtaaaccaaaagtgagaggagacattaagattttcattcttaccggg 11 i &#943;111Π11i11i1111 111!IJ11 i11Π 1111 U 11 Η 1111 Η I i gctgtaaaccaaaagtgagaggagacattaagatttteattcttaccggg ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact 1111Π11IIΠ11 H i11111II11II11111111II11 Π1111II11 ttgtcttcttcctgaagagcaatggagccgcttttacttggaagaggact aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa 195) 50 50 96 100 96 150 120 200 170 250 220 300 270 337 v.l 301 aatcgtatatctaatgttcctcctgttaaaattctcaaaagcaattgaaa 350 v.28 271 taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc 1 ! 1 I 1 | j | 1 1 1 I | 1 || 1 | j 1 I i 1 1 1 I I I 1 1 1 1 I 1 ! 1 I 1 | 1 1 I 1 j [ j ] j ! i 320 v.l 351 1 1 I 1 M i 1 I 1 1 1 I 1 1 1 I 1 1 1 1 I I I 1 ι I f i 1 1 ι ι 1 ι ! 1 ι 1 ι i 1 1 ! I 1 1 1 1 ! taccatcttcagttcaacaggttccaacaatcataaaacagtcaaaagtc 400 v.28 321 caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagetaa | 1 ! II I II 1 I 1 1 1 I 1 II I l| I II II 1 1 II 1 1 I 1 1 I I II 1 I 1 I 1 It I II II 370 v. 1 401 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I ι ι ι I 1 1 1 1 1 1 1 1 1 1 1 1 I caagttgcctttcccttcgatgagtattttcaaattgaatgtgaagctaa 450 v.28 371 aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 1 1 1 1 1! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 ! I 1 1 11 111 11 III 1 II 1 1 I 1 1 1 II 1 1 I 420 v. 1 451 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 I 1 I II aggaaatccagaaccaacattttcgtggactaaggatggcaacccttttt 500 v. 28 421 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 III ! 1 1 1 1 I III 1 1 1 1 111 1 1 1 1 1 1 1 1 1 1 1 ! 470 v.l 501 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I I I 1 I 1 I I II 1 atttcactgaccatcggataattccatcgaacaattcaggaacattcagg 550 v.28 471 atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt 1 1 1 1 11 11 1 1 1 1 1 1 ! 1 1 1 1 1 I 1 1 II1 111 1 II111 1 1 1 1 1 1 1 1 11 1 1 1 1 1 520 v.l -551 1 1 I 1 1 I I 1 1 I 1 1 1 1 1 1 II 1 I 1 1 1 1 II 1 1 1 1 II 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 ll ! atcccaaacgaggggcacatatctcactttcaagggaaataccgctgctt 600 v.28 521 tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 &#943; III 1 1 H M 1 1 570 v.l 601 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I I I I I I 1 1 tgcttcaaataaactgggaatcgctatgtcagaagaaatagaatttatag 650 v.28 571 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg 1 1 I 1 11 | I | 1 | 1 I | | I I | | I | 1 | I | | 1 | I 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 620 v.l 651 ι 1 1 i I 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 ! 1 ! ! 1 1 1 1 1 ! 1 1 1 1 1 ι 1 1 1 1 1 1 1 1 ttccaagtgttccaaaactcccaaaagaaaaaattgaccctcttgaagtg 700 v.28 621 gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc I I 1 I I I I 1 II II I 1 1 1 | 1 1 I I I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 670 v.l 701 I 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 I 1 1 1 ! gaggagggagatccaattgtcctcccatgcaatcctcccaaaggcctccc 750 v.2 8 671 acctttacacatttattggatgaatattgaattagaacacatcgaacaag II 1 II ! II II II II II II 1 I 1 1 II 1 I 1 I 1 I || 1 1 I II | 1 1 1 I I 1 1 ] 1 II I 720 v.l 751 1 1 I 1 I 1 1 1 ! 1 ! 1 1 1 1 1 I 1 1 1 1 ( 1 I I I 1 1 1 1 1 1 1 I I I I I 1 1 I I &#943; I 1 ! 1 I i 1 acctttacacatttattggatgaatattgaattagaacacatcgaacaag 800 v.28 721 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg I I 1 1 i 1 1 1 1 1 1 ! I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 I I 1 1 1 1 770 v.l 801 1 1 1,1 1 I 1 II 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 I 1 1 I 1 1 I 1 I 1 1 1 I 1 1 1 atgaaagagtatacatgagccaaaagggagatctatacttcgcaaacgtg 850 v.28 771 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag II111111 1 1 1 1 11 I 1 1 1 1 1 1 1 i1 I I 1 1 II 1 II 1 1 1 !! II 1 1 1 1 ! 1 1 1 &#943; I 820 v.l 851 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gaagaaaaggacagtcgcaatgactactgttgctttgctgcatttccaag .900 v.28 821 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt I 111II I 1 1 1 1 1 I 1 1 1 1 1 1 111 11 1 1 1 1 I ! 1 1 1 I 1 I 1 1 1 1 1 1 1 1 II 1 1 1 1 870 v.l 901 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 U 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 attaaggactattgtacagaaaatgccaatgaaactaacagttaacagtt 950 v.28 871 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca 1 I I I 1 1 1 I 1 1 1 1 1 1 |l 1 1 1 j II |l 1 1 1 1 1 It 1 1 1 1 1 j II 1 1 1 j 1 II 1 1 II 92 0 V.l 951 1 1 1 1 I I 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 taaagcatgctaatgactcaagttcatccacagaaattggttccaaggca 1000 v.28 921 aattccatcaagcaaagaaaacccaaactgctgttgectcccactgagag 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 970 v.l 1001 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I I π 1 1 1 1 1 I 1 II I 1 1 1 1 1 1 1 1 1 1 aattccatcaagcaaagaaaacccaaactgctgttgcctcccactgagag 1050 v.28 971 tggcagtgagtcttcaattaccatcctcaaaggggaaatcttgctgcttg 11 11 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 II 1 1 II 1 &#943; 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1020 v.l 1051 11 1 1 1 1 1 1 1 11 1 11 1 1 1 11 1 11 1 1 I 111 1 11 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I tggcagtgagtcttcaattaccatcctcaaaggggaaatcttgctgcttg 1100 338 vt2 8 1021 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt | 1 11 I I I 1 I 1 1 I I 1 I I I I I 1 It I 1 I It II I 1 I II I I 1 I 11 1 I 1 I I 1 II 1 1 1070 v.l 1101 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1. 1 1 II 1 1 1 1 1 1 1 1 1 1 agtgttttgctgaaggcttgccaactccacaggttgattggaacaaaatt 1150 ν. 2 8 1071 crgtqgtgacttaccaaaggggagagaaacaaaagaaaatt atggcaagac II III ill 1 1 11 1 I 11 Illlllllll | I | III II 1 1 111 II lllll III | 1120 v.l 1151 1 1 1 1 1 ! I 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! I 1 1 I 1 1 ! 1 1 1 I I ! 1 I I I 1 I 1 1 1 I 1 ggtggtgacttaccaaaggggagagaaacaaaagaaaattatggcaagac 1200 V.28 1121 tttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca | 1 1 1 1 1 1 1 II 1 j 1 II I 1 1 II 1 1 1 1 1 I 1 1 I 1 I II II II 1 1 1 1 II 1 1 1 1 II 1 1170 ν. 1 1201 1 1 I 1 1 1 1 1 I 1 1 II 1 1 1 II II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II If il 1 1 1 1 1 1 1 1 I tttgaagatagagaatgtctcctaccaggacaaaggaaattatcgctgca 1250 v.28 1171 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta II 1 1 1 1 1 1 1 1 1 II 1 II II II I II 1 1 I II 1 II II 1 II j I 1 II II II II II 1 1220 v.l 1251 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! ι ι I 1 1 ! 1 1 1 1 cagccagcaatttcttgggaacagccactcacgattttcacgttatagta 1300 v.28 1221 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtatagcac II I I I 1 II 1 1 1 11 1 1 1 I 1 1 I 11 1 I I I 1 1 1 1 I I I 1 1 1 II II 1 1 I I I I 1 1 1 1 1270 v.l 1301 1 1 i 1 1 i 1 1 1 1 I 1 I 1 i I 1 1 1 1 I I 1 1 1 i i I 1 I 1 1 I 1 1 1 1 ! 1 1 1 1 i I 1 1 1 i 1 1 gaagagcctcctcgctggacaaagaagcctcagagtgctgtgtatagcac 1350 v.28 1271 cggaaqcaatqgcatcttgttatgtgaggctgaaggagaacctcaaccca II |I HU Hill 11 1 11 1 11 1 II III II 1II1IIIIII1 ΙΙΙΙΙΙΙΙΙΙ 1320 v.l 1351 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 cggaagcaatggcatcttgttatgtgaggctgaaggagaacctcaaccca 1400 V v.28 1321 caatcaagtggagagtcaatggctccccagttgacaatcatccatttgct II 1 1 1 1 1 1 II II 1 1 1 II II 1 II 1 1 II 1 1 1 1 1 1 II 1 II 1 1 1 j II 1 1 1 1 I 1 I 1370 v. 1 1401 1 1 I 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 &#943; 1 I I 1 caatcaagtggagagtcaatggctccccagttgacaatcatccatttgct 1450 v.28 1371 ggtgatgttgtcttccccagggaaatcagttttaccaacc ttcaaccaaa | 1 1 I 1 1 1 1 I T 1 1 1 II 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 II 1 1 1 1 II 1 1420 v.l 1451 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 II I ggtgatgttgtcttccccagggaaatcagttttaccaaccttcaaccaaa 1500 V.28 1421 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 111II 1 1 II 1 1 1 1 1 1 II 1 1 1 1 1470 v.l 1501 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 tcatactgctgtgtaccagtgtgaagcctcaaatgtccatggaactatcc 1550 v.2 8 1471 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 | | | | | | | 1 | | | 1 | I 1 | 1 | 1 | 1 I 1 1 i | | | | I | 1 1 | 1520 v.l 1551 1 1 ι 1 1 i 1 1 1 1 I I 1 1 I 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 I 1 1 1 ι 1 1 I II I 1 1 1 1 1 1 1 ttgccaatgccaatattgatgttgtggatgtccgtccattgatacaaacc 1600 v.28 1521 aaagatggagaaaattacgctacagtggttgggtacagtgctttcttaca 1 1 1 η &#943; II ! I 1 1 1 1 1 1 1 II II I! Ν Η 11 1 1 1 1 1 1 1 III HI 1 I II Η II 1570 v. 1 1601 1 i ι I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 I 1 1 1 1 I 1 I 1 ( I ι I I 1 I 1 1 1 1 I ! I 1 1 1 1 ι &#943; aaagatggagaaaattacgctacagtggttgggtacagtgctttcttaca 1650 V.28 1571 ttgcgagttctttgcttcacctgaggcagtcgtgtcctggcagaaggtgg | II 1 1 1 1 1 1 II 1 1 1 1 1 1 1 j 1 1 1 II I I 1 II 1 1 II 1 II 1 1 II 1 1 1 1 1 1 II II 1620 v.l 1651 1 1 1 1 1 I I 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 I 1 1 1 1 ttgcgagttctttgcttcacctgaggcagtcgtgtcctggcagaaggtgg 1700 v.28 1621 aagaagtgaaacccctggaggqcaqgcqqtatcatatctatgaaaatggc 1 1 11 III II IlllllllllllllIII IIII111II11111II 1 II 1 II II 1670 v.l 1701 1 1 1 1 1 1 II 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 aagaagtgaaacccctggagggcaggcggtatcatatctatgaaaatggc 1750 v.28 1671 acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg | 1 1 1 1 1 1 I II 1 1 |J 1 1 1 1 II 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1720 v.l 1751 1 1 1 I 1 I 1 1 II 1 1 1 i 1 1 1 1 1 1 II 1 1 1 1 I 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 I 1 1 I I acattgcagatcaacagaaccaccgaagaagatgctgggtcttactcatg 1800 v.28 1721 ttgggtagaaaatgctataggaaaaactgcagtcacagccaatttggata [ I Η I Η Η I I I I I I I I I 1 11 I I 1 1 1 I 1 1 1 j 1 1 1 1 1 I 1 II j 1 j| 1 I 11 I 1 1770 v.l 1801 1 1 1 1 1 1 ll 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I.l 1 ttgggtagaaaatgctataggaaaaactgcagtcacagccaatttggata 1850 v.28 1771 ttagaaatgctacaaaacttagagtttctcctaagaatcc tcgtatcccc 1 1 1 1 1 1 1 11111111111 1 1 1 1 1 11 1 1 1 1 1 1111111II111111111f1 1820 v.l 1851 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ttagaaatgctacaaaacttagagtttctcctaagaatcctcgtatcccc 1900 339 Λ V Λ', v.28 1821 aaattgcatatgcttgaattacattgtgaaagcaaatgtgactcacattt I II I I I I 1 I I j II Π II 1 1 || I ( 1 I 1 | | I I 1 II I I II If II II j I | II I I 1870 v.l 1901 1 ι ι 1 I 1 ! 1 I 1 1 1 1 1 ι 1 11 1 1 I I 1 i 1U 1 II II I 1 I I I II » 1 1 1 1 1 I 1 1 I 1 aaattgcatatgcttgaattacattgtgaaagcaaatgtgacfccacattt .195 0 v. 2 3 1871 gaaacacagtttgaagttgtcctggagtaaagatggagaagcctttgaaa 1 1 1 11 1 1 11 I 1 1 II 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 t1H 1 1 11 1 1 1 1 1 1 I 1 192 0 v.l 1951 1 1 > I 1 | &#943; I ! I Π I It if 1 1 1 1 1 1 II 1 i 1 f 1 1 ι (I I I S i 1 I 11 I 1 I 1 I &#943; 11 gaaacacagtttgaagttgtcctggagtaaagatggagaagcctttgaaa 2000 v.28 1921 ttaatqgcacagaagatggcaggataattattgatggagctaatttgacc llllllllllllllllllllllllllllllllllllllllllllllllll 1970 v.l 2001 1 [ f ( 1 1 I 1 I &#943; 1 1 I H I 1 1 1 1 1 1 1 J 1 11 &#943; 1 1 1 1 } 1 1 1 I 1 1 I 1 J 1 I I 1 If 1 1 ttaatggcacagaagatggcaggataattattgatggagctaatttgacc 2050 v.28 1971 atatctaatgtaactttagaggaccaaggtatttactgctgttcagctca I 1 I I I ! 1 j I 1 1 1 1 I I I II 1 j II I I 1 I 1 1 ! I I ) 1 I ] J 1 I j I I I 1 I I I I 1 1 I 2020 v.l 2051 &#943; i ι I ! t 1 ! 1 &#943; I 1 Ν Ν N 1 I 1 1 Η ι &#943; Η 1 Ii Ν &#943; 1 N I 1 &#943; &#943; &#943; &#943; Ν Ν &#943; &#943; &#943; afcatctaatgtaactttagaggaccaaggtatttactgctgttcagctca 2100 v.28 2021 tactgctctagacagtgctgccgatataactcaagtaactgttcttgatg It 1 I I 1 1 I 1 I I I 1 1 1 1 1 1 I I 1 II j 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 II 1 1 I 1 I II 1 2070 v.l 2101 1 I 1 1 I 1 I 1 1 &#943; I I 1 1 1 1 I 1 1 1 1 1 1 I 1 II 1 I I &#943; 1 I I II 1 I 1 I 1 1 1 1 ι I 1 1 1 I tactgctctagacagtgctgccgatataactcaagtaactgttcttgatg 2150 v.28 2071 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 2120 v.l 2151 i 1 1 1 1 H I I 1 i 1 ! 1 ! 1 I 1 1 I I I 1 1 t I t 1 1 1 1 1 I I I 1 1 I I 1 I 1 1 1 1 i i I i 1 ttccggatccaccagaaaaccttcacttgtctgaaagacagaacaggagt 2200 v.28 2121 gttcqqctgacctgggaagctggagctgaccacaacagcaatattagcga 1111 11 1 1 1II 1 1 III! 1 11 1 11 II1! 1II 1III 1 1 1 1II 1 1 II I INI 1 2170 v.l 2201 ι 1 II Η 1 I 1 &#943; II ι ! II Η 1 i J 1 Η 1 1 1 l 1 IS 1 1 1 J 1 1 I ) 1 1 1 1 1 i 1 ) J 1 1 gttcggctgacctgggaagctggagctgaccacaacagcaatattagcga 2250 v.28 2171 gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg 1 j I II 1 I I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 II 1 j 1 I 1 j 1 1 1 1 1 1 1 1 1 2220 v.l 2251 1 Η 1 Η 1 1 1 H i 1 &#943; I 1 1 Η Η 1 1 I I i I 1 &#943; I I 1 ι 1 Η I I Η Η Η &#943; I Η 1 J gtatattgttgaatttgaaggaaacaaagaagagcctggaaggtgggagg 2300 v.28 2221 aactgaccagagtccaaggaaagaaaaccacagttatcttacctttggct 1 1 I 1 1 1 1 1 1 I 1 I 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 f I 1 1 2270 v.l 2301 1 I 1 II ι I 1 Η ι t 1 S 1 1 1 1 I I I 1 l 1 1 1 1 1 ! 1 1 1 1 1 I I 1 1 1 It ! 1 1 1 1 1 1 H aactgaccagagtccaaggaaagaaaaccacagtfcafccttaccttfcggct 2350 v.28 2271 ccatttgtgagataccagttcagggtcatagccgtgaacgaagtagggag llllII11IIII1111II11IIII III 11II1 III II1II111 1 111 111 2320 V.l 2351 1 1 1 I I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 1 I 1 I 1 l 1 H 1 1 I I 1 I 1 1 I 1 1 1 1 1 1 I 1 1 1 1 ccatttgtgagataccagttcagggtcatagccgtgaacgaagtagggag 2400 v.28 2321 aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc 1 11 1 1 1 1 1 I 1 II j I 1 I 1 j 1 1 1 II II 1 1 II II II II 1 1 1 1 I 1 1 II 1 1 1 1 j 1 2370 v.l 2401 II ll 1 U Ii { I I i 1 ι N 1 1 Η 1 I I I 1 1 1 1 1 1 I Π 1 II I H If 1 1 1 1 If 1 I aagtcagcctagccagccgtcagaccatcatgaaacaccaccagcagctc 2450 v.28 2371 cagataggaatccacaaaacataagggttcaagcctctcaacccaaggaa I t| I 1 1 I I 1 1 1 I 1 1 II 1 1 1 1 1 I 1 1 1 I 1 I 11 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 2420 v.l 2451 I ι I j I 1 1 J If I 1 1 1 1 1 1 1 I1 1 ι I J 1 1 1 I 1 i 1 1 I 1 1 SI 1 1 Η Η 1 &#943; 1 1 1 ι 1 cagataggaatccacaaaacataagggttcaagcctctcaacccaaggaa 2500 V.28 2421 atgattataaagtgggagcctttgaaatccatggagcagaatggaccagg I 1 1 1 II 1 1 I 1 1 1 1 I 1 1 ! Il 1 1 1 I 1 1 1 | | II 1 | | 1 II 1 1 1 1 1 1 II 1 1 1 1 1 1 2470 v.l 2501 Η I 1 I i u ι ι ι ι i 1 i > < ι 1 1 1 1 1 Ι &#943; I < Η ι 1 I 1 i 1 1 I ! 1 1 1 I ! 1 11 H ! I atgattataaagtgggagcctttgaaatccatggagcagaatggaccagg 2550 v.28 2471 cctagagtacagagtgacctggaagccacagggagccccagtggagtggg 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 I 1 1 1 1 1 1 1 I 1 1 1 1 2520 v.l 2551 Il 1 1 1 1 1 I I 1 1 1 1 1 J 1 i J 1 I 1 1 I J I f 11 1 1j !1 ! 1 I I 1 I I 1 I I I 1 1 1 1 I 1 cctagagtacagagtgacctggaagccacagggagccccagtggagtggg 2600 v.28 2521 aagaagaaacagtcacaaaccacacattgcgggtgatgacgcctgctgtc II 1 I 1 II I 1 I 11 II II I I I I 11 I 1 II 1 1 1 1 1 j 11 1 II II 1 I 1 I I I 1 n I I 2570 V.l 2601 1 1 1 $ { 1 1 I S Η I I I 1 I H t ι I 1 ι 1 1 1 I 1 i 1 ι &#943; Η Η &#943; Η Η Π I H f f Η aagaagaaacagtcacaaaccacacattgcgggtgatgacgcctgctgtc 2650 v.28 2571 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg 2620 340 , ν. 1 2651 tatgccccttatgatgtcaaggtccaggctatcaatcaactaggatctgg 2700 ν.28 2621 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata I 1 I 1 1 I II j 1 I 1 1 1 II i 1 I 1 1 II I 1 II 1 1 1 1 1 1 II I (I 1 1 1 1 II 11 1 1 II 2670 v.l 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι 1 1 1 1 I 1 ι ι ι 11111 ι 1 1 1 I I 1 I I 1 2701 gcctgaccctcagtcagtgactctctattctggagaagactatcctgata 2750 ν.28 2671 cagctccagtgatccatggggtggacgttataaacagtacattagttaaa I I 1 I 1 II 1 1 I 1 1 Ij II 11 I I l| I 1 II II 1 1 I I I )l 1 1 I 1 I 1 I 1 II II I II 2720 v.l · 1 1 1 1 I I ! 1 I 1 1 1 1 ! 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 ! 1 1 1 1 1 1 ! 1 ! 1 1 I ! ! 1 1 ! ! 1 2751 cagctccagtgatccatggggtggacgttataaacagtacattagttaaa 2800 ν.28 2721 gttacctggtcaacagttccaaaggacagagtacatggacgtctgaaagg I I I I I I I I 1 1 1 1 1 1 1 1 1 II I 1 1 I II II 1 1 I 1 j 1 1 1 II 1 1 I 1 1 II l| II 1 1 2770 v.l I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 II 1 1 i 1 1 1 ! I 1 1 1 1 1.1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 2801 gttacctggtcaacagttccaaaggacagagtacatggacgtctgaaagg 2850 ν.28 2771 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac I 1 I I I || ι ι 1 III ||] INI 1 II 1II 1 ill 1 1 II 1 Nil III INI 1 II 1 2820 v.l 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 2851 ctatcagataaattggtggaaaacaaaaagtctgttggatggaagaacac 2900 ν.2 8 2821 atcccaaagaagtgaacattctaagattttcaggacaaagaaactctgga l| 1 1 1 1 II 1 1 I II II 1 II 1 1 1 I II 1 I 1 II II 1 II II l| II II II II 1 1 1 1 2870 ν. 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 II I 1 1 1 1 ! 2901 atcccaaagaagtgaacattctaagattttcaggacaaagaaactetgga 2950 ν.28 2871 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc 1.11 1 1 1 I 1 1 1 1 1 1 1 II I 1 1 II 1 1 I 1 I 1 1 1 II 1 II 1 1 1 ll 1 1 1 1 II 1 1 1 II 2920 v.l hl 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 ,1 1 1 1 1 1 1 1 1 1 2951 atggttccttccttagatgcctttagtgaatttcatttaacagtcttagc 3000 ν.28 2921 ctataactctaaaggagctggtcctgaaagtgagccttatatatttcaaa II 1 II 1 1 1 1 1 1 II 1 1 II 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 II 1 I II 1 2970 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3001 ctataactctaaaggagctggtcctgaaagtgagccttatatatttcaaa 3050 ν.28 2971 caccagaaggagtacctgaacagccaacttttctaaaggtcatcaaagtt | 1 1 1 II 1 1 1 1 II 1 II I 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 1 1 1 1 1 1 II II II 1 1 1 3020 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1! 1 1 1 I 1 1 1 3051 caccagaaggagtacctgaacagccaacttttctaaaggtcatcaaagtt 3100 ν.28 3021 gataaagacactgccactttatcttggggactacctaagaaattaaatgg 11 1 1 1 1 1 1 1 1 1 1 II 1 1 1 11 1 1 1 1 II 1 I) II 1 1 II 1 1 II 1 1 II 1 1 1 1 1 1 II 3070 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 II 1 I 1 1 I 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 3101 gataaagacactgccactttatcttggggactacctaagaaattaaatgg 3150 ν.28 3071 aaacttaactggctatcttttgcaatatcagataataaatgacacctacg • N 1 1 II II 1 1 N 1 ! 11 1 11 ! 1 1 1iII1111!1!1111!II!1II 11 1 11 1 3120 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 11 1 1 II 1 1 1 1 1 1 1 I II II 1 1 1 1 1 1 1 1 1 3151 aaacttaactggctatcttttgcaatatcagataataaatgacacctacg 3200 ν.28 3121 agattggagaattaaatgatattaacattacaactccatcaaagcccagc II II 1 1 1 1 II 1 II II Η II II II 1 II III 11 II 1 II 1 1 1 1 II 11 1 (I 1 1 1 3170 v.l i 1 1 1 1 II 1 11 1 I I 1 I 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ll 1 1 1 II 3201 agattggagaattaaatgatattaacattacaactccatcaaagcccagc 3250 ν.28 3171 tggcacctctcaaacctgaatgcaactaccaagtacaaattctacttgag J 1 1 1 1 1 1 1 1 1 1 II 1 II 1 j 1 II I) 1 1 1 1 II 1 1 II II 1 1 1 1 1 1 II II I 1 1 II 3220 ν. 1 1 1 1 I 1 1 11 11 1 1 I 1 IIII 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 II 1 I 11 1 1 ll 1 3251 tggcacctctcaaacctgaatgcaactaccaagtacaaattctacttgag 3300 ν.2 8 3221 ggcttgcacttcacagggctgtggaaaaccgatcacggaggaaagctcca 1 I Η ι I | 111 I ι ι ι 11 ι ι | ι ! Ν ι ! I 1 ι ι ι ι ι ι ι ι 11 ι ι ι ι | ι ι ι ι | ι ι ι 3270 V.1 &#943; I 1 1 ! ι 1 ι ι ι I ι ι 1 ι ι ι ι 1 ι ι > Ιι ι I 1 ι ι ι I ι ι 1 1 1 | ι ι ι ι ι 1 ι ι ι ι ι ι ι 3301 ggcttgcacttcacagggctgtggaaaaccgatcacggaggaaagctcca 3350 ν.2β 3271 ccttaggagaagggagtaaaggtatcgggaagatatcaggagtaaatctt II 1 1 1 1 I 1 1 II 1 1 1 1 II II Π 1 1 1 II 1 I 1 1 1 II II 1 1 1 1 II 1 II 1 1 II II 3320 ν. 1 1 1 1 1 1 1 I 111 1 1 1 1 1 II I I II1 1 11 1 1 1 1 1 II 1 1 1 1 1 I 1 1 1 II 1 1 i 1 1 1 1 3351 ccttaggagaagggagtaaaggtatcgggaagatatcaggagtaaat.ctt 3400 ν.28 3321 actcaaaagactcacccaatagaggtatttgagccgggagctgaacatat II 1 II II I 1 j 11 1 II II II 11 1 II II II 1 II 1 1 I 1 1 1 II I 1 (I j I 1 II 1 1 3370 ν.1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3401 actcaaaagactcacccaatagaggtatttgagccgggagctgaacatat 3450 ν.28 3371 agttcgcctaatgactaagaattggggcgataacgatagcatttttcaag 3420 341 v.l 3451 agttcgcctaatgactaagaattggggcgataacgatagcatttttcaag 3500 v.28 3421 atgtaattgagacaaqagqqagagaatatgctggtttatatgatgacatc ιιιιII1!1iιιι &#943;ι&#970;ιιι]ιιιιιιιj ιιιιιιιι&#943; ISj 1 | ι ι ι I jj l 1 3470 ν. 1 3 5 01 1 1 1 1 ! I 1 I 1 1 1 1 1 1 1 I 1 1 1 I i 1 1 1 1 1 I ι 1 1 1 1 I 1 1 1 1 1 ι ι 1 1 1 1 1 1 1 1 1 1 atgtaattgagacaagagggagagaatatgctggtttatatgatgacatc 3550 v.28 3471 tccactcaaggctggtttattggactgatgtgtgcgattgctcttctcac 1 1 i 1 i ! i 1 111 IIIII1 111 II 11 1 1 II II ill IIII 1 II 1 1 1 IN 1 I 1 1 3520 v.l 3551 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 tcca'ctcaaggctggtttattggactgatgtgtgcgattgctcttctcac 3600 v.28 3521 actactattattaactgtttgctttgtgaagaggaatagaggtggaaagt 11111 I 1 I 1111111II III II 11 III IIIIII III 1 III II II II 1 III 3570 v.l 3501 I 1 ι 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 1 1 I I 1 1 1 actactattattaactgtttgctttgtgaagaggaatagaggtggaaagt 3650 v.28 3571 actcagttaaagaaaaggaagatttgcatccagacccagaaattcagtca I I 1 I I 1 I 1 I I I 1 I I I 11 I 1 1 1 I 1 1 I I 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 II I 3620 v.l 3651 ! 1 I 1 1 1 1 I 1 1 1 ! 1 I 1 1 1 1 1 1 1 ! 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 ! 1 1 1 I 1 1 1 ι actcagttaaagaaaaggaagatttgcatccagacccagaaattcagtca 3700 v.28 3621 gtaaaagatgaaacctttggtgaatacagtgacagtgatgaaaagcctct | 1 1 1 1 I I I 1 I 1 I I 1 I 1 1 1 1 1 1 1 II 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 II 1 1 1 3670 v.l 3701 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 i 1 1 1 1 i 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 gtaaaagatgaaacctttggtgaatacagtgacagtgatgaaaagcctct 3750 v.28 3671 caaaggaagccttcggtcccttaatagggatatgcagcctactgaaagtg 1 111111II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1!111111 1 I 1 1 1 1 1 1 1 1 1 1 3720 v.l 3751 i I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 i 1 1 I I 1 1 1 1 1 1 1 1 I I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 caaaggaagccttcggtcccttaatagggatatgcagcctactgaaagtg 3800 v.28 3721 ctgacagcttagtcgaatacggagagggagaccatggtctcttcagtgaa I 1 I 1 I II 1 1 I 1 I II I I 1 I 1 I 1 1 1 j 1 1 1 1 I 1 1 I I I I 1 1 i 1 1 I I 1 1 1 1 1 1 i 1 3770 v.l 3801 1 1 1 1 1 I ι ι I I I 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 I I 1 1 I 1 ι 1 1 1 1 1 1 1 I 1 1 1 ctgacagcttagtcgaatacggagagggagaccatggtctcttcagtgaa 3850 v.28 3771 gatggatcatttattggtgcctacgctggatctaaggagaagggatctgt I I 1 I I II I I I I I I I I [ I I 1 1 1 j 1 1 1 1 1 1 1 1 1 1 ! I 1 1 1 1 1 1 1 1 I 1 1 II 1 1 ] 3820 v.l 3851 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gatggatcatttattggtgcctacgctggatctaaggagaagggatctgt 3900 v.28 3821 tgaaaqcaatggaaqttctacagcaacttttccccttcgggcataaacac I I 1 I I I 1 1 1 HI II 1 I 1 11 I 1 I 1 1 1 I I 1 i 1 1 1 I i 1 I I III II 1 1 1 1 I 1 1 1 3870 v. 1 3901 i ι 1 1 I I ! I 1 I 1 1 ! 1 ι ι ι &#943; ι I I I 1 ι ι 1 1 ι 1 I 1 ! 1 &#943; 1 1 1 ι I 1 1 1 I 1 1 ι i 1 I 1 tgaaagcaatggaagttctacagcaacttttccccttcgggcataaacac 3950 v.28 3871 aacatatgtaagcaacgctactggttcaccccaaccttccatatttatct I I 1 1 1 1 1 I 1 1 1 I 1 1 1 II I II 1 1 1 1 1 II 1 1 1 1 I II 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 3920 v.l 3951 I ! 1 1 1 1 I 1 1 1 I ! I 1 1 I I 1 I 1 1 ! 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 I ! 1 1 ! I 1 1 1 1 I ι 1 aacatatgtaagcaacgctactggttcaccccaaccttc-catatttatct 4000 V.28 3921 gttcaaaggagcaagaactttcatataggaatagaaacatgctggccgaa j 1 I 1 1 1 I | || |l I || II 1 1 1 1 1 1 1 I I 1 I I 1 1 1 l|l 1 I 1 I 1 1 I || 1 1 3970 v.l 4001 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 gttcaaaggagcaagaactttcatataggaatagaaacatgctggccgaa 4050 v.28 3971 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac i I I &#943; 1 i i 1 II 1 I 1 I 1 i 1 I 11 i i i I i I I I I I 1 &#943; 1 I 1 I 1 II II I I I 1 j j &#943; 1 ] 4020 v.l 4051 1 1 1 1 1 1 I 1 1 11 1 1 1 1 1 i 1 I 1 1 1 1 1 i 1 1 1 1 I 1 I 1 1 1 1 i 1 1 1 1 1 II 1 I 1 1 1 1 gatttcatccagaagtcaacatcctgcaattatgttgaaaagagtagtac 4100 v.28 4021 tttcttcaaaatataaaatgccaagcacttcaggcctatgttttgcttat 1 1 1 1 I 1 1 1 1 II 1 1 1 1 1 1 1 1 1 I 1 1 1 II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4070 v.l 4101 I 1 1 1 1 1 I I 1 11 I 1 1 1 ! 1 II 1 11 1 II II 1 1 1 1 1 1 i 1 1 1 1 1 I 1 1 1 It 1 1 1 1 1 tttcttcaaaatataaaatgccaagcacttcaggcctatgttttgcttat 4150 v.28 4071 attgttttcaggtgctcaaaafcgcaaaacaeaaaacaaatcctgcattta 1 I I I 1 I I 1 I 1 I 1 1 1 II 1 1 j II I) 1 1 I 1 I II II II ill 1 1 II I i 1 1 1 1 1 1 1 4120 v.l 4151 1 1 1 1 1 1 1 1 1 I 1 II 1 1 1 1 1II 1 Π 1 11 li 1 1 1 1 II 1 I 1 1 1 1 1 1 II 1 1 1 1 1 1 attgttttcaggtgctcaaaatgcaaaacacaaaacaaatcctgcattta 4200 v.28 4121 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg | I 1 I II I I 1 1 1 1 1 I 1 If 1 I 1 1 1 1 1 1 1 1 1 1 1 1 ! I 1 II 1 1 1 1 1 1 1 I 1 1 1 1 1 1 4170 v.l 4201 1 1 I 1 1 1 1 i I 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 Η 1 1 1 i 1 1 t 1 1 I I 1 1 1 1 1 1 1 I 1 1 1 1 1 gatacacctcaactaaatccaaagtccccattcagtatattccatatttg 4250 342 ,y.28 4171 cctgattttactattcggtgtgtttgcatagatgttgctacttggtgggt | 1 I II I I It 1 i 1 1 I 1 I I I I I I 11 1 1 I 11 I I 11 1 1 I 1 I 1 1 I 1 I I It 1 I |l 1 4220 v.l ι 1111 ι 11 &#943; 11111111 1111111111 11111 111 ι 111 11 111111 ι 11 4251 cctgattttactattcggtgtgtttgcatagatgttgctacttggtgggt 4300 v.28 4221 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga | 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 1 1 4270 v.l 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι ι 1 1 1 1 I 1 I 1 1 1 I 1 1 4301 ttttctccgtatgcacattggtatacagtctctgagaactggcttggtga 4350 v.28 4271 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa | 1 1 1 1 1 II 1 1 II 1 1 1 1 1 II 1 1 II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 4320 v.l 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 4351 ctttgcttcactacaggttaaaagaccataagcaaactggttatttaaaa 4400 v.28 4321 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac | II I II , I 1 1 I II 11 1 II II II II I I I II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II II 4370 v.l 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 44 01 tgtaaaaaggaatatgaaagtcttattaaaacacttcattgaaaatatac 4450 v.28 43 71 agtctaaatttattatttaaattttactagcaaaagtcttaggtgaacaa | I I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 4420 v.l 1 1 1 &#943; 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 4451 agtctaaatttattatttaaattttactagcaaaagtcttaggtgaacaa 4500 v.28 4421 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa 1 1 1 1 1 1 1 1 111 11 1 1 H i 1 1 ! 1 1111 1 ! 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 4470 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II i 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 I 1 1 1 1 1 1 1 4501 tcaactagtatttgttgagctcctatttgcccagagatggtcatatttaa 4550 v.28 4471 acagaagtatacgtttttcagtttcaacatgaatttttttatttctgtca II I I I I I II I I 1 1 1 1 1 1 1 1 1 1 II 1 II II I 1 1 1 1 1 1 1 11 1 II 1 l| 1 II 1 II 4520 v.l 1 i 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4551 acagaagtatacgtttttcagtttcaacatgaatttttttatttctgtca 4600 v.28 4521 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct | II 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 II 1 II 1 II 1 1 1 1 II II 1 1 4570 v.l 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 4601 gttatgacatccacgagcatcactttttgtgtctgtttttttttttttct 4650 v.28 4571 tggactaaattcaactgcatggaagcggtggtcagaaggttgttttatac | 1 1 1 II 1 1 1 1 1 II 1 1 1 II I 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 II 1 1 1 4620 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1- 1 4 651 tggactaaattcaactgcatggaagcggtggtcagaaggttgttttatac 4700 v.28 4621 gagaacaqqcagaaaqtqcccattgttcaggattctaatagctacatcta 11111 1 III ι π ι ι II II I I II 1 ill I ι π || II I II I ι || HI I 1 1 I 1 &#943; 4670 v.l 1 I 1 1 1 ! ι I I I 1 1 i 1 1 1 1 ι ! I 1 I I ! 1 1 I ! ! 1 I ! I 1 1 I 1 1 ι! 1 ! 1 1 ! 1 1 1 1 I 47 01 gagaacaggcagaaagtgcccattgttcaggattctaatagctacatcta 4750 v.28 4 671 cttaatatcttcatttctaaattgactgcttttacctttttctcatgttt - I I 1 |'-| I I I I I I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 4720 v. 1 1 1 1 II I 1 II ! ! II 1 1 1 ! II i I ! 1 1 ! I I I I 1 1 1 1 ! 1 1 1 1 ! 1 1 1 1 1 1 1 II 1 1 47 51 cttaatatcttcatttctaaattgactgcttttacctttttctcatgttt 4800 v.28 4721 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg | 1 1 II 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 I 1 1 II 1 1 1 1 II 1 1 1 1 1 1 I II 4770 v.l 1 1 1 1 I 1 1 1 I 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 I 1 ! 1 1 1 1 1 1 1 1 1 1 48 01 atataatggtatgcttgcatatatttcatgaatacattgtacatattatg 4850 v.28 4771 ttaatatttacacaatttaaaatatagatgtgttttattttgaagtgaga | II I 1 1 1 1 I 1 1 1 1 I 1 1 I | I 1 1 1 1 1 11 II 1 II 1 1 I 1 1 1 I 1 1 1 1 1 1 II 1 II 1 4820 v.l 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4 851 ttaatatttacacaatttaaaatatagatgtgttttattttgaagtgaga 4900 v.28 4 8 21 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat I I 1 11 I I I 1 II I II 1.1 1 I II 1 j 1 1 II 1 1 1 1 II I Η Η II 1 1 1 1 1 II 1 1 1 1 4870 v.l II 1 I 1 I 1 1 1 1 1 II 1 1 I 1 1 I 1 1 1 1 1 1 1 II II 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 ! I 1 1 4901 aaatgaacattaacaggcatgtttgtacagctagaatatattagtaagat 4950 v.28 4 871 actgtttttcgtcattccagagctacaactaataacacgaggttccaaag | 1 II 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I) II 1 1 !| II 1 1 1 II II j 1 1 1 4920 v.l 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 4951 actgtttttcgtcattccagagctacaactaataacacgaggttccaaag 5000 v.28 4921 ctgaagactttgtataaagtatttgggttttgttcttgtattgctttctt 11 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 II 1 1 1 1 1 II 1 II 1 I 1 j 1 1 1 1 1 1 II II I 1 1 1 1 II 4970 v.l 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 i 1 I 1 1 1 1 1 1 I 1 1 1 I 1 1 I 1 1 i 1 1 1 1 I 1 1 II 1 1 1 1 5001 ctgaagactttgtataaagtatttgggttttgttcttgtattgctttctt 5050 343 v.28 4 971 tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc I I I I 1 1 1 1 1 I 1 I I II 1 I 1 I 1 I I r 1 1 | | 1 1 II I 1 1 II 1 II 1 I 1 1 1 I I I I II 5020 v. 1 5 051 1 1 1 1 1 1 1 1 1111 I 1111 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l ll111111 1 tcaacagtttcaaaataaaatatcatacaaatattgagggaaatgttttc 5100 v. 28 5021 atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc 1 1 1 1 1 1 1 1 1 111 1 11 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 II 1 1 1 11 1 1 5070 v.l 5101 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 I I 1 1 I 1 1 1 1 atatttttcaaaataggtttttattgttgaatgtacatctaccccagccc 5150 v. 28 5071 ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 II 1 1 II 1 1 5120 v.l 5151 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ctcaaaagaaaaactgtttacatagaaattcctacacatacgtttgcgta 5200 v.28 5121 tatgttattttaaacatctttgtggtgagaattttttccccgatattctc 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5170 v. 1 5201 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 tatgttattttaaacatctttgtggtgagaattttttceccgatattctc 5250 v.28 5171 cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5220 v.l 5251 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 cttctgtcaaagtcagaacaaattcagggaatttattttctggcagttgt 5300 v.28 '5221 gctccagtccttttaaaattgtacatgaacatgttttagaaacaatatgg 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5270 v.l 5301 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 | 1 1 1 1 1 1 1 1 1 1 1 1 1 gctccagtccttttaaaattgtacatgaacatgttttiagaaacaatatgg 5350 v.28 5271 aqqatgatgcatacatgtcggtcaagttcagcgctcgacattttatggaa 1111111 11 | | | | | | 1 1 1 1 111 mini IIIIII III III II 1 INI II 5320 v. 1 5351 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 aggatgatgcatacatgtcggtcaagttcagcgctcgacattttatggaa 5400 v.28 5321 agatttttttaaccttaccacgaaatacttaactactgtttaagtgaatt 1 1 II I I I I II I II 1 1 I II 1 1 II II 1 1 1 II II 1 l| 1 I 1 1 II 1 1 1 1 1 1 II 11 5370 v.l 5401 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 agatttttttaaccttaccacgaaatacttaactactgtttaagtgaatt 5450 v.28 5371 gacttatttcactttagtttttgaactgtgattattggtatactgttata 111 N II11IIII1111111 i!1II1111II111111111111IIIII11 gacttatttcactttagtttttgaactgtgattattggtatactgttata 5420 v.l 5451 5500 v.28 5421 tcctcaacttggatttatcgtaaccccttttagttcatggaqaccaaaat II N 11111II .1111 i 11&#938;! 111 i 1111II1 i 111 Μ 1111 &#970; 11 III 111 tcctcaacttggatttatggtaacccctttt'agttcatggagaccaaaat 5470 v.l 5501 5550 v.28 5471 ttgbggtatttataatagtcagcgcaggaatgcacatggaatatctactt 1 1Ι&#938;1 1 1 ! II 1 N 1 1II1 I I II N 1 N 1 11 II 1 II 1 1 1 1 N 1! 1 II II 1 1 5520 v.l 5551 1 1 1 1 1 1 1 I 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ttggggtatttataatagtcagcgcaggaatgcacatggaatatctactt 5600 v.28 5521 gtccttttgaacctcacgagtcatccagaatgtatagacaggaaaagcat 1 111111 1 1 II II II 1 II 1 1 1 1 1 1 I 1 1 1 1111 1 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5570 v.l 5601 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gtccttttgaacctcacgagtcatccagaatgtatagacaggaaaagcat 5650 v.2 8 5571 gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg | I l| 1 II II II 11 1 II 1 11 II I 1 1 1 1 1 1 II II 1 II 1 j 1 I) II 1 1 1 II 1 1 1 5620 v.l 5651 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 gtcttatttaaaactgtaatttatgggctcaggatctgaccgcagtcccg 5700 v.28 5621 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga 1 1 1 1 1 II 1 1 II N I 1 N N 1 N II 1 II 1 I 1 1 1 1 1 1 1 1 1 I 111 N N 1 1 1 1 5670 v.l 5701 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 ggagtaagcatttcaaagggggaaggcagtgtggtccctaccctgtgtga 5750 v.28 5671 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc I 1 II I II I I I I II II j| |l I II !| 1 II 1 !| II 1 1 1 II 1 I I II 1 II I'l l 1 1 5720 v.l 5751 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 i 1 ι 1 1 1 1 1 1 1 1 I 1 1 atgtgaggatgtagacatccatcagtgcaactcgagctccatcctcctcc 5800 v.28 5721 gatttctaaggctccagttttctggagggacagtcatcatgttttgattt 5770 344 yql 5801 gatttctaaggctccagttttctggagggacagtcatcatgttttgattt 5850 v.28 5771 atctgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga II 1 1 1 II 11 1 1 II 1 1 1 I I II I II I I ll 1 1 II I 1 II 1 II 1 1 li 1 I 1 I 11 1 1 5820 v.l 5851 II 1 1 1 1 I 1 1 1 1 II 1 1 1 1 11 1 1 I 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 1 1 1 atetgggagaaaactgtggtgcacagcttgtgaggagggcaaggttgtga 5900 V.28 5 821 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcag 1 1 1 1 1 I 1 II 1 11II1 111111 I I 1 I 1 1 1 1 1 1 1 1 1 1 1 I! 1 1 1 ! 1 1 I II 1 1 I 5870 V.l 5901 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l l l 1 l ι ι 1 cgttcgagcttagttctggtgttattctgtctcctcttctttgtcatcag 5950 V.28 5871 ccaaaacgtggtttttaaagagagtcatgcaggttagaaataatgtcaaa 1 1 1 1 11III 11 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11II 1 1I1 111 1 1 1 1 1 1 1 5920 v.l 5951 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ccaaaacgtggtttttaaagagagtcatgcaggttagaaataatgtcaaa 6000 v.28 5921 aatatttaggaatttaataacctttaagtcagaaactaaaacaaatactg 1 1 1 II 1 1 1 1 1 II 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 ] 1 1 I 5970 v.l 6001 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i i 1 1 1 1 1 1 1 I i 1 1 1 I 1 1 1 1 1 1 1 aatatttaggaatttaataacctttaagtcagaaactaaaacaaatactg 6050 v.28 5971 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat | I I I 1 I I I I I I II I 1 I I I I I I I I I I 1 1 1 1 1 II 1 II 1 1 1 1 1 1 1 11 1 1 11 1 1 6020 v.l 6051 1 1 1 1 1 1 1 I 1 1 1 1 II 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 I 1 1 1 1 1 1 1 I I 1 1 aaatattagctcttcctacacttcgtgttcccctttagctgcctgaaaat 6100 v.28 6021 caagattgctcctactcagatcttctgagtggctaaaacttatggatatg | 1.1 1 1 1 II 1 1 1 1 1 1 1 j 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 6070 v. 1 6101 1 I 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1.1 1 1 1 1 1 1 1 1 caagattgctcctactcagatcttctgagtggctaaaacttatggatatg 6150 v.2S 6071 aaaaatgagattgaatgatgactatgctttgctatcattgttacctttcc 1 111 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11II 1 1 ! 1 1 1 6120 v.l 6151 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 aaaaatgagattgaatgatgactatgctttgctatcattgttacctttcc 6200 v.28 6121 tcaatactatttggcaactactgggactcttcagcacaaaaggaatagat 1 1 1 1 1 1 II 1 1 I 1 1 11111111II11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11111 6170 v.l 6201 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 I 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 tcaatactatttggcaactactgggactcttcagcacaaaaggaatagat 6250 v.28 6171 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt 1 1 1 1 ! I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 6220 v.l 6251 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ctatgattgaccctgattttaattgtgaaattatatgattcatatatttt 6300 v.28 6221 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1II11111 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 ) 1 6270 v.l 6301 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 I! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 atgaatcagaataaccttcaaataaaataaatctaagtcggttaaaatgg 6350 v.28 6271 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa | 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 I 1 1 II 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 6320 v.l 6351 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 atttcatgattttccctcagaaaatgagtaacggagtccacggcgtgcaa 6400 v.28 6321 tggtaattataaattggtgatgcttgtttgcaaattgcccactcgtgata 1 1 1 1 1 1 1 1 111 11 111 11111111111 111 1 1111111 1 1 1 1 1 1 1 1 II 1 ! 6370 v.l 6401 1 1 ! 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 tggtaattataaattggtgatgcttgtttgcaaattgcccactcgtgata 6450 v.28 6371 agtcaacagccaatatttaaaactttgttcgttactggctttaccctaac 1 1 1 1 1 1 1 1 1 II11 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 II II 1 1 6420 V.l 6451 I 1 I 1 I 1 I 1 1 ! 1 1 Η II I 1 I ! ! 1 ! II 1 1 11 1 11 1 1 1 I 1 1 11 ! 1 I I I 1 ! I I 1 agtcaacagccaatatttaaaactttgttcgttactggctttaccctaac 6500 v.28 6421 tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag | I 1 I 1 1 I 1 1 1 I 1 I j H II !| II 1 1 II 1 II II 1 I 1 I 11 11 1 Π 1 1 N II 1 I 6470 v.l 6501 II 111 1 1 1 1 1 II 1 1 1 1 1 11 1 1 1 1 1 11 I II1 II 1 11 II 1 1 1 1 1 1 1 1 1 1 1 1 I tttctctagtctactgtcaatatcattttaatgtaattgattgtatatag 6550 v.28 6471 tctcaagaatggttggtgggcatgagttcctagagaactgtccaagggtt ! 1 1 1 I 1 I 1 1 i 1 1 &#943; 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 1 1 1 1 I 6520 v.l 6551 1 1 1 1 1 1 1 1 1 1 1 I 1 1 I 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 1 1 1 1 1 1 1 I 1 1 1 tctcaagaatggttggtgggcatgagttcctagagaactgtccaagggtt 6600 v.28 6521 gggaaaatccaaattctcttcctggctccagcactgattttgtacataaa 6570 345

III11111 in 1111111 fl I H 11 H 111 II 1111111111111!! I v.l 6601 gggaaaatccaaattctcttcctggctccagcactgattttgtacataaa 6650 v. 28 6571 cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa 1 I 1 1 I 1 ! j i 1 j I 1 I 1 1 I 1 1 I 1 I 1 I 1 1 1 I 1 I 1 1 1 i I I 1 1 1 1 1 1 I I I 1 I 1 I 1 6620 v.l 6651 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 ι 1 1 1 1 1 1 1 1 i 1 1 1 I 1 I 1 1 ι 1 1 1 cattaggcaggttgcttaacctttttatttcaaactctctcaactctaaa 6700 v.28 6621 gtgctaataataatctcagttaccttatctttgtcacagggtgttctttt I 1 1 1 [ 1 I 1 11 ! 1 I 1 | | | | I 1 1 1 II 11 1 1 1 1 I II 1 II II 1 II 1 II II 1 1 1 1 6'67 0 v.l 6701 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1, 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gtgctaataataatctcagttaccttatctttgtcacagggtgttctttt 6750 v.28 6671 ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc II 1 II 1 II 1 1 1 I II II 1 1 II 1 1 1 1 1 1 II II 1 1 II 1 1 II II j 1 I II 1 1 1 l| 6720 V. 1 6751 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 ttatgaagaaaaatttgaaaatgataaaagctaagatgccttctaacttc 6800 v.28 6721 ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc | II 1 II 1 II 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 6770 v.l 6801 1 1 1 I 1 1 1 I 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ataagcaaacctttaactaattatgtatctgaaagtcacccccacatacc 6850 v.28 6771 aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca | 1 1 1 II 1 ] 1 1 1 1 1 1 1 1 1 1 1 1 1 j 1 1 1 II 1 II II 1 1 1 II 1 1 1 I II 1 1 11 1 1 1 6820 v.l 6851 1 1 1 1 1 1 1 1 1 1 1 I 1 I 1 1 1 1 1 ! 1 i 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 aactcaacttttttcctgtgaacacataaatatatttttatagaaaaaca 6900 v.28 6821 aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat (' II 1 II 1 1 1 1 1 1 1 1 II 1 1 j I 1 1 1 1 1 1 1 1 1 11 1 1 1 1 1 1 II 1 |] 1 II 1 1 1 1 1 6870 v. 1 6901 1 1 1 1 1 1 1 1 I 1 1 1 I 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 aatctacataaaataaatctactgtttagtgagcagtatgacttgtacat 6950 v.28 6871 gccattgaaaattattaatcagaagaaaattaagcagggtctttgctata | 1 II 1 II II 1 1 I I 1 II 1 1 1 1 I 1 1 II II 1 I 1 i 1 I 1 j 1 II II |.| II 1 1 II II 6920 V. 1 6951 1 i 1 I 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gccattgaaaattattaatcagaagaaaattaagcagggtctttgctata 7000 v.28 6921 caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga | 1 II II 1 1 1 11 1 1 1 1 II 1 II 1 II 1 II II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 6970 v.l 7001 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 caaaagtgttttccactaattttgcatgcgtatttataagaaaaatgtga 7050 v.28 6971 atttggtggttttattctatcggtataaaggcatcgatattttagatgca I 1 I 1 111 II Π 1 Η 1 1 1 Η Η Η Π ! Π Π Η 1 Π II Η Π 1 II II Η H 7020 v. 1 7051 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 atttggtggttttattctatcggtataaaggcatcgatattttagatgca 7100 v.28 7021 cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca i I 11II,II1 M 1 I 1 !! 1 I I I 1 1 1 1 1 I 1 I I 11 1 I 1 I 1 I I 1 1 1 1 I 1 I I 11 1 7070 v. 1 7101 1 1 i 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 I 1 i 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 cccgtgtttgtaaaaatgtagagcacaatggaattatgctggaagtctca 7150 v.28 7071 aataatatttttttcctattttatactcatggaagagataagctaaagag II 1 II 1 II Η II II II 1 II II II II II II II 1 1 1 1 1 1 ! 1 1 1 1 II II 11 1 1 7120 v. 1 7151 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 l 1 1 i 1 1 1 1 I 1 aataatatttttttcctattttatactcatggaagagataagctaaagag 7200 v.28 7121 gggacaataatgagaaatgttggtgtgcttttctaagcatttaaaacata 1 1 I 1 1 1 1 1 1 1 1 1 1 I 1 1 1 I 1 1 I 1 1 I Η Η ι 1 I I I 1.1 ι ι | ι ι ι ι | i | ! I l j | 7170 v.l 7201 1 1 1 1 1 1 1 I 1 1 1 I ι 1 ι ι ι 1 ι 1 1 ι ι 1 I ι 1 ι ι 1 ι ι ι 1 1 ι ι 1 ι ι 1 ι 1 1 ι ι ι ι ι ι gggacaataatgagaaatgttggtgtgcttttctaagcatttaaaacata 7250 v.28 7171 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc 7220 v.l 7251 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 i I 1 1 1 1 II II 1 1 II II 1 1 1 1 1 1 1 attgccaattgaaaccctaaatatgtttacataccattaagatatgattc 7300 v.28 7221 atgtaacaatgttaaattaattataatgggattgggtttgttatctgtgg II II 1 1 II II 1 1 II I 1 1 II II II II II 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 II |j II 7270 v. 1 73 01 1 1 1 1 1 1 1 1 I 1 ! 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 atgtaacaatgttaaattaattataatgggattgggtttgttatctgtgg 7350 v.28 7271 tagtatatatcctagtgttcctatagtgaaataagtagggttcagccaaa H IIII 111 1 1 1 H 1 1 II ! ! Π H 1 1 H 1 1 111 1 1 1 1 1 1 ll1 1II 1 II 1 1 7320 v.l 7351 1 i 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 tagtatatatcctagtgttcctatagtgaaataagtagggttcagccaaa 7400 346 &amp;#943; "V.28 .»T -. 7321 gctttctttgttttgtaccttaaattgttcgattacgtcatcaaaagaga | I I II 1 I I I 1 1 I I 1 I I 1 II I 1 I II 1 1 1 I 1 I I II 1 I I 1 1 1 1 1 1 I II 1 1 II I 7370 v.l 7401 11 1 I 1 I 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ι ι 1 1 II 1 1 1 1 1 1 1 1 gctttctttgttttgtaccttaaattgt'tcgattacgtcatcaaaagaga 7450 v.28 7371 tqaaaggtatgtagaacaggttcacgtgattacctttttcttttggcttg 1 &amp;#970; II 1 I 1 1 1 1 I 1 I I 1 1 1 1 I 1 1 1 1 1 1 &amp;#970; 1 1 1 1 I 1 I 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 1 1 1 7420 v. 1 7451 1 i 1 l 1 I I 1 I 1 I 1 1 1 1 1 1 I 1 1 1 1 1 I 1 1 1 1 I 1 1 1 1 I I I 1 i 1 1 1 1 1 1 1 1 1 i 1 1 tgaaaggtatgtagaacaggttcacgtgattacctttttcttttggcttg 7500 v.28 7421 gattaatattcatagtagaactttataaaacgtqtttgtattqtaggtgg II I I ι 1 III ι 1 I || 11 I| 1 1 || ι ι I 1 || I I Hi || ι llll 1 II II III II 7470 v. 1 7501 1 1 1 I 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I I I 1 1 1 i I 1 1 gattaatattcatagtagaactttataaaacgtgtttgtattgtaggtgg 7550 v.28 7471 tgtttgtattatgcttatgactatgtatggtttgaaaatattttcattat 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 7520. v. 1 7551 1 I t 1 1 1 1 1 I I 1 1 1 1 ! 1 1 1 1 1 1 I 1 1 II I I. 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 I 1 1 tgtttgtattatgcttatgactatgtatggtttgaaaatattttcattat 7600 v.28 7521 acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa | 1 1 1 1 1 1 1 I 1 1 1 1 1 II 1 1 1 1 1 1 1 1 I 1 1 1 II 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 7570 v.l 7601 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 I i acatgaaattcaactttccaaataaaagttctacttcatgtaatccaaaa 7650

Table LIVh. Peptide sequences of protein coded by 282P1G03 v.28 (SEQ ID NO: 196) MEPLLLGRGL IVYLMFLLLK FSKAIEIPSS VQQVPTIIKQ SKVQVAFPFD EYFQIECEAK 60 GNPEPTFSWT KDGNPFYFTD HRIIPSNNSG TFRIPNEGHI SHFQGKYRCF ASNKLGIAMS 120 EEIEFIVPSV PKLPKEKIDP LEVEEGDPIV LPCNPPKGLP PLHIYWMNIE LEHIEQDERV 180 YMSQKGDLYF ANVEEKDSRN DYCCFAAFPR LRTIVQKMPM KLTVNSLKHA NDSSSSTEIG 240 SKANSIKQRK PKLLLPPTES GSESSITILK GEILLLECFA EGLPTPQVDW NKIGGDLPKG 300 RETKENYGKT LKIENVSYQD KGNYRCTASN FLGTATHDFH VIVEEPPRWT KKPQSAVYST 360 GSNGILLCEA EGEPQPTIKW RVNGSPVDNH PFAGDWFPR EISFTNLQPN HTAVZQCEAS 42 0 NVHGTILANA NIDWDVRPL IQTKDGENYA TWGYSAFLH CEFFASPEAV VSWQKVEEVK 48 0 PLEGRRYHIY ENGTLQINRT TEEDAGSYSC WVENAIGKTA VTANLDIRNA TKLRVSPKNP 54 0 RIPKLHMLEL HCESKCDSHL KHSLKLSWSK DGEAFEINGT EDGRIIIDGA NLTISNVTLE 600 DQGIYCCSAH TALDSAADIT QVTVLDVPDP PENLHLSERQ NRSVRLTWEA GADHNSNISE 660 YIVEFEGNKE EPGRWEELTR VQGKKTTVIL PLAPFVRYQF RVIAVNEVGR SQPSQPSDHH 720 ETPPAAPDRN PQNIRVQASQ PKEMIIKWEP LKSMEQNGPG LEYRVTWKPQ GAPVEWEEET 780 VTNHTLRVMT PAVYAPYDVK VQAINQLGSG PDPQSVTLYS GEDYPDTAPV IHGVDVINST 840 LVKVTWSTVP KDRVHGRLKG YQINWWKTKS LLDGRTHPKE VNILRFSGQR NSGMVPSLDA 900 FSEFHLTVLA YNSKGAGPES EPYIFQTPEG VPEQPTFLKV IKVDKDTATL SWGLPKKLNG 96 0 NLTGYLLQYQ IINDTYEIGE LNDINITTPS KPSWHLSNLN ATTKYKFYLR ACTSQGCGKP 1020 ITEESSTLGE GSKGIGKISG VNLTQKTHPI EVFEPGAEHI VRLMTKNWGD NDSIFQDVIE 1080 TRGREYAGLY DDISTQGWFI GLMCAIALLT LLLLTVCFVK RNRGGKYSVK EKEDLHPDPE 1140 IQSVKDETFG EYSD*SDEKPL KGSLRSLNRD MQPTESADSL VEYGEGDHGL FSEDGSFIGA 1200 YAGSKEKGSV ESNGSSTATF PLRA 1224

Table LVh. Amino acid sequence alignment of 282P1G03 v.1 (SEQ ID NO: 197) and 282P1G03 v.28 (SEQ ID NO: 198) v.28 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD. | II II 1 I I 1 II !! II 1 I 1 II 1 I 1 1 1 I 1 1 1 I 1 1 1 II 1 11 1 1 1 II 1 1 1 1 1 1 1 50 v. 1 1 11111111 1 1 1 1 i 1 I 1 i 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11 1111 1 II 1 1 1 MEPLLLGRGLIVYLMFLLLKFSKAIEIPSSVQQVPTIIKQSKVQVAFPFD 50 v.2 8 51 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 1 1 1 I 1 1 1 1 .1 II 1 I I 1 I I 1 1 I 1 1 1 1 I I 1 I 1 I 1 I 1 1 I 1 I I 1 I | ( | I I 1 j 1 | 1 100 . v. 1 51 11 I 11111111111 11II1U11111II1111 1 I 1 1 11 1 1 1 1 1 1 1 11 1 1 1 EYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHI 100 v.28 101 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV I 1 1 1 1 1 I ) 1 l| II 1 1 1 I III 1 ι I 1 I 1 II 1 1 1 1 1 1 II 1 I I 1 1 1 1 1 1 1 ill 1 150 v.l 101 1 1 1 1 1 II 1 1 II 1 i 1 1 I 11 1 1 I 1 H 1 1 1 1 1 1 11 1 I 1 11111II I 11IIII1 SHFQGKYRCFASNKLGIAMSEEIEFIVPSVPKLPKEKIDPLEVEEGDPIV 150 v.28 151 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYF ANVEEKDSRN 1 1 1 1 1 1 1 1 II 1 1 1 1 1 l| 1 li 1 1 II I 1 1 1 1 1 I 1 1 1 II 1 1 1 II 1 1 1 11 1 i 1 I 200 v.l 151 11111 I I 1iIt 11 1 111111111 I 11111 I I 11 1 1 1 1 1 I I 1 1 1 II 1 1 ! 1 1 LPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRN 200 v.28 201 dyccfaafprlrtivqkmpmkltvnslkhandssssteigskansikqrk 250 347 v.l 201 DYCCFAAFPRLRTIVQKMPMKLTVNSLKHAHDSSSSTEIGSKANSIKQRK 250 v.28 251 PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQVDOTKIGGDLPKG | I lil II 1 1 1 II 1 1 I 1 1 I 1 I II I I 1 it 1 1 i 1 1 li I 1 1 1 II 1 1 1 11 1 1 1 II 300 v.l 251 1 1 1 i I 1 I Ι ι ι 1 ι 1 I 1 i ι ι 1 ι I 1 1 ι ι ι I 1 I 1 1 I 1 ! 1 1 1 1 1 I 1 1 1 1 I ι ! 1 ι ι PKLLLPPTESGSESSITILKGEILLLECFAEGLPTPQWTOKIGGDLPKG 300 v.28 301 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT II II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 II 1 1 1 1 II 1 1 1 1 II 1 1 1 1 350 v.l 301 1 f i 1 I 1 1 I 1 1 l 1 i i i 1 1 1 1 1 I 1 ι ι i i i 1 1 1 I 1 1 1 1 1 1 1 i i 1 i 1 1 I i 1 1 1 1 RETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEEPPRWT 350 v.28 351 KKPQSAVYSTGSNGXLLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR I I 1 I I 1 1 1 1 I I 1 1 1 II 1 1 H 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 I II 1 1 I 1 400 v.l 351 111II111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I II111 11111 1 II 1 1 1 1 1 1 1 1 1 1 1 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDWFPR 400 v.28 401 El S FTNLQPNHTAVYQCEASNVHGTXLANANIDWDVRPLIQTKDGENYA 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 45 0 v.l 401 I i 1 il 1 [ 1 1 I 1 1 i I I 1 I I 1 i 1 I 1 I I 1 1 1 1 1 i I I I t I I 1 1 J 1 1 I 1 1 1 1 1 I 1 450 v.28 451 TWGYSAFEHCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENGTLQINRT 1 1 1 1 1 1 1 1 1 f 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 500 v.l ’ 451 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 TWGYSAFLHCEFFASPEAWSWQKVEEVKPLEGRRYHIYENGTLQINRT 500 v.28 501 TEEDAGSYSCWVENAIGKXAVTANLDIRNATKLRVSPKNPRIPKLHMLEL IN 1 1 1 ! 1 I 1 !!! 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 t 1 1 1 1 1 1 i I 1 1 1 1 1 1 1 II 1 1 550 v.l 501 1 1 1 1 1 1 1 1 1 11 1 1 1 1 111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 1 1 TEEDAGSYSCWVENAIGKTAVTANLDIRNATKLRVSPKNPRIPKLHMLEL 550 v.28 551 HCESKCDSHL KHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLE I 1 1 1 1 1 1 1 1 I 1 1 1 1 ! 1 ! 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 ! 1 1 1 600 v.l' 551 1 I II 1 ! 1 1 1 1 1 1 ! I II ! I 11!11111 il ! 1 1 1 1 1 ! 1 1 1 1 1 I!1111 1 1 I 1 HCESKCDSHLKHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNrVTLE 600 v.28 601 DQGIYCCSAHTALD SAAD ITQVTVLDVPDPPENLHLSERQNRS VRLTWEA 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 650 v.l 601 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 DQGIYCCSAHTALDSAADITQVTVLDVPDPPENLHLSERQNRSVRLTWEA 650 v.2 8 651 GADHNSNISEYIVEFEGNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQF ' I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 700 v.l 651 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 gadhnsniseyivefegnkeepgkweeltrvqgkkttvilplapfvryqf 700 v.28 701 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 1 ! 1 1 II 1 I 1 1 1 I 11 11 1 I 1 1 I ! 1 1 1 1 1 I I I I 1 1 1 1 1 1 I I I I 1 1 I I 1 1 1 I 1 750 v.l 701 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 RVIAVNEVGRSQPSQPSDHHETPPAAPDRNPQNIRVQASQPKEMIIKWEP 750 v.28 751 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK | 1 1 1 1 I 1 1 1 1 1 j 1 1 1 1 I 1 1 1 I 1 II 1 1 1 II 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 I 1 i 1 1 1 800 v.l 751 II 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 11111 I 1111111 I 1 1 1 I 1 1 1 1 111111 I 1 1 1 1 LKSMEQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVMTPAVYAPYDVK 800 v.28 801 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLVKVTWSTVP | 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1. j 1 1 850 v.l 801 1 i 1 I I I ! 1 1 I 1 1 ! I 1 Η 1 I 11 ! ! ! 1 ! I 1 1 11111 I 1 ! 1 I 111 I! ! I 1 I I 1 VQAINQLGSGPDPQSVTLYSGEDYPDTAPVIHGVDVINSTLVKVTWSTVP 850 v.28 851 KDRVHGRLKGYQINWWKTKSLIiDGRTHPKEVNILRFSGQRNSGMVPSLDA 1 1 I I 1 I 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I ,1 1 1 I 1 1 1 1 1 ! 1 1 1 I 1 1 1 900 v.l 851 1 1 1 1 1 1 1.1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 II 1 1 1 1 1 1 1 1 1 1 1 1 I ! 1 II 1 1 1 1 1 1 1 1 1 KDRVHGRLKGYQINWWKTKSLLDGRTHPKEVNILRFSGQRNSGMVPSLDA 900 v.28 901 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1 I 1 1 II 950 v.l 901 II 1 1 1 1 1 I I 1 1 1 1 1 1 1 1 I 1 1 1 1 111 1111 1 1 1 I 1 1 1 1 1 1 1 1 1 1 1 II 1 1 1 1 FSEFHLTVLAYNSKGAGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATL 950 v.28 951 SWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITTPSKPSWHLSNLN i II ! I 1 1 &amp;#943; i i 1 ! 1 1 1 Η i 1 1 1 1 1 1 1 1 1 1 1 1 i ! 1 1 ! 1 1 1 i 1 1 1 1 i i 1 1 1 1 1 1000 V.l 951 111 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ! 1 1 I 1 I 1 1 1 111 I I I! ! ι 1 SWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITTPSKPSWHLSNLN 1000 V.28 1001 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNLTQKTHPI 1050 348 v.l 1001 ATTKYKFYLRACTSQGCGKPITEESSTLGEGSKGIGKISGVNLTQKTHPI 1050 ν.28 1051 EVFEPGAEHXVRLMTKNWGDNDSIFQDVIETRGREYAGLYDDISTQGWFI I 1 I I II 1 I I I I II II 1 1 1 I II II 1 I 1 1 1 1 1 1 II II 1 1 1 1 1 1 1 I 1 1 1 1 1 1 1 1100 ν. 1 1051 1 1 ! 11 1 I 1 ! I 1 1 1 II II 1 1 1 1 1 1 11 1 i I 1 1 II 1J I 1 1 1 1 1 I I II I 1 1 1 II EVFEPGAEHIVRLMTKNWGDNDSIFQDVIETRGREYAGLYDDISTQGWFI 1100 ν.28 1101 GLMCAIALLTLLLLTVCFVKKNRGGKYSVKEKEDLHPDPEIQSVKDETFG 1150 v.l 1101 II1 Ii Ii 1 Ii1 H 1 i 111111II iil 1II11 il i IIII11IIII i i II11 GLMCAIALLTLLLLTVCFVKRNRGGKYSVKEKEDLHPDPE1QSVKDETFG 1150 ν.28 1151 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1200 v.l 1151 EYSDSDEKPLKGSLRSLNRDMQPTESADSLVEYGEGDHGLFSEDGSFIGA 1200 ν.28 1201 YAGSKEKGSVESNGSSTATFPLRA 1224 | j 1 I M 1 1 1 I 1 M I H 1 1 1 1 { I 1 I v.l 1201 1 II 1 I 1 1 I 1 1 1 I 1 1 1 1 1 1 1 1 1 ! 1 1 YAGSKEKGSVESNGSSTATFPLRA 1224 349

SEQUENCE LISTING <110> Agensys, Inc.

Faris, Mary Challita-Eid, Pia M.

Jakobovits, Aya Raitano, Arthur B.

Ge, Wangmao <120> Nucleic Acids and Corresponding Proteins

Entitled 282P1G3 Useful in Treatment and Detection of Cancer <130> 511582008440 <140> <141> 2003 09 <150 60/404,306 <151> 2002 16 <150> 60/423,290 <151> 2002 01 <160> 208 <170> FastSEQ for Windows Version 4.0 <210> 1 <211> 321 <212> DNA <213> Homo sapians <400> 1 gatcgcgttt cggaggcggc gcagtttcca ggttaactaa ggtctcagct gtaaaccaaa 60 agtgagagga gacattaaga ttttcattct taccgggttg tcttcttcct gaagagcaat 120 ggagccgctt ttacttggaa gaggactaat cgtatatcta atgttcctcc tgttaaaatt 180 ctcaaaagca attgaaatac catcttcagt tcaacaggtt ccaacaatct taaaacagtc 240 aaaagtccaa gttgcctttc ccttcgatga gtattttcaa attgaatgtg aagctaaagg 300 aaatccagaa ccaacatttt c 321 <210 2 <211> 7650 <212> DNA <213> Homo sapians <220> <221> CDS <222> (272).(3946) <221> misc feature <222> 320 <223> SNP = C/T = v.9 <221> misc feature <222> 668 <223> SNP = C/T = v.10 <221> misc_feature <222> 1178 <223> SNP = A/G = v.ll 350 <221> misc_feature <222> 3484 <223> SNP = C/T = v.12 <221> misc_feature <222> 4615 <223> SNP = G/A = v. 13 <221> misc_feature <222> (0).(0 ) <223> Pos.: 5078:

SNP C/T = v.15 <221> misc_£eature <222> (0).(0) <223> Pos.: 5530; <221> misc_feature <222> (0).(0) <223> Pos.: 5812;

SNP T/A = v.16 SNP = C/T = v.17 <221> misc_feature <222> (0).(0) <223> Pos.: 6114;

SNP A/G = v.li <221> misc_feature <222> (0).(0) <223> Pos.: 6229; SNP = C/T = v.19 <221> misc_feature <222> (0).(0) <223> Pos.: 6383; SNP = G/A = v. 20 <221> misc_feature <222> (0).(0) <223> Pos.: 6626 ; SNP = C/T = v.21 <221> misc feature <222> (0). <223> Pos. (0) 6942 ; SNP = C/T = v.22 <221> misc_feature <222> (0).(0) <223> Pos.: 7085:

SNP C/T = v.2) <221> misc_feature <222> (0).(0) <223> Pos.: 2684; SNP = A/G = V.24 <221> misc_feature <222> (0).(0) <223> Pos.: 3705; SNP = T/C = v. 25 Pos . : 5768; SNP = T/C = v.26 ?OS · a 6125; SNP = C/T = v.27 Though these SNP variants are they can also occur in any combinations and in any of the transcript variants listed in Figures 2A -21. <400> 2 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 351 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ctt tta ctt gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 aga Arg gga Gly eta Leu 10 ate lie gta Val tat Tyr eta Leu atg Met 15 ttc Phe etc Leu ctg Leu tta Leu aaa Lys 20 ttc Phe tea Ser aaa Ly s 340 gca att gaa ata cca tet tea gtt caa cag gtt cca aca ate ata aaa 388 Ala lie Glu He Pro Ser Ser Val Gin Gin Val Pro Thr lie He Lys 25 30 35 cag tea aaa gtc caa gtt gcc ttt ccc ttc gat gag tat ttt caa att 436 Gin Ser Lys Val Gin Val Ala Phe Pro Phe Asp Glu Tyr Phe Gin lie 40 45 50 55 gaa tgt gaa get aaa gga aat cca gaa cca aca ttt teg tgg act aag 484 Glu Cys Glu Ala Lys Gly Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys 60 65 70 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532 Asp Gly Asn Pro Phe Tyr Phe Thr Asp His Arg He He Pro Ser Asn 75 80 85 aat tea gga aca ttc agg ate cca aac gag ggg cac ata tet cac ttt 580 Asn Ser Gly Thr Phe Arg He Pro Asn Glu Gly His lie Ser His Phe 90 95 100 caa ggg aaa tac ege tgc ttt get tea aat aaa ctg gga ate get atg 628 Gin Gly Lys Tyr Arg Cys Phe Ala Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca agt gtt cca aaa etc cca aaa 676 Ser Glu Glu He Glu Phe He Val Pro Ser Val Pro Lys Leu Pro Lys 120 125 130 135 gss SSo. att gac cct ctt gaa gtg gag CfclCJ gga gat cca att gtc etc 724 Glu Lys lie Asp Pro Leu Glu Val Glu Glu Gly Asp Pro He Val Leu 140 145 150 cca tgc aat cct CCC &lt;3. ct Θ. ggc etc cca cct tta cac att tat tgg atg 772 Pro Cys Asn Pro Pro Lys Gly Leu Pro Pro Leu His He Tyr Trp Met 155 160 165 aat att gaa tta gaa cac ate gaa caa gat gaa aga gta tac atg age 820 Asn He Glu Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser 170 175 180 caa aag gga gat eta tac ttc gca aac gtg gaa gaa aag gac agt ege 868 Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg 185 190 195 aat gac tac tgt tgc ttt get gca ttt cca ci ci tta agg act att gta 916 Asn Asp Tyr Cys cys Phe Ala Al a Phe Pro Arg Leu Arg Thr He Val 200 205 210 215 cag aaa atg cca atg cl &amp;amp; ci eta aca gtt aac agt tta aag cat get aat 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn 220 225 230 352 gac Asp tea Ser agt Ser tea Ser 235 tee Ser aca Thr gaa Glu att lie ggt Gly 240 tee Ser aag Lys gca Ala aat Asn tee Ser 245 ate He aag Lys 1012 caa aga aaa ccc 9.9.9. ctg ctg ttg cct ccc act gag agt ggc agt gag 1060 Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 250 255 260 tct tea att acc ate etc aaa ggg gaa ate ttg ctg ett gag tgt ttt 1108 Ser Ser lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe 265 270 275 get gaa ggc ttg cca act cca cag gtt gat tgg aac ctaa. att ggt ggt 1156 Ala Glu Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly 280 285 290 295 gac tta cca aag ggg aga gaa aca aaa gaa aat tat ggc aag act ttg 1204 Asp Leu Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr· Gly Lys rpk -V- HiJ. Leu 300 305 310 aag ata gag aat gtc tee tac cag gac aaa gga aat tat ege tgc aca 1252 Lys He Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr 315 320 325 gee age aat ttc ttg gga aca gee act cac gat ttt cac gtt ata gta 1300 Ala Ser Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val 330 335 340 gaa gag cct cct ege tgg aca aag aag cct cag agt get gtg tat age 1348 Glu Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser 345 350 355 acc gga age aat ggc ate ttg tta tgt gag get gaa gga gaa cct caa 1396 Thr Gly Ser Asn Gly lie Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin 360 365 370 375 ccc aca ate aag tgg aga gtc aat ggc tee cca gtt gac aat cat cca 1444 Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro 380 385 390 ttt get ggt gat gtt gtc ttc CCC agg gaa ate agt ttt acc aac ett 1492 Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe Thr Asn Leu 395 400 405 caa cca aat cat act get gtg tac cag tgt gaa gee tea aat gtc cat 1540 Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His 410 415 420 gga act ate ett gee aat gee aat att gat gtt gtg gat gtc cgt cca 1588 Gly Thr He Leu Ala Asn Ala Asn He Asp Val Val Asp Val Arg Pro 425 430 435 ttg ata caa acc aaa gat gga gaa aat tac get aca gtg gtt ggg tac 1636 Leu lie Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr 440 445 450 455 agt get ttc tta cat tgc gag ttc ttt get tea cct gag gca gtc gtg 1684 Ser Ala Phe Leu His cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val 460 465 470 tee tgg cag aag gtg gaa gaa gtg aaa ccc ctg gag ggc agg egg tat 1732 353

Ser Trp Gin Lys 475 Val Glu Glu Val Lys 480 Pro Leu Glu Gly Arg 485 Arg Tyr cat ate tat gaa aat ggc aca ttg cag ate aac aga acc acc gaa gaa 1780 His lie Tyr Glu Asn Gly Thr Leu Gin lie Asn Arg Thr Thr Glu Glu 490 495 500 rra+- rr/~· 4-C ggg tct tac tc a tgt tgg gta gaa aat get ata gga aaa act 1828 Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He Gly Lys Thr 505 510 515 gca gtc aca gcc aat ttg gat att aga aat get aca aaa ett aga gtt 1876 Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val 520 525 530 535 tct cct aag aat cct cgt ate ccc aaa ttg cat atg ett gaa tta cat 1924 Ser Pro Lys Asn Pro Arg He Pro Lys Leu His Met Leu Glu Leu His 540 545 550 tgt gaa age aaa tgt gac tea cat ttg aaa cac agt ttg aag ttg tcc 1972 Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser 555 560 565 tgg agt aaa gat gga gaa gcc ttt gaa att aat ggc aca gaa gat ggc 2020 Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly 570 575 580 agg ata att att gat gga get aat ttg acc ata tct aat gta act tta 2068 Arg lie Xie lie Asp Gly Ala Asn Leu Thr He Ser Asn Val Thr Leu 585 590 595 gag gac caa ggt att tac tgc tgt tea get cat act get eta gac agt 2116 Glu Asp Gin Gly lie Tyr Cys Cys Ser Ala His Thr Ala Leu Asp Ser 600 605 610 615 get gcc gat ata act caa gta act gtt ett gat gtt ccg gat cca cca 2164 Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro 620 625 630 gaa aac ett cac ttg tct gaa a cj cag aac agg agt gtt egg ctg acc 2212 Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val Arg Leu Thr 635 640 645 tgg qaa get gga get gac cac ct ci C age aat att age gag tat att gtt 2260 Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr lie Val 650 655 660 gaa ttt gaa gga aac aaa gaa gag cct gga agg tgg gag gaa ctg acc 2308 Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr 665 670 675 aga gtc C cL gga aag aaa acc aca gtt ate tta cct ttg get cca ttt 2356 Arg Val Gin Gly Lys Lys Thr Thr Val lie Leu Pro Leu Ala Pro Phe 680 685 690 695 gtg aga tac cag ttc agg gtc ata gcc gtg aac gaa gta ggg aga agt 2404 Val Arg Tyr Gin Phe Arg Val He Al a Val Asn Glu Val Gly Arg Ser 700 705 710 cag cct age cag ccg tea gac cat cat gaa aca cca cca gca get cca 2452 Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro 715 720 725 354 gat agg aat Asp Arg Asn 730 cca caa Pro Gin aac ata agg Asn lie Arg 735 gtt caa gcc Val Gin Ala tct caa Ser Gin 740 ccc aag gaa Pro Lys Glu 2500 atg att ata Met lie lie aag tgg Lys Trp gag cct ttg Glu Pro Leu aaa tcc atg Lys Ser Met gag cag Glu Gin aat gga cca Asn Glv Pro 2548 ggc eta gag Gly Leu Glu 760 tac aga Tyr Arg gtg acc tgg Val Thr Trp 765 aag cca cag Lys Pro Gin 770 gga gcc Gly Ala cca gtg Pro Val gag

Glu 775 2596 tgg gaa gaa Trp Glu Glu gaa aca Glu Thr 780 gtc aca aac Val Thr Asn cac aca ttg His Thr Leu 785 egg gtg Arg Val atg aeg Met Thr 790 cct

Pro get gtc tat Ala Val Tyr gcc cct Ala Pro 795 tat gat gtc Tyr Asp Val aag gtc cag Lys Val Gin 800 get ate Ala lie aat caa eta Asn Gin Leu 805 2692 gga tct ggg Gly Ser Gly 810 cct gac Pro Asp cct cag tea Pro Gin Ser 815 gtg act etc Val Thr Leu tat tct Tyr Ser 820 gga gaa Gly Glu gac

Asp 2740 tat cct gat Tyr Pro Asp 825 aca get Thr Ala cca gtg ate Pro Val He 830 cat ggg gtg His Gly Val gac gtt Asp Val 835 ata aac agt lie Asn Ser 2788 aca tta gtt Thr Leu Val 840 aaa gtt Lys Val acc tgg tea Thr Trp Ser 845 aca gtt cca Thr Val Pro 850 aag gac Lys Asp aga gta cat Arg Val His 855 2836 gga cgt ctg Gly Arg Leu aaa ggc Lys Gly 860 tat cag ata Tyr Gin He aat tgg tgg Asn Trp Trp 865 aaa aca Lys Thr aaa agt ctg Lys Ser Leu 870 2884 ttg gat gga

Leu Asp Gly aga aca Arg Thr 875 cat ccc aaa His Pro Lys gaa gtg aac

Glu Val Asn 880 att eta

He Leu aga ttt tea

Arg Phe Ser 885 2932 gga caa aga Gly Gin Arg 890 aac tct Asn Ser gga atg gtt Gly Met Val 895 cct tcc tta Pro Ser Leu gat gcc Asp Ala 900 ttt agt gaa Phe Ser Glu 2980 ttt cat tta Phe His Leu 905 aca gtc Thr Val tta gcc tat Leu Ala Tyr 910 aac tct aaa Asn Ser Lys gga get Gly Ala 915 ggt cct gaa Gly Pro Glu 3028 agt gag cct Ser Glu Pro 920 tat ata Tyr He ttt caa aca Phe Gin Thr 925 cca gaa gga Pro Glu Gly 930 gta cct Val Pro gaa cag cca Giu Gin Pro 935 3076 act ttt eta Thr Phe Leu aag gtc Lys Val 940 ate aaa gtt He Lys Val gat aaa gac Asp Lys Asp 945 act gcc Thr Ala act tta tct Thr Leu Ser 950 3124 tgg gga eta Trp Gly Leu cct aag Pro Lys 955 aaa tta aat Lys Leu Asn gga aac tta Gly Asn Leu 960 act ggc Thr Gly tat ett ttg Tyr Leu Leu 965 3172 caa tat cag ata ata aat gac acc tac gag att gga gaa tta aat gat 3220 355

Gin Tyr Gin 970 lie lie Asn Asp Thr 975 Tyr Glu He Gly Glu 980 Leu Asn Asp att aac att aca act cca tea aag ccc age tgg cac etc tea aac ctg 3268 lie Asn lie 985 Thr Thr Pro Ser 99C Lys 1 Pro Ser Trp His 995 Leu i Ser Asn Leu aat act acc aag tac aaa ttc tac ttg agg get tgc act tea cag -χ n r JO1O Asn Ala 1000 Thr Thr Lys Tyr Lys 1005 Phe Tyr Leu Arg 101C Ala 1 Cys Thr Ser Gin 1015 ggc tgt gga aaa ccg ate aeg gag gaa age tcc acc tta gga gaa ggg 3364 Gly Cys Gly Lys Pro lie 1020 Thr Glu Glu Ser 1025 Ser Thr Leu Gly Glu 103C Gly 1 agt aaa ggt ate ggg aag ata tea gga gta aat ett act caa aag act 3412 Ser Lys Gly lie Gly 1035 Lys lie Ser Gly 104C Val 1 Asn Leu Thr Gin Lys 1045 Thr cac cca ata gag gta ttt gag ccg gga get gaa cat ata gtt ege eta 3460 His Pro lie 105C Glu ) Val Phe Glu Pro Gly 1055 Ala Glu His lie 106C Val 1 Arg Leu atg act aag aat tgg ggc gat aac gat age att ttt caa gat gta att 3508 Met Thr Lys 1065 Asn Trp Gly Asp 107C Asn 1 Asp Ser lie Phe 1075 Gin Asp Val He gag aca aga ggg aga gaa tat get ggt tta tat gat gac ate tcc act 3556 Glu Thr 1080 Arg Gly Arg Glu Tyr 1085 Ala Gly Leu Tyr Asp 1090 Asp He Ser Thr 1095 caa ggc tgg ttt att gga ctg atg tgt geg att get ett etc aca eta 3604 Gin Gly Trp Phe lie HOC Gly I Leu Met Cys Ala 1105 lie Ala Leu Leu Thr 111C Leu 1 eta tta tta act gtt tgc ttt gtg aag agg aat aga ggt gga aag tac 3652 Leu Leu Leu Thr 1115 Val Cys Phe Val Lys 112C Arg 1 Asn Arg Gly Gly Lys 1125 Tyr tea gtt a. gaa aag gaa gat ttg cat cca gac cca gaa att cag tea 3700 Ser Val Lys 113C Glu Lys Glu Asp Leu His 1135 Pro Asp Pro Glu 114C lie 1 Gin Ser gta aaa gat gaa acc ttt ggt gaa tac agt gac agt gat gaa aag cct 3748 Val Lys 1145 Asp Glu Thr Phe Gly 1150 Glu 1 Tyr Ser Asp Ser 1155 Asp 1 Glu Lys Pro etc aaa gga age ett egg tcc ett aat agg gat atg cag cct act gaa 3796 Leu 1160 Lys 1 Gly Ser Leu Arg 1165 Ser 1 Leu Asn Arg Asp 117C Met I Gin Pro Thr Glu 1175 agt get gac age tta gtc gaa tac gga gag gga gac cat ggt etc ttc 3844 Ser Ala Asp Ser Leu 1180 Val 1 Glu Tyr Gly Glu 1185 Gly Asp His Gly Leu 119C Phe 1 agt gaa gat gga tea ttt att ggt gc c tac get gga tet 5. a gag aag 3 8 9 2 Ser Glu Asp Gly 1195 Ser Phe lie Gly Ala 1200 Tyr 1 Ala Gly Ser Lys 1205 Glu f Lys gga tet gtt gaa age aat gga agt tet aca gca act ttt ccc ett egg 3940 Gly Ser Val 1210 Glu Ser Asn Gly Ser 1215 Ser Thr Ala Thr Phe 122C Pro 1 Leu Arg 356 gca taa acacaacata tgtaagcaac gctactggtt caccccaacc ttccatattt Ala * 3996 atctgttcaa aggagcaaga actttcatat aggaatagaa acatgctggc cgaagatttc 4056 atccagaagt caacatcctg caattatqtt gaaaagagta gtactttctt caaaatataa 4116 aatgccaagc acttcaggcc tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa 4176 aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt 4236 atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt 4296 gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc 4356 ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg 4416 aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta 4476 ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag 4536 atggtcatat ttaaacagaa gtatacgttt ttcagtttca acatgaattt ttttatttct 4596 gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt ttcttggact 4656 aaattcaact gcatggaagc ggtggtcaga aggttgtttt atacgagaac aggcagaaag 4716 tgcccattgt tcaggattct aatagctaca tctacttaat atcttcattt ctaaattgac 4776 tgcttttacc tttttctcat gtttatataa tggtatgctt gcatatattt catgaataca 4836 ttgtacatat tatgttaata tttacacaat ttaaaatata gatgtgtttt attttgaagt 4896 gagaaaatga acattaacag gcatgtttgt acagctagaa tatattagta agatactgtt 4956 tttcgtcatt ccagagctac aactaataac acgaggttcc aaagctgaag actttgtata 5016 aagtatttgg gttttgttct tgtattgctt tctttcaaca gtttcaaaat aaaatatcat 5076 acaaatattg agggaaatgt tttcatattt ttcaaaatag gtttttattg ttgaatgtac 5136 atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg 5196 cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg 5256 tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa 5316 aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag 5376 ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac 5436 tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt 5496 tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg 5556 tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca 5616 cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg 5676 gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc 5736 cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc 5796 ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg 5856 gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc 5916 tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc 5976 atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac 6036 taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga 6096 aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat 6156 gagattgaat gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca 6216 actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt 6276 gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa 6336 gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt 6396 gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa 6456 cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg 6516 tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag 6576 ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg 6636 attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc 6696 taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga 6756 agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa 6816 ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca 6876 taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag 6936 tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc 6996 tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg 7056 tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa 7116 tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac 7176 tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa 7236 gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg 7296 attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat 7356 atatcctagt gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt 7416 357 accttaaatt gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg tgattacctt tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt tgtattgtag gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca ttatacatga aattcaactt tccaaataaa agttctactt catgtaatcc aaaa <210> 3 <211> 1224

<212> PRT <213> Homo sapians 7476 7536 7596 7650 <400> 3

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 5 5 6 0 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 2 6 0 265 270 lie T ι e u Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 J -J His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Al a Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu lie Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 358 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Al a Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 Ren V V Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Al a Gly Ala Asp His Asn Ser 645 650 655 Asn lie Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val lie Ala 690 695 700 Val Asn Glu Val dy Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Th.2? Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin lie Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 359

Ser Lys Gly 900 Ala Gly Pro Glu Ser 905 Glu Pro Tyr lie Phe 910 Gin Thr Pro Glu Gly 915 Val Pro Glu Gin Pro 920 Thr Phe Leu Lys Val 925 He Lys Val Asp Lys 930 Asp Thr Ala Thr Leu 935 Ser Trp Gly Leu Pro 940 Lys Lys Leu Asn Gly 945 Asn Leu Thr Gly Tyr 950 Leu Leu Gin Tyr Gin 955 lie He Asn Asp Thr 960 Tyr Glu lie Gly Glu 965 Leu Asn Asp lie Asn 970 lie Thr Thr Pro Ser 975 Lys Pro Ser Trp His 980 Leu Ser Asn Leu Asn 985 Ala Thr Thr Lys Tyr 990 Lys Phe Tyr Leu Arg 995 Ala Cys Thr Ser Gin 100C Gly 1 Cys Gly Lys Pro 1005 He Thr Glu Glu Ser 101C Ser I Thr Leu Gly Glu 1015 Gly Ser Lys Gly He 102C Gly 1 Lys He Ser Gly 1025 Val Asn Leu Thr Gin 103C Lys 1 Thr His Pro lie 1035 Glu 1 Val Phe Glu Pro 1040 Gly Ala Glu His lie 1045 Val Arg Leu Met Thr 1050 Lys 1 Asn Trp Gly Asp lose Asn Asp Ser lie Phe 106C Gin 1 Asp Val lie Glu 1065 Thr Arg Gly Arg Glu 1070 Tyr 1 Ala Gly Leu Tyr 1075 Asp Asp lie Ser Thr 108C Gin 1 Gly Trp Phe He 1085 Gly Leu Met Cys Ala 109C lie 1 Ala Leu Leu Thr 1095 Leu > Leu Leu Leu Thr HOC Val 1 Cys Phe Val Lys 1105 Arg Asn Arg Gly Gly me Lys 1 Tyr Ser Val Lys 1115 Glu 1 Lys Glu Asp Leu 1120 His Pro Asp Pro Glu 1125 lie Gin Ser Val Lys 1130 Asp 1 Glu Thr Phe Gly 1135 Glu Tyr Ser Asp Ser 1140 Asp 1 Glu Lys Pro Leu 1145 Lys Gly Ser Leu Arg 1150 Ser 1 Leu Asn Arg Asp 1155 Met Gin Pro Thr Glu 116C Ser 1 Ala Asp Ser Leu 1165 Val Glu Tyr Gly Glu 1170 Gly 1 Asp His Gly Leu 1175 Phe Ser Glu Asp Gly 1180 Ser 1 Phe He Gly Ala 1185 Tyr 1 Al a Gly Ser Lys 1190 Glu Lys Gly Ser Val 1195 Glu Ser Asn Gly Ser 1200 Ser Thr Ala Thr Phe 1205 Pro Leu Arg Ala 1210 1215 1220 <210> 4 <211> 7491

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272).(3787) <400> 4 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ctt tta ctt gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 aga gga eta ate gta tat eta atg ttc etc ctg tta aaa ttc tea aaa 340 360

Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys 20 Phe Ser Lys gca att gaa ata cca tct tea gtt caa cag gtt cca aca ate ata aaa 388 Ala lie Glu He Pro Ser Ser Val Gin Gin Val Pro Thr He He Lys 25 30 35 cag tea aaa gtc caa gtt gcc ttt ccc ttc gat gag tat ttt caa att 436 Gin Ser Lys Val Gin Val Ala Phe Pro Phe Asp Glu Tyr Phe Gin He 40 45 50 55 gaa tgt gaa get aaa gga aat cca gaa cca aca ttt teg tgg act aag 484 Glu Cys Glu Ala Lys Gly Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys 60 65 70 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532 Asp Gly Asn Pro Phe Tyr Phe Thr Asp His Arg He He Pro Ser Asn 75 80 85 aat tea gga aca ttc agg ate cca aac gag ggg cac ata tct cac ttt 580 Asn Ser Gly Thr Phe Arg He Pro Asn Glu Gly His He Ser His Phe 90 95 100 caa ggg aaa tac ege tgc ttt get tea aat aaa ctg gga ate get atg 628 Gin Gly Lys Tyr Arg Cys Phe Ala Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca agt gtt cca aaa ttc cca aaa 676 Ser Glu Glu He Glu Phe He Val Pro Ser Val Pro Lys Phe Pro Lys 120 125 130 135 gaa aaa att gac cct ett gaa gtg gag gag gga gat cca att gtc etc 724 Glu Lys He Asp Pro Leu Glu Val Glu Glu Gly Asp Pro lie Val Leu 140 145 150 cca tgc aat cct ccc aaa ggc etc cca cct tta cac att tat tgg atg 772 Pro Cys Asn Pro Pro Lys Gly Leu Pro Pro Leu His He Tyr Trp Met 155 160 165 aat att gaa tta gaa cac ate gaa caa gat gaa aga gta tac atg age 820 Asn He Glu Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser 170 175 180 caa aag gga gat eta tac ttc gca aac gtg gaa gaa aag gac agt ege 868 Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg 18 5 190 195 aat gac tac tgt tgc ttt get gca ttt cca aga tta agg act att gta 916 Asn Asp Tyr cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val 200 205 210 215 cag aaa atg cca atg aaa eta aca gtt aac agt tta aag cat get aat 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn 220 225 230 gac tea agt tea tcc aca gaa att ggt tcc aag gca aat tcc ate aag 1012 Asp Ser Ser Ser Ser Thr Glu lie Gly Ser Lys Ala Asn Ser lie Lys 235 240 245 caa aga aaa ccc aaa ctg ctg ttg cct ccc act gag agt ggc agt gag 1060 Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 250 255 260 361 tct tea Ser Ser 265 get gaa Ala Glu 2 8 0 gac tta Asp Leu aag ata Lys lie gcc age Ala Ser gaa gag Glu Glu 345 acc gga Thr Gly 360 ccc aca Pro Thr ttt get Phe Ala caa cca Gin Pro gga act Gly Thr 4 2 5 ttg ata Leu lie 440 agt get Ser Ala tee tgg Ser Trp cat ate His He gat get att acc Xie Thr ggc ttg

Gly Leu cca aag Pro Lys gag aat Glu Asn 315 aat ttc Asn Phe 330 cct cct Pro Pro age aat Ser Asn ate aag lie Lys ggt gat Gly Asp 395 aat cat

Asn His 410 ate ett lie Leu caa acc Gin Thr ttc tta Phe Leu cag aag Gin Lys 475 tat gaa Tyr Glu 490 ggg tct ate etc lie Leu cca act Pro Thr 285 ggg aga Gly Arg 300 gtc tee Val Ser ttg gga Leu Gly ege tgg Arg Trp ggc ate Gly lie 365 tgg aga Trp Arg 380 gtt gtc Val Val act get

Thr Ala gcc aat Ala Asn aaa gat Lys Asp 445 cat tgc His Cys 460 gtg gaa Val Glu aat ggc Asn Gly tac tea aaa ggg Lys Gly 270 cca cag Pro Gin gaa gca Glu Ala tac cag Tyr Gin aca gcc Thr Aid 335 aca aag Thr Lys 350 ttg tta Leu Leu gtc aat Val Asn ttc ccc Phe Pro gtg tac

Val Tyr 415 gcc aat Ala Asn 430 gga gaa Gly Glu gag ttc Glu Phe gaa gtg Glu Val aca ttg Thr Leu 495 tgt tgg gaa ate Glu lie gtt gat Val Asp aas ga.ci Lys Glu 305 gac aaa Asp Lys 320 act cac Thr His aag cct Lys Pro tgt gag Cys Glu ggc tee Gly Ser 385 agg gaa Arg Glu 400 cag tgt Gin Cys att gat lie Asp aat tac Asn Tyr ttt get Phe Ala 465 aaa ccc Lys Pro 480 cag ate Gin lie gta gaa ttg ctg Leu Leu 275 tgg aac

Trp Asn 290 aat tat Asn Tyr gga aat Gly Asn gat ttt &amp;#902; O vs Dl·} £5.inO j—' i. ilk— cag agt Gin Ser 355 get gaa Ala Glu 370 cca gtt Pro Val ate agt lie Ser gaa gcc Glu Ala gtt gtg Val Val 435 get aca Ala Thr 450 tea cct Ser Pro ctg gag Leu Glu aac aga Asn Arg aat get ett gag Leu Glu tgt ttt Cys Phe 1108 aaa att Lys lie ggc aag Gly Lys tat ege Tyr Arg 325 cac gtt His Val 340 get gtg Ala Val gga gaa Gly Glu gac aat Asp Asn ttt acc Phe Thr 405 tea aat ssr Asn 420 gat gtc Asp Val gtg gtt Val Val gag gca Glu Ala ggc agg Gly Arg 485 acc acc Thr Thr 500 ata gga ggt ggt Gly Gly 295 act ttg Thr Leu 310 tgc aca Cys Thr 1156 1204 1252 ata gta

Tl &amp;#906;

X Xtf VOX 1300 tat age Tyr Ser 1348 cct caa Pro Gin 375 cat cca His Pro 390 aac ett Asn Leu 1396 1444 1492 gtc cat Val His 1540 cgt cca Arg Pro 1588 ggg tac Gly Tyr 455 gtc gtg Val Val 470 egg tat Arg Tyr 1636 1684 1732 gaa gaa Glu Glu 1780 aaa act 1828 362

Asp Ala 505 Gly Ser Tyr Ser Cys 510 Trp Val Glu Asn Ala 515 He Gly Lys Thr gca gtc aca gcc aat ttg gat att aga aat get aca aaa ett aga gtt 1876 Ala Val Thr Al a Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val 520 525 530 535 tct cct aag aat cct cgt ate ccc aaa ttg cat atg ett gaa tta cat 1924 Ser Pro Lys As n Pro Arg He Pro Lys Leu His Met Leu Glu Leu His 540 545 550 tgt gaa age aaa tgt gac tea cat ttg aaa cac agt ttg aag ttg tcc 1972 Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser 555 560 565 tgg agt aaa gat gga gaa gcc ttt gaa att aat ggc aca gaa gat ggc 2020 Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly 570 575 580 agg ata att att gat gga get aat ttg acc ata tct aat gta act tta 2068 Arg lie lie lie Asp Gly Ala Asn Leu Thr He Ser Asn Val Thr Leu 585 590 595 gag gac caa ggt att tac tgc tgt tea get cat act get eta gac agt 2116 Glu Asp Gin Gly lie Tyr Cys Cys Ser Al a His Thr Ala Leu Asp Ser 600 605 610 615 get gcc gat ata act caa gta act gtt ett gat gtt ccg gat cca cca 2164 Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro 620 625 630 gaa aac ett cac ttg tct gaa aga cag aac agg agt gtt egg ctg acc 2212 Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val Arg Leu Thr 635 640 645 tgg gaa get gga get gac cac aac age aat att age gag tat att gtt 2260 Trp Glu Al a Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr He Val 650 655 660 gaa ttt gaa gga aac aaa Cj ctci gag cct gga agg tgg gag gaa ctg acc 2308 Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr 665 670 675 aga gtc caa gga aag aaa acc aca gtt ate tta cct ttg get cca ttt 2356 Arg Val Gin Gly Lys Lys Thr Thr Val lie Leu Pro Leu Al a Pro Phe 680 685 690 695 gtg aga tac cag ttc agg gtc ata gcc gtg aac gaa gta ggg aga agt 2404 Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser 700 705 710 cag cct age cag ccg tea gac cat cat gaa aca cca cca gca get cca 2452 Gin Pro Ser Gin Pro Ser Asp His His Glu Thi? P 270 Pro Ai a Al a Pro 715 720 725 gat agg aat cca caa aac ata agg gtt caa gcc tct caa ccc aag gaa 2500 Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin Pro Lys Glu 730 735 740 atg att ata aag tgg gag cct ttg aa 3. tcc atg gag cag aat gga cca 2548 Met lie lie Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro 745 750 755 363 ggc eta Gly Leu 760 tgg gaa Trp Glu gag tac Glu Tyr gaa gaa Glu Glu get gtc Ala Val gga tet Gly Ser tat cct Tyr Pro 825 aca tta Thr Leu 840 gga cgt Gly Arg tat gcc Tyr Ala 795 ggg cct Gly Pro 810 gat aca Asp Thr aga gtg Arg Val 765 aca gtc Thr Val 780 cct tat Pro Tyr gac cct Asp Pro get cca Ala Pro acc tgg Thr Trp aca aac Thr Asn gat gtc Asp Val aag cca Lys Pro ttg gat Leu Asp gga caa Gly Gin ttt cat Phe His 905 agt gag Ser Glu 9 2 0 act ttt Thr Phe tgg gga Trp Gly caa tat Gin Tyr gtt aaa Val Lys ctg aaa Leu Lys gga aga Gly Arg 875 aga aac Arg Asn 890 tta aca

Leu Thr cct tat Pro Tyr att aac lie Asn 985 aat gca eta aag Leu Lys eta cct Leu Pro 955 cag ata Gin He 970 att aca He Thr act acc gtt acc Val Thr 845 ggc tat Gly Tyr 860 aca cat Thr His tet gga Ser Gly gtc tta

Val Leu ata ttt He Phe 925 gtc ate Val lie 940 aag aaa Lys Lys ata aat He Asn act cca Thr Pro aag tac cag tea Gin Ser 815 gtg ate Val lie 830 tgg tea Trp Ser cag ata Gin He ccc aaa Pro Lys atg gtt Met Val 895 gcc tat

Ala Tyr 910 csa acs Gin Thr aaa gtt Lys Val tta aat Leu Asn gac acc Asp Thr 975 tea aag Ser Lys 990 aaa ttc cac aca His Thr 785 aag gtc Lys Val 800 gtg act Val Thr cat ggg His Gly aca gtt Thr Val aat tgg Asn Trp 865 gaa gtg Glu Val 880 cct tcc Pro Ser aac tet Asn Ser cca gaa Pro Glu gat aaa Asp Lys 945 gga aac Gly Asn 960 tac gag Tyr Glu ccc age Pro Ser tac ttg cag gga Gin Gly 770 ttg egg Leu Arg gcc cca Ala Pro gtg atg Val Met cag get Gin Ala etc tat Leu Tyr gtg gac Val Asp 835 cca aag Pro Lys 850 tgg aaa Trp Lys aac att Asn He tta gat Leu Asp aaa gga Lys Gly 915 gga gta Gly Val 930 gac act Asp Thr tta act Leu Thr att gga He Gly tgg cac Trp His 99 agg get ate aat He Asn 805 tet gga Ser Gly 820 gtt ata gac aga Asp Arg aca aaa Thr Lys eta aga Leu Arg 885 gcc ttt Ala Phe 900 get ggt Ala Gly cct gaa Pro Glu gcc act Ala Thr ggc tat Gly Tyr 965 gaa tta Glu Leu 980 etc tea Leu Ser tgc act gtg gag Val Glu 775 aeg cct Thr Pro 790 caa eta Gin Leu gaa gac Glu Asp aac agt X-X .J X x ,3. X. gta cat Val His 855 agt ctg Ser Leu 870 ttt tea Phe Ser agt gaa Ser Glu cct gaa Pro Glu cag cca Gin Pro 935 tta tet Leu Ser 950 ctt ttg Leu Leu aat gat Asn Asp aac ctg Asn Leu tea cag 2596 2644 2740 2788 2836 2884 2932 2980 3028 3076 3124 3172 3220 3268 3316 364

Asn Ala 1000 Thr Thr Lys Tyr Lys 1005 Phe Tyr Leu Arg 101C Ala I Cys Thr Ser Gin 1015 ggc tgt gga aaa ccg ate aeg gag gaa age tec acc tta gga gaa ggg 3364 Gly Cys Gly Lys Pro lie 1020 Thr Glu Glu Ser Ser 1025 Thr Leu Gly Glu 103C Giy 1 aaa tat get ggt tta tat gat gac ate tec act caa ggc tgg ttt att 3412 Lys Tyr Ala Gly Leu 1035 Tyr Asp Asp He 104C Ser I Thr Gin Gly Trp 1045 Phe He gga ctg atg tgt geg att get ett etc aca eta eta tta tta act gtt 3460 Gly Leu Met Cys 1050 Ala lie Ala Leu Leu 1055 Thr Leu Leu Leu Leu 1060 Thr Val tgc ttt gtg aag agg aat aga ggt gga aag tac tea gtt aaa gaa aag 3508 Cys Phe Val 1065 Lys Arg Asn Arg 107C Gly ) Gly Lys Tyr Ser 1075 Val Lys Glu Lys gaa gat ttg cat cca gac cca gaa att cag tea gta aaa gat gaa acc 3556 Glu 108C Asp 1 Leu His Pro Asp 1085 Pro Glu lie Gin Ser 1090 Val 1 Lys Asp Glu Thr 1095 ttt ggt gaa tac agt gac agt gat gaa aag ect etc aaa gga age ett 3604 Phe Gly Glu Tyr Ser Asp 1100 Ser Asp Glu Lys Pro 1105 Leu Lys Gly Ser me Leu 1 egg tcc ett aat agg gat atg cag ect act gaa agt get gac age tta 3652 Arg Ser Leu Asn 1115 Arg 1 Asp Met Gin Pro 112C Thr 1 Glu Ser Ala Asp 1125 Ser 1 Leu gtc gaa tac gga gag gga gac cat ggt etc ttc agt gaa gat gga tea 3700 Val Glu Tyr 1130 Gly 1 Glu Gly Asp His 1135 Gly Leu Phe Ser Glu 114C Asp 1 Gly Ser ttt att ggt gcc tac get gga tet aag gag aag gga tet gtt gaa age 3748 Phe lie 1145 Gly Ala Tyr Ala Gly 1150 Ser t Lys Glu Lys Gly 1155 Ser l Val Glu Ser aat Asn 1160 gga Gly agt Ser tet Ser aca Thr gca Ala 1165 act Thr ttt Phe ccc Pro ett Leu egg Arg 1170 gca Ala taa &#9733; acacaacata 3797 tgtaagcaac gctactggtt caccccaacc ttccatattt atctgttcaa aggagcaaga 3857 actttcatat aggaatagaa acatgctggc cgaagatttc atccagaagt caacatcctg 3917 caattatgtt gaaaagagta gtactttctt caaaatataa aatgccaagc acttcaggcc 3977 tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa aacacaaaac aaatcctgca 4037 tttagataca cctcaactaa atccaaagtc cccattcagt atattccata tttgcctgat 4097 tttactattc ggtgtgtttg catagatgtt gctacttggt gggtttttct ccgtatgcac 4157 attggtatac agtctctgag aactggcttg gtgactttgc ttcactacag gttaaaagac 4217 cataagcaaa ctggttattt aaaatgtaaa aaggaatatg aaagtcttat taaaacactt 4277 cattgaaaat atacagtcta aatttattat ttaaatttta ctagcaaaag tcttaggtga 4337 acaatcaact agtatttgtt gagctcctat ttgcccagag atggtcatat ttaaacagaa 4397 gtatacgttt ttcagtttca acatgaattt ttttatttct gtcagttatg acatccacga 4457 gcatcacttt ttgtgtctgt tttttttttt ttcttggact aaattcaact gcatggaagc 4517 ggtggtcaga aggttgtttt atacgagaac aggcagaaag tgcccattgt tcaggattct 4577 aatagctaca tctacttaat atcttcattt ctaaattgac tgcttttacc tttttctcat 4637 gtttatataa tggtatgctt gcatatattt catgaataca ttgtacatat tatgttaata 4697 tttacacaat ttaaaatata gatgtgtttt attttgaagt gagaaaatga acattaacag 4757 gcatgtttgt acagctagaa tatattagta agatactgtt tttcgtcatt ccagagctac 4817 aactaataac acgaggttcc aaagctgaag actttgtata aagtatttgg gttttgttct 4877 tgtattgctt tctttcaaca gtttcaaaat aaaatatcat acaaatattg agggaaatgt 4937 365 tttcatattt ttcaaaatag gtttttattg ttgaatgtac atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt accttaaatt gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg tgattacctt tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt tgtattgtag gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca ttatacatga aattcaactt tccaaataaa agttctactt catgtaatcc aaaa <210> 5 <211> 1171

<212> PRT <213> Homo sapians 4997 5057 5117 5177 5237 5297 5357 5417 5477 5537 5597 5657 5717 5777 5837 5897 5957 6017 6077 6137 6197 6257 6317 6377 6437 6497 6557 6617 6677 6737 6797 6857 6917 6977 7037 7097 7157 7217 7277 7337 7397 7457 7491 <400> 5

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 366

Glu Gly His He 100 Ser His Phe Gin Gly 105 Lys Tyr Arg Cys Phe 110 Ala Ser Asn Lys Leu Gly He Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Ly s Λ 1 o il _L CA 7\ &lt;-» *-t ΓΤ.Ο ii Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys ciy Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu lie Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Al a Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gl v ---i Lys Thr Ala Val Thr A. la A.S Π Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 367

Thr lie Ser 595 Asn Val Thr Leu Glu 600 Asp Gin Gly He Tyr 605 Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Al a Gly 7\1 a Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Al a Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Al a Phe Ser 1U Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Al a Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Al a Cys Thr Ser Gin Gly '-a — m w "-‘-‘-J T .t 7 a ‘-‘J &amp;#908; He Thr Glu Π ,, &amp;#908; -L U 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Lys Tyr Ala Gly Leu Tyr Asp Asp He 1025 1030 1035 1040 Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys Ala He Ala Leu Leu 1045 1050 1055 Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly Gly 1060 1065 1070 Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His Pro Asp Pro Glu He 1075 1080 1085 368

Gin Ser Val 1090 Lys Asp Glu Thr 1095 Phe Gly Glu Tyr Ser Asp 1100 Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin Pro 1105 1110 1115 1120 Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His Gly 1125 1130 113 5 Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala Tyr Ala Gly Ser Lys &#938; ±40 1145 1150 Glu Lys Gly Ser Val Glu Ser Asn dy Ser Ser Thr Ala Thr Phe Pro 1155 1160 1165 Leu Arg Ala 1170 <210> 6 <211> 6487

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272).(2953) <400> 6 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ctt tta ctt gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 aga gga eta ate gta tat eta atg ttc etc ctg tta aaa ttc tea aaa 340

Arg Gly Leu lie Val Tyr Leu Met Phe Leu Leu Leu Lys Phe Ser Lys 10 15 20 gca att gaa ata cca tet tea gtt caa cag gtt cca aca ate ata aaa 388

Ala He Glu He Pro Ser Ser Val Gin Gin Val Pro Thr He He Lys 25 30 35 cag tea aaa gtc caa gtt gcc ttt ccc ttc gat gag tat ttt caa att 436

Gin Ser Lys Val Gin Val Ala Phe Pro Phe Asp Glu Tyr Phe Gin He 40 45 50 55 gaa tgt gaa get aaa gga aat cca gaa cca aca ttt teg tgg act aag 484

Glu Cys Glu Ala Lys Gly Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys 60 65 70 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532

Asp Gly Asn Pro Phe Tyr Phe Thr Asp His Arg He He Pro Ser Asn 75 80 85 aat tea gga aca ttc agg ate cca aac gag ggg cac ata tet cac ttt 580

Asn Ser Gly Thr Phe Arg He Pro Asn Glu Gly His lie Ser His Phe 90 95 100 caa ggg aaa tac ege tgc ttt get tea aat aaa ctg gga ate get atg 628

Gin Gly Lys Tyr Arg Cys Phe Ala Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca agt gtt cca aaa etc cca aaa 676

Ser Glu Glu He Glu Phe He Val Pro Ser Val Pro Lys Leu Pro Lys 369 120 125 130 135 gaa Glu aaa Lys att He gac Asp cct Pro 140 ett Leu gaa Glu gtg Val gag Glu gag Glu 145 gga ciy gat Asp cca Pro att He gtc Val 150 etc Leu 724 cca tgc aat cct ccc aaa ggc etc cca cct tta cac att tat tgg atg 772 Pro Cys Asn Pro Pro Lys Gly Leu Pro Pro Leu His lie Tyr Trp Met 155 160 165 aat att gaa tta gaa cac ate gaa caa gat gaa aga gta tac atg age 820 Asn lie Glu Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser 170 175 180 caa aag gga gat eta tac ttc gca aac gtg gaa gaa aag gac agt ege 868 Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg 185 190 195 aat ^ac tac tgt 4- 4 4- ^•»Z-x4-yq L- yCS ttt cca aga tta agg act att gta 916 Asn Asp Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val 2 00 205 210 215 cag aaa atg cca atg aaa eta aca gtt aac agt tta aag cat get aat 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn 220 225 230 gac tea agt tea tcc aca gaa att ggt tcc aag gca aat tcc ate aag 1012 Asp Ser Ser Ser Ser Thr Glu lie Gly Ser Lys Ala Asn Ser He Lys 235 240 245 caa aga aaa ccc aaa ctg ctg ttg cct ccc act gag agt ggc agt gag 1060 Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 250 255 260 tct tea att acc ate etc aaa ggg gaa ate ttg ctg ett gag tgt ttt 1108 Ser Ser He Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe 265 270 275 get gaa ggc ttg cca act cca C &amp;g gtt gat tgg aac aaa att ggt ggt 1156 Al a Glu Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys lie Gly Gly 280 285 290 295 gac tta cca aag ggg aga gaa acs aaa gaa aat tat ggc aag act ttg 1204 Asp Leu Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu 300 305 310 aag ata gag aat gtc tcc tac cag gac aaa gga aat tat ege tgc aca 1252 Lys He Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr 315 320 325 gcc age aat ttc ttg gga aca gcc act cac gat ttt cac gtt ata gta 1300 Ala Ser Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val 330 335 340 gaa gag cct cct ege tgg aca aag aag cct cag agt get gtg tat age 1348 Glu Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser 345 350 355 acc gga age aat ggc ate ttg tta tgt gag get gaa gga gaa cct caa 1396 Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin 360 365 370 375 370 ccc Pro aca Thr ate He aag Lys tgg Trp 380 aga Arg gtc Val aat Asn ggc Gly tcc Ser 385 cca Pro gtt Val gac Asp aat Asn cat His 390 cca Pro 1444 ttt get ggt gat gtt gtc ttc ccc agg gaa ate agt ttt acc aac ett 1492 Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe Thr Asn Leu 395 400 405 caa cca aat cat 3C t get gtg tac cag tgt gaa gcc tea aat gtc cat 1540 Gin Pro Asn His Thr Al a Val Tyr Gin Cys Glu Ala Ser Asn Val His 410 415 420 gga act ate ett gcc aat gcc aat att gat gtt gtg gat gtc cgt cca 1588 Gly Thr He Leu Ala Asn Ala Asn He Asp Val Val Asp Val Arg Pro 425 430 435 ttg ata caa acc aaa gat gga gaa aat tac get aca gtg gtt ggg tac 1636 Leu lie Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr 440 Λ A C hi hi a 450 455 agt get ttc tta cat tgc gag ttc ttt get tea cct gag gca gtc gtg 1684 Ser Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val 460 465 470 tcc tgg cag aag gtg gaa gaa gtg aaa ccc ctg gag ggc agg egg tat 17 3 2 Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr 475 480 485 cat ate tat gaa aat ggc aca ttg cag ate aac aga acc acc gaa gaa 1780 His He Tyr Glu Asn Gly Thr Leu Gin lie Asn Arg Thr Thr Glu Glu 490 495 500 gat get ggg tct tac tea tgt tgg gta gaa aat get ata gga aaa act 1828 Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Al a He Gly Lys Thr 505 510 515 gca gtc scs gcc aat ttg gat att aga aat get aca SSd ett aga gtt 1876 Ala Val Thr Ala Asn Leu Asp lie Arg Asn Al a Thr Lys Leu Arg Val 520 52 5 530 535 tct cct aag aat cct cgt ate ccc aaa ttg cat atg ett gaa tta cat 1924 Ser Pro Lys Asn Pro Arg lie Pro Lys Leu His Met Leu Glu Leu His 540 545 550 tgt CJ age aaa tgt gac tea cat ttg aaa cac agt ttg aag ttg tcc 1972 Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser 555 560 565 tgg agt aaa gat gga gaa gcc ttt gaa att aat ggc aca gaa gat ggc 2020 Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly 570 575 580 agg ata att att gat gga get Sdt +- +- <t - acc 55 +- 55 V4. 1— CA tct 55 O +-U.U. u gta act tta Ο Λ £ O z. U u o Arg He He He Asp Gly Ala Asn Leu Thr He Ser Asn Val Thr Leu 585 590 595 gag gac caa ggt att tac tgc tgt tea get cat act get eta gac agt 2116 Glu Asp Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala Leu Asp Ser 600 605 610 615 get gcc gat ata act caa gta act gtt ett gat gtt ccg gat cca cca 2164 Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro 371 620 625 630 gaa Glu aac Asn ctt Leu cac His 635 ttg Leu tet Ser gaa Glu aga Arg cag Gin 640 aac Asn agg Arg agt Ser gtt Val egg Arg 645 ctg Leu acc Thr 2212 tgg gaa get gga get gac cac aac age aat att age gag tat att gtt 2260 Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr He Val 650 655 660 gaa ttt gaa gga aac aaa gaa gag cct gga agg tgg gag gaa ctg acc 2308 Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr 6 6 5 670 675 aga gtc CSS gga aag aaa acc aca gtt ate tta cct ttg get cca ttt 2356 Arg Val Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu Ala Pro Phe 680 685 690 695 gtg 3. Cj 3. 13.C C SCJ ttc agg y tc ata gee gtg aac gaa gta ggg aga agt 2404 Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser 700 705 710 cag cct age cag ccg tea gac cat cat gaa aca cca cca gca get cca 2452 Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro 715 720 725 gat agg aat cca caa aac ata agg gtt caa gee tet caa ccc aag gaa 2500 Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin Pro Lys Glu 730 735 740 atg att ata aag tgg gag cct ttg aaa tee atg gag cag aat gga cca 2548 Met lie He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro 745 750 755 ggc eta gag tac aga gtg acc tgg aag cca cag gga gee cca gtg gag 2596 Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu 760 765 770 775 tgg gaa gaa gaa scs Cf uC aca aac cac aca ttg egg q t q atg aeg cct 2644 Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val Met Thr Pro 780 785 790 get gtc tat gee cct tat gat gtc aag gtc cag get ate aat caa eta 2692 Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He Asn Gin Leu 795 800 805 gga tet ggg cct gac cct cag tea gtg act etc tat tet gga gaa gac 2740 Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp 810 815 820 tat cct gat aca get cca gtg ate cat ggg gtg gac gtt ata aac aca 2788 Tyr Pro Asp Thr Ala Pro Val He His Gly Val Asp Val He Asn Thr 825 830 835 aca tat gta age aac get act ggt tea ccc caa cct tee ata ttt ate 2836 Thr Tyr Val Ser Asn Ala Thr Gly Ser Pro Gin Pro Ser He Phe He 840 845 850 855 tgt tea aag gag caa gaa ctt tea tat agg aat aga aac atg ctg gee 2884 Cys Ser Lys Glu Gin Glu Leu Ser Tyr Arg Asn Arg Asn Met Leu Ala 860 865 870 372 gaa gat ttc ate cag aag tea aca tcc tgc aat tat gtt gaa aag agt Glu Asp Phe lie Gin Lys Ser Thr Ser Cys Asn Tyr Val Glu Lys Ser 875 880 885 agt act ttc ttc aaa ata taa aatgccaagc acttcaggcc tatgttttgc Ser Thr Phe Phe Lys He * 890 2932 2983 ttatattgtt ttcaggtgct caaaatgcaa aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag atggtcatat ttaaacagaa gtatacgttt ttcagtttca acatgaattt ttttatttct gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt ttcttggact aaattcaact gcatggaagc ggtggtcaga aggttgtttt atacgagaac aggcagaaag tgcccattgt tcaggattct aatagctaca tctacttaat atcttcattt ctaaattgac tgcttttacc tttttctcat gtttatataa tggtatgctt gcatatattt catgaataca ttgtacatat tatgttaata tttacacaat ttaaaatata gatgtgtttt attttgaagt gagaaaatga acattaacag gcatgtttgt acagctagaa tatattagta agatactgtt tttcgtcatt ccagagctac aactaataac acgaggttcc aaagctgaag actttgtata aagtatttgg gttttgttct tgtattgctt tctttcaaca gtttcaaaat aaaatatcat acaaatattg agggaaatgt tttcatattt ttcaaaatag gtttttattg ttgaatgtac atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt gttcctatag tgaaataagt 3043 3103 3163 3223 3283 3343 3403 3463 3523 3583 3643 3703 3763 3823 3883 3943 4003 4063 4123 4183 4243 4303 4363 4423 4483 4543 4603 4663 4723 4783 4843 4903 4963 5023 5083 5143 5203 5263 5323 5383 5443 5503 5563 5623 5683 5743 5803 5863 5923 5983 6043 6103 6163 6223 373 agggttcagc gagatgaaag tattcatagt atgactatgt agttctactt caaagctttc gtatgtagaa agaactttat atggtttgaa catgtaatcc tttgttttgt caggttcacg aaaacgtgtt aatattttca aaaa accttaaatt tgattacctt tgtattgtag ttatacatga gttcgattac tttcttttgg gtggtgtttg aattcaactt gtcatcaaaa cttggattaa tattatgctt tccaaataaa 6283 6343 6403 6463 6487 <2 10> 7 <2 11> 893 <2 12> PRT <2 13> Homo <4 00> 7

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala Xie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe 7\ r* Glu Tyr TiU I'llC Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe Xie Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tvr -J. — Arg Px/ci ''j ~ Thi? Δ 2.3. Ser Asn Phe Leu Gly nfU -X- X lit Ai a Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 374

Glu He Ser Phe Thr 405 Asn Leu Gin Pro Asn 410 His Thr Ala Val Tyr 415 Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser T ΤΤΓ-. Z^TTO Asp Ser Hrs Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Pal Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tvr — J. — Pro Asn ---ΣΤ Thr Ala Pro Val T &#906;_θ H J. s 820 825 830 Gly Val Asp Val He Asn Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser 835 840 845 Pro Gin Pro Ser He Phe He Cys Ser Lys Glu Gin Glu Leu Ser Tyr 850 855 860 Arg Asn Arg Asn Met Leu Ala Glu Asp Phe He Gin Lys Ser Thr Ser 865 870 875 880 Cys Asn Tyr Val Glu Lys Ser Ser Thr Phe Phe Lys He 885 890 375 <210> 8 <211> 7329

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272).(3625) <400> 8 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggegeegg acagatcgcg ttteggagge ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a aga gga eta ate gta tat eta atg ttc Arg Gly Leu lie Val Tyr Leu Met Phe 10 15 gca att gaa ata cca tet tea gtt caa

Ala He Glu He Pro Ser Ser Val Gin 25 30 cag tea aaa gtc caa gtt gcc ttt ccc

Gin Ser Lys Val Gin Val Ala Phe Pro 40 45 gaa tgt gaa get aaa gga aat cca gaa

Glu Cys Glu Ala Lys Gly Asn Pro Glu 60 gat ggc aac ect ttt tat ttc act gac Asp Gly Asn Pro 7 5 Phe Tyr Phe Thr Asp 80 aat tea gga aca ttc agg ate cca aac Asn Ser Gly 90 Thr Phe Arg He Pro 95 Asn caa ggg aaa tac ego tgc ttt get tea Gin Gly 105 Lys Tyr Arg Cys Phe 110 Ala Ser tea gaa gaa ata gaa ttt ata gtt cca Ser 120 Glu Glu He Glu Phe 125 He Val Pro gaa aaa att gac ect ett gaa gtg gag Glu Lys lie Asp Pro 140 Leu Glu Val Glu cca tgc aat ect ccc aaa ggc etc cca Pro Cys Asn Pro 155 Pro Lys Gly Leu Pro 160 aat att gaa tta gaa cac ate gaa caa Asn He Glu Leu Glu His He Glu Gin atg gag ccg ett tta ett gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 etc ctg tta aaa ttc tea aaa 340

Leu Leu Leu Lys Phe Ser Lys 20 cag gtt cca aca ate ata aaa 388

Gin Val Pro Thr He He Lys 35 ttc gat gag tat ttt caa att 436

Phe Asp Glu Tyr Phe Gin He 50 55 cca aca ttt teg tgg act aag 484

Pro Thr Phe Ser Trp Thr Lys 65 70 cat egg ata att cca teg aac 532

His Arg He He Pro Ser Asn 85 gag ggg cac ata tet cac ttt 580

Glu Gly His He Ser His Phe 100 aat aaa ctg gga ate get atg 628

Asn Lys Leu Gly He Ala Met 115 agt gtt cca aaa etc cca aaa 676

Ser Val Pro Lys Leu Pro Lys 130 135 gag gga gat oca att gtc etc 724 Glu Gly Asp Pro lie Val Leu 145 150 ect tta cac att tat tgg atg 772

Pro Leu His He Tyr Trp Met 165 gat gaa aga gta tac atg age 820

Asp Glu Arg Val Tyr Met Ser 376 170 175 180 caa Gin aag Lys 185 gga Gly gat Asp eta Leu tac Tyr ttc Phe 190 gca Ala aac Asn gtg Val gaa Glu gaa Glu 195 aag Lys gac Asp agt Ser ege Arg 868 aat gac tac tgt tgc ttt get gca ttt cca aga tta agg act att gta 916 Asn Asp Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val 200 205 210 215 cag aaa atg cca atg aaa eta aca gtt aac agt tta aag cat get aat 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn 220 225 230 gac tea agt tea tcc aca gaa att ggt tcc aag gca aat tcc ate aag 1012 Asp Ser Ser Ser Ser Thr Glu lie Gly Ser Lys Ala Asn Ser He Lys 235 240 245 caa aga aaa ccc aaa ctg ctg ttg cct ccc act gag agt ggc agt gag 1060 Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 250 255 260 tct tea att acc ate etc aaa ggg gaa ate ttg ctg ett gag tgt ttt 1108 Ser Ser lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe 265 270 275 get gaa ggc ttg cca act cca cag gtt gat tgg aac aaa att ggt ggt 1156 Ala Glu Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly 280 285 290 295 gac tta cca aag ggg aga gaa aca aaa gaa aat tat ggc aag act ttg 1204 Asp Leu Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu 300 305 310 aag ata gag aat gtc tcc tac cag gac aaa gga aat tat ege tgc aca 1252 Lys lie Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg cys Thr 315 320 325 gee age aat ttc ttg gga aca gcc act cac gat ttt cac gtt ata gta 1300 Ala Ser Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val J_ le Val 330 335 340 gaa gag cct cct ego tgg aca aag aag cct cag agt get gtg tat age 1348 Glu Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser 345 350 355 acc gga age aat ggc ate ttg tta tgt gag get gaa gga gaa cct caa 1396 Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin 360 365 370 375 ccc aca ate aag tgg aga gtc aat ggc tcc cca gtt gac aat cat cca 1444 Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro 380 385 3 9 0 ttt get ggt gat gtt gtc ttc ccc agg gaa ate agt ttt SCC aac ett 14 92 Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe Thr Asn Leu 395 400 405 caa cca aat cat act get gtg tac cag tgt gaa gcc tea aat gtc cat 1540 Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His 410 415 420 377 gga act ate ett Gly Thr lie Leu 425 ttg ata caa acc Leu He Gin Thr 440 agt get ttc tta Ser Ala Phe Leu tcc tgg cag aag Ser Trp Gin Lys 475 cat ate tat gaa His He Tyr Glu 490 gat get ggg tet Asp Ala Gly Ser 505 gca gtc aca gee Ala Val Thr Ala 520 tet cct aag aat Ser Pro Lys Asn gee aat gee aat Ala Asn Ala Asn 430 aaa gat gga gaa Lys Asp Gly Glu 445 cat tgc gag ttc His Cys Glu Phe 460 gtg gaa gaa gtg Val Glu Glu Val tgt gaa age aaa Cys Glu Ser Lys 555 tgg agt aaa gat Trp Ser Lys Asp 570 agg ata att att Arg He He He 585 gag gac caa ggt Glu Asp Gin Gly 600 get gee gat ata Ala Ala Asp He aat ggc aca ttg Asn Gly Thr Leu 495 tac tea tgt tgg Tyr Ser Cys Trp 510 aat ttg gat att Asn Leu Asp He 525 cct cgt ate ccc Pro Arg lie Pro 540 tgt gac tea cat Cys Asp Ser His gaa aac ett cac Glu Asn Leu His 635 tgg gaa get gga Trp Glu Ala Gly 650 gaa ttt gaa gga Glu Phe Glu Gly gga gaa gee ttt Gly Glu Ala Phe 575 gat gga get aat Asp Gly Ala Asn 590 att tac tgc tgt He Tyr Cys Cys 605 act caa gta act Thr Gin Val Thr 620 ttg tet gaa. aga Leu Ser Glu Arg get gac cac aac Ala Asp His Asn 655 aac aaa gaa gag Asn Lys Glu Glu att gat gtt gtg gat He Asp Val Val 435 Asp aat tac get aca gtg Asn Tyr Ala 450 Thr Val ttt get tea cct gag Phe Ala 465 Ser Pro Glu aaa ccc ctg gag ggc Lys 480 Pro Leu Glu Gly cag ate aac aga acc Gin He Asn Arg Thr 500 gta gaa aat get ata Val Glu Asn Ala 515 He aga aat get aca aaa Arg Asn Ala 530 Thr Lys aaa ttg cat atg ett Lys Leu 545 His Met Leu ttg aaa cac agt ttg Leu 560 Lys His Ser Leu gaa att aat ggc aca Glu He Asn Gly Thr 580 ttg acc ata tet aat Leu Thr He Ser 595 Asn tea get cat act get Ser Ala His 610 Thr Ala gtt ett gat gtt ccg Val Leu 625 Asp Val Pro nan aac A CICi a rfb rttt — — ΣΙ ZJ — — -,-- Gin 640 Asn Arg Ser Val age aat att age gag Ser Asn lie Ser Glu 660 cct gga agg tgg gag Pro Gly Arg Trp Glu gtc cgt cca 1588 Val Arg Pro gtt ggg tac 1636

Val Gly Tyr 455 gca gtc gtg 1684 Ala Val Val 470 agg egg tat 1732

Arg Arg Tyr 485 acc gaa gaa 1780 Thr Glu Glu gga aaa act 1828 Gly Lys Thr ett aga gtt 1876 Leu Arg Val 535 gaa tta cat 1924 Glu Leu His 550 aag ttg tec 1972

Lys Leu Ser 565 gaa gat ggc 2020 Glu Asp Gly gta act tta 2068 Val Thr Leu eta gac agt 2116 Leu Asp Ser 615 gat cca cca 2164 Asp Pro Pro 630 egg ctg acc 2212

Arg Leu Thr 645 tat att gtt 2260 Tyr He Val gaa ctg acc 2308 Glu Leu Thr 378 665 670 675 aga Arg 680 gtc Val caa Gin gga Gly aag Lys aaa Lys 685 acc Thr aca Thr gtt Val ate He tta Leu 690 cct Pro ttg Leu get Ala cca Pro ttt Phe 695 2356 gtg aga tac cag ttc agg gtc ata gee gtg cS cS C* Qclcl gta ggg a. agt 2404 val Arg Tyr Gin Phe Arg Val lie Ala Val Asn Glu Val Gly Arg Ser 700 705 710 cag cct age cag ccg tea gac cat cat gaa aca cca cca gca get cca 2452 Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro 715 720 725 gat agg aat cca caa aac ata agg gtt CSS gee tet caa ccc aag gaa 2500 Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin Pro Lys Glu 730 735 740 A +" ΓΤ A ft g/ta +- Γ&#910;ΓΤ rr a rr /-* + 4--f-rr AAA tee a a 4- O C Λ Q Λ A g '-•J-J C- C- -J lUdU. ga 4- g y CiCj “ s C4.CA (- gga cca s. Met lie He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro 745 750 755 ggc eta gag tac aga gtg acc tgg aag cca cag gga gee cca gtg gag 2596 Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu 760 765 770 775 tgg gaa gaa gaa aca gtc aca aac cac aca ttg egg gtg atg aeg cct 2644 Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val Met Thr Pro 780 785 790 get gtc tat gee cct tat gat gtc aag gtc cag get ate aat caa eta 2692 Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He Asn Gin Leu 795 800 805 gga tet ggg cct gac cct cag tea gtg act etc tat tet gga gaa gac 2740 Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp 810 815 820 tta cct gaa cag cca act ttt Ct a aag gtc ate 6.6.3. gtt gat a a a gac 2788 Leu Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp Lys Asp 825 830 835 act gee act tta tet tgg gga eta cct aag sss tta aat gga aac tta 2836 Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly Asn Leu 840 845 850 855 act ggc tat ett ttg caa tat cag ata ata aat gac acc tac gag att 2884 Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr Glu He 860 865 870 gga gaa tta aat gat att aac att aca act cca tea aag CCC age tgg 2932 Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro Ser Trp 875 880 885 cac etc tea aac ctg aat gca act acc aag tac aaa ttc tac ttg agg 2980 His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr Leu Arg 890 895 900 get tgc act tea cag ggc tgt gga aaa ccg ate aeg gag gaa age tcc 3028 Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu Ser Ser 905 910 915 379 3076 acc tta gga gaa ggg agt aaa ggt ate ggg aag ata tea gga gta aat Thr 920 Leu Gly Glu Gly Ser 925 Lys Gly He Gly Lys 930 He Ser Gly Val Asn 935 ctt act caa aag act cac cca ata gag gta ttt gag ccg gga get gaa Leu Thr Gin Lys Thr 940 His Pro He Glu Val 945 Phe Glu Pro Gly Al a 950 Glu cat ata gtt c go eta atg act aag aat tgg ggc gat aac gat age att His I le Val Arg 955 Leu Met Thr Lys Asn 960 Trp Gly Asp Asn Asp 965 Ser He ttt caa gat gta att gag aca aga ggg aga gaa tat get ggt tta tat Phe Glu Asp 970 Val He Glu Thr Arg 975 Gly Arg Glu Tyr Ala 980 Gly Leu Tyr gat gac ate too act caa ggc tgg ttt att gga ctg atg tgt geg att Asp Asp He 9 8 5 Ser Thr Gin Gly Trp 990 Phe He Gly Leu 995 Met ! Cys Ala He get ctt etc aca eta eta tta tta act gtt tgc ttt gtg aag agg aat Ala Leu 1000 Leu Thr Leu Leu 1005 Leu Leu Thr Val Cys 101C Phe 1 Val Lys Arg Asn 1015 aga ggt gga aag tac tea gtt aaa gaa aag gaa gat ttg cat cca gac Arg Gly Gly Lys Tyr 102C Ser 1 Val Lys Glu Lys 1025 Glu Asp Leu His Pro 103C Asp 1 cca gaa att cag tea gta aaa gat gaa acc ttt ggt gaa tac agt gac Pro Glu lie Gin 1035 Ser Val Lys Asp Glu 104C Thr 1 Phe Gly Glu Tyr 1045 Ser Asp agt gat gaa aag cct etc aaa gga age ctt egg tcc ctt aat agg gat Ser Asp Glu Lys 1050 Pro Leu Lys Gly Ser 1055 Leu Arg Ser 106C Asn 1 Arg Asp atg cag cct act gaa agt get gac age tta gtc gaa tac gga gag gga Met Gin 10 6 5 Pro Thr Glu Ser Ala 107C Asp Ser Leu V Si 1 Glu 1075 Tyr Gly Glu Gly gac cat ggt etc ttc agt gaa gat gga tea ttt att ggt gcc tac get Asp 1080 His 1 Gly Leu Phe Ser 1085 Glu Asp Gly Ser Phe 1090 He 1 Gly Ala Tyr Ala 1095 gga tet aag gag aag gga tet gtt gaa age aat gga agt tet aca gca Gly Ser Lys Glu Lys 1100 Gly Ser Val Glu Ser 1105 Asn Gly Ser Ser Thr 1110 Ala act Thr ttt Phe CCC Pro ctt Leu 1115 egg Arg gca Ala taa * acacaacata tgtaagcaac gctactggtt 3124 3172 3220 3268 3316 3364 3412 3460 3508 3556 3604 3655 caccccaacc ttccatattt atctgttcaa aggagcaaga actttcatat aggaatagaa acatgctggc cgaagatttc atccagaagt caacatcctg caattatgtt gaaaagagta gtactttctt caaaatataa aatgccaagc acttcaggcc tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag atggtcatat ttaaacagaa gtatacgttt ttcagtttca Ο &#906; 1 R O / J. 3775 3835 3895 3955 4015 4075 4135 4195 4255 380 acatgaattt ttttatttct gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt ttcttggact aaattcaact gcatggaagc ggtggtcaga aggttgtttt atacgagaac aggcagaaag tgcccattgt tcaggattct aatagctaca tctacttaat atcttcattt ctaaattgac tgcttttacc tttttctcat gtttatataa tggtatgctt gcatatattt catgaataca ttgtacatat tatgttaata tttacacaat ttaaaatata gatgtgtttt attttgaagt gagaaaatga acattaacag gcatgtttgt acagctagaa tatattagta agatactgtt tttcgtcatt ccagagctac aactaataac acgaggttcc aaagctgaag actttgtata aagtatttgg gttttgttct tgtattgctt tctttcaaca gtttcaaaat aaaatatcat acaaatattg agggaaatgt tttcatattt ttcaaaatag gtttttattg ttgaatgtac atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt accttaaatt gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg tgattacctt tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt tgtattgtag gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca ttatacatga aattcaactt tccaaataaa agttctactt catgtaatcc aaaa <210> 9 <211> 1117

<212> PRT <213> Homo sapians <400> 9

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 15 10 15

Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 4315 4375 4435 4495 4555 4615 4675 4735 4795 4855 4915 4975 5035 5095 5155 5215 5275 5335 5395 5455 5515 5575 5635 5695 5755 5815 5875 5935 5995 6055 6115 6175 6235 6295 6355 6415 6475 6535 6595 6655 6715 6775 6835 6895 6955 7015 7075 7135 7195 7255 7315 7329 381 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg lie Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe lie Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 16 5 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr lie Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn A &amp;#9633; c; T J J 440 44 5 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 382 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He lie lie Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn lie Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro a c λ v υ v 665 67 0 ciy Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tvr - J. — Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Leu Pro Glu Gin Pro Thr Phe Leu Lys 820 825 830 Val He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro 835 840 845 Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin lie 850 855 860 He Asn Asp Thr Tyr Glu He Gly Glu Leu Asn Asp He Asn He Thr 865 870 875 880 Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr 885 890 895 Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys 900 905 910 Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He 915 920 925 Gly Lys lie Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu 930 935 940 Val Phe Glu Pro Gly Ala Glu His lie Val Arg Leu Met Thr Lys Asn 945 950 955 960 Trp Gly Asp Asn Asp Ser lie Phe Gin Asp Val He Glu Thr Arg Gly 965 970 975 Arg Glu Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe 980 985 990 He Gly Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr 995 1000 1005 Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 383 1010 1015 1020 Lys Glu Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1025 1030 1035 104 Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser 1045 1050 1055 Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser 1060 1065 1070 Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly 1075 1080 1085 Ser Phe He Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu 1090 1095 1100 Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Al a 1105 1110 1115

<210> 10 <211> 7602 <212> DNA <220> <221> CDS <222> (272) <400> 10 cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg (3898 ) gcgcccccgt acagatcgcg atactgcaaa taaggtctca ttgtcttctt cccggctccc ggccggctcg ggggagaagg cgcccgaggg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa caaatcatag tggaactaag gggaacttaa tttactgttt gctgtaaacc aaaagtgaga ggagacatta agattttcat cctgaagagc a atg gag ccg ctt tta ctt gga

Met Glu Pro Leu Leu Leu Gly 1 5 60 120 180 240 292 aga gga eta ate gta tat eta atg Arg Gly Leu lie Val Tyr Leu Met 10 15 ttc etc ctg tta Phe Leu Leu Leu aaa ttc tea aaa Lys Phe Ser Lys 20 340 gca att Ala He 25 gaa ata cca tet Glu He Pro Ser tea gtt caa cag gtt cca Ser Val Gin Gin Val Pro 30 35 aca ate ata aaa Thr He He Lys 388 cag tea aaa gtc caa gtt gcc ttt Gin Ser Lys Val Gin Val Ala Phe 40 45 ccc ttc gat gag Pro Phe Asp Glu 50 tat ttt caa att Tyr Phe Gin He 55 436 gaa tgt gaa get aaa gga aat cca Glu Cys Glu Ala Lys Gly Asn Pro 60 gaa cca aca ttt Glu Pro Thr Phe 65 teg tgg act aag Ser Trp Thr Lys 70 484 gat ggc aac cct ttt tat ttc act Asp Gly Asn Pro Phe Tyr Phe Thr 75 gac cat egg ata Asp His Arg He 80 att cca teg aac He Pro Ser Asn 85 532 aat tea gga aca ttc agg ate cca Asn Ser Gly Thr Phe Arg He Pro 90 95 aac gag ggg cac Asn Glu Gly His ata tet cac ttt lie Ser His Phe 100 580 caa ggg

Gin Gly 105 aaa tac ege tgc Lys Tyr Arg Cys ttt get tea aat aaa ctg Phe Ala Ser Asn Lys Leu 110 115 gga ate get atg Gly lie Ala Met 628 tea gaa gaa ata gaa ttt ata gtt cca agt gtt cca aaa etc cca aaa 676 384

Ser 120 Glu Glu He Glu Phe 125 He Val Pro Ser Val 130 Pro Lys Leu Pro Lys 135 gaa aaa att gac cct ett gaa gtg gag gag gga gat cca att gtc etc 724 Glu Lys He Asp Pro Leu Glu Val Glu Glu Gly Asp Pro He Val Leu 140 145 150 cca tgc aat cct ccc aaa ggc etc cca cct tta cac att tat tgg atg 772 Pro Cys Asn Pro Pro Lys Gly Leu Pro Pro Leu His He Tyr Trp Met 155 160 165 aat att gaa tta gaa cac ate gaa caa gat gaa aga gta tac atg age 820 Asn lie Glu Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser 170 175 180 caa aag gga gat eta tac ttc gca aac gtg gaa gaa aag gac agt ege 868 Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg 185 190 195 aat gac tac tgt tgc ttt get gca ttt cca aga tta agg act att gta 916 Asn Asp Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val 200 205 210 215 cag aaa atg cca atg aaa eta aca gtt aac agt tea aat tcc ate aag 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Ser Asn Ser He Lys 220 225 230 caa aga aaa ccc aaa ctg ctg ttg cct ccc act gag agt ggc agt gag 1012 Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 235 240 245 tet tea att acc ate etc aaa ggg gaa ate ttg ctg ett gag tgt ttt 1060 Ser Ser He Thr He Leu Lys Gly Glu lie Leu Leu Leu Glu Cys Phe 250 255 260 get gaa ggc ttg cca act cca cag gtt gat tgg aac aaa att ggt ggt 1108 Ala Glu Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly 2 6 5 270 275 gac tta cca aag ggg aga gaa aca aaa gaa aat tat ggc aag act ttg 1156 Asp Leu Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu 280 285 290 295 aag ata gag aat gtc tcc tac cag gac aaa gga aat tat ege tgc aca 1204 Lys lie Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr 300 305 310 gcc age aat ttc ttg gga aca gcc act cac gat ttt cac gtt ata gta 1252 Ala Ser Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val 315 320 325 gaa gag cct cct ege tgg aca aag aag cct cag agt get gtg tat age 1300 Glu Γ* &amp;#906; ,, ux u. Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala val Tyr Ser 330 335 340 acc gga age aat ggc ate ttg tta tgt gag get gaa gga gaa cct caa 1348 Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin 345 350 355 ccc aca ate aag tgg aga gtc aat ggc tcc cca gtt gac aat cat cca 1396 Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro 360 365 370 375 385 1444 ttt get Phe Ala

CSS CCS

Gin Pro gga act Gly Thr ttg ata Leu lie 425 agt get Ser Ala 440 tcc tgg Ser Trp cat ate His He gat get Asp Ala gca gtc Ala Val 505 tet cct Ser pro 520 tgt gaa Cys Glu tgg agt Trp Ser agg ata Arg He gag gac Glu Asp 585 get gee Ala Ala 600 gaa aac ggt gat Gly Asp aat cat Asn His 395 ate ett He Leu 410 caa acc Gin Thr ttc tta Phe Leu cag aag Gin Lys tat gaa Tyr Glu 475 ggg tet Gly Ser 490 scs gee Thr Ala aag aat Lys Asn age aaa Ser Lys aaa gat Lys Asp 555 att att He lie 570 caa ggt Gin Gly gat ata Asp He ett cac gtt gtc Val Val 380 act get Thr Ala gee aat Ala Asn aaa gat Lys Asp cat tgc His Cys 445 gtg gaa Val Glu 460 aat ggc Asn Gly tac tea Tyr Ser aat ttg Asn Leu cct cgt Pro Arg 525 tgt gac Cys Asp 540 gga gaa Gly Glu gat gga Asp Gly att tac He Tyr act caa Thr Gin 605 ttg tet ttc ccc Phe Pro gtg tac Val Tyr gee aat Ala Asn 415 gga gaa Gly Glu 430 gag ttc Glu Phe gaa gtg Glu Val aca ttg Thr Leu tgt tgg Cys Trp 495 gat att Asp lie 510 ate ccc He Pro tea cat Ser His gee ttt Ala Phe get aat Ala Asn 575 tgc tgt Cys Cys 590 gta act Val Thr gaa aga agg gaa Arg Glu 385 cag tgt Gin Cys 400 att gat He Asp aat tac Asn Tyr ttt get Phe Ala aaa ccc Lys Pro 465 cag ate Gin He 480 gta gaa Val Glu aga aat Arg Asn aaa ttg Lys Leu ttg aaa Leu Lys 545 gaa att Glu He 560 ttg acc Leu Thr tea get Ser Ala gtt ett Val Leu ate agt He Ser gaa gee Glu Ala gtt gtg Val Val get aca Ala Thr 435 tea cct Ser Pro 450 ctg gag Leu Glu aac aga Asn Arg aat get Asn Ala get aca Ala Thr 515 cat atg His Met 530 cac agt His Ser aat ggc Asn Gly ata tet He Ser cat act His Thr 595 gat gtt Asp Val 610 agg agt ttt acc Phe Thr tea aat Ser Asn 405 gat gtc Asp Val 420 gtg gtt Val Val gag gca Glu Ala ggc agg Gly Arg acc acc Thr Thr 485 ata gga. He Gly 500 aaa ett Lys Leu ett gaa Leu Glu ttg aag Leu Lys aca gaa Thr Glu 565 aat gta Asn Val 580 get eta Ala Leu ccg gat Pro Asp gtt egg aac ett Asn Leu 390 gtc cat Val His 1492 cgt cca Arg Pro 1540 ggg tac Gly Tyr 1588 gtc gtg Val Val 455 egg tat Arg Tyr 470 gaa gaa Glu Glu 1636 1684 1732 aaa act Lys Thr 1780 aga gtt Arg Val 1828 tta cat Leu His 535 ttg tcc Leu Ser 550 gat ggc Asp Gly 1876 1924 1972 act tta Thr Leu 2020 gac agt Asp Ser 2068 cca cca

Pro Pro 615 ctg acc 2116 2164 386

Glu Asn Leu His Leu 620 Ser Glu Arg Gin Asn 625 Arg Ser Val Arg Leu 630 Thr tgg gaa get gga get gac cac aac age aat att age gag tat att gtt 2212 Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr He Val 635 640 645 gaa ttt gaa gga aac aaa gaa gag cct gga agg tgg gag gaa ctg acc 2260 Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr 650 655 660 aga gtc caa gga aag aaa acc aca gtt ate tta cct ttg get cca ttt 2308 Arg Val Gin Gly Lys Lys Thr Thr Val lie Leu Pro Leu Ala Pro Phe 665 670 675 gtg aga tac cag ttc agg gtc ata gcc gtg aac gaa gta ggg aga agt 2356 Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Giy Arg Ser 680 685 690 695 cag cct age cag ecg tea gac cat cat gaa aca cca cca gca get cca 2404 Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro 700 705 710 gat agg aat cca caa aac ata agg gtt caa gcc tct caa ccc aag gaa 2452 Asp Arg Asn Pro Gin Asn lie Arg Val Gin Ala Ser Gin Pro Lys Glu 715 720 725 atg att ata aag tgg gag cct ttg aaa tee atg gag cag aat gga cca 2500 Met lie He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro 730 735 740 ggc eta gag tac aga gtg acc tgg aag cca cag gga gcc cca gtg gag 2548 Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu 745 750 755 tgg gaa gaa gaa aca gtc aca aac cac aca ttg egg gtg atg aeg cct 2596 Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val Met Thr Pro 760 765 770 775 get gtc tat gcc cct tat gat gtc aag gtc cag get ate aat caa eta 2644 Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala lie Asn Gin Leu 780 785 790 gga tct ggg cct gac cct cag tea gtg act etc tat tct gga gaa gac 2692 Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp 795 800 805 tat cct gat aca get cca gtg ate cat ggg gtg gac gtt ata aac agt 2740 Tyr Pro Asp Thr Ala Pro Val He His Gly Val Asp Val lie Asn Ser 810 815 820 aca tta gtt aaa gtt acc tgg tea aca gtt cca aag gac aga gta cat 2788 Thr Leu Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp Arg Val His 825 830 835 gga cgt ctg aaa ggc tat cag ata aat tgg tgg aaa aca aaa agt ctg 2836 Gly Arg Leu Lys Gly Tyr Gin He Asn Trp Trp Lys Thr Lys Ser Leu 840 845 850 855 ttg gat gga aga aca cat ccc aaa gaa gtg aac att eta aga ttt tea 2884 Leu Asp Gly Arg Thr His Pro Lys Glu Val Asn He Leu Arg Phe Ser 860 865 870 387 gga Gly caa Gin aga Arg aac Asn 875 tet Ser gga Gly atg Met gtt Val cct Pro 880 tcc Ser tta Leu gat Asp gcc Ala ttt Phe 885 agt Ser gaa Glu 2932 ttt cat tta aca gtc tta gcc tat aac tet aaa gga get ggt cct gaa 2980 Phs His Leu 890 Thr Val Leu Ala Tyr 895 Asn Ser Lys Gly Al a 900 /&amp;#943; *1. Pro Glu agt gag cct tat ata ttt caa aca cca gaa gga gta cct gaa cag cca 3028 Ser Glu 905 Pro Tyr He Phe Gin 910 Thr Pro Glu Gly Val 915 Pro Glu Gin Pro act ttt eta aag gtc ate aaa gtt gat aaa gac act gcc act tta tet 3076 Thr 920 Phe Leu Lys Val He 925 Lys Val Asp Lys Asp 930 Thr Ala Thr Leu Ser 935 tgg gga eta cct aag aaa tta aat gga aac tta act ggc tat ctt ttg 3124 Trp Gly Leu Pro Lys 940 Lys Leu Asn Gly Asn 945 Leu Thr Gly Tyr Leu 950 Leu caa tat cag ata ata aat gac acc tac gag att gga gaa tta aat gat 317 2 Gin Tyr Gin He 955 He Asn Asp Thr Tyr 960 Glu lie Gly Glu Leu 965 Asn Asp att aac att aca act cca tea aag ccc age tgg cac etc tea aac ctg 3220 He Asn He 970 Thr Thr Pro Ser Lys 975 Pro Ser Trp His Leu 980 Ser Asn Leu aat gca act acc aag tac aaa ttc tac ttg agg get tgc act tea cag 3268 Asn Ala Thr 985 Thr Lys Tyr Lys Phe 990 Tyr Leu Arg Ala Cys 995 Thr Ser Gin ggc tgt gga aaa ccg ate aeg gag gaa age tcc acc tta gga gaa ggg 3316 Gly 100C Cys 1 Gly Lys Pro He 1005 Thr Glu Glu Ser Ser 101C Thr 1 Leu Gly Glu Gly 1015 agt sas ggt ate ggg aag ata tea gga gta aat ctt act caa aag act 3364 Ser Lys Gly He Gly 102C Lys 1 He Ser Gly Val 1025 Asn Leu Thr Gin Lys 103C Thr 1 cac cca ata gag gta ttt gag ccg gga get gaa cat ata gtt ege eta 3412 His Pro lie Glu Val 1035 Phe Glu Pro Gly Ala 1040 Glu His He Val Arg 1045 Leu atg act aag aat tgg ggc gat aac gat age att ttt caa gat gta att 3460 Met Thr Lys 1050 Asn Trp Gly Asp Asn 1055 Asp Ser Xie Phe Gin 106C Asp 1 Val lie gag aca aga ggg aga gaa tat get ggt tta tat gat gac ate tcc act 3508 Glu Thr 1065 Arg Gly Arg Glu Tyr 107C Ala 1 Gly Leu Tyr Asp 1075 Asp He Ser Thr caa ggc tgg ttt att gga ctg atg tgt geg att get ctt etc aca eta 3556 Gin 1080 dy 1 Trp Phe lie Gly 1085 Leu 1 Met Cys Ala He 109C Ala I Leu Leu Thr Leu 1095 eta tta tta act gtt tgc ttt gtg aag agg aat aga ggt gga aag tac 3604 Leu Leu Leu Thr Val 1100 Cys Phe Val Lys Arg 1105 Asn Arg Gly Gly Lys me Tyr tea gtt aaa gaa aag gaa gat ttg cat cca gac cca gaa att cag tea 3652 388

Ser Val Lys Glu 1115 Lys 1 Glu Asp Leu His 112C Pro 1 Asp Pro Glu He Gin 1125 Ser gta aaa gat gaa acc ttt ggt gaa tac agt gac agt gat gaa aag cct 3700 Val Lys Asp 113C Glu 1 Thr Phe dy Glu 1135 Tyr Ser Asp Ser Asp 114C Glu ) Lys Pro etc aaa gga age ett egg tee ett aat agg gat atg cag cct act gaa 3748 Leu Lys Gly 1145 Ser Leu Arg Ser 115C Leu 1 Asn Arg Asp Met 1155 Gin Pro Thr Glu agt get gac age tta gtc gaa tac gga gag gga gac cat ggt etc ttc 3796 Ser 116C Ala I Asp Ser Leu Val 1165 Glu Tyr Gly Glu Gly 117C Asp 1 His Gly Leu Phe 1175 agt gaa gat gga tea ttt att ggt gcc tac get gga tct aag gag aag 3844 Ser Glu Asp Gly Ser 118C Phe 1 lie Gly Ala Tyr 1185 Ala Gly Ser Lys Glu 1190 Lys 1 gga tct gtt gaa age aat gga agt tct aca gca act ttt ccc ett egg 3892 Gly Ser Val Glu 1195 Ser Asn Gly Ser Ser 1200 Thr 1 Ala Thr Phe Pro 1205 Leu Arg gca taa acacaacata tgtaagcaac gctactggtt . caccccaacc ttccatattt 3948

Ala * atctgttcaa aggagcaaga actttcatat aggaatagaa acatgctggc cgaagatttc 4008 atccagaagt caacatcctg caattatgtt gaaaagagta gtactttctt caaaatataa 4068 aatgccaagc acttcaggcc tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa 4128 aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt 4188 atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt 4248 gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc 4308 ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg 4368 aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta 4428 ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag 4488 atggtcatat ttaaacagaa gtatacgttt ttcagtttca acatgaattt ttttatttct 4548 gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt ttcttggact 4608 aaattcaact gcatggaagc ggtggtcaga aggttgtttt atacgagaac aggcagaaag 4668 tgcccattgt tcaggattct aatagctaca tctacttaat atcttcattt ctaaattgac 4728 tgcttttacc tttttctcat gtttatataa tggtatgctt gcatatattt catgaataca 4788 ttgtacatat tatgttaata tttacacaat ttaaaatata gatgtgtttt attttgaagt 4848 gagaaaatga acattaacag gcatgtttgt acagctagaa tatattagta agatactgtt 4908 tttcgtcatt ccagagctac aactaataac acgaggttcc aaagctgaag actttgtata 4968 aagtatttgg gttttgttct tgtattgctt tctttcaaca gtttcaaaat aaaatatcat 5028 acaaatattg agggaaatgt tttcatattt ttcaaaatag gtttttattg ttgaatgtac 5088 atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg 5148 cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg 5208 tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa 5268 aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag 5328 ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac 5388 tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt 5448 tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg 5508 tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca 5568 cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg 5628 gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc 5688 cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc 5748 ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg 5808 gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc 5868 tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc 5928 atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac 5988 taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga 6048 389 aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat 610 gagattgaat gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca 616 actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt 622 gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa 628 gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt 634 gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa 640 cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg 646 tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag 652 ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg 658 attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc 664 taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga 670 agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa 676 ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca 682 taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag 688 tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc 694 tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg 700 tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa 706 tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac 712 tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa 718 gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg 724 attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat 730 atatcctagt gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt 736 accttaaatt gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg 742 tgattacctt tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt 748 tgtattgtag gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca 754 ttatacatga aattcaactt tccaaataaa agttctactt catgtaatcc aaaa 760 <210> 11 <211> 1208

<212> PRT <213> Homo sapians <400> 11

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys dy Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro lie Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Ser Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 390 225 230 235 240 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 245 250 255 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 260 265 270 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 275 280 285 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 290 295 300 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 305 310 315 320 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 325 330 335 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 340 345 350 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 355 360 365 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg -) -J Λ &#9633; i \J 3 75 380 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 385 3 9 0 395 400 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn lie 405 410 415 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 420 425 430 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 435 440 445 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 450 455 460 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 465 470 475 480 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 485 490 495 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 500 505 510 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg I le Pro Lys 515 520 525 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 530 535 540 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 545 550 555 560 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 565 570 575 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr Cys Cys Ser 580 585 590 Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val 595 600 605 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 610 615 620 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 625 630 635 640 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 645 650 655 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 660 665 670 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 675 680 685 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 690 695 700 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 705 710 715 720 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 391 725 730 735 Ser Met Glu Gin Asn 740 Gly Pro Gly Leu Glu Tyr 745 Arg Val Thr Trp Lys 750 Pro Gin Gly Ala Pro 755 Val Glu Trp Glu Glu Glu 760 Thr Val Thr Asn His 765 Thr Leu Arg Val Met 770 Thr Pro Ala Val Tyr Ala 775 Pro Tyr Asp Val Lys 780 Val 785 Gin Ala lie Asn Gin Leu Gly Ser Gly Pro 790 795 Asp Pro Gin Ser Val 800 Thr Leu Tyr Ser Gly 805 Glu Asp Tyr Pro Asp Thr 810 Ala Pro Val He His 815 Gly Val Asp Val He 820 Asn Ser Thr Leu Val Lys 825 Val Thr Trp Ser Thr 830 Val Pro Lys Asp Arg 835 Val His Gly Arg Leu Lys 840 Gly Tyr Gin lie Asn 845 Trp Trp Lys Thr Lys 850 Ser Leu Leu Asp Gly Arg 855 Thr His Pro Lys Glu 860 Val 865 Asn He Leu Arg Phe Ser Gly Gin Arg Asn 870 875 Ser Gly Met Val Pro 880 Ser Leu Asp Ala Phe 885 Ser Glu Phe His Leu Thr 890 Val Leu Ala Tyr Asn 895 Ser Lys Gly Ala Gly 900 Pro Glu Ser Glu Pro Tyr 905 He Phe Gin Thr Pro 910 Glu Gly Val Pro Glu 915 Gin Pro Thr Phe Leu Lys 920 Val He Lys Val Asp 925 Lys Asp Thr Ala Thr 930 Leu Ser Trp Gly Leu Pro 935 Lys Lys Leu Asn Gly 940 Asn 945 Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He 950 955 lie Asn Asp Thr Tyr 960 Glu He Gly Glu Leu 965 Asn Asp He Asn He Thr 970 Thr Pro Ser Lys Pro 975 Ser Trp His Leu Ser 980 Asn Leu Asn Ala Thr Thr 985 Lys Tyr Lys Phe Tyr 990 Leu Arg Ala Cys Thr 995 Ser Gin Gly Cys Gly Lys 1000 Pro He Thr Glu Glu 1005 Ser Ser Thr Leu Gly 1010 Glu Gly Ser Lys Gly He 1015 Gly Lys lie Ser Gly 1020 Val 1025 Asn Leu Thr Gin Lys Thr His Pro He Glu 1030 1035 Val Phe Glu Pro Gly . 1040 Ala Glu His He Val 1045 Arg Leu Met Thr Lys Asn , 1050 Trp Gly Asp Asn Asp 1055 Ser He Phe Gin Asp 1060 Val He Glu Thr Arg Gly 1065 Arg Glu Tyr Ala Gly 1070 Leu Tyr Asp Asp He 1075 Ser Thr Gin Gly Trp Phe 1080 He Gly Leu Met Cys 1085 Ala He Ala Leu Leu 1090 Thr Leu Leu Leu Leu Thr 1095 Val Cys Phe Val Lys 1100 Arg 1105 Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 1110 1115 Lys Glu Asp Leu His , 1120 Pro Asp Pro Glu He 1125 Gin Ser Val Lys Asp Glu 1130 Thr Phe Gly Glu Tyr 1135 Ser Asp Ser Asp Glu 1140 Lys Pro Leu Lys Gly Ser 1145 Leu Arg Ser Leu Asn 1150 Arg Asp Met Gin Pro 1155 Thr Glu Ser Ala Asp Ser 1160 Leu Val Glu Tyr Gly 1165 Glu Gly Asp His Gly 1170 Leu Phe Ser Glu Asp Gly 1175 Ser Phe He Gly Ala 1180 Tyr 1185 Thr Ala Gly Ser Lys 1 Ala Thr Phe Pro 1205 Glu Lys Gly Ser Val Glu 1190 1195 Leu Arg Ala Ser Asn Gly Ser Ser , 1200 392 <210> 12 <211> 7527

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272).(3823) <400> 12 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ett tta ett gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 aga Arg gga Gly eta Leu 10 ate He gta Val tat Tyr eta Leu atg Met 15 ttc Phe etc Leu ctg Leu tta Leu aaa Lys 20 ttc Phe tea Ser aaa Lys 340 gca att gaa ata cca tet tea gtt caa cag gtt cca aca ate ata aaa 388 Ala lie Glu He Pro Ser Ser Val Gin Gin Val Pro Thr He He Lys 25 30 35 cag tea aaa gtc caa gtt gee ttt ccc ttc gat gag tat ttt caa att 436 Gin Ser Lys Val Gin Val Ala Phe Pro Phe Asp Glu Tyr Phe Gin He 40 45 50 55 gaa tgt gaa get aaa gga aat cca gaa cca aca ttt teg tgg act aag 484 Glu Cys Glu Ala Lys Gly Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys 60 65 70 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532 Asp Gly Asn Pro Phe Tyr Phe Thr Asp His Arg He He Pro Ser Asn 75 80 85 aat tea gga aca ttc agg ate cca aac gag ggg cac ata tet cac ttt 580 Asn Ser Gly Thr Phe Arg He Pro Asn Glu Gly His He Ser His Phe 90 95 100 caa ggg aaa tac ege tgc ttt get tea aat 3.3.3. ctg gga ate get atg 628 Gin Gly Lys Tyr Arg Cys Phe Ala Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca aaa tta gaa cac ate gaa caa 676 Ser Glu Glu He Glu Phe He Val Pro Lys Leu Glu His He Glu Gin 120 125 130 135 gat gaa aga gta tac atg age caa aag gga gat eta tac ttc gca aac 724 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 140 145 150 gtg gaa gaa aag gac agt ege aat gac tac tgt tgc ttt get gca ttt 772 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 155 160 165 cca aga tta agg act att gta cag aaa atg cca atg aaa eta aca gtt 820 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 170 175 180 393 aac agt tta aag cat get Asn Ser Leu Lys His Ala 185 tcc aag gca aat tcc ate Ser Lys Ala Asn Ser lie 200 205 ccc act gag agt ggc agt Pro Thr Glu Ser Gly Ser 220 ate ttg ctg ett gag tgt He Leu Leu Leu Glu Cys 235 gat tgg aac aaa att ggt Asp Trp Asn Lys lie Gly 250 gaa aat tat ggc aag act Glu Asn Tyr Gly Lys Thr 265 aaa gga aat tat ege tgc Lys Gly Asn Tyr Arg Cys 280 285 cac gat ttt cac gtt ata His Asp Phe His Val He 300 cct cag agt get gtg tat Pro Gin Ser Ala Val Tyr 315 gag get gaa gga gaa cct Glu Ala Glu Gly Glu Pro 330 tcc cca gtt gac aat cat Ser Pro Val Asp Asn His 345 gaa ate agt ttt acc aac Glu He Ser Phe Thr Asn 360 365 tgt gaa gcc tea aat gtc Cys Glu Ala Ser Asn Val 380 gat gtt gtg gat gtc cgt Asp Val Val Asp Val Arg 395 tac get aca gtg gtt ggg Tyr Ala Thr Val Val Gly 410 get tea cct gag gca gtc aat gac tea agt tea tcc Asn 190 Asp Ser Ser Ser Ser 195 aag caa aga aaa ccc aaa Lys C-ln Arg Lys Pro 210 Lys gag tct tea att acc ate Glu Ser Ser He 225 Thr He ttt get gaa ggc ttg cca Phe Ala Glu 240 Gly Leu Pro ggt gac tta cca aag ggg Gly Asp 255 Leu Pro Lys Gly ttg aag ata gag aat gtc Leu 270 Lys He Glu Asn Val 275 aca gcc age aat ttc ttg Thr Ala Ser Asn Phe 290 Leu gta gaa gag cct cct ege Val Glu Glu Pro 305 Pro Arg age acc gga age aat ggc Ser Thr Gly 320 Ser Asn Gly caa ccc aca ate aag tgg Gin Pro 335 Thr lie Lys Trp l-l fi -a G* G*» ttt get ggt gat gtt Pro 350 Phe Ala Gly Asp Val 355 Gtt caa cca aat cat act Leu Gin Pro Asn His 370 Thr cat gga act ate ett gcc His Gly Thr He 385 Leu Ala cca ttg ata caa acc aaa Pro Leu He 400 Gin Thr Lys tac agt get ttc tta cat Tyr Ser 415 Ala Phe Leu His gtg tcc tgg cag aag gtg aca gaa att ggt 868

Thr Glu He Gly ctg ctg ttg cct 916

Leu Leu Leu Pro 215 etc aaa ggg gaa 964

Leu Lys Gly Glu 230 act cca cag gtt 1012

Thr Pro Gin Val 245 aga gaa aca aaa 1060

Arg Giu Thr Lys 2 60 tcc tac cag gac 1108

Ser Tyr Gin Asp gga aca gcc act 1156

Gly Thr Ala Thr 295 tgg aca aag aag 1204

Trp Thr Lys Lys 310 ate ttg tta tgt 1252

He Leu Leu Cys 325 aga gtc aat ggc 1300

Arg Val Asn Gly 340 gtc ttc ccc agg 1348

Val Phe Pro Arg get gtg tac cag 1396

Ala Val Tyr Gin 375 aat gcc aat att 1444

Asn Ala Asn He 390 gat gga gaa aat 1492

Asp Gly Glu Asn 405 tgc gag ttc ttt 1540

Cys Glu Phe Phe 420 gaa gaa gtg aaa 1588 394

Ala Ser 425 Pro Glu Ala Val Val 430 Ser Trp Gin Lys Val 435 Glu Glu Val Lys ccc ctg gag ggc agg egg tat cat ate tat gaa aat ggc aca ttg cag 1636 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 4 4 0 4 4 5 450 455 ate aac aga acc acc gaa gaa gat get ggg tet tac tea tgt tgg gta 1684 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 460 465 470 gaa aat get ata gga aaa act gca gtc aca gee aat ttg gat att aga 1732 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 475 480 485 aat get aca aaa ett aga gtt tet cct aag aat cct cgt ate ccc aaa 1780 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 490 495 500 ttg cat atg ett gaa tta cat tgt gaa age aaa tgt gac tea cat ttg 1828 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 505 510 515 aaa cac agt ttg aag ttg tcc tgg agt aaa gat gga gaa gee ttt gaa 1876 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Al a Phe Glu 520 525 530 535 att aat ggc aca gaa gat ggc agg ata att att gat gga get aat ttg 1924 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 540 545 550 acc ata tet aat gta act tta gag gac caa ggt att tac tgc tgt tea 1972 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 555 560 5 6 5 get cat act get eta gac agt get gee gat ata act caa gta act gtt 2020 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 570 575 580 ett gat gtt ccg gat cca cca gaa aac ett cac ttg tet gaa aga cag 2068 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 585 590 595 aac agg agt gtt egg ctg acc tgg gaa get gga get gac cac aac age 2116 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 600 605 610 615 aat att age gag tat att gtt gaa ttt gaa gga aac aaa gaa gag cct 2164 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 620 625 630 gga agg tgg gag gaa ctg acc aga gtc caa gga aag aaa acc aca gtt 2212 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 635 640 645 ate tta cct ttg get cca ttt gtg aga tac cag ttc agg gtc ata gee 2260 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 650 655 660 gtg aac gaa gta ggg aga agt cag cct age cag ccg tea gac cat cat 2308 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 665 670 675 395 gaa Glu 680 aca Thr cca Pro cca Pro gca Ala get Ala 685 cca Pro gat Asp agg Arg aat Asn cca Pro 690 caa Gin aac Asn ata He agg Arg gtt Val 695 2356 caa gcc tct caa ccc aag gaa atg att ata aag tgg gag cct ttg aaa 2404 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 700 705 710 tcc atg gag cag aat gga cca ggc eta gag tac aga gtg acc tgg aag 2452 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 715 720 725 cca cag gga gcc cca gtg gag tgg gaa gaa gaa aca gtc aca aac cac 2500 Pro Gin Gly Al a Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 730 735 740 aca ttg egg gtg atg aeg cct get gtc tat gcc cct tat gat gtc aag 2548 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 745 750 755 gtc cag get ate aat caa eta gga tct ggg cct gac cct cag tea gtg 2596 Val Gin Ala lie Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 760 765 770 775 act etc tat tct gga gaa gac tat cct gat aca get cca gtg ate cat 2644 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 780 785 790 ggg gtg gac gtt ata aac agt aca tta gtt aaa gtt acc tgg tea aca 2692 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 795 800 805 gtt cca aag gac aga gta cat gga cgt ctg aaa ggc tat cag ata aat 2740 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 810 815 820 tgg tgg aaa aca aaa agt ctg ttg gat gga aga aca cat ccc aaa gaa 2788 Trp Tirp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 825 830 835 gtg aac att eta aga ttt tea gga caa aga aac tct gga atg gtt cct 2836 Val Asn lie Leu Arg Phe Ser Gly Gin Arg Asn Ser ciy Met Val Pro 840 845 850 855 tcc tta gat gcc ttt agt gaa ttt cat tta aca gtc tta gcc tat aac 2884 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 860 865 870 tct aaa gga get ggt cct gaa agt gag cct tat ata ttt caa aca cca 2932 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr lie Phe Gin Thr Pro 875 880 885 gaa gga gta cct gaa cag cca act ttt eta aag gtc ate aaa gtt gat 2980 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 890 895 900 aaa gac act gcc act tta tct tgg gga eta cct aag aaa tta aat gga 3028 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 905 910 915 aac tta act ggc tat ett ttg caa tat cag ata ata aat gac acc tac 3076 396 3124

Asn Leu 920 gag att Glu lie

Thr Gly gga gaa Gly Glu age tgg Ser Trp ttg agg Leu Arg age tcc Ser Ser 985 gta aat Val Asn 1000 get gaa Ala Glu cac etc His Leu 955 get tgc Ala Cys 970 acc tta Thr Leu ett act Leu Thr cat ata His lie age att Ser He tta tat Leu Tyr geg att Ala He 1065 agg aat Arg Asn 1080 cca gac Pro Asp agt gac Ser Asp agg gat Arg Asp

Tyr Leu 925 tta aat Leu Asn 940 tea aac Ser Asn act tea Thr Ser gga gaa Gly Glu ttt caa Phe Gin 1035 gat gac Asp Asp 1050 get ett Ala Leu aga ggt Arg Gly cca gaa Pro Glu gag gga Glu Gly 1145 tac get

Tyr Ala 1160

Leu Gin gat att Asp He ctg aat Leu Asn

Tyr Gin caa aag Gin Lys 1005 gtt ege Val Arg 1020 gat gta Asp Val cag ggc Gin Gly 9 7 5 ggg agt Gly Ser 990 act cac Thr His aac att

Asn lie 945 gca act Ala Thr 960 tgt gga Cys Gly lie He 930 aca act

Thr Thr acc aag Thr Lys aaa ccg Lys Pro

Asn Asp cca tea

Pro Ser ate tec He Ser etc aca Leu Thr agt gat Ser Asp 1115 atg cag Met Gin 1130 gac cat Asp His gga tct Gly Ser aaa ggt Lys Gly cca ata Pro He eta atg Leu Met att gag He Glu gga aag Gly Lys 1085 att cag lie Gin 1100 gaa aag Glu Lys act caa Thr Gin 1055 eta eta Leu Leu 1070 tac tea Tyr Ser act aag Thr Lys 1025 aca aga Thr Arg 1040 ggc tgg Gly Trp ate ggg He Gly 995 gag gta Glu Val 1010 aat tgg

Asn Trp ggg aga Gly Arg ttt att Phe He tta tta Leu Leu gtt aaa Val Lys cct act Pro Thr ggt etc Gly Leu tea gta Ser Val cct etc Pro Leu aag gag Lys Glu 1165 gaa agt Glu Ser 1135 ttc agt Phe Ser 1150 aag gga Lys Gly aaa gat Lys Asp 1105 aaa gga Lys Gly 1120 get gac Ala Asp act gtt Thr Val 1075 gaa aag Glu Lys 1090 gaa acc Glu Thr age ett Ser Leu age tta Ser Leu gaa gat Glu Asp tct gtt Ser Val tac aaa Tyr Lys 965 ate aeg He Thr 980 aag ata Lys He ttt gag Phe Glu ggc gat

Gly Asp

Thr Tyr 935 aag ccc

Lys Pro 950 ttc tac Phe Tyr gag gaa Glu Glu tea gga Ser Gly gaa tat Glu Tyr 1045 gga ctg Gly Leu 1060 tgc ttt Cys Phe gaa gat Glu Asp ttt ggt Phe Gly gga tea Gly Ser 1155 gaa age Glu Ser 1170 3172 3220 3268 ccg gga Pro Gly 1015 aac gat

Asn Asp 1030 get ggt Ala Gly atg tgt Met Cys gtg aag Val Lys egg tcc Arg Ser 1125 gtc gaa Val Glu 1140 ttt att Phe He ttg cat Leu His 1095 gaa tac Glu Tyr 1110 ett aat Leu Asn tac gga Tyr Gly ggt gcc Gly Ala 3316 3364 3412 3460 3508 3556 3604 3652 3700 3748 aat gga Asn Gly 3796 agt tct

Ser Ser 1175 397 3843 aca gca act ttt ccc ett egg gca taa acacaacata tgtaagcaac Thr Ala Thr Phe Pro Leu Arg Ala * 1180 gctactggtt caccccaacc ttccatattt atctgttcaa aggagcaaga actttcatat aggaatagaa acatgctggc cgaagatttc atccagaagt caacatcctg caattatgtt gaaaagagta gtactttctt caaaatataa aatgccaagc acttcaggcc tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag atggtcatat ttaaacagaa gtatacgttt ttcagtttca acatgaattt ttttatttct gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt ttcttggact aaattcaact gcatggaagc ggtggtcaga aggttgtttt atacgagaac aggcagaaag tgcccattgt tcaggattct aatagctaca tctacttaat atcttcattt ctaaattgac tgcttttacc tttttctcat gtttatataa tggtatgctt gcatatattt catgaataca ttgtacatat tatgttaata tttacacaat ttaaaatata gatgtgtttt attttgaagt gagaaaatga acattaacag gcatgtttgt acagctagaa tatattagta agatactgtt tttcgtcatt ccagagctac aactaataac acgaggttcc aaagctgaag actttgtata aagtatttgg gttttgttct tgtattgctt tctttcaaca gtttcaaaat aaaatatcat acaaatattg agggaaatgt tttcatattt ttcaaaatag gtttttattg ttgaatgtac atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat gatgactatg etttgetate attgttacct ttcctcaata ctatttggca actactggga ctcttcagca caaaaggaat agatetatga ttgaccctga ttttaattgt gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatetaa gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaaeggag tccacggcgt gcaatggtaa ttataaattg gtgatgcttg tttgeaaatt gcccactcgt gataagteaa cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta ataataatet cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt gaaaatgata aaagetaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt atetgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgaettgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt etateggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga gataagetaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt gttcctatag tgaaataagt 3903 3963 4023 4083 4143 4203 4263 4323 4383 4443 4503 4563 4623 4683 4743 4803 4863 4923 4983 5043 5103 5163 5223 5283 5343 5403 5463 5523 5583 5643 5703 5763 5823 5883 5943 6003 6063 6123 6183 6243 6303 6363 6423 6483 6543 6603 6663 6723 6783 6843 6903 6963 7023 7083 7143 7203 7263 398 agggttcagc caaagctttc tttgttttgt accttaaatt gttcgattac gtcatcaaaa 7323 gagatgaaag gtatgtagaa caggttcacg tgattacctt tttcttttgg cttggattaa 7383 tattcatagt agaactttat aaaacgtgtt tgtattgtag gtggtgtttg tattatgctt 7443 atgactatgt atggtttgaa aatattttca ttatacatga aattcaactt tccaaataaa 7503 agttctactt catgtaatcc aaaa 7527 <2 10> 13 <2 11> 1183 <2 12> PRT <2 13> Homo <4 00> 13

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 X? liC Asp r> 1 ,, Tyr Phe /-, 1 — U±H He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Al a Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 245 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Glu 290 295 300 Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly 305 310 315 320 Ser Δ.3 n Gly He Leu Leu Cys Glu Ala Glu /-,1,. uiy /-,1,, kj-L U Pro Gin Pro Thr 325 330 335 lie Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala 340 345 350 Gly Asp Val Val Phe Pro Arg Glu lie Ser Phe Thr Asn Leu Gin Pro 355 360 365 Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr 370 375 380 lie Leu Ala Asn Ala Asn He Asp Val Val Asp Val Arg Pro Leu He 385 390 395 400 399

Gin Thr Lys Asp Gly 405 Glu Asn Tyr Ala Thr 410 Val Val Gly Tyr Ser 415 Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp 420 425 430 Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He 435 440 445 Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala 450 455 460 Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala lie Gly Lys Thr Ala Val 465 470 475 480 Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro 485 490 495 Lys Asn Pro Arg He Pro Lys Leu His Met Leu Glu Leu His Cys Glu 500 505 510 Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser 515 520 525 Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He 530 535 540 He He Asp Gly Ala Asn Leu Thr He Ser Asn Val Thr Leu Giu Asp 545 550 555 560 Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala 565 570 575 Asp lie Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn 580 585 590 Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu 595 600 605 Ala Gly Al a Asp His Asn Ser Asn He Ser Glu Tyr He Val Glu Phe 610 615 620 Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val 625 630 635 640 Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg 645 650 655 Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro 660 665 670 Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg 675 680 685 Asn Pro Gin Asn lie Arg Val Gin Ala Ser Gin Pro Lys Glu Met He 690 695 700 He Lys Trp Glu PXO Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu 705 710 715 720 Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu 725 730 735 Glu Glu Thr Val Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val 740 745 750 Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser 755 760 765 Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro 770 775 780 Asp Thr Ala Pro Val He His Gly Val Asp Val lie Asn Ser Thr Leu 785 790 795 800 Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg 805 810 815 Leu Lys Gly Tyr Gin Tl o x ±6 Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp 820 825 830 Gly Arg Thr His Pro Lys Glu Val Asn He Leu Arg Phe Ser Gly Gin 835 840 845 Arg Asn Ser Gly Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His 850 855 860 Leu Thr Val Leu Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu 865 870 875 880 Pro Tyr He Phe Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe 885 890 895 400

Leu Lys Val He 900 Lys Val Asp Lys Asp 905 Thr Ala Thr Leu Ser 910 Trp Gly Leu Pro Lys 915 Lys Leu Asn Gly Asn 920 Leu Thr Gly Tyr Leu 925 Leu Gin Tyr Gin He 930 He Asn Asp Thr Tyr 935 Glu He Gly Glu Leu 940 Asn Asp He Asn He Thr 945 Thr Pro Ser Lys 950 Pro Ser Trp His Leu 955 Ser Asn Leu A.S π Ala 960 Thr Thr Lys Tyr Lys 965 Phe Tyr Leu Arg Ala 970 Cys Thr Ser Gin Gly 975 Cys Gly Lys Pro He 980 Thr Glu Glu Ser Ser 985 Thr Leu Gly Glu Gly 990 Ser Lys Gly lie Gly 995 Lys He Ser Gly Val 100C Asn 1 Leu Thr Gin Lys 1005 Thr His Pro He Glu 101C Val 1 Phe Glu Pro Gly 1015 Ala Glu His He Val 102C Arg I Leu Met Thr Lys Asn 1025 Trp Gly Asp Asn 103C Asp I Ser He Phe Gin 1035 Asp Val He Glu Thr 1040 7\ r' i ,» rxx y kJ j_y 7\ IX. »— 2 L y /-> &#906;. u± u 'X'y 27 1045 Ala Gly Leu Tyr Asp 1050 Asp 1 He Ser Thr Gin 1055 Gly Trp Phe He Gly 106C Leu 1 Met cys Ala He 1065 Ala Leu Leu Thr Leu 107C Leu 1 Leu Leu Thr Val 1075 Cys 1 Phe Val Lys Arg 108C Asn 1 Arg Gly Gly Lys 1085 Tyr 1 Ser Val Lys Glu 1090 Lys 1 Glu Asp Leu His 1095 Pro Asp Pro Glu lie HOC Gin 1 Ser Val Lys Asp Glu 1105 Thr Phe Gly Glu me Tyr 1 Ser Asp Ser Asp 1115 Glu Lys Pro Leu Lys 1120 Gly Ser Leu Arg Ser 1125 Leu Asn Arg Asp Met 1130 Gin 1 Pro Thr Glu Ser 1135 Ala Asp Ser Leu Val 114C Glu 1 Tyr Gly Glu Gly 1145 Asp His Gly Leu Phe 115C Ser 1 Glu Asp Gly Ser 1155 Phe He Gly Ala Tyr 1160 Ala 1 Gly Ser Lys Glu 1165 Lys 1 Gly Ser Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1170 1175 1180 <210> 14 <211> 7686

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272).(3982) <400> 14 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ctt tta ctt gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 aga gga eta ate gta tat eta atg ttc etc ctg tta aaa ttc tea aaa 340

Arg Gly Leu lie Val Tyr Leu Met Phe Leu Leu Leu Lys Phe Ser Lys 10 15 20 ata cca He Pro tet

Ser tea gtt caa Ser Val Gin cag gtt Gin Val cca aca ate ata aaa Pro Thr He He Lys 388 gca att gaa

Ala He Glu 401 25 30 35 cag Gin 40 tea Ser aaa Lys gtc Val caa Gin gtt Val 45 gcc Ala ttt Phe ccc Pro ttc Phe gat Asp 50 gag Glu tat Tyr ttt Phe caa Gin att He 55 436 gaa tgt gaa get aaa gga aat cca gaa cca aca ttt teg tgg act aag 484 Glu Cys Glu Ala Lys Gly Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys 60 65 7 0 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532 Asp ciy Asn Pro Phe Tyr Phe Thr Asp His Arg He He Pro Ser Asn 75 80 85 aat tea gga aca ttc agg ate cca aac gag ggg cac ata tct cac ttt 580 Asn Ser Gly Thr Phe Arg lie Pro Asn Glu Gly His He Ser His Phe 90 95 100 caa ggg aaa tac ege tgc ttt get tea aat aaa ctg gga ate get atg 628 Gin Gly Lys Tyr Arg cys Phe Al a Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca agt gtt cca aaa etc cca aaa 676 Ser Glu Glu He Glu Phe He Val Pro Ser Val Pro Lys Leu Pro Lys 120 125 130 135 gaa aaa att gac cct ett gaa gtg gag gag gga gat cca att gtc etc 724 Glu Lys He Asp Pro Leu Glu Val Glu Glu Gly Asp Pro He Val Leu 140 145 150 cca tgc aat cct ccc aaa ggc etc cca cct tta cac att tat tgg atg 772 Pro Cys Asn Pro Pro Lys Gly Leu Pro Pro Leu His He Tyr Trp Met 155 160 165 aat att gaa tta gaa cac ate gaa caa gat gaa aga gta tac atg age 820 Asn lie Glu Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser 170 175 180 caa aag gga gat eta tac ttc gca S&amp;amp;C gtg gaa gaa aag gac agt ege 868 Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg 185 190 195 aat gac tac tgt tgc ttt get gca ttt cca aga tta agg act att gta 916 Asn Asp Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr lie Val 200 205 210 215 cag aaa atg cca atg aaa eta aca gtt aac agt tta aag cat get aat 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn 220 225 230 gac tea agt tea tcc aca gaa att ggt tcc aag gca aat tcc ate aag 1012 Asp Ser Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser lie Lys 235 240 245 caa aga aaa ccc aaa ctg ctg ttg cct ccc act gag agt ggc agt gag 1060 Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 250 255 260 tct tea att acc ate etc aaa ggg gaa ate ttg ctg ett gag tgt ttt 1108 Ser Ser He Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe 265 270 275 402 1156 get gaa Ala Glu 280 gac tta Asp Leu aag ata Lys lie gcc age Ala Ser gaa gat Glu Asp 345 ege tgg Arg Trp 360 ggc ate Gly He tgg aga Trp Arg gtt gtc Val Val act get Thr Ala 425 gcc aat Ala Asn 440 aaa gat Lys Asp cat tgc His Cys ytg gaa Val Glu aat ggc Asn Gly 505 tac tea

Tyr Ser ggc ttg Gly Leu cca aag Pro Lys gag aat Glu Asn 315 aat ttc Asn Phe 330 aac ate Asn lie aca aag Thr Lys ttg tta Leu Leu gtc aat Val Asn 395 ttc ccc Phe Pro 410 gtg tac Val Tyr gcc aat Ala Asn gga gaa Gly Glu gag ttc Glu Phe 475 gaa gtg Glu Val 490 aca ttg Thr Leu tgt tgg Cys Trp cca act Pro Thr 285 ggg aga Gly Arg 300 gtc tcc Val Ser ttg gga Leu Gly tet cat Ser His aag cct Lys Pro 365 tgt gag Cys Glu 380 ggc tcc Gly Ser agg gaa Arg Glu cag tgt Gin Cys att gat He Asp 445 aat tac Asn Tyr 460 ttt get Phe Ala aaa ccc Lys Pro cag ate Gin He gta gaa Val Glu cca cag Pro Gin gaa aca Glu Thr tac cag Tyr Gin aca gcc Thr Ala 335 gag etc Glu Leu 350 cag agt Gin Ser get gaa Ala Glu cca gtt Pro Val ate agt He Ser 415 gaa gcc Glu Ala 430 gtt gtg Val Val get aca Ala Thr tea cct Ser Pro ctg gag Leu Glu 495 aac aga Asn Arg 510 aat get Asn Ala gtt gat Val Asp aa.a qa.&amp;amp; Lys Glu 305 gac aaa Asp Lys 320 act cac Thr His ttc act Phe Thr get gtg Ala Val gga gaa Gly Glu 385 gac aat Asp Asn 400 ttt acc Phe Thr tea aat Ser Asn gat gtc Asp Val gtg gtt Val Val 465 gag gca Glu Ala 480 ggc agg Gly Arg acc acc Thr Thr ata gga He Gly tgg aac Trp Asn 290 aat tat Asn Tyr gga aat Gly Asn gat ttt Asp Phe tta cat Leu His 355 tat age Tyr Ser 370 cct caa Pro Gin cat cca His Pro aac ctt Asn Leu gtc cat Val His 435 cgt cca Arg Pro 450 ggg tac Gly Tyr gtc gtg Val Val egg tat Arg Tyr gaa gaa Glu Glu 515 aaa act Lys Thr aaa att Lys lie qcjo ctcicj Gly Lys tat ege Tyr Arg 325 cac gtt His Val 340 cca gag Pro Glu acc gga Thr Gly ccc aca Pro Thr ttt get Phe Ala 405 caa cca Gin Pro 420 gga act Gly Thr ttg ata Leu He agt get Ser Ala tcc tgg Ser Trp 485 cat ate His He 500 gat get Asp Ala gca gtc Ala Val ggt ggt Gly Gly 295 act ttg Thr Leu 310 tgc aca Cys Thr 1204 1252 ata gta He Val 1300 cct cct Pro Pro 1348 age aat Ser Asn 375 ate aag He Lys 390 ggt gat Gly Asp 1396 1444 1492 aat cat Asn His 1540 ate ctt He Leu 1588 caa acc Gin Thr 455 ttc tta Phe Leu 470 cag aag Gin Lys 1636 1684 1732 tat gaa Tyr Glu 1780 ggg tet Gly Ser 1828 1876 aca gcc

Thr Ala 403 520 525 530 535 aat Asn ttg Leu gat Asp att He aga Arg 540 aat Asn get Ala aca Thr aaa Lys ett Leu 545 aga Arg gtt Val tet Ser cct Pro aag Lys 550 aat Asn 1924 cct cgt ate ccc aaa ttg cat atg ett y as. 4- j___ U UCJ. cat tgt ga&amp; age aaa 197 2 Pro Arg He Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys 5 55 560 565 tgt gac tea cat ttg aaa cac agt ttg aag ttg tcc tgg agt ci ci gat 2020 Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp 570 575 580 gga gaa gcc ttt gaa att aat ggc aca gaa gat ggc agg ata att att 2068 Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg lie He He 585 590 595 gat yya get aat ttg acc ata tet aat gta act tta gag gac caa ggt 2116 Asp Gly Ala Asn Leu Thr lie Ser Asn Val Thr Leu Glu Asp Gin Gly 600 605 610 615 att tac tgc tgt tea get cat act get eta gac agt get gcc gat ata 2164 lie Tyr Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie 620 625 630 act cas gta act gtt ett gat gtt ccg gat cca cca gaa aac ett cac 2212 Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His 635 640 645 ttg tet gaa aga cag aac agg agt gtt egg ctg acc tgg gaa get gga 2260 Leu Ser Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly 650 655 660 get gac cac aac age aat att age gag tat att gtt gaa ttt gaa gga 2308 Ala Asp His Asn Ser Asn He Ser Glu Tyr He Val Glu Phe Glu Gly 665 670 675 aac aaa gaa gag cct gga agg tgg gag gaa ctg acc aga gtc caa gga 2356 Asn Lys Glu Giu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly 680 685 690 695 aag aaa acc aca gtt ate tta cct ttg get cca ttt gtg aga tac cag 2404 Lys Lys Thr Thr Val lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin 700 705 710 ttc agg gtc ata gcc gtg aac gaa gta ggg aga agt cag cct age cag 2452 Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin 715 720 725 ccg tea gac cat cat gaa aca cca cca gca get cca gat agg aat cca 2500 Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro 730 7 3 5 740 caa aac ata agg gtt caa gcc tet caa ccc aag gaa atg att ata aag 2 54 8 Gin Asn He Arg Val Gin Ala Ser Gin Pro Lys Glu Met He He Lys 745 750 755 tgg gag cct ttg aaa tcc atg gag cag aat gga cca ggc eta gag tac 2596 Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr 760 765 770 775 404 aga Arg gtg Val acc Thr tgg Trp aag Lys 780 cca Pro cag Gin gga Gly gcc Ala cca Pro 785 gtg Val gag Glu tgg Trp gaa Glu gaa Glu 790 gaa Glu 2644 aca gtc aca aac cac aca ttg egg gtg atg aeg cct get gtc tat gcc 2692 Thr Val Thr Asn 795 His Thr Leu Ar c$ Val 800 Met Thr Pro Ala Val 805 Tyr Ala cct tat gat gtc aag gtc cag get ate aat caa eta gga tct ggg cct 2740 Pro Tyr Asp 810 Val Lys Val Gin Ala 815 He Asn Gin Leu Gly 820 Ser Gly Pro gac cct cag tea gtg act etc tat tct gga gaa gac tat cct gat aca 2788 Asp Pro 825 Gin Ser Val Thr Leu 830 Tyr Ser Gly Glu Asp 835 Tyr Pro Asp Thr get cca gtg ate cat ggg gtg gac gtt ata aac agt aca tta gtt aaa 2836 Ala 840 Pro Val He His Gly 845 Val Asp Val lie Asn n c O &#9633; U Ser Thr Leu Val Lys 855 gtt acc tgg tea aca gtt cca aag gac aga gta cat gga cgt ctg aaa 2884 Val Thr Trp Ser Thr 860 Val Pro Lys Asp Arg 865 Val His Gly Arg Leu 870 Lys ggc tat cag ata aat tgg tgg aaa aca aaa agt ctg ttg gat gga aga 2932 Gly Tyr Gin He 875 Asn Trp Trp Lys Thr 880 Lys Ser Leu Leu Asp 885 Gly Arg aca cat ccc aaa gaa gtg aac att eta aga ttt tea gga caa aga aac 2980 Thr His Pro 890 Lys Glu Val Asn He 895 Leu Arg Phe Ser Gly 900 Gin Arg Asn tct gga atg gtt cct tcc tta gat gcc ttt agt gaa ttt cat tta aca 3028 Ser Gly 905 Met Val Pro Ser Leu 910 As p Ala Phe Ser Glu 915 Phe His Leu Thr gtc tta gcc tat aac tct 999 gga get ggt cct gaa agt gag cct tat 3076 Val 920 Leu Ala Tyr Asn Ser 925 Lys Gly Ala Gly Pro 93 0 Glu Ser Glu Pro Tyr 935 ata ttt caa aca cca gaa gga gta cct gaa cag cca act ttt eta aag 3124 lie Phe Gin Thr Pro 940 Glu Gly Val Pro Glu 945 Gin Pro Thr Phe Leu 950 Lys gtc ate aaa gtt gat aaa gac act gcc act tta tct tgg gga eta cct 3172 Val He Lys Val 955 Asp Lys Asp Thr Ala 960 Thr Leu Ser Trp dy 965 Leu Pro aag aaa tta aat gga aac tta act ggc tat ett ttg caa tat cag ata 3220 Lys Lys Leu 970 Asn Gly Asn Leu Thr 975 Gly Tyr Leu Leu Gin 980 Tyr Gin He ata aat rt λ p acc gag att gga gaa tta aat gat att aac att aca η n t- η JZOO He Asn 985 Asp Thr Tyr Glu He 99C Gly 1 Glu Leu Asn Asp 995 He Asn He Thr act cca tea aag ccc age tgg cac etc tea aac ctg aat gca act acc 3316 Thr 1000 Pro Ser Lys Pro Ser 1005 Trp His Leu Ser Asn 101C Leu I Asn Ala Thr Thr 1015 aag tac aaa ttc tac ttg agg get tgc act tea cag ggc tgt gga aaa 3364 Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys 405 1020 1025 1030 ccg Pro ate lie aeg Thr gag gaa Glu Glu 1035 age Ser tcc Ser acc Thr tta gga Leu Gly 1040 gaa Glu ggg Giy agt Ser aaa Lys 1045 ggt Gly ate He 3412 ggg aag ata tea gga gta aat ett act caa aag act cac cca ata gag 3460 Gly Lys He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro lie Glu 1050 1055 1060 gta ttt gag ccg gga get gaa cat ata gtt ege eta atg act aag aat 3508 Val Phe Glu Pro Gly Ala Glu His lie Val Arg Leu Met Thr Lys Asn 1065 1070 1075 tgg ggc gat aac gat age att ttt caa gat gta att gag aca aga ggg 3556 Trp Gly Asp Asn Asp Ser He Phe Gin Asp Val He Glu Thr Arg Gly 1080 1085 1090 1095 a rra rr a a j do. t st get uyt 4- J--- LOG. tat gat gac ate tec act caa ggc tgg ttt 3 604 Arg Glu Tyr Ala Gly Leu Tyr Asp Asp lie Ser Thr Gin Gly Trp Phe 1100 1105 1110 att gga ctg atg tgt geg att get ett etc aca eta eta tta tta act 3652 lie Gly Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr 1115 1120 1125 gtt tgc ttt gtg aag agg aat aga ggt gga aag tac tea gtt aaa gaa 3700 Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 1130 1135 1140 aag gaa gat ttg cat cca gac cca gaa att cag tea gta aaa gat gaa 3748 Lys Glu Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1145 1150 1155 acc ttt ggt gaa tac agt gac agt gat gaa aag cct etc aaa gga age 3796 Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser 1160 1165 1170 1175 Gtt egg tcc ett aat agg gat atg cag cct act gaa agt get gac age 3844 Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser 1180 1185 1190 tta gtc tac gga gag gga gac cat ggt etc ttc agt gaa gat gga 3892 Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly 1195 1200 1205 tea ttt att ggt gcc tac get gga tct aag gag aag gga tct gtt gaa 3940 Ser Phe He Gly Ala Tyr Al a Gly Ser Lys Glu Lys Gly Ser Val Glu 1210 1215 1220 age aat gga agt tct aca gca act ttt ccc ett egg gca taa 3982 Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala * 1225 1230 1235 acacaacata tgtaagcaac gctactggtt caccccaacc ttccatattt atctgttcaa 4042 aggagcaaga actttcatat aggaatagaa acatgctggc cgaagatttc atccagaagt 4102 caacatcctg caattatgtt gaaaagagta gtactttctt caaaatataa aatgccaagc 4162 acttcaggcc tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa aacacaaaac 4222 aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt atattccata 4282 tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt gggtttttct 4342 ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc ttcactacag 4402 gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg aaagtcttat 4462 406 taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta ctagcaaaag 4522 tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag atggtcatat 4582 ttaaacagaa gtatacgttt ttcagtttca acatgaattt ttttatttct gtcagttatg 4642 acatccacga gcatcacttt ttgtgtctgt tttttttttt ttcttggact aaattcaact 4702 gcatggaagc ggtggtcaga aggttgtttt atacgagaac aggcagaaag tgcccattgt 4762 tcaggattct aatagctaca tctacttaat atcttcattt ctaaattgac tgcttttacc 4822 tttttctcat gtttatataa tggtatgctt gcatatattt catgaataca ttgtacatat 4882 tatgttaata tttacacaat ttaaaatata gatgtgtttt attttgaagt gagaaaatga 4942 acattaacag gcatgtttgt acagctagaa tatattagta agatactgtt tttcgtcatt 5002 ccagagctac aactaataac acgaggttcc aaagctgaag actttgtata aagtatttgg 5062 gttttgttct tgtattgctt tctttcaaca gtttcaaaat aaaatatcat acaaatattg 5122 agggaaatgt tttcatattt ttcaaaatag gtttttattg ttgaatgtac atctacccca 5182 gcccctcaaa agaaaaactg tttacataga aattcctaca catacgtttg cgtatatgtt 5242 attttaaaca tctttgtggt gagaattttt tccccgatat tctccttctg tcaaagtcag 5302 aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat 5362 gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc 5422 gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg 5482 aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca 5542 acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat 5602 agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc 5662 agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc 5722 tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt 5782 gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc 5842 taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg 5902 tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt 5962 ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta 6022 gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat 6082 actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat 6142 tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat 6202 gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca actactggga 6262 ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt gaaattatat 6322 gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa gtcggttaaa 6382 atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt gcaatggtaa 6442 ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa cagccaatat 6502 ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat 6562 tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga 6622 actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca 6682 taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta 6742 ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt 6802 gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt 6862 atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt 6922 tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgacttgt 6982 acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag 7042 tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt 7102 ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac 7162 aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga 7222 gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa 7282 cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa 7342 caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt 7402 gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt accttaaatt 7462 gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg tgattacctt 7522 tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt tgtattgtag 7582 gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca ttatacatga 7642 aattcaactt tccaaataaa agttctactt catgtaatcc aaaa 7686 <210> 15 <211> 1236 <212> PRT <213> Homo sapians <400> 15 Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 407 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 4 5 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 5 5 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 7 0 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Asp Asn He Ser His Glu Leu Phe 340 345 350 Thr Leu His Pro Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala 355 360 365 Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly 370 375 380 Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp 385 390 395 400 Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe 405 410 415 Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser 420 425 430 Asn Val His Gly Thr He Leu Ala Asn Ala Asn He Asp Val Val Asp 435 440 445 Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val 450 455 460 Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu 465 470 475 480 Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly 485 490 495 Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr 408 500 505 510 Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He 515 520 525 Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys 530 535 540 Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys Leu His Met Leu 545 550 555 560 Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu 565 570 575 Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr 580 585 590 Glu Asp Gly Arg He lie He Asp Gly Ala Asn Leu Thr He Ser Asn 595 600 605 Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala 610 615 620 Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val Leu Asp Val Pro 625 630 635 640 Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val 645 650 655 Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn lie Ser Glu 660 665 670 Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu 675 680 685 Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu 690 695 700 Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val 705 710 715 720 Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro 725 730 735 Ala Ala Pro Asp Arg Asn Pro Gin Asn He Ar g Val Gin Ala Ser Gin 740 745 750 Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin 755 760 765 Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala 770 775 780 Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val 785 790 795 800 Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Al a He 805 810 815 Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser 820 825 830 Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His Gly Val Asp Val 835 840 845 lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp 850 855 860 Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn Trp Trp Lys Thr 865 870 875 880 Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu Val Asn He Leu 885 890 895 Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro Ser Leu Asp Ala 900 905 910 Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn Ser Lys Gly Ala 915 920 925 Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro Glu Gly Val Pro 930 935 940 Glu Gin Pro Thr Phe Leu Lys Val lie Lys Val Asp Lys Asp Thr Ala 945 950 955 960 Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly Asn Leu Thr Gly 965 970 975 Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr Glu lie Gly Glu 980 985 990 Leu Asn Asp lie Asn He Thr Thr Pro Ser Lys Pro Ser Trp His Leu 409 995 1000 1005

Ser Asn Leu Asn 1010 Ala Thr Thr Lys 1015 Tyr Lys Phe Tyr Leu Arg Ala Cys 1020 Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu Ser Ser Thr Leu 1025 1030 1035 > 1040 Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly Val Asn Leu Thr 1045 1050 1055 Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly Ala Glu His He 1060 1065 1070 Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp Ser He Phe Gin 1075 1080 1085 Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly Leu Tyr Asp Asp 1090 1095 1100 lie Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys Ala He Ala Leu 1105 1110 1115 » 1120 Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly 1125 1130 1135 Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His Pro Asp Pro Glu η ι λ r\ X X H: U 1145 1150 He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr Ser Asp Ser Asp 1155 1160 1165 Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin 1170 1175 1180 Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His 1185 1190 1195 . 1200 Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala Tyr Ala Gly Ser 1205 1210 1215 Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe 1220 1225 1230 Pro Leu Arg Ala 1235 <210> 16 <211> 7563

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272).(3859) <400> 16 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ctt tta ctt gga 292

Met Glu Pro Leu Leu Leu Gly 1 5 aga gga eta ate gta tat eta atg ttc etc ctg tta aaa ttc tea aaa Arg Gly Leu 10 He u-, i ναι Leu Met 15 Phe Leu Leu Leu Lys 20 Phe Ser Lys gca att gaa ata cca tet tea gtt caa cag gtt cca aca ate ata aaa Ala He 25 Glu He Pro Ser Ser 30 Val Gin Gin Val Pro 35 Thr He He Lys cag tea a ci a gtc caa gtt gcc ttt ccc ttc gat gag tat ttt caa att Gin 40 Ser Lys Val Gin Val 45 Ala Phe Pro Phe Asp 50 Glu Tyr Phe Gin He 55 410 gaa Glu tgt Cys gaa Glu get Ala aaa Lys 60 gga Gly aat Asn cca Pro gaa Glu cca Pro 65 aca Thr ttt Phe teg Ser tgg Trp act Thr 70 aag Lys 484 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532 Asp Gly Asn Pro Phe Tyr Phe Thr Asp His Arg He He Pro Ser Asn 75 80 85 aat tea gga aca ttc agg ate cca aac gag ggg cac ata tct cac ttt 580 Asn Ser Gly Thr Phe Arg He Pro Asn Glu Gly His He Ser His Phe 90 95 100 caa ggg aaa tac ege tgc ttt get tea aat aaa ctg gga ate get atg 628 Gin Gly Lys Tyr Arg Cys Phe Ala Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca aaa tta gaa cac ate gaa caa 676 Ser 1. UXU Glu He Glu Phe He Val Pro Lys Leu Glu His He Glu Gin 120 12 5 130 135 gat gaa aga gta tac atg age caa aag gga gat eta tac ttc gca aac 724 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 140 145 150 gtg gaa gaa aag gac agt ege aat gac tac tgt tgc ttt get gca ttt 772 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr cys Cys Phe Ala Ala Phe 155 160 165 cca aga tta agg act att gta cag aaa atg cca atg aaa eta aca gtt 820 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 170 175 180 aac agt tta aag cat get aat gac tea agt tea tcc aca gaa att ggt 868 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 185 190 195 tcc aag gca aat tcc ate aag caa aga aaa ccc aaa ctg ctg ttg cct 916 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Lgu Leu Leu Pro 200 205 210 215 ccc act gag agt ggc agt gag tct tea att acc ate etc aaa ggg gaa 964 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr lie Leu Lys Gly Glu 220 225 230 ate ttg ctg ett gag tgt ttt get gaa ggc ttg cca act cca cag gtt 1012 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 235 240 245 gat tgg aac aaa att ggt ggt gac tta cca aag ggg aga gaa aca aaa 1060 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 250 255 260 gaa aat tat ggc aag act ttg aag ata gag aat gtc tcc tac cag gac 1108 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 265 270 275 aaa gga aat tat ege tgc aca gcc age aat ttc ttg gga aca gcc act 1156 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 280 285 290 295 cac gat ttt cac gtt ata gta gaa gat aac ate tct cat gag etc ttc 1204 411

His Asp Phe His Val 300 He Val Glu Asp Asn 305 He Ser His Glu Leu 310 Phe act tta cat cca gag cct cct ege tgg aca aag aag cct cag agt get 1252 Thr Leu His Pro Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala 315 320 325 gtg tat age acc gga age aat ggc ate ttg tta tgt gag get gaa gga 1300 Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly 330 335 340 gaa cct caa ccc aca ate aag tgg aga gtc aat ggc tcc cca gtt gac 1348 Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly Ser Pro Val Asp 345 350 355 aat cat cca ttt get ggt gat gtt gtc ttc ccc agg gaa ate agt ttt 1396 Asn His Pro Phe Al a Gly Asp Val Val Phe Pro Arg Glu He Ser Phe 360 365 370 375 acc aac ett caa cca aat cat act get gtg tac cag tgt gaa gcc tea 1444 Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser 380 385 390 aat gtc cat gga act ate ett gcc aat gcc aat att gat gtt gtg gat 1492 Asn Val His Gly Thr He Leu Ala Asn Ala Asn He Asp Val Val Asp 395 400 405 gtc cgt cca ttg ata caa acc aaa gat gga gaa aat tac get aca gtg 1540 Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val 410 415 420 gtt ggg tac agt get ttc tta cat tgc gag ttc ttt get tea cct gag 1588 Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu 425 430 435 gca gtc gtg tcc tgg cag aag gtg gaa gaa gtg aaa ccc ctg gag ggc 1636 Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly 440 445 450 455 agg egg tat cat ate tat gaa aat ggc aca ttg cag ate aac aga acc 1684 Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr 460 465 470 acc gaa gaa gat get ggg tct tac tea tgt tgg gta gaa aat get ata 1732 Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He 475 480 485 gga aaa act gca gtc aca gcc aat ttg gat att aga aat get aca aaa 1780 Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys 490 495 500 ett aga gtt tct cct aag aat cct cgt ate ccc aaa ttg cat atg ett 1828 T Λ-Κ,·, xjc: ui Ar g Val Ser Pro Lys Asn Pro Arg He Pro Lys Leu His Met Leu 505 510 515 gaa tta cat tgt gaa age aaa tgt gac tea cat ttg aaa cac agt ttg 1876 Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu 520 525 530 535 aag ttg tcc tgg agt aaa gat gga gaa gcc ttt gaa att aat ggc aca 1924 Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu lie Asn Gly Thr 540 545 550 412 gaa Glu gat Asp ggc Gly agg Arg 555 ata lie att He att He gat Asp gga Gly 560 get Ala aat Asn ttg Leu acc Thr ata He 565 tet Ser aat Asn 1972 gta act tta gag gac caa ggt att tac tgc tgt tea get cat act get 2020 Val Till? Leu Glu Asp Gin rl tt He Tyr Cys Cys Ser Ala His Thr Ala 570 575 580 eta gac agt get gcc gat ata act caa gta act gtt ctt gat gtt ccg 2068 Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro 585 590 595 gat cca cca gaa aac ctt cac ttg tet gaa aga cag aac agg agt gtt 2116 Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val 600 605 610 615 egg ctg acc tgg gaa get gga get gac cac aac age aat att age gag 2164 Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu 620 625 630 tat att gtt gaa ttt gaa gga aac aaa gaa gag cct gga agg tgg gag 2212 Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu 635 640 645 gaa ctg acc aga gtc caa gga aag aaa acc aca gtt ate tta cct ttg 2260 Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu 650 655 660 get cca ttt gtg aga tac cag ttc agg gtc ata gee gtg aac gaa gta 2308 Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val 665 670 675 ggg aga agt cag cct age cag ccg tea gac cat cat gaa aca cca cca 2356 Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro 680 685 690 695 eje a get cca gat agg aat cca caa aac ata agg gtt caa gcc tet caa 2404 Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin 700 705 710 ccc aag gaa atg att ata aag tgg gag cct ttg aaa tcc atg gag cag 2452 Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin 715 720 725 aat gga cca ggc eta gag tac aga gtg acc tgg aag cca cag gga gcc 2500 Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala 730 735 740 cca gtg gag tgg gaa gaa gaa aca gtc aca aac cac aca ttg egg gtg 2548 Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val 745 750 7 5 5 atg aeg cct get gtc tat gcc cct tat gat gtc aag gtc cag get ate 2596 Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Al a He 760 765 770 775 aat caa eta gga tet ggg cct gac cct cag tea gtg act etc tat tet 2644 Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser 780 785 790 gga gaa gac tat cct gat aca get cca gtg ate cat ggg gtg gac gtt 2692 413 2740

Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val lie His Gly Val Asp Val 795 800 805 ata aac agt He Asn Ser 810 aca tta gtt aaa gtt Thr Leu Val Lys Val 815 acc tgg tea aca gtt Thr Trp Ser Thr Val 820 cca aag gac Pro Lys Asp aga gta cat Arg Val His 825 gga cgt ctg aaa ggc Gly Arg Leu Lys Gly 830 tat cag ata aat tgg Tyr Gin He Asn Trp 835 tgg aaa aca Trp Lys Thr 2788 aaa agt ctg Lys Ser Leu 840 ttg gat gga aga aca Leu Asp Gly Arg Thr 845 cat ccc aaa gaa gtg His Pro Lys Glu Val 850 aac att eta Asn He Leu 855 2836 aga ttt tea Arg Phe Ser gga caa aga aac tet Gly Gin Arg Asn Ser 860 gga atg gtt cct tcc Gly Met Val Pro Ser 865 tta gat gcc Leu Asp Ala 870 2884 ttt agt gaa Phe Ser Glu ttt cat tta aca gtc Phe His Leu Thr Val 875 tta gcc tat aac tet Leu Ala Tyr Asn Ser 880 aaa gga get Lys Gly Ala 885 2932 ggt cct gaa Gly Pro Glu 890 agt gag cct tat ata Ser Glu Pro Tyr lie 895 ttt caa aca cca gaa Phe Gin Thr Pro Glu 900 gga gta cct Gly Val Pro 2980 gaa cag cca Glu Gin Pro 905 act ttt eta aag gtc Thr Phe Leu Lys Val 910 ate aaa gtt gat aaa lie Lys Val Asp Lys 915 gac act gcc Asp Thr Ala 3028 act tta tet Thr Leu Ser 920 tgg gga Cta cct aag Trp Gly Leu Pro Lys 925 aaa tta aat gga aac Lys Leu Asn Gly Asn 930 tta act ggc Leu Thr Gly 935 3076 tat ett ttg Tyr Leu Leu caa tat cag ata ata Gin Tyr Gin lie lie 940 aat gac acc tac gag

Asn Asp Thr Tyr Glu 945 att gga gaa He Gly Glu 950 3124 tta aat gat Leu Asn Asp att aac att aca act He Asn He Thr Thr 955 cca tea aag ccc age Pro Ser Lys Pro Ser 960 tgg cac etc Trp His Leu 965 3172 tea aac ctg Ser Asn Leu 970 aat gca act acc aag Asn Ala Thr Thr Lys 975 tac aaa ttc tac ttg Tyr Lys Phe Tyr Leu 980 agg get tgc Arg Ala Cys 3220 act tea cag Thr Ser Gin 985 ggc tgt gga aaa ccg Gly Cys Gly Lys Pro 990 ate aeg gag gaa age He Thr Glu Glu Ser 995 tcc acc tta Ser Thr Leu 3268 gga gaa ggg Gly Glu Gly 1000 agt aaa ggt ate ggg Ser Lys Gly He Gly 1005 aag ata tea gga gta aat ett act Lys lie Ser Gly Val Asn Leu Thr 1010 1015 3316 caa aag act Gin Lys Thr cac cca ata gag gta His Pro lie Glu Val 1020 ttt gag ccg gga get Phe Glu Pro Gly Ala 1025 3364 atg act aag aat tgg Met Thr Lys Asn Trp 1035 ggc gat aac gat age Gly Asp Asn Asp Ser 1040 att ttt caa He Phe Gin 1045 gaa cat ata

Glu His He 1030 3412 gtt ege cta

Val Arg Leu 414 gat Asp gta Val att gag He Glu 1050 aca Thr aga Arg ggg Gly aga gaa Arg Glu 1055 tat Tyr get Ala ggt Gly tta Leu 106C tat Tyr 1 gat Asp gac Asp 3460 ate tcc act caa ggc tgg ttt att gga ctg atg tgt geg att get ett 3508 He Ser Thr Gin 1065 Giy Trp Phe 107C He Gly 1 Leu Met Cys Ala 1075 He Ala Leu etc aca eta eta tta tta act gtt tgc ttt gtg aag agg aat aga ggt 3556 Leu Thr 1080 Leu Leu Leu Leu 1085 Thr Val Cys Phe Val 109C Lys 1 Arg Asn Arg Gly 1095 gga aag tac tea gtt aaa gaa aag gaa gat ttg cat cca gac cca gaa 3604 Gly Lys Tyr Ser Val 110C Lys 1 Glu Lys Glu Asp 1105 Leu His Pro Asp Pro me Glu 1 att cag tea gta aaa gat gaa acc ttt ggt gaa tac agt gac agt gat 3652 He Gin Ser Val 1115 Lys Asp Glu Thr Phe 112C Gly I Glu Tyr Ser Asp 1125 Ser Asp gaa aag cct etc aaa gga age ett egg tcc ett aat agg gat atg cag 3700 Glu Lys Pro Leu 1130 Lys Gly Ser Leu Arg 1135 Ser Leu Asn Arg 1140 Asp 1 Met Gin cct act gaa agt get gac age tta gtc gaa tac gga gag gga gac cat 3748 Pro Thr 1145 Glu Ser I Ala Asp Ser 1150 Leu Val Glu Tyr Gly 1155 Glu 1 Gly Asp His ggt etc ttc agt gaa gat gga tea ttt att ggt gcc tac get gga tct 3796 Gly 1160 Leu 1 Phe Ser Glu Asp 1165 Gly Ser Phe He Gly 1170 Ala 1 Tyr Ala Gly Ser 1175 aag gag aag gga tct gtt gaa age aat gga agt tct aca gca act ttt 3844 Lys Glu Lys Gly Ser 1180 Val 1 Glu Ser Asn Gly 1185 Ser 1 Ser Thr Ala Thr 1190 Phe 1 ccc Pro ett Leu egg gca Arg Ala 1195 taa •k acacaacata tgtaagcaac gctactggtt . caccccaacc 3899 ttccatattt atctgttcaa aggagcaaga actttcatat aggaatagaa acatgctggc 3959 cgaagatttc atccagaagt caacatcctg caattatgtt gaaaagagta gtactttctt 4019 caaaatataa aatgccaagc acttcaggcc tatgttttgc ttatattgtt ttcaggtgct 4079 caaaatgcaa aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc 4139 cccattcagt atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt 4199 gctacttggt gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg 4259 gtgactttgc ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa 4319 aaggaatatg aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat 4379 ttaaatttta ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat 4439 ttgcccagag atggtcatat ttaaacagaa gtatacgttt ttcagtttca acatgaattt 4499 ttttatttct gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt 4559 ttcttggact aaattcaact gcatggaagc ggtggtcaga aggttgtttt atacgagaac 4619 aggcagaaag tgcccattgt tcaggattct aatagctaca tctacttaat atcttcattt 4679 ctaaattgac tgcttttacc tttttctcat gtttatataa tggtatgctt gcatatattt 4739 catgaataca ttgtacatat tatgttaata tttacacaat ttaaaatata gatgtgtttt 4799 attttgaagt gagaaaatga acattaacag gcatgtttgt acagctagaa tatattagta 4859 agatactgtt tttcgtcatt ccagagctac aactaataac acgaggttcc aaagctgaag 4919 actttgtata aagtatttgg gttttgttct tgtattgctt tctttcaaca gtttcaaaat 4979 aaaatatcat acaaatattg agggaaatgt tttcatattt ttcaaaatag gtttttattg 5039 ttgaatgtac atctacccca gcccctcaaa agaaaaactg tttacataga aattcctaca 5099 catacgtttg cgtatatgtt attttaaaca tctttgtggt gagaattttt tccccgatat 5159 415 tctccttctg tcaaagtcag aacaaattca gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat gaacatgttt tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc gacattttat ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg aattgactta tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca acttggattt atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat agtcagcgca ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc agaatgtata gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc tgaccgcagt cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt gtgaatgtga ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc taaggctcca gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg tggtgcacag cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt ctgtctcctc ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta gaaataatgt caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat actgaaatat tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat tgctcctact cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat gatgactatg ctttgctatc attgttacct ttcctcaata ctatttggca actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt accttaaatt gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg tgattacctt tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt tgtattgtag gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca ttatacatga aattcaactt tccaaataaa agttctactt catgtaatcc aaaa <210> 17 <211> 1195

<212> PRT <213> Homo sapians 5219 5279 5339 5399 5459 5519 5579 5639 5699 5759 5819 5879 5939 5999 6059 6119 6179 6239 6299 6359 6419 6479 6539 6599 6659 6719 6779 6839 6899 6959 7019 7079 7139 7199 7259 7319 7379 7439 7499 7559 7563 <400> 17

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He I le Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 416

Asn Lys Leu 115 Gly He Ala Met Ser 120 Glu Glu He Glu Phe 125 He Val Pro Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Al a Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr lie Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 245 250 255 Pro Lys Gly 7\ -—»-« Glu mk — X iiX Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Asp 290 295 300 Asn lie Ser His Glu Leu Phe Thr Leu His Pro Glu Pro Pro Arg Trp 305 310 315 320 Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He 325 330 335 Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg 340 345 350 Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val 355 360 365 Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala 370 375 380 Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn 385 390 395 400 Ala Asn lie Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp 405 410 415 Gly Glu Asn 'Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys 420 425 430 Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu 435 440 445 Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly 450 455 460 Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser 465 470 475 480 Cys Trp Val Glu Asn Ala He Gly Lys Thr Al a Val Thr Ala Asn Leu 485 490 495 Asp lie Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg 500 505 510 lie Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp 515 520 525 Ser His Leu Lys His Ser T HCU Lys Leu Ser Trp Ser Lys Asp Gly Glu 530 535 540 Ala Phe Glu lie Asn Gly Thr Glu Asp Gly Arg He lie He Asp Gly 545 550 555 560 Ala Asn Leu Thr lie Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr 565 570 575 Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin 580 585 590 Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser 595 600 605 417

Glu Arg 610 Gin Asn Arg Ser Val Arg 615 Leu Thr Trp Glu 620 Ala Gly Ala Asp His Asn Ser Asn lie Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys 625 630 635 640 Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys 645 650 655 Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg 660 665 670 Val lie Ala Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser 675 680 685 Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn 690 695 700 He Arg Val Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu 705 710 715 720 Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val 725 730 735 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val 740 745 750 Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr 755 760 765 Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro 770 775 780 Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro 785 790 795 800 Val lie His Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr 805 810 815 Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr 820 825 830 Gin lie Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His 835 840 845 Pro Lys Glu Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly 850 855 860 Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu 865 870 875 880 Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe 885 890 895 Gin Thr Pro Glu dy Val Pro Glu Gin Pro Thr Phe Leu Lys Val He 900 905 910 Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys 915 920 925 Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn 930 935 940 Asp Thr Tyr Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro 945 950 955 960 Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr 965 970 975 Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He 980 985 990 Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly lie Gly Lys 995 1000 1005 lie Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe 1010 1015 1020 Glu Pro Gly Ala /“«I ,, Ui U His He Val Arg Leu Met Thr Lys Asn Trp Gly 1025 1030 1035 1041 Asp Asn Asp Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu 1045 1050 1055 Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly 1060 1065 1070 Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys 1075 1080 1085 Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu 1090 1095 1100 418

Asp Leu His Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe 1105 1110 1115 112 Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg 1125 1130 1135 Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val 114 0 1145 1150 Glu Tyr Gly Glu Gly Asp His Gly Lgu Phe Ser Glu Asp Gly Ser Phe 1155 1160 1165 He Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn 1170 1175 1180 Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1185 1190 1195 <210> 18 <211> 7570

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (192).(3866) <400> 18 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg gaggegeegg acagatcgcg ttteggagge ggcgcagttt ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt cctgaagagc a atg gag ccg ett tta ett gga aga gga eta ate gta tat

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr 1 5 10 60 120 180 230 eta Leu atg Met 15 ttc Phe etc Leu ctg Leu tta Leu aaa Lys 20 ttc Phe tea Ser aaa Lys gca Ala att He 25 gaa Glu ata He cca Pro tot Ser 278 tea gtt caa cag gtt cca aca ate ata aaa cag tea aaa gtc caa gtt 326 Ser Val Gin Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val 30 3 5 40 45 gcc ttt ccc ttc gat gag tat ttt caa att gaa tgt gaa get aaa gga 374 Ala Phe Pro Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly 50 55 60 aat cca gaa cca aca ttt tog tgg act aag gat ggc aac cct ttt tat 422 Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr 65 70 75 ttc act gac cat egg ata att cca teg aac aat tea gga aca ttc agg 470 Phe Thr Asp His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg 80 85 90 ate cca aac gag ggg cac ata tet cac ttt caa ggg aaa tac ege tgc 518 He Pro Asn Glu -jj_y His τ&amp;#942;. Ser Hrs Phe Gin Gly Lys Tyr Arg Cys 95 100 105 ttt get tea aat aaa ctg gga ate get atg tea gaa gaa ata gaa ttt 566 Phe Ala Ser Asn Lys Leu Gly He Ala Met Ser Glu Glu lie Glu Phe 110 115 120 125 ata gtt cca agt gtt cca aaa etc cca aaa gaa aaa att gac cct ett 614 He Val Pro Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu 130 135 140 419 662 gaa gtg Glu Val ggc etc Gly Leu ate gaa lie Glu 175 ttc gca Phe Ala 190 get gca Ala ~i p) eta aca Leu Thr gaa att Glu He ctg ttg Leu Leu 255 aaa ggg Lys Gly 270 cca cag

Pro Gin gaa aca Glu Thr tac cag Tyr Gin aca gcc Thr Ala 335 aca aag Thr Lys 350 ttg tta Leu Leu gtc aat gag gag Glu Glu 145 cca cct Pro Pro 160 caa gat Gin Asp aac gtg Asn Val ttt cca Phe Pro gtt aac Val Asn 225 ggt tcc Gly Ser 240 cct ccc Pro Pro gaa ate Glu He gtt gat Val Asp aaa gaa Lys Glu 305 gac aaa Asp Lys 320 act cac Thr His aag cct Lys Pro tgt gag Cys Glu ggc tcc gga gat Gly Asp tta cac Leu His gaa aga Glu Arg gaa gaa Glu Glu 195 aga tta Λ T - m nc u 210 agt tta Ser Leu aag gca Lys Ala act gag Thr Glu ttg ctg Leu Leu 275 tgg aac Trp Asn 290 aat tat Asn Tyr gga aat Gly Asn gat ttt Asp Phe cag agt Gin Ser 355 get gaa

Ala Glu 370 cca gtt cca att Pro lie att tat He Tyr 165 gta tac Val Tyr 180 aag gac Lys Asp agg act aag cat Lys His aat tcc Asn Ser 245 agt ggc Ser Gly 260 ett gag Leu Glu aaa att Lys He ggc aag Gly Lys tat ege Tyr Arg 325 cac gtt His Val 340 get gtg Ala Val gga gaa Gly Glu gac aat gtc etc Val Leu 150 tgg atg Trp Met atg age Met Ser agt ege Ser Arg att gta T &amp;#906; _ ττ_ 1 X-L'e ναι 215 get aat Ala Asn 230 ate aag He Lys agt gag Ser Glu tgt ttt Cys Phe ggt ggt Gly Gly 295 act ttg Thr Leu 310 tgc aca Cys Thr ata gta He Val tat age Tyr Ser cct caa Pro Gin 375 cat cca cca tgc Pro Cys aat att Asn He caa aag Gin Lys 185 aat gac Asn Asp 200 cag aaa Gin Lys gac tea Asp Ser caa aga Gin Arg tct tea Ser Ser 265 get gaa Ala Glu 280 gac tta Asp Leu aag ata Lys He gcc age Ala Ser gaa gag Glu Glu 345 acc gga Thr Gly 360 ccc aca Pro Thr ttt get aat cct Asn Pro 155 gaa tta Glu Leu 170 gga gat Gly Asp tac tgt Tyr Cys atg cca

Met Pro agt tea Ser Ser 235 aaa ccc Lys Pro 250 att acc He Thr ggc ttg Gly Leu cca aag Pre Lys gag aat Glu Asn 315 aat ttc Asn Phe 330 cct cct Pro Pro age aat Ser Asn ate aag He Lys ggt gat ccc aaa Pro Lys gaa cac Glu His 710 eta tac Leu Tyr 758 tgc ttt Cys Phe 205 atg aaa Met Lys 220 tcc aca Ser Thr 806 854 902 aaa ctg Lys Leu 950 ate etc He Leu 998 cca act Pro Thr 285 ggg aga Gly Arg 300 gtc tcc Val Ser 1046 1094 1142 ttg gga Leu Gly 1190 ege tgg Arg Trp 1238 ggc ate Gly He 365 tgg aga Trp Arg 380 gtt gtc 1286 1334 1382 420 val Asn Gly Ser 385 Pro Val Asp Asn His 390 Pro Phe Ala Gly Asp 395 Val Val ttc ccc agg gaa ate agt ttt acc aac ett caa cca aat cat act get 1430 Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala 400 405 410 gtg tac cart --Zl + Cft- — 3 — Γ&#943; A A rmr-z> — tG3 33t rr-f- r' Z3 r* sj &#905; rrn n Z) Z) act ate ett SIS'· S'· sa a -j- 1478 Val Tyr Gin Cys Glu Ala Ser Asn Val His Giy Thr He Leu Ala Asn 415 420 425 gcc aat att gat gtt gtg gat gtc cgt cca ttg ata caa acc aaa gat 1526 Ala Asn He Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp 430 435 440 445 gga gaa aat tac get aca gtg gtt ggg tac agt get ttc tta cat tgc 1574 Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys 450 455 460 gag ttc ttt get tea cct gag gca gtc gtg tcc tgg cag aag gtg gaa 1622 Glu Phe Phe Al a Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu 465 470 475 gaa gtg aaa ccc ctg gag ggc agg egg tat cat ate tat gaa aat ggc 1670 Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly 480 485 490 aca ttg cag ate aac aga acc acc gaa gaa gat get ggg tct tac tea 1718 Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser 495 500 505 tgt tgg gta gaa aat get ata gga aaa act gca gtc aca gcc aat ttg 1766 Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu 510 515 520 525 gat att aga aat get aca aaa ett aga gtt tct cct aag aat cct cgt 1814 Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg 530 535 540 ate ccc aaa ttg cat atg ett gaa tta cat tgt CJ ci. age 3.33. tgt g 3.C 18 62 lie Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp 545 550 555 tea c at ttg 3.3.3. cac agt ttg aag ttg tcc tgg agt aaa gat gga gaa 1910 Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Giy Glu 560 565 570 gcc ttt gaa att aat ggc aca gaa gat ggc agg ata att att gat gga 1958 Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He lie He Asp Gly 575 580 585 get aat ttg 3CC ata tct aat gta act tta gag gac caa ggt att tac 2006 Ala Asn Leu Thr lie Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr 590 595 600 605 tgc tgt tea get cat act get eta gac agt get gcc gat ata act caa 2054 cys cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin 610 615 620 gta act gtt ett gat gtt ccg gat cca cca gaa aac ett cac ttg tct 2102 Val Thr Val Leu Asp a 1 Pro Asp Pro Pro Glxi Asn Leu His L@u Ser 625 630 635 421 2150 gaa

Glu aga cag aac agg agt gtt Arg Gin Asn Arg Ser Val 640 egg ctg acc tgg gaa get gga get gac Arg Leu Thr Trp Glu Ala Gly Ala Asp 645 650 ci fo*

His aac age aat att age gag

Asn Ser Asn He Ser Glu £ RR ccn tat att gtt gaa ttt gaa gga aac aaa Tyr He Val Glu Phe Glu Gly Asn Lys 2 198 gaa

Glu 670 acc

Thr gag cct Glu Pro gga agg tgg gag Gly Arg Trp Glu 675 gaa ctg acc aga gtc caa gga aag aaa Glu Leu Thr Arg Val Gin Gly Lys Lys 680 685 2246 gtc

Val gac

Asp ata lie cct

Pro 750 acc

Thr aca

Thr gat

Asp cag

Gin gtg

Val 830 tgg

Trp cag

Gin ccc aca gtt Thr Val ata gcc He Ala cat cat His His 720 agg gtt Arg Val 735 ttg aaa Leu Lys tgg aag Trp Lys aac cac

Asn His gtc aag Val Lys )00 ate tta cct ttg He Leu Pro Leu 690 gtg aac gaa gta Val Asn Glu Val 705 gaa aca cca cca Glu Thr Pro Pro get cca ttt gtg aga tac cag ttc agg Ala Pro Phe Val Arg Tyr Gin Phe Arg 695 700 ggg aga agt cag cct age cag ccg tea Gly Arg Ser Gin Pro Ser Gin Pro Ser 710 715 gca get cca gat agg aat cca caa aac Ala Ala Pro Asp Arg Asn Pro Gin Asn 725 730 2294 2342 2390 caa gcc tet caa Gin Ala Ser Gin 740 tec atg gag cag Ser Met Glu Gin 755 cca cag gga gcc Pro Gin Gly Ala 770 aca ttg egg gtg Thr Leu Arg Val 785 gtc cag get ate Val Gin Ala He tea gtg Ser Val 815 act etc Thr Leu tat tet Tyr Ser 820 ate cat ggg gtg gac gtt Asp 835 ccc aag gaa atg Pro Lys Glu Met att

He 745 ata aag tgg gag He Lys Trp Glu 2438 aat gga cca ggc eta Asn Gly Pro Gly Leu 760 cca gtg gag tgg gaa Pro Val Glu Trp Glu 775 gag tac aga gtg Glu Tyr Arg Val 765 gaa gaa aca gtc Glu Glu Thr Val 780 atg aeg cct get gtc Met Thr Pro Ala Val 790 aat caa eta gga tet Asn Gin Leu Gly Ser 805 tat gcc cct tat Tyr Ala Pro Tyr 795 ggg cct gac cct Gly Pro Asp Pro 810 2486 2534 2582 2630 gga gaa gac tat Gly Glu Asp Tyr cct

Pro 825 gat aca get cca Asp Thr Ala Pro ata aac agt aca tta He Asn Ser Thr Leu 840 gtt aaa gtt acc Val Lys Val Thr 845 2678 2726 tea aca gtt cca aag gac aga gta cat gga cgt Ser Thr Val Pro Lys Asp Arg Val His Gly Arg 850 855 ata aat tgg tgg aaa aca aaa agt ctg ttg gat He Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp 865 870 ctg aaa ggc tat Leu Lys Gly Tyr 86 0 gga aga aca cat Gly Arg Thr His 875 aaa gaa gtg aac att eta aga ttt tea gga caa aga aac tet gga 2774 2822 2870 422

Pro Lys Glu 880 Val Asn He Leu Arg 885 Phe Ser Gly Gin Arg 890 Asn Ser Gly atg gtt cct tcc tta gat gcc ttt agt gaa ttt cat tta aca gtc tta 2918 Met Val 895 Pro Ser Leu Asp Ala 900 Phe Ser Glu Phe His 905 Leu Thr Val Leu gcc tat aac tct dclcl gga get ggt cct gaa agt gag cct tat ata ttt 2 9 6 6 Ala 910 Tyr Asn Ser Lys Gly 915 Ala Gly Pro Glu Ser 920 Glu Pro Tyr He Phe 925 caa aca cca gaa gga gta cct gaa cag cca act ttt eta aag gtc ate 3014 Gin Thr Pro Glu Gly 930 Val Pro Glu Gin Pro 935 Thr Phe Leu Lys Val 940 He aaa gtt gat aaa gac act gcc act tta tct tgg gga eta cct aag aaa 3062 Lys Val Asp Lys 945 Asp Thr Ala Thr Leu 950 Ser Trp Gly Leu Pro 955 Lys Lys tta aat qqci aac tta act ggc tat ett ttg caa tat cag ata ata aat 3110 Leu Asn Gly 960 Asn Leu Thr Gly Tyr 965 Leu Leu Gin Tyr Gin 970 He lie Asn gac acc tac gag att gga gaa tta aat gat att aac att aca act cca 3158 Asp Thr 975 Tyr Glu He Gly Glu 980 Leu Asn Asp He Asn 985 He Thr Thr Pro tea aag ccc age tgg cac etc tea aac ctg aat gca act acc aag tac 3206 Ser 99C Lys I Pro Ser Trp His Leu 995 Ser Asn Leu Asn 100C Ala I Thr Thr Lys Tyr 1005 aaa ttc tac ttg agg get tgc act tea cag ggc tgt gga aaa ccg ate 3254 Lys Phe Tyr Leu Arg 101C Ala 1 Cys Thr Ser Gin 1015 Gly Cys Gly Lys Pro 102C He I aeg gag gaa age tcc acc tta gga gaa ggg agt aaa ggt ate ggg aag 3302 Thr Glu Glu Ser 1025 Ser Thr Leu Gly Glu 103C Gly 1 Ser Lys Gly He 1035 Gly Lys ata tea gga gta aat ett act caa aag act cac cca ata gag gta ttt 3350 lie Ser Gly 104C Val 1 Asn Leu Thr Gin 1045 Lys Thr His Pro He 105C Glu 1 Val Phe gag ccg gga get gaa cat ata gtt ege eta atg act aag aat tgg ggc 3398 Glu Pro 1055 Gly Ala Glu His lie 106C Val ) Arg Leu Met Thr Lys 1065 Asn Trp Gly gat aac gat age att ttt caa gat gta att gag aca aga ggg aga gaa 3446 Asp 1070 Asn 1 Asp Ser lie Phe 1075 Gin Asp Val He Glu 108C Thr 1 Arg Gly Arg Glu 1085 tat get ggt tta tat gat gac ate tcc act caa ggc tgg ttt att gga 3494 Tyr 1 id. Gly Leu Tyr 109C Asp 1 Asp He Ser Thr 1095 Gin Gly Trp Phe He 110C Gly 1 ctg atg tgt geg att get ett etc aca eta eta tta tta act gtt tgc 3542 Leu Met Cys Ala 1105 He Ala Leu Leu Thr me Leu 1 Leu Leu Leu Thr 1115 Val Cys ttt gtg aag agg aat aga ggt gga aag tac tea gtt aaa gaa aag gaa 3590 Phe Val Lys 1120 Arg Asn Arg Gly Gly 1125 Lys Tyr Ser Val Lys 113C Glu 1 Lys Glu 423 gat Asp ttg Leu 1135 cat His cca Pro gac Asp cca Pro gaa Glu 114C att lie 1 cag Gin tea Ser gta Val aaa gat Lys Asp 1145 gaa Glu acc Thr ttt Phe 3638 ggt gaa tac agt gac agt gat gaa aag cct etc aaa gga age ett egg 3686 Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg 1150 1155 1160 1165 tcc ett aat agg gat atg cag cct act gaa agt get gac age tta gtc 3734 Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val 1170 1175 1180 gaa tac gga gag gga gac cat ggt etc ttc agt gaa gat gga tea ttt 3782 Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe 1185 1190 1195 att ggt gcc tac get gga tct aag gag aag gga tct gtt gaa age aat 3830 lie Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn 1200 1205 1210 gga agt tct aca gca act ttt CCC ett egg gca taa acacaacata 3876 Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1215 1220 tgtaagcaac gctactggtt caccccaacc ttccatattt atctgttcaa aggagcaaga 3936 actttcatat aggaatagaa acatgctggc cgaagatttc atccagaagt caacatcctg 3996 caattatgtt gaaaagagta gtactttctt caaaatataa aatgccaagc acttcaggcc 4056 tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa aacacaaaac aaatcctgca 4116 tttagataca cctcaactaa atccaaagtc cccattcagt atattccata tttgcctgat 4176 tttactattc ggtgtgtttg catagatgtt gctacttggt gggtttttct ccgtatgcac 4236 attggtatac agtctctgag aactggcttg gtgactttgc ttcactacag gttaaaagac 4296 cataagcaaa ctggttattt aaaatgtaaa aaggaatatg aaagtcttat taaaacactt 4356 cattgaaaat atacagtcta aatttattat ttaaatttta ctagcaaaag tcttaggtga 4416 acaatcaact agtatttgtt gagctcctat ttgcccagag atggtcatat ttaaacagaa 4476 gtatacgttt ttcagtttca acatgaattt ttttatttct gtcagttatg acatccacga 4536 gcatcacttt ttgtgtctgt tttttttttt ttcttggact aaattcaact gcatggaagc 4596 ggtggtcaga aggttgtttt atacgagaac aggcagaaag tgcccattgt tcaggattct 4656 aatagctaca tctacttaat atcttcattt ctaaattgac tgcttttacc tttttctcat 4716 gtttatataa tggtatgctt gcatatattt catgaataca ttgtacatat tatgttaata 4776 tttacacaat ttaaaatata gatgtgtttt attttgaagt gagaaaatga acattaacag 4836 gcatgtttgt acagctagaa tatattagta agatactgtt tttcgtcatt ccagagctac 4896 aactaataac acgaggttcc aaagctgaag actttgtata aagtatttgg gttttgttct 4956 tgtattgctt tctttcaaca gtttcaaaat aaaatatcat acaaatattg agggaaatgt 5016 tttcatattt ttcaaaatag gtttttattg ttgaatgtac atctacccca gcccctcaaa 5076 agaaaaactg tttacataga aattcctaca catacgtttg cgtatatgtt attttaaaca 5136 tctttgtggt gagaattttt tccccgatat tctccttctg tcaaagtcag aacaaattca 5196 gggaatttat tttctggcag ttgtgctcca gtccttttaa aattgtacat gaacatgttt 5256 tagaaacaat atggaggatg atgcatacat gtcggtcaag ttcagcgctc gacattttat 5316 ggaaagattt ttttaacctt accacgaaat acttaactac tgtttaagtg aattgactta 5376 tttcacttta gtttttgaac tgtgattatt ggtatactgt tatatcctca acttggattt 5436 atggtaaccc cttttagttc atggagacca aaatttgggg tatttataat agtcagcgca 5496 ggaatgcaca tggaatatct acttgtcctt ttgaacctca cgagtcatcc agaatgtata 5556 gacaggaaaa gcatgtctta tttaaaactg taatttatgg gctcaggatc tgaccgcagt 5616 cccgggagta agcatttcaa agggggaagg cagtgtggtc cctaccctgt gtgaatgtga 5676 ggatgtagac atccatcagt gcaactcgag ctccatcctc ctccgatttc taaggctcca 5736 gttttctgga gggacagtca tcatgttttg atttatctgg gagaaaactg tggtgcacag 5796 cttgtgagga gggcaaggtt gtgacgttcg agcttagttc tggtgttatt ctgtctcctc 5856 ttctttgtca tcagccaaaa cgtggttttt aaagagagtc atgcaggtta gaaataatgt 5916 caaaaatatt taggaattta ataaccttta agtcagaaac taaaacaaat actgaaatat 5976 tagctcttcc tacacttcgt gttccccttt agctgcctga aaatcaagat tgctcctact 6036 cagatcttct gagtggctaa aacttatgga tatgaaaaat gagattgaat gatgactatg 6096 424 ctttgctatc attgttacct ttcctcaata ctatttggca actactggga ctcttcagca caaaaggaat agatctatga ttgaccctga ttttaattgt gaaattatat gattcatata ttttatgaat cagaataacc ttcaaataaa ataaatctaa gtcggttaaa atggatttca tgattttccc tcagaaaatg agtaacggag tccacggcgt gcaatggtaa ttataaattg gtgatgcttg tttgcaaatt gcccactcgt gataagtcaa cagccaatat ttaaaacttt gttcgttact ggctttaccc taactttctc tagtctactg tcaatatcat tttaatgtaa ttgattgtat atagtctcaa gaatggttgg tgggcatgag ttcctagaga actgtccaag ggttgggaaa atccaaattc tcttcctggc tccagcactg attttgtaca taaacattag gcaggttgct taaccttttt atttcaaact ctctcaactc taaagtgcta ataataatct cagttacctt atctttgtca cagggtgttc ttttttatga agaaaaattt gaaaatgata aaagctaaga tgccttctaa cttcataagc aaacctttaa ctaattatgt atctgaaagt cacccccaca taccaactca acttttttcc tgtgaacaca taaatatatt tttatagaaa aacaaatcta cataaaataa atctactgtt tagtgagcag tatgacttgt acatgccatt gaaaattatt aatcagaaga aaattaagca gggtctttgc tatacaaaag tgttttccac taattttgca tgcgtattta taagaaaaat gtgaatttgg tggttttatt ctatcggtat aaaggcatcg atattttaga tgcacccgtg tttgtaaaaa tgtagagcac aatggaatta tgctggaagt ctcaaataat atttttttcc tattttatac tcatggaaga gataagctaa agaggggaca ataatgagaa atgttggtgt gcttttctaa gcatttaaaa cataattgcc aattgaaacc ctaaatatgt ttacatacca ttaagatatg attcatgtaa caatgttaaa ttaattataa tgggattggg tttgttatct gtggtagtat atatcctagt gttcctatag tgaaataagt agggttcagc caaagctttc tttgttttgt accttaaatt gttcgattac gtcatcaaaa gagatgaaag gtatgtagaa caggttcacg tgattacctt tttcttttgg cttggattaa tattcatagt agaactttat aaaacgtgtt tgtattgtag gtggtgtttg tattatgctt atgactatgt atggtttgaa aatattttca ttatacatga aattcaactt tccaaataaa agttctactt catgtaatcc aaaa <210> 19 <211> 1224

<212> PRT <213> Homo sapians 6156 6216 6276 6336 6396 6456 6516 6576 6636 6696 6756 6816 6876 6936 6996 7056 7116 7176 7236 7296 7356 7416 7476 7536 7570 <400> 19

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His lie Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 425

Ser Lys Ala Asn Ser 245 lie Lys Gin Arg Lys 250 Pro Lys Leu Leu Leu 255 Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 2 80 2 85 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His ciy Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val ciy Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Al a Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala lie Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr cys cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 &#902;ςη Arg Ser Val Arg Leu Thr <T> ν·»-&#906; x-*-1/ Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 6 7 5 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val ciy Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg As n Pro Gin Asn lie Arg Val 725 730 735 426

Gin Ala Ser Gin 740 Pro Lys Glu Met He 745 He Lys Trp Glu Pro 750 Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 7 95 ΟΛΛ O V V Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He lie Asn Asp Thr Tyr 965 970 975 Glu lie Gly Giu Leu Asn Asp He Asn lie Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys TTix* His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val Xie Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 10 85 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Cx-v -.- Val T V v /-, ny o 7\ Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Λ1 a 1220 427 <210> 20 <211> 1224

<212> PRT <213> Homo sapians <2 2 0> <221> <222> <223> <221> <222> <223> <221> <222> <223> <221> <222> <223> <221> <222> <223>

VARIANT 17 AA varaiation; L to F = v.9

VARIANT 133 AA variation;

VARIANT 303 AA variation;

VARIANT 805 AA variation;

VARIANT 1198 AA variation; L to F = v.10 T to A = v.11 N to D = v.24 I to T = v.25

Though these amino acid variations are shown seperately, they can also occur in any combinations and in any of the proteins shown in Figure 2 and Figure 3. <400> 20 Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Al a lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He lie Lys Gin Ser Lys Val 1 n Val A1 a Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg lie Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 17 5 Asp Glu Arg Val Tyr Met Ser Gin Ly s Gly Asp Leu Tyr Phe Ala As n 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys cys Phe Ala AI Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 428

Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Al a Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Ρχ*Ο P27O Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn lie Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 429

Glu Thr Pro Pro Ala Ala 725 Pro Asp Arg Asn 730 Pro Gin Asn He Arg 7 3 5 Val Gin Ala Ser Gin Pro Lys 740 Glu Met He He 745 Lys Trp Glu Pro 750 Leu Lys Ser Met Glu 755 Gin Asn Gly Pro Gly 760 Leu Glu Tyr Arg Val 765 Thr Trp Lys Pro Gin 770 Gly Ala Pro Val Glu 775 Trp Glu Glu Glu Thr 780 Val Thr Asn His Thr 785 Leu Arg Val Met Thr 790 Pro Ala Val Tyr Ala 795 Pro Asp Val Lys 800 Val Gin Ala He Asn Gin 805 Leu Gly Ser Gly 810 Pro Asp Pro Gin Ser 815 Val Thr Leu Tyr Ser Gly Glu 820 Asp Tyr Pro Asp 825 Thr Ala Pro Val 830 lie His Gly Val Asp 835 Val He Asn Ser Thr 840 Leu Val Lys Val Thr 845 Trp Ser Thr Val Pro 850 Lys Asp Arg Val His 855 Gly Arg Leu Lys Gly 860 Tyr Gin He Asn Trp 865 Trp Lys Thr Lys Ser 870 Leu Leu Asp Gly Arg 875 Thr His Pro Lys Glu 880 Val Asn lie Leu Arg Phe 885 Ser Gly Gin Arg 890 Asn Ser Gly Met Val 895 Pro Ser Leu Asp Ala Phe Ser 900 Glu Phe His Leu 905 Thr Val Leu Ala 910 Tyr Asn Ser Lys dy 915 Ala Gly Pro Glu Ser 920 Glu Pro Tyr lie Phe 925 Gin Thr Pro Glu Gly 930 Val Pro Glu Gin Pro 935 Thr Phe Leu Lys Val 940 lie Lys Val Asp Lys 945 Asp Thr Ala Thr Leu 950 Ser Trp Gly Leu Pro 955 Lys Lys Leu Asn Gly 960 Asn Leu Thr Gly Tyr Leu 965 Leu Gin Tyr Gin 970 He He Asn Asp Thr 975 Tyr Glu lie Gly Glu Leu Asn 980 Asp He Asn He 985 Thr Thr Pro Ser 990 Lys Pro Ser Trp His 995 Leu Ser Asn Leu Asn 100C Ala Thr 1 Thr Lys Tyr Lys 1005 Phe Tyr Leu Arg 101C Ala 1 Cys Thr Ser Gin 1015 Gly I Cys Gly Lys Pro 10 2 C lie 1 Thr Glu Glu Ser 1025 Ser Thr Leu Gly Glu 103C Gly 1 Ser Lys Gly He 10 3 5 Gly Lys He Ser Gly 1040 Val Asn Leu Thr Gin Lys 1045 Thr His Pro He 105C Glu 1 Val Phe Glu Pro 1055 Gly Ala Glu His lie Val Arg 1060 Leu Met Thr Lys 1065 Asn Trp Gly Asp 10 / C Asn Asp Ser He Phe 1075 Gin Asp Val He Glu 108C Thr Arg 1 Gly Arg Glu Tyr 1085 Ala Gly Leu Tyr 109C Asp 1 Asp He Ser Thr 1095 Gin Gly Trp Phe He 110C Gly Leu Met Cys Ala 1105 He Ala Leu Leu Thr 1110 Leu 1 Leu Leu Leu Thr 1115 Val Cys Phe Val Lys 1120 Δ rn Asn Arg Gly Gly Lys 1125 m-ιτ-ν- Ser v cxx by o 1130 /-« 1 ,, QrXU 1 T , . xjy Glu Asp Leu 1135 His Pro Asp Pro Glu He Gin 1140 Ser Val Lys Asp 1145 Glu Thr Phe Gly 115C Glu 1 Tyr Ser Asp Ser 1155 Asp Glu Lys Pro Leu 116C Lys Gly 1 Ser Leu Arg Ser 1165 Leu Asn Arg Asp 1170 Met 1 Gin Pro Thr Glu 1175 Ser Ala Asp Ser Leu 118C Val I Glu Tyr Gly Glu 1185 Gly Asp His Gly Leu 1190 Phe Ser Glu Asp Gly 1195 Ser Phe He Gly Ala 1200 Tyr Ala Gly Ser Lys Glu 1205 Lys Gly Ser Val 1210 Glu 1 Ser Asn Gly Ser 1215 Ser 430

Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 21

<211> 1171 <212> PRT <213> Homo sapians <400> 21

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Al a Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 2 7 0 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly As π Φτζ V Arg Cys rp -v X iiJ. A *1 —\ Ser As n Phe Leu j.y Thr Ala. Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu ciy G1 u Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 431

Cys Glu Ala Ser 420 Asn Val His Gly Thr 425 He Leu Ala Asn Ala 430 Asn He Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 47 5 4 8 0 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He lie Asp Gly Ala Asn Leu 580 585 590 Thr lie Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 7 2 0 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 -> gz r\ ! 0 V 7 65 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Τλζτ - j — m w Glu Asp Tyr Pro As ρ mU v X ilX. Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Ar g Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 432

Ser Lys Gly 915 Ala Gly Pro Glu Ser 920 Glu Pro Tyr He Phe 925 Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 Q -] A J ! \J 975 Glu lie Giy Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro lie Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Lys Tyr Ala Gly Leu Tyr Asp Asp He 1025 1030 1035 1040 Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys Ala lie Ala Leu Leu 1045 1050 1055 Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly Gly 1060 1065 1070 Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His Pro Asp Pro Glu He 1075 1080 1085 Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu 1090 1095 1100 Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin Pro 1105 1110 1115 1120 Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His Gly 1125 1130 1135 Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala Tyr Ala Gly Ser Lys 1140 1145 1150 Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro 1155 1160 1165 Leu Arg 1170 Ala <210> 22 <211> 893

<212> PRT <213> Homo sapians <400> 22

Met 1 X Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Sei Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie ne Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Til 25 Phe UCL ΓΠ lip mu X HX Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Giy Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Al a Met Ser Glu Glu lie Glu Phe lie Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 433

Pro Leu His lie Tyr 165 Trp Met Asn He Glu 170 Leu Glu His He Glu 175 Gin Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Al a Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Al a Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His cys Glu Phe Phe 450 455 460 A1. Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 4 80 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Lsu Lys Leu Ser 'T'v-vx Ser T T7O XJ^ o Asp Gly r· 1 ,, U Ala nk x ilC Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He lie Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 434

Asn He Ser Glu 660 Tyr He Val Glu Phe 665 Glu Gly Asn Lys Glu 670 Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 6 9 5 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser 835 840 845 Pro Gin Pro Ser He Phe He Cys Ser Lys Glu Gin Glu Leu Ser Tyr 850 855 860 Arg Asn Arg Asn Met Leu Ala Glu Asp Phe He Gin Lys Ser Thr Ser 865 870 875 880 Cys Asn Tyr Val Glu Lys Ser Ser Thr Phe Phe Lys He 885 890 <210> 23

<211> 1117 <212> PRT <213> Homo sapians <400> 23

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val tpy-j. Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Al a Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg lie Pro Asn 85 90 95 Glu Gly His He Ser His PhS Gin cl Lys J. Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 435

Val Glu Glu 195 Lys Asp Ser Arg Asn 200 Asp Tyr Cys Cys Phe 205 Ala Ala Phe Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 2 2 5 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 4 9 0 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 50 5 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He lie Asp Gly Ala Asn Leu 580 585 590 rpi Vx v J-Xli I le Ser 7\ r-x noil 17-,1 v ax Thx Leu /-i 1. &#908;Χ U Asp Gin Gly He Tyr Cys cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp Ile Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 436 lie Leu 690 Pro Leu Ala Pro Phe 695 Val Arg Tyr Gin Phe 700 Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 1 A C / Ten / u υ Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Leu Pro Glu Gin Pro Thr Phe Leu Lys 820 825 830 Val He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro 835 840 845 Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin lie 850 855 860 lie Asn Asp Thr Tyr Glu He Gly Glu Leu Asn Asp lie Asn He Thr 865 870 875 880 Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr 885 890 895 Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys 900 905 910 Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He 915 920 925 Gly Lys He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu 930 935 940 Val Phe Glu Pro Gly Ala Glu His He Val Arg Leu Met Thr Lys Asn 945 950 955 960 Trp Gly Asp Asn Asp Ser He Phe Gin Asp Val He Glu Thr Arg Gly 965 970 975 Arg Glu Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe 980 985 990 He Gly Leu Met Cys Ala He 1 LiGU Leu Thr Leu Leu Lo u ren Thr 995 1000 1005 Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 1010 1015 1020 Lys Glu Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1025 1030 1035 10 4 0 Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser 1045 1050 1055 Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser 1060 1065 1070 Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly 1075 1080 1085 Ser Τ'» 1-. --. jriits He /-,1. Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu 1090 1095 1100 Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1105 1110 1115 <210> 24 <211> 1208 <212> PRT <213> Homo sapians <400> 24 437

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu c n J V 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg lie Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Al a Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Ser Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 225 230 235 240 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 245 250 255 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 260 265 270 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 275 280 285 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 290 295 300 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 305 310 315 320 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 325 330 335 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 340 345 350 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg V a 1 Asn Gly 355 360 365 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 370 375 380 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 385 390 395 400 Cys Glu Ala Ser Asn val His Gly Thr He Leu Ala Asn Ala Asn He 405 410 415 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 420 425 430 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 435 440 44 5 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 450 455 4 6 0 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 465 470 475 480 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 485 490 495 438

Glu Asn Ala He 500 Gly Lys Thr Ala Val 505 Thr Ala Asn Leu Asp 510 He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 515 520 525 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 530 535 540 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 545 550 555 560 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 565 570 575 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr Cys Cys Ser 580 585 590 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 595 600 60 5 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 610 615 620 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 625 630 635 640 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 645 650 655 dy Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 660 665 670 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 675 680 685 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 690 695 700 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 705 710 715 720 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 725 730 735 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 740 745 750 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 755 760 765 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 770 775 780 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 785 790 795 800 Thr Leu Tyr Ser Giy Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 805 810 815 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 820 825 830 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 835 840 84b Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 850 855 860 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 865 870 875 880 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 885 890 895 Ser Lys Gly Ala Gly Pro Glu Ser Giu Pro Tyr He Phe Gin Thr Pro 900 905 910 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 915 920 925 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 930 935 940 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 945 950 955 960 Glu lie θ&amp;#943;γ Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 965 970 975 Ser Trp His Leu Ser Asn Leu As n Ala Thr Thr Lys Tyr Lys Phe Tyr 980 985 990 439

Leu Arg Ala 995 Cys Thr Ser Gin Gly Cys 1000 Gly Lys Pro He 1005 Thr 1 Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys lie Ser Gly 1010 1015 1020 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1025 ) 1030 1035 1040 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp iUDU 1UOO Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1060 1065 1070 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1075 1080 1085 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1090 1095 1100 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1105 1110 1115 1120 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1125 1130 1135 Ser Asp Ser Asp Glu T.vfi — j. ~ Pro Leu Lys m v --a Ser Leu Arg Ser Leu Asn 1140 1145 1150 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1155 1160 1165 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe lie Gly Ala 1170 1175 1180 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1185 1190 1195 1200 Thr Ala Thr Phe Pro Leu Arg Ala 1205 <210> 25

<211> 1183 <212> PRT <213> Homo sapians <400> 25

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu lie Gly Ser Lys Al a Asn Ser He Lys Gin Arg 195 200 205 440

Lys Pro 210 Lys Leu Leu Leu Pro 215 Pro Thr Glu Ser Gly 220 Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 24 5 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 2 6 0 2 65 2 7 0 Glu Asn Val Ser Tvr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Glu 290 295 300 Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly 3 05 310 315 320 Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr 325 330 335 He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala 340 345 350 dy Asp Val Val Phe Pro Ara ----J Glu I le Ser Phe Thr Asn Leu Gin Pro 355 360 365 Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr 370 375 380 He Leu Ala Asn Ala Asn He Asp Val Val Asp Val Arg Pro Leu He 385 390 395 400 Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala 405 410 415 Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp 420 425 430 Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He 435 440 445 Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala 450 455 460 Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val 465 470 475 480 Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro 485 490 495 Lys Asn Pro Arg He Pro Lys Leu His Met Leu Glu Leu His Cys Glu 500 505 510 Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser 515 520 525 Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He 530 535 540 He He Asp Gly Ala Asn Leu Thr lie Ser Asn Val Thr Leu Glu Asp 54 5 550 555 560 Gin Gly He Tyr Cys Cys Ser Al a His Thr Ala Leu Asp Ser Ala Ala 565 570 575 Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn 580 585 590 Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu 595 600 605 Ala Gly Ala Asp His Asn Ser Asn lie Ser Glu Tyr He Val Glu Phe 610 615 620 Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val 625 630 635 640 Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg 645 650 655 Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro 660 665 670 Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg 675 680 685 Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin Pro Lys Glu Met He 690 695 700 441 lie Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu 705 Glu Tyr Arg Val Thr 710 Trp Lys Pro Gin Gly 715 720 Ala Pro Val Glu Trp Glu Glu Glu Thr Val 725 Thr Asn His Thr Leu 730 Arg 735 Val Met Thr Pro Ala Val Tyr Ala Pro 740 Tyr Asp Val Lys 745 Val Gin Ala 750 He Asn Gin Leu Gly Ser Gly Pro 7 55 Asp Pro Gin Ser Val 760 Thr Leu Tyr 7 65 Ser Gly Glu Asp Tyr Pro Asp 770 Thr Ala Pro Val He 775 His Gly Val Asp 780 Val He Asn Ser Thr Leu 785 Val Lys Val Thr Trp 790 Ser Thr Val Pro Lys 795 800 Asp Arg Val His Gly Arg Leu Lys Gly Tyr 805 Gin He Asn Trp Trp 810 Lys 815 Thr Lys Ser Leu Leu Asp Gly Arg Thr 820 His Pro Lys Glu 825 Val Asn He 830 Leu Arg Phe Ser Gly Gin Λ rrr Z! As π 835 Ssr m w Μθ-h Val Pro 840 Ser· T.eu 845 Ala Phe Ser Glu Phe His Lgu. 850 Thr Val Leu Al 3 Tyr 855 Asn Ser Lys Gly 860 Ala Gly Pro Glu Ser Glu 865 Pro Tyr He Phe Gin 870 Thr Pro Glu Gly Val 875 880 Pro Glu Gin Pro Thr Phe Leu Lys Val He 885 Lys Val Asp Lys Asp 890 Thr 895 Ala Thr Leu Ser Trp Gly Leu Pro Lys 900 Lys Leu Asn Gly 905 Asn Leu Thr 910 Gly Tyr Leu Leu Gin Tyr Gin He 915 He Asn Asp Thr Tyr 920 Glu lie Gly 925 Glu Leu Asn Asp He Asn He 930 Thr Thr Pro Ser Lys 935 Pro Ser Trp His 940 Leu Ser Asn Leu Asn Ala 945 Thr Thr Lys Tyr Lys 950 Phe Tyr Leu Arg Ala 955 960 Cys Thr Ser Gin Gly Cys Gly Lys Pro He 965 Thr Glu Glu Ser Ser 970 Thr 975 Leu Gly Glu Gly Ser Lys Gly He Giy 980 Lys Xie Ser Giy 985 Val Asn Leu 990 Thr Gin Lys Thr His Pro lie Glu 995 Val Phe Glu Pro Gly 1000 Ala Glu His 1005 He Val Arg Leu Met Thr Lys 1010 Asn Trp Gly Asp Asn 1015 Asp Ser lie Phe 1020 Gin Asp Val lie Glu Thr 1025 Arg Gly Arg Glu Tyr 1030 Ala ) Giy Leu Tyr Asp 1035 1040 Asp He Ser Thr Gin Gly Trp Phe He Gly 1045 Leu Met Cys Ala He 1050 1055 Ala Leu Leu Thr Leu Leu Leu Leu Thr Val 106C Cys 1 Phe Val Lys 1065 Arg Asn Arg 1070 Gly Gly Lys Tyr Ser Val Lys Glu 1075 Lys Glu Asp Leu His 1080 Pro Asp Pro 1085 Glu He Gin Ser Val Lys Asp 1090 Glu Thr Phe Gly Glu 1095 Tyr Ser Asp Ser 1100 Asp Glu Lys Pro Leu Lys 1105 Gly 1 Ser Leu Arg Ser 1110 Leu I Asn Arg Asp Met 1115 1120 Gin Pro Thr Glu Ser Ala Asp Ser Leu Val 1125 Glu Tyr Gly Glu Gly 1130 1135 Asp His Gly Leu Phe Ser Glu Asp Gly Ser 1140 Phe i He Gly Ala 1145 Tyr Ala Gly 1150 Ser Lys Glu Lys Gly Ser Val Glu 1155 Ser 1 Asn Gly Ser Ser 1160 Thr Ala Thr 1165 Phe Pro Leu Arg Ala 1170 1175 1180 442 <210> 26 <211> 1236

<212> PRT <213> Homo sapians <400> 26

Met 1 X Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 1 c X Phe Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Glv Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu dy He Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys A 1_ Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pl"O Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 2 9 0 2 9 5 3 0 0 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Asp Asn He Ser His Glu Leu Phe 340 345 350 Thr Leu Hrs Pro Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala 355 360 365 Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu cys Glu Ala Glu Gly 370 375 380 Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp 385 390 395 400 Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe 405 410 415 Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Al a Ser 420 425 430 Asn Val His Gly Thr lie Leu Ala Asn Al a Asn He Asp Val Val Asp 435 440 445 443

Val Arg 450 Pro Leu He Gin Thr 455 Lys Asp Gly Glu Asn 460 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu 465 470 475 480 Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly 485 490 495 Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr cnn V V CAC J V cm -J X \J Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala lie 515 520 525 Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys 530 535 540 Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys Leu His Met Leu 545 550 555 560 Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu 565 570 575 Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr 580 585 590 Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu Thr He Ser Asn 595 600 605 Val Thr Leu Glu Asp Gin Gly He Tyr Cys cys Ser Ala His Thr Ala 610 615 620 Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro 625 630 635 640 Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val 645 650 655 Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu 660 665 670 Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu 675 680 685 Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu 690 695 700 Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val 705 710 715 720 Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro 725 730 735 Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin 740 745 750 Pro Lys Glu Met He 1 ± e Lys Trp Glu Pro Leu Ly s Ser Met Glu Gin 755 760 765 Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala 770 775 780 Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val 785 790 7 9 5 800 Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He 805 810 815 Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser 820 825 830 Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His Gly Val Asp Val 835 840 845 lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp 850 855 860 Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn Trp Trp Lys Thr 865 870 875 880 Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu Val Asn He Leu 885 890 895 Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro Ser Leu Asp Al a 900 905 910 Phe Ser Glu Phe His Leu Thr Val Lsu 7k 1 a Tyr Asn Ser Lys Gly Ala 915 920 925 Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro Glu Gly \7 a. 1 Pro 930 935 940 444

Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp Lys Asp Thr Ala 945 Thr Leu Ser Trp Gly 950 Leu Pro Lys Lys Leu 955 Asn Gly Asn Leu Thr 960 Gly Tyr Leu Leu Gin 965 Tyr Gin He He Asn 970 Asp Thr Tyr Glu He 975 Gly Glu Leu Asn Asp 980 He Asn He Thr Thr 985 Pro Ser Lys Pro Ser 990 Trp His Leu Ser Asn 995 Leu Asn Ala Thr Thr 1000 Lys I Tyr Lys Phe Tyr 1005 Leu Arg Ala Cys Thr 1010 Ser i Gin Gly Cys Gly 1015 Lys Pro lie Thr Glu 1020 Glu 1 Ser Ser Thr Leu 1025 Gly Glu Gly Ser Lys 1030 Gly lie Gly Lys lie 1035 Ser Gly Val Asn Leu 1040 Thr Gin Lys Thr His 1045 Pro He Glu Val Phe 1050 Glu 1 Pro Gly Ala Glu 1055 His » lie Val Arg Leu 1060 Met Thr Lys Asn Trp 1065 Gly Asp Asn Asp Ser 1070 lie 1 Phe Gin Asp Val 1075 He 1 Glu Thr Arg Gly 1080 Arg 1 Glu Tyr Ala Gly 1085 Leu Tyr Asp Asp lie 1090 Ser 1 Thr Gin Gly Trp 1095 Phe He Gly Leu Met HOC Cys 1 Ala He Ala Leu 1105 Leu Thr Leu Leu Leu 1110 Leu 1 Thr Val Cys Phe 1115 Val Lys Arg Asn Arg 1120 Gly Gly Lys Tyr Ser 1125 Val Lys Glu Lys Glu 113C Asp I Leu His Pro Asp 1135 Pro 1 Glu He Gin Ser 1140 Val Lys Asp Glu Thr 1145 Phe Gly Glu Tyr Ser 1150 Asp 1 Ser Asp Glu Lys 1155 Pro 1 Leu Lys Gly Ser 1160 Leu 1 Arg Ser Leu Asn 1165 Arg Asp Met Gin Pro 1170 Thr 1 Glu Ser Ala Asp 1175 Ser Leu Val Glu Tyr 118C Gly I Glu Gly Asp His 1185 Gly Leu Phe Ser Glu 1190 Asp 1 Gly Ser Phe He 1195 Gly Ala Tyr Ala Gly 1200 Ser Lys Glu Lys Gly 1205 Ser Val Glu Ser Asn 1210 Gly Ser Ser Thr Ala 1215 Thr Phe Pro Leu Arg 1235 1220 Ala 1 1225 1230 <210> 27 <211> 1195 <212> PRT <213> Homo <400> 27

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin 17-, &amp;#906; v ax Pro nru -u-X iiX He τ ι --. x xc Lys Gin Ser Lys Val &amp;#906; χ-, &lt;5 J_ii Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 As n Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 445

Lys Leu 130 Glu His He Glu Gin 135 Asp Glu Arg Val Tyr 140 Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr lie Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 1 n c iO J ι η λ X Z! V Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu lie Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 245 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cvs Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Asp 290 295 300 Asn lie Ser His Glu Leu Phe Thr Leu His Pro Glu Pro Pro Arg Trp 305 310 315 320 Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He 325 330 335 Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg 340 345 350 Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val 355 360 365 Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala 370 375 380 Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn 385 390 395 400 Ala Asn He Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp 405 410 415 Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu Hrs Cys 420 425 430 Glu Phe Phe Al a Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu 435 440 445 Glu Val Lys Pro Leu Glu Giy Arg Arg Tyr His lie Tyr Glu Asn Gly 450 455 460 Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser 465 470 475 480 Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu 485 490 495 Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg 500 505 510 He Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp 515 520 525 Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu 530 C QC J D 540 Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He He lie Asp Gly 545 550 555 560 Ala Asn Leu Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr 565 570 57 5 Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin 580 585 590 Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser 595 600 605 Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp 610 615 620 446

His 625 Asn Ser Asn He Ser 630 Glu Tyr He Val Glu 635 Phe Glu Gly Asn Lys 640 Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys 645 650 655 Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg 660 665 670 Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser 675 680 685 Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn 690 695 700 lie Arg Val Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu 705 710 715 720 Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val 725 730 735 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val 740 745 750 Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr 755 760 765 Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro 770 775 780 Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro 785 790 795 800 Val He His Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr 805 810 815 Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr 820 825 830 Gin lie Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His 835 840 845 Pro Lys Glu Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly 850 855 860 Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu 865 870 875 880 Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe 885 890 895 Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He 900 905 910 Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys 915 920 925 Leu Asn Gly As n Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn 930 935 940 Asp Thr Tyr Glu He Gly Glu Leu Asn Asp lie Asn He Thr Thr Pro 945 950 955 960 Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr 965 9 7 0 975 Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He 980 985 990 Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys 995 1000 1005 lie Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe 1010 1015 1020 /-1,, "O V* x-\ /-1,, 7\ 1 -, /-1,, Hrs τ 1 Λ TT« 1 Arg Lsu Met mV, ·— Lys 7\ m /-1,, &amp;#908; J- U h 1- &lt;2 j- y ΛΧ. CL U-LU 1J.C v a. j. X ilX 1025 1030 1035 1040 Asp Asn Asp Ser lie Phe Gin Asp Val lie Glu Thr Arg Gly Arg Glu 1045 1050 1055 Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe lie Gly 1060 1065 1070 Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys 1075 1080 1085 Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu 1090 1095 1100 Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe 1105 1110 1115 1120 447

Gly Glu Tyr Ser Asp 1125 Ser Asp Glu Lys Pro 1130 Leu Lys Gly Ser Leu Arg 1135 Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val 1140 1145 1150 Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe 1155 1160 1165 lie Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn 1170 1175 1180 Gly Ser Ser Thr Ala Thr Phs Pro Leu Arg Ala 1185 1190 1195 <210> 28 <211> 1224 <212> PRT <213> Homo : sapians <400> 28 Μθ t Glu Px*o £.θυ Lgu Lau m iz &amp; rrr m iz Lou He Val Tvr Lou Met Phe j —-* j 1 5 10 15 Phe Leu Leu Ly s Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His lie Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr lie Leu Lys Gly Giu 260 265 270 He Leu Leu Leu Glu Cvr — J. — Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 448

Pro Gin Ser 355 Ala Val Tyr Ser Thr 360 Gly Ser Asn Gly He 365 Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin A n c *iUJ A &amp;#906; Λ ± U 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr I le Val Glu Phe Glu Giy Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Giu Gin Asn Giy Pro Giy Leu Giu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 449

Val Pro 850 Lys Asp Arg Val His 855 Gly Arg Leu Lys Gly 860 Tyr Gin He Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn lie Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 8 9 0 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 9 0 0 905 η ι λ y ± υ Ser Lys Gly A_la Cl v — “ J. Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val lie Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu lie Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tvr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys dy Ser Leu Arg Ser Leu Asn 115! 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Ly s Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 29

<211> 1224 <212> PRT <213> Homo sapians <400> 29

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 450

Phe Asp 50 Glu Tyr Phe Gin He 55 Glu Cys Glu Ala Lys 60 Gly Asn Pro Glu Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro Xie 17 a 1 Leu Pro Cys As n Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His lie Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu T,vs —a ~ Α=:η ---r~ Ser Arn ----J Asn Asn ---£. Tyr fvs ~ J. ~ PVA Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr lie Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 4 00 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Al a Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 451

Leu 545 His Met Leu Glu Leu 550 His Cys Glu Ser Lys 555 Cys Asp Ser His Leu 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 5 9 5 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 As n Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn lie Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin Tie He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala cys Thr Ser Gin Gly Cys Gly Lys Pro Tie Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 452

Val Asn Leu Thr Gin 1045 Lys Thr His Pro He 1050 Glu 1 Val Phe Glu Pro 1055 Gly Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1 r\ n r ι λ n c i 1 η n X U 27 U x u y D χ χ v υ Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Glv Ser Phe He Glv Ala 1185 1190 1195 12 0 0 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 30 <211> 1224

<212> PRT <213> Homo sapians <400> 30

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He lie Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He 'val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser SS3S Ser Ser Thr Glu He Gly 225 230 235 240 453

Ser Lys Ala Asn Ser 245 lie Lys Gin Arg Lys 250 Pro Lys Leu Leu Leu 255 Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr lie Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Giy Arg Glu Ala Lys 290 2 9b 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu lie Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly Xie Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Giy Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 454

Gin Ala Ser Gin 740 Pro Lys Glu Met lie 745 lie Lys Trp Glu Pro 750 Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 7 9 0 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val lie His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin lie He Asn Asp Thr Tyr 965 970 975 Glu lie Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro lie Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys lie Ser Gly 1025 10 3 0 103 5 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 10 8 0 10 85 i Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu τ 1 X 1C UrXli Ser Val Lys As jj /-1 1. O1U Thr Phe Gly Glu. Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Al a 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr 3. ci Thr Phe Pro Leu Arg Ala 1220 455 <210> 31

<211> 1224 <212> PRT <213> Homo sapians

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu. Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Al a He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Glv Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Al a Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu 2 60 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 456

Asp Val Val 435 Asp Val Arg Pro Leu 440 lie Gin Thr Lys Asp 445 Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin /inc *4 O &amp;#9633; /inn λ n c *4 J He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr 1· .j. Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He Tie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 7 80 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asp Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 dy Val Asp 'val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 457

Glu Gly 930 Val Pro Glu Gin Pro 935 Thr Phe Leu Lys Val 940 He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu lie Gly Glu Leu Asn Asp lie Asn He Thr Thr Pro Ser Lys Pro q q n J \J V QQK jj O a QQA JS JS \J Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 32 <211> 1224

<212> PRT <213> Homo sapians <400> 32

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 /*« 1 kJili V al Pro x ill. He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 4 5 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser As n Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 458

Ser Val 130 Pro Lys Leu Pro Lys 135 Glu Lys He Asp Pro 140 Leu Glu Val Glu Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 1 o A 1 o u 185 &amp;#943; η λ i :7 U Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys cys Phe Al a Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 2 3 0 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 4 4 5 Tyr Ala Thr Val Val ciy Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 4 6 5 4 7 0 475 4 80 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Al a His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 459

Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val C Π c υ / -> C O A υ ο v < o c U U -J lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val lie His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin lie Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu G1 y Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Sex' Thi' Leu Gly Giu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1031 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His Tie Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 10 6 5 1070 Ser He P he Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 460

Arg Asn Arg Gly Gly Lys 1125 Tyr Ser Val Lys 1130 Glu Lys Glu Asp Leu 1135 His Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1 1 "7 ι ---,-. inn/? XX/' LZ 11 / J X X O U Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe Thr Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 33 <211> 1224 <212> PRT <213> Homo ι sapians <400> 33 Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 16 5 170 17 5 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 Τ Λ A ZL -± V Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro ol n Val 275 280 285 Asp Trp Asn Lys He Gly Giy Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 461

Lys Gly Asn Tyr Arg 325 Cys Thr Ala Ser Asn 330 Phe Leu Gly Thr Ala 335 Thr His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 37 0 37 5 3 8 0 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Al a Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr lie Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin T.vs — J _ Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala lie Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg lie He lie Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 67 0 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val lie Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Al a Ser Gin Pro Lys Glu Met He Ils Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 462

Thr Leu Tyr Ser 820 Gly Glu Asp Tyr Pro Asp 825 Thr Ala Pro Val 830 lie His Gly Val Asp Val lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu O r c OTA ο c q q n ODJ O / U u / -2 u uu Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He lie Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp lie Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Sex? Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 117 5 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 34 <211> 1224

<212> PRT <213> Homo sapians <400> 34

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 15 10 15 463

Leu Leu Leu Lys 20 Phe Ser Lys Ala lie 25 Glu He Pro Ser Ser 30 Val Gin Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp n r\ 00 / u 1 O O U His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tvr ~ j. ~ Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr lie Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu ciy Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu 7k 1 a Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Giu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val 17 1 Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Giu Glu Val Lys 465 470 475 480 Pro Leu Glu ciy Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Al a Gly Ser Tyr Ser Cys Trp Val 500 505 510 464

Glu Asn Ala 515 He Gly Lys Thr Ala 520 Val Thr Ala Asn Leu 525 Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 c n r\ D / U C "7 C &amp;#9633; / -J lie Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly A1 a Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala 1 Asp lie Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu ciy Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala lie Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 82 5 830 Gly Val Asp Val lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 465

Leu Arg Ala Cys Thr Ser Gin Gly Cys 1015 Gly Lys Pro 1020 He Thr Glu Glu 1010 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 10 50 1055 Ala Glu His lie Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp men 1 nee i mn X V V V X V W X V / V Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe lie Gly Leu Met cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 35

<211> 1224 <212> PRT <213> Homo sapians <400> 35

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Al a He Glu 1 le Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 5 0 55 0 u Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He /-il. Phe He TT« 1 ναι Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 V a 1 Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 466

Pro Arg 210 Leu Arg Thr He Val 215 Gin Lys Met Pro Met 220 Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 2 6 0 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys ciy Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tvr " -£ “ Ser Thr Cl v --J. Ser Asn Gly He Leu Leu Cvs - J. — 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu lie Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His ciy Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Giu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Al a Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys As p Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He lie Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 64 5 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 467

Val 705 Asn Glu Val Gly Arg 710 Ser Gin Pro Ser Gin 715 Pro Ser Asp His His 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Giy Pro Giy Leu Glu Tyr Arg Val Thr Trp Lys / b b 7 6&#908; 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val. Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Giy Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lvs Asp Arc Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn lie Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr lie Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu lie Gly Glu Leu Asn Asp He Asn lie Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg 7\. -1 · gX. Cys Thr Ser Gin θ&#943;γ Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Giy Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His lie Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val lie Glu Thr Arg Giy Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 > 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Giy 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe lie Gly Ala 1185 1190 1195 1200 468

Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215

Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 36 <211> 1208

<212> PRT <213> Homo sapians <400> 36

Met 1 Glu Leu Pro Leu 5 Cys Gly Arg Gly Leu 10 He Leu Ser Leu He 15 Phe Leu Leu Leu Lys Leu Ser Ala Ala Glu He Pro Leu Ser Val Gin Gin 20 25 30 Val Pro Thr He Val Lys Gin Ser Tyr Val Gin Val Ala Phe .Pro Phe 35 40 45 Asp Glu Tyr Phe Gin He Glu Cvs ' -i ~ Glu Ala Lys Gly Asn Pro Glu Pro 50 55 60 lie Phe Ser Trp Thr Lys Asp Asp Lys Pro Phe Asp Leu Ser Asp Pro 65 70 75 80 Arg He He Ala Ala Asn Asn Ser Gly Thr Phe Lys He Pro Asn Glu 85 90 95 Gly His He Ser His Phe Gin Gly Lys Tyr Arg cys Phe Ala Ser Asn 100 105 110 Arg Leu Gly Thr Ala Val Ser Glu Glu He Glu Phe He Val Pro Gly 115 120 125 Val Pro Lys Phe Pro Lys Glu Lys He Glu Pro He Asp Val Glu Glu 130 135 140 Gly Asp Ser He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro Pro 145 150 155 160 Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin Asp 165 170 175 Glu Arg Val Tyr Met Ser Gin Arg Gly Asp Leu Tyr Phe Ala Asn Val 180 185 190 Glu Glu Asn Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe Pro 195 200 205 Lys Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val Asn 210 215 220 Ser Ser Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro 2 2 5 230 235 240 Ala Gin Met Gly Ser Leu Ser Ala Lys Thr Val Leu Lys Gly Asp Thr 245 250 2 5 5 Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro His Tie Gin 260 265 270 Trp Ser Lys Pro Gly Ser Glu Leu Pro Glu Gly Arg Ala Thr He Glu 275 280 285 Val His Glu Lys Thr Leu Lys He Glu Asn He Ser Tyr Gin Asp Arg 290 295 300 Gly Asn Tyr Arg Cys Thr Ala Asn Asn Leu Leu Gly Lys Ala Ser His 305 310 315 320 Asp Phe His Val Thr Val Glu Glu Pro Pro Arg Trp Lys Lys Lys Pro 325 330 335 Gin Ser Ala Val Tyr Ser Thr Gly Ser Ser Gly lie Leu Leu Cys Glu 340 345 350 Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Leu Asn Gly Leu 355 360 365 Pro He Glu Lys His Pro Phe Pro Gly Asp Phe Met Phe Pro Arg Glu 370 375 380 He Ser Phe Thr Asn Leu Leu Pro Asn His Thr Gly Val Tyr Gin Cys 385 390 395 400 469

Glu Ala Ser Asn He 405 His Gly Thr lie Leu 410 Ala Asn Ala Asn He 415 Asp Val He Asp Val lie Pro Leu He Lys Thr Lys Asn Glu Glu Asn Tyr 420 425 430 Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His cys Glu Tyr Phe Ala 435 440 445 Ser Pro Lys Ala Thr Val Val Trp Glu Val Ala Asp Glu Thr His Pro Λ C A J U A C C n a a λ £ n t &amp;#908; v Leu Glu Gly Asp Arg Tyr His Thr His Glu Asn Glv Thr Leu Glu lie 465 470 4 7 5 480 Tyr Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val Asp 485 490 495 Asn Ala Met Gly Lys Ala Val He Thr Ala Asn Leu Asp He Arg Asn 500 505 510 Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys Ser 515 520 525 His Val Leu Glu Leu Tyr Cys Glu Ser Gin Cys Asp Ser His Leu Lys 530 535 540 His Ser Leu Lvs Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu Met 545 550 555 560 Asn Gly Thr Glu Asp Gly Arg He Val lie Asp Gly Ala Tyr Leu Thr 565 570 575 lie Ser Asn He Thr Ala Glu Asp Gin Gly Val Tyr Ser cys Ser Ala 580 585 590 Gin Thr Ser Leu Asp Ser Thr Ser Lys Lys Thr Gin Val Thr Val Leu 595 600 605 Gly Val Gly Asp Pro Pro Glu Thr Phe Thr Cys Gin Lys Asp Lys Asn 610 615 620 Arg Ser Val Arg Leu Leu Arg Glu Ala Gly Asp Asp His Asn Ser Lys 625 630 635 640 Ser Ala Ser Thr He Val Glu Phe Glu Gly Asn Arg Glu Glu Pro Gly 645 650 655 Lys Trp Glu Glu Leu Thr Arg Val Gin Gly Glu Glu Thr Asp Val Val 660 665 670 Leu Ser Leu Ala Pro Tyr Val Arg Tyr Gin Phe Arg Val Thr Ala Val 675 680 685 Asn Glu Val Gly Arg Ser His Ala Ser Leu Pro Ser Asp His His Glu 690 695 700 Thr Pro Pro Al a Ala Pro Asp Lys As n Pro Gin Asn He Arg Val Gin 705 710 715 720 Ala Ser Gin Pro Lys Glu Met He lie Lys Trp Glu Pro Leu Lys Ser 725 730 735 Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Lys Val Ser Trp Lys Pro 740 745 750 Gin Gly Ala Pro Glu Glu Trp Glu Glu Glu He Val Thr Asn His Thr 755 760 765 Leu Arg Val Met Thr Pro Thr Val Tyr Ala Pro Tyr Asp Val Lys Val 770 775 780 Gin Ala He Asn Gin Leu Gly Ser Ser Pro Asp Pro Gin Pro Val Thr 785 790 795 800 Leu Tyr Ser Gly Glu Asp Tyr Pro Ser Thr Ala Pro Val lie Gin Arg 805 810 815 Val Asp Val Met Asn Ser Thr Leu Val Lys Val Thr Trp Ser Ser He 820 825 830 Pro Lys Glu Thr Val His Gly Leu Leu Arg Gly Tyr Gin He Asn Trp 835 840 845 Trp Lys Thr Lys Ser Leu Leu Asp Gly Ar g Thr His Pro Lys Glu Val 850 855 860 Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro Ser 865 870 875 880 Leu Asp Pro Phe Ser Glu Phe His Leu Thr Val Leu A1. lx Tyr Asn Ser 885 890 895 470

Lys Gly Ala Gly 900 Pro Glu Ser Glu Pro 905 Tyr He Phe Gin Thr 910 Pro Glu Gly Val Pro Glu Gin Pro Ser Phe Leu Lys Val He Lys Val Asp Lys 915 920 925 Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly Asn 930 935 940 Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He lie Asn Asp Thr Tyr Glu 945 950 9 5 5 n c. n JUU Leu Gly Glu Leu Asn Glu He Asn Val Thr Thr Pro Ser Lys Ser Ser 965 970 975 Trp His Leu Ser Asn Leu Asn Ser Thr Thr Lys Tyr Lys Phe Tyr Leu 980 985 990 Arg Ala Cys Thr Ser Arg Gly Cys Gly Lys Pro He Ser Glu Glu Gly 995 1000 1005 Ala Thr Leu Gly Glu Gly Ser Lys Gly lie Arg Lys He Thr Glu Gly 1010 1015 1020 Val Asn Val Thr Gin Lys He His Pro Val Glu Val Leu Val Pro Gly 1025 1030 1035 1040 Ala Glu His He Val His Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1045 1050 1055 Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1060 1065 1070 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1075 1080 1085 Ala He Ala Leu Leu Thr Leu lie Leu Leu Thr He cys Phe Val Lys 1090 1095 1100 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1105 1110 1115 1120 Pro Asp Pro Glu Val Gin Ser Ala Lys Asp Glu Thr Phe Gly Glu Tyr 1125 1130 1135 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1140 1145 1150 Arg Asn Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1155 1160 1165 Glu Gly Asp Gin Ser He Phe Asn Glu Asp Gly Ser Phe He Gly Ala 1170 1175 1180 Tyr Thr Gly Ala Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1185 1190 1195 1200 Thr Ala Thr Phe Pro Leu Arg Ala 1205 <210> 37 <211> 14

<212> PRT <213> Tetanus toxoid <400> 37

Gin Tyr lie Lys Ala Asn Ser Lys Phe He Gly He Thr Glu 15 10 <210> 38 <211> 21

<212> PRT <213> Plasmodium falciparum <400> 38

Asp He Glu Lys Lys He Ala Lys Met Glu Lys Ala Ser Ser Val Phe 1 5 10 15 Asn Val Val Asn Ser 20 471 <210> <211> <212> <213> 39 16 PRT Streptococcus <400> 39

Gly Ala Val Asp Ser He Leu Gly Gly Val Ala Thr Tyr Gly Ala Ala 1 5 10 15 <210> <211> <212> <213> 40 12 PRT Artificial Sequence <220> <223> pan—DR—binding epitope peptide <221> <222> <223> VARIANT 3 Xaa = cyclohexylalanine, phenylalanine, or tyrosine <221> <222> <223> VARIANT 1, 13 Xaa = D-alanine or L-alanine <400> 40

Xaa Lys Xaa Val Ala Ala Trp Thr Leu Lys Ala Xaa 15 10 <210> <211> <212> <213> 41 14 DNA Artificial Sequence <220> <223> cDNA synthesis primer <400> 41 ttttgatcaa gctt <210> <211> <212> <213> 42 42 DNA Artificial Sequence <220> <223> Primer <400> 42 ctaatacgac tcactatagg gctcgagcgg ccgcccgggc ag 42 <210> <211> <212> <213> 43 12 DNA Artificial Sequence <220> 472 <223> Primer <400> 43 gatcctgccc gg 12 <210> <211> <213> 44 40 DNA Artificial Sequence <220> <223> Primer <400> 44 gtaatacgac tcactatagg gcagcgtggt cgcggccgag 40 <210> <211> <212> <213> 45 10 DNA Artificial Sequence <220> <223> Primer <400> 45 gatcctcggc 10 <210> <211> <212> <213> 46 22 DNA Artificial Sequence <220> <223> PCR Primer <400> 46 ctaatacgac tcactatagg gc 22 <210> <211> <212> <213> 47 22 DNA Artificial Sequence <220> <223> Nested Primer (NP)1 <400> 47 tcgagcggcc gcccgggcag ga 22 <210> <2 1 i> <212> <213> 48 2 0 DNA Artificial Sequence <220> <223> Nested Primer (NP)2 <400> 48 agcgtggtcg cggccgagga 20 <210> 49 <211> 25 473

<212> DNA <213> Artificial Sequence <220> <223> Primer <400> 49 atfitCyCCyC yCtCCjtCytC yaCafl <210> 50 <211> 26

<212> DNA <213> Artificial Sequence <220> <223> Primer <400> 50 agccacacgc agctcattgt agaagg <210> 51 <211> 25

<212> DNA <213> Artificial Sequence <220> <223> RT-PCR Primer <400> 51 taaggtctca gctgtaaacc aaaag 26 25 <210> 52 <211> 25

<212> DNA <213> Artificial Sequence <220> <223> RT-PCR Primer <400> 52 ctgttttaag attgttggaa cctgt 25 <210> 53 <211> 24

<212> DNA <213> Artificial Sequence <220> <223> FLAG Tag <4u0> 53 gattacaagg atgacgacga taag 24 <210> 54 <211> 4

<212> PRT <213> Homo sapians <400> 54

Asn Asn Ser Gly 1 474 <210> 55 <211> 4 <212> PRT <213> Homo sapians <400> 55 7\ z~. v-, a a non na 1 ip DCJ- UCL <210> 56 <211> 4 <212> PRT <213> Homo sapians <400> 56

Asn Val Ser Tyr 1 <210> 57 <211> 4

<212> PRT <213> Homo sapians <400> 57

Asn His Thr Ala 1 <210> 58 <211> 4

<212> PRT <213> Homo sapians <400> 58

Asn Gly Thr Leu 1 <210> 59 <211> 4

<212> PRT <213> Homo sapians <400> 59

Asn Arg Thr Thr 1 <210> 60 <211> 4

<212> PRT <213> Homo sapians <400> 60

Asn Ala Thr Lys 1 <210> 61 475 <211> 4

<212> PRT <213> Homo sapians <400> 61

Asn Gly Thr Glu 1 <210> 62 <211> 4

<212> PRT <213> Homo sapians <400> 62

Asn Leu Thr lie 1 <210> 63 <211> 4

<212> PRT <213> Homo sapians <400> 63

Asn Val Thr Leu 1 <210> 64 <211> 4

<212> PRT <213> Homo sapians <400> 64

Asn Arg Ser Val 1 <210> 65 <211> 4

<212> PRT <213> Homo sapians <400> 65

Asn He Ser Glu 1 <210> 66 <211> 4

<212> PRT <213> Homo sapians <4 0 0> 6 6

Asn His Thr Leu 1 <210> 67 <211> 4

<212> PRT 476 <213> Homo sapians <400> 67

Asn Ser Thr Leu 1 <211> 4

<212> PRT <213> Homo sapians <400> 68

Asn Leu Thr Gly 1 <210> 69 <211> 4

<212> PRT <213> Homo sapians <400> 69

Asn Asp Thr Tyr 1 <210> 70 <211> 4

<212> PRT <213> Homo sapians <400> 70

Asn lie Thr Thr 1 <210> 71 <211> 4

<212> PRT <213> Homo sapians <400> 71

Asn Ala Thr Thr 1 <210> 72 <211> 4

<212> PRT <213> Homo sapians <400> 72

Asn Leu Thr Gin 1 <210> 73 <211> 4

<212> PRT <213> Homo sapians 477 <400> 73

Asn Asp Ser lie 1 <210> 74 <211> 4 <2 12> PRT <213> Homo sapians <400> 74 Asn Gly Ser Ser 1 <210> 75 <211> 15 <212> PRT <213> Homo sapians <400> 75 Thr Leu Tyr Ser Gly 1 5 <210> 76 <211> 15 <212> PRT <213> Homo sapians <400> 76 Gly Arg Glu Tyr Ala 1 5 <210> 77 <211> 15 <2 12> PRT <2 13> Homo sapians <400> 77 Lys Asp Glu Thr Phe 1 5 <210> 78 <211> 15 <212> PRT <213> Homo sapians <400> 7 8 Ser Al .a Asp Ser Leu 1 5 <210> 7 g <211> 4 <212> PRT <2 13> Homo sapians <400> 79

Lys Lys Thr Thr

Glu Asp Tyr Pro Asp Thr Ala Pro Val He 10 15

Gly Leu Tyr Asp Asp He Ser Thr Gin Gly 10 15

Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro 10 15

Val Glu Tyr Gly Glu Gly Asp His Gly Leu 10 15 478 <210> 80 <211> 4

<212> PRT <213> Homo sapians <400> 80

Ser Arg Asn Asp 1 <210> 81 <211> 4

<212> PRT <213> Homo sapians <400> 81

Ser Ser Thr Glu 1 <210> 82 <211> 4 <212> PRT <213> Homo sapians <400> 82 Ser Gly Ser Glu 1 <210> 83 <211> 4 <212> PRT <213> Homo sapians <400> 83 Ser Tyr Gin Asp 1 <210> 84 <211> 4 <212> PRT <213> Homo sapians <400> 84

Ser Pro Val Asp 1 <210> 85 <211> 4

<212> PRT <213> Homo sapians <400> 85

Thr Thr Glu Glu 1 479 <210> 86 <211> 4 <212> PRT <213> Homo sapians <400> 86 Thr Glu Glu Asy 1 <210> 87 <211> 4 <212> PRT <213> Homo sapians <400> 87

Ser Lys Cys Asp 1 <210> 88 <211> 4

<212> PRT <213> Homo sapians <400> 88

Thr Leu Glu Asp 1 <210> 89 <211> 4

<212> PRT <213> Homo sapians <400> 89

Thr Ala Leu Asp 1 <210> 90 <211> 4

<212> PRT <213> Homo sapians <400> 90

Ser Ala Ala Asp 1 <210> 91 <211> 4

<212> PRT <213> Homo sapians <400> 91

Thr Val Leu Asp 1 <210> 92 480 <211> 4 <212> PRT <213> Homo sapians <400> 92 Ser G1 .y Pro Asp 1 <210> 93 <211> 4 <212> PRT <213> Homo sapians <400> 93 Ser Gly Glu Asp 1 <210> 94 <211> 4 <212> PRT <213> Homo sapians <400> 94 Ser Leu Leu Asp 1 <210> 95 <211> 4 <212> PRT <213> Homo sapians <400> 95 Thr Leu Gly Glu 1 <210> 96 <211> 4 <212> PRT <213> Homo sapians <400> 96 Ser Val Lys Glu 1 <210> 97 <2 11> 4 <212> PRT <213> Homo sapians <400> 97

Ser Val Lys Asp 1 <210> 98 <211> 4

<212> PRT 481 <213> Homo sapians <400> 98 Thr Phe Gly Glu 1 <210> Ω Ω J J <211> 4 <212> PRT <213> Homo sapians <400> 99

Ser Asp Ser Asp 1 <210> 100 <211> 4

<212> PRT <213> Homo sapians <400> 100

Ser Leu Val Glu 1 <210> 101 <211> 6 <212> PRT <213> Homo sapians <400> 101 Lys Pro Leu Arg Arg 1 5

Tyr <210> 102 <211> 6 <212> PRT <213> Homo sapians <400> 102 Gly I le Ala Met Ser 1 5

Glu <210> 103 <211> 6 <212> PRT <2 13> Homo sapians <400> 103 Gly Ser Lys Ala Asn 1 5

Ser <210> 104 <211> 6 <212> PRT <213> Homo sapians 482 <400> 104 Gly Ser Glu Ser Ser 1 5 <210> 105 <211> 6 PRT <213> Homo sapians <400> 105 Gly Asn Tyr Arg Cys 1 5 <210> 106 <211> 6 <212> PRT <213> Homo sapians <400> 106 Gly He Leu Leu Cys 1 5 <210> 107 <211> 6 <212> PRT <213> Homo sapians <400> 107 Gly Thr He Leu Ala 1 5 <210> 108 <211> 6 <212> PRT <213> Homo sapians <400> 108 Gly Ser Tyr Ser Cys 1 5 <210> 109 <211> 6 <212> PRT <213> Homo sapians <400 &#906; A Π 1U? Gly Thr Glu Asp Gly 1 5 <210> 110 <211> 6 <212> PRT <213> Homo sapians <400> 110

Gly Ala Asn Leu Thr lie 483 <210> <211> <2 12> <213> 111 6 PRT Homo sapians <400> 111

Gly lie Tyr Cys Cys Ser 1 5 <210> <211> <212> <213> 112 6 PRT Homo sapians <400> 112

Gly Ala Asp His Asn Ser 1 5 <210> <211> <212> <213> 113 6 PRT Homo sapians <400> 113

Gly Gin Arg Asn Ser Gly 1 5 <210> <211> <212> <213> 114 6 PRT Homo sapians <400> 114

Gly Met Val Pro Ser Leu 1 5 <210> <211> <212> <213> 115 6 PRT Homo sapians <400> 115

Gly Asn Leu Thr Gly Tyr 1 5 <210> <211> <212> <213> 116 6 PRT Homo sapians <400> 116

Gly Val Asn Leu Thr Gin 1 5 484 <210> 117 <211> 6

<212> PRT <213> Homo sapians <400> 117

Gly Lsu Met Cys Al 1 5 <210> 118 <211> 6

<212> PRT <213> Homo sapians <400> 118

Gly Gly Lys Tyr Ser Val 1 5 <210> 119 <211> 6

<212> PRT <213> Homo sapians <400> 119

Gly Ser Leu Arg Ser Leu 1 5 <210> 120 <211> 6

<212> PRT <213> Homo sapians <400> 120

Gly Ser Phe lie Gly Ala 1 5 <210> 121 <211> 6

<212> PRT <213> Homo sapians <400> 121

Gly Ala Tyr Ala Gly Ser 1 5 <210> 122 <211> 6

<212> PRT <213> Homo sapians <4 0 0> 122

Gly Ser Val Glu Ser Asn 1 5 <210> 123 485 <211> 6

<212> PRT <213> Homo sapians <400> 123

Gly Ser Ser Thr Ala Thr 1 5 <210> 124 <211> 4

<212> PRT <213> Homo sapians <400> 124

Glu Gly Arg Arg 1 <210> 125 <211> 4

<212> PRT <213> Homo sapians <400> 125

Gin Gly Lys Lys 1 <210> 126

<211> 1224 <212> PRT <213> Homo sapians <400> 126

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He I le Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro P he Tyr Phe Thr Asp 65 70 7 5 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg lie Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu He Glu Phe lie Val Pro lie χ χ a χζ&amp;#971; 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr cys cys Phe Ala Ala Phe 195 2 0 0 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 486 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 He Leu Leu Le11 Glu Pvo '“'J ux Phe Ala Glu m xr Leu Pro Thy Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala lie Gly Lys Thr Ala. Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys ,., * Leu Lys Leu L^y s Asp G±y Glu Ala η&amp;#905;θ G1 u HIS ser il'p &amp;#972;β&amp;#970; 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 /"'&amp;#906;Α ozu Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Sey Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Cj -L. U Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 487 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn Hrs 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He lie Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn lie Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 100C 1 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro lie Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser ciy 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu Hrs He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 108C ι 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys line X X V —' 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 116C ι 116 5 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe lie Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 488 1205

Thr Ala Thr Phe Pro Leu Arg Ala 1220 1210 1215 <210> 127 <211> 17

<212> PRT <213> Homo sapians <400> 127

Phe lie Val Pro Ser Val Pro Lys Phe Pro Lys Glu Lys lie Asp Pro 1

Leu 10 15 <210> <211> <212> 128 17

PRT <213> Homo sapians <400> 128

Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys Glu Asn Tyr Gly Lys Thr 1

Leu 10 15 <210> 129 <211> 17

<212> PRT <213> Homo sapians <400> 129

Glu Ser Ser Thr Leu Gly Glu Gly Lys Tyr Ala Gly Leu Tyr Asp Asp 1

He 10 15 <210> 130 <211> 19

<212> PRT <213> Homo sapians <400> 130

Glu Phe He Val Pro Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp 15 10 15

Pro Leu Glu <210> 131 <211> 19

<212> PRT <213> Homo sapians <400> 131

Gly Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys Glu Asn Tyr Gly Lys 1 5 10 15

Thr Leu Lys 489 <210> 132 <211> 19

<212> PRT <213> Homo sapians <400> 132

Glu Glu Ser Ser Thr Leu Gly Glu Gly Lys Tyr Ala Gly Leu Tyr Asp 15 10 15

Asp lie Ser <210> 133 <211> 29

<212> PRT <213> Homo sapians <400> 133

Met 1 Ser Glu Glu He 5 Glu Phe lie Val Pro 10 Ser Val Pro Lys Phe Pro 15 Lys Glu Lys He 20 Asp Pro Leu Glu Val 25 Glu Glu Gly Asp <210> 134 <211> 29

<212> PRT <213> Homo sapians <400> 134

Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys 1 5 10 15 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser 20 25 <210> 135 <211> 29

<212> PRT <213> Homo sapians <400> 135

Gly 1 Lys Pro lie Thr 5 Glu Glu Ser Ser Thr Leu Gly 10 Glu Gly Lys Tyr 15 Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe 20 25 <210> 136 <211> 70

<212> PRT <213> Homo sapians <400> 136

Val 1 He His Gly Val 5 Asp Val He Asn Thr 10 Thr Tyr Val Ser Asn 15 Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser Pro Gin Pro Ser lie Phe He 20 25 30 Cys Ser Lys Glu Gin Glu Leu Ser Tyr Arg Asn Arg Asn Met Leu Ala 490 35 40 45

Glu Asp Phe lie Gin Lys Ser Thr Ser Cys Asn Tyr Val Glu Lys Ser 50 55 60

Ser Thr Phe Phe Lys He 65 70 Z" 1 n-. 137 <211> 71

<212> PRT <213> Homo sapians <400> 137

Pro 1 Val He His Gly 5 Val Asp Val He Asn 10 Thr Thr Tyr Val Ser 15 Asn Thr Thr Tyr Val Ser Asn AT a. Thr Gly Ser Pro Gin Pro Ser He Phe 20 25 30 He Cys Ser Lys Glu Gin Glu Leu Ser Tyr Arg Asn Arg Asn Met Leu 35 40 4 5 Ala Glu Asp Phe Ire Gin Lys Ser Thr Ser Cys Asn Tyr Val Glu Lys 50 55 60 Ser Ser Thr Phe Phe Lys lie 65 70 <210> 138 <211> 76

<212> PRT <213> Homo sapians <400> 138

Tyr 1 Pro Asp Thr Ala 5 Pro Val He His Gly 10 Val Asp Val He Asn 15 Thr Thr Tyr Val Ser Asn Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser Pro 20 25 30 Gin Pro Ser lie Phe He Cys Ser Lys Glu Gin Glu Leu Ser Tyr Arg 35 40 45 Asn Arg Asn Met Leu Ala Glu Asp Phe He Gin Lys Ser Thr Ser cys 5 0 55 60 Asn Tyr Val Glu Lys Ser Ser Thr Phe Phe Lys He 65 70 75 <210> 139 <211> 17

<212> PRT <213> Homo sapians <400> 139

Val Thr Leu Tyr Ser Gly Glu Asp Leu Pro Glu Gin Pro Thr Phe Leu 15 10 15

Lys <210> 140 <211> 19

<212> PRT <213> Homo sapians <400> 140

Ser Val Thr Leu Tyr Ser Gly Glu Asp Leu Pro Glu Gin Pro Thr Phe 491 15 10 15

Leu Lys Val <210> 141 <211> 29

<212> PRT <213> Homo sapians <400> 141

Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Leu Pro 1 5 10 15 Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp Lys 20 25 <210> 142 <211> 17

<212> PRT <213> Homo sapians <400> 142

Pro Met Lys Leu Thr Val Asn Ser Ser Asn Ser lie Lys Gin Arg Lys 15 10 15

Pro <210> 143 <211> 19

<212> PRT <213> Homo sapians <400> 143

Met Pro Met Lys Leu Thr Val Asn Ser Ser Asn Ser lie Lys Gin Arg 15 10 15

Lys Pro Lys <210> 144 <211> 29

<212> PRT <213> Homo sapians <400> 144

Thr 1 He Val Gin Lys 5 Met Pro Met Lys Leu 10 Thr Val Asn Ser Ser Asn 15 Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro 20 25 <210> 145 <211> 17

<212> PRT <213> Homo sapians <400> 145

Glu Glu He Glu Phe He Val Pro Lys Leu Glu His lie Glu Gin Asp 15 10 15

Glu 492 <210> 146 <211> 19

<212> PRT <213> Homo sapians <400> 146

Ser Glu Glu lie Glu Phe He Val Pro Lys Leu Glu His He Glu Gin 15 10 15

Asp Glu Arg <210> 147 <211> 29 <212> PRT <213> Homo sapians <400> 147

Leu Gly lie Ala Met Ser Glu Glu He Glu Phe He Val Pro Lys Leu 1 5 10 15 Glu His lie Glu Gin Asp Glu Arg Val Tyr Met Ser Gin 20 25 <210> 148 <211> 28

<212> PRT <213> Homo sapians <400> 148

His Asp Phe His Val He Val Glu Asp Asn He Ser His Glu Leu Phe 1 5 10 15 Thr Leu His Pro Glu Pro Pro Arg Trp Thr Lys Lys 20 25 <210> 149 <211> 30 <212> PRT <213> Homo sapians <400> 149 Thr His Asp Phe His 1 5 Phe Thr Leu His Pro 20

Val He Val Glu Asp 10 Glu Pro Pro Arg 25 Trp

Asn lie Ser His Glu 15 Thr Lys Lys Pro 30

Leu <210> 150 <211> 40

<212> PRT <213> Homo sapians <400> 150

Phe 1 Leu Gly Thr Ala 5 Thr His Asp Phe His 10 Val He Val Glu Asp 15 Asn He Ser His Glu Leu Phe Thr Leu His Pro Glu Pro Pro Arg Trp Thr 20 25 30 Lys Lys Pro Gin Ser Ala Val Tyr 493 35 40 <210> 151 <211> 7491

<212> DNA <213> Homo sapians <400> 151 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagq atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaattc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaagca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc 3000 ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg 3060 agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt 3120 atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca 3180 494 gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga agggaaatat gctggtttat atgatgacat ctccactcaa ggctggttta ttggactgat gtgtgcgatt gctcttctca cactactatt attaactgtt tgctttgtga agaggaatag aggtggaaag tactcagtta aagaaaagga agatttgcat ccagacccag aaattcagtc agtaaaagat gaaacctttg gtgaatacag tgacagtgat gaaaagcctc tcaaaggaag ccttcggtcc cttaataggg atatgcagcc tactgaaagt gctgacagct tagtcgaata cggagaggga gaccatggtc tcttcagtga agatggatca tttattggtg cctacgctgg atctaaggag aagggatctg ttgaaagcaa tggaagttct acagcaactt ttccccttcg ggcataaaca caacatatgt aagcaacgct actggttcac cccaaccttc catatttatc tgttcaaagg agcaagaact ttcatatagg aatagaaaca tgctggccga agatttcatc cagaagtcaa catcctgcaa ttatgttgaa aagagtagta ctttcttcaa aatataaaat gccaagcact tcaggcctat gttttgctta tattgttttc aggtgctcaa aatgcaaaac acaaaacaaa tcctgcattt agatacacct caactaaatc caaagtcccc attcagtata ttccatattt gcctgatttt actattcggt gtgtttgcat agatgttgct acttggtggg tttttctccg tatgcacatt ggtatacagt ctctgagaac tggcttggtg actttgcttc actacaggtt aaaagaccat aagcaaactg gttatttaaa atgtaaaaag gaatatgaaa gtcttattaa aacacttcat tgaaaatata cagtctaaat ttattattta aattttacta gcaaaagtct taggtgaaca atcaactagt atttgttgag ctcctatttg cccagagatg gtcatattta aacagaagta tacgtttttc agtttcaaca tgaatttttt tatttctgtc agttatgaca tccacgagca tcactttttg tgtctgtttt tttttttttc ttggactaaa ttcaactgca tggaagcggt ggtcagaagg ttgttttata cgagaacagg cagaaagtgc ccattgttca ggattctaat agctacatct acttaatatc ttcatttcta aattgactgc ttttaccttt ttctcatgtt tatataatgg tatgcttgca tatatttcat gaatacattg tacatattat gttaatattt acacaattta aaatatagat gtgttttatt ttgaagtgag aaaatgaaca ttaacaggca tgtttgtaca gctagaatat attagtaaga tactgttttt cgtcattcca gagctacaac taataacacg aggttccaaa gctgaagact ttgtataaag tatttgggtt ttgttcttgt attgctttct ttcaacagtt tcaaaataaa atatcataca aatattgagg gaaatgtttt catatttttc aaaataggtt tttattgttg aatgtacatc taccccagcc cctcaaaaga aaaactgttt acatagaaat tcctacacat acgtttgcgt atatgttatt ttaaacatct ttgtggtgag aattttttcc ccgatattct ccttctgtca aagtcagaac aaattcaggg aatttatttt ctggcagttg tgctccagtc cttttaaaat tgtacatgaa catgttttag aaacaatatg gaggatgatg catacatgtc ggtcaagttc agcgctcgac attttatgga aagatttttt taaccttacc acgaaatact taactactgt ttaagtgaat tgacttattt cactttagtt tttgaactgt gattattggt atactgttat atcctcaact tggatttatg gtaacccctt ttagttcatg gagaccaaaa tttggggtat ttataatagt cagcgcagga atgcacatgg aatatctact tgtccttttg aacctcacga gtcatccaga atgtatagac aggaaaagca tgtcttattt aaaactgtaa tttatgggct caggatctga ccgcagtccc gggagtaagc atttcaaagg gggaaggcag tgtggtccct accctgtgtg aatgtgagga tgtagacatc catcagtgca actcgagctc catcctcctc cgatttctaa ggctccagtt ttctggaggg acagtcatca tgttttgatt tatctgggag aaaactgtgg tgcacagctt gtgaggaggg caaggttgtg acgttcgagc ttagttctgg tgttattctg tctcctcttc tttgtcatca gccaaaacgt ggtttttaaa gagagtcatg caggttagaa ataatgtcaa aaatatttag gaatttaata acctttaagt cagaaactaa aacaaatact gaaatattag ctcttcctac acttcgtgtt cccctttagc tgcctgaaaa tcaagattgc tcctactcag atcttctgag tggctaaaac ttatggatat gaaaaatgag attgaatgat gactatgctt tgctatcatt gttacctttc ctcaatacta tttggcaact actgggactc ttcagcacaa aaggaataga tctatgattg accctgattt taattgtgaa attatatgat tcatatattt tatgaatcag aataaccttc aaataaaata aatctaagtc ggttaaaatg gatttcatga ttttccctca gaaaatgagt aacggagtcc acggcgtgca atggtaatta taaattggtg atgcttgttt gcaaattgcc cactcgtgat aagtcaacag ccaatattta aaactttgtt cgttactggc tttaccctaa ctttctctag tctactgtca atatcatttt aatgtaattg attgtatata gtctcaagaa tggttggtgg gcatgagttc ctagagaact gtccaagggt tgggaaaatc caaattctct tcctggctcc agcactgatt ttgtacataa acattaggca ggttgcttaa cctttttatt tcaaactctc tcaactctaa agtgctaata ataatctcag ttaccttatc tttgtcacag ggtgttcttt tttatgaaga aaaatttgaa aatgataaaa gctaagatgc cttctaactt cataagcaaa cctttaacta attatgtatc tgaaagtcac ccccacatac caactcaact tttttcctgt gaacacataa atatattttt atagaaaaac aaatctacat aaaataaatc tactgtttag tgagcagtat gacttgtaca tgccattgaa aattattaat cagaagaaaa ttaagcaggg tctttgctat acaaaagtgt tttccactaa ttttgcatgc gtatttataa gaaaaatgtg aatttggtgg 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 495 ttttattcta tcggtataaa ggcatcgata ttttagatgc acccgtgttt gtaaaaatgt 6960 agagcacaat ggaattatgc tggaagtctc aaataatatt tttttcctat tttatactca 7020 tggaagagat aagctaaaga ggggacaata atgagaaatg ttggtgtgct tttctaagca 7080 tttaaaacat aattgccaat tgaaacccta aatatgttta cataccatta agatatgatt 7140 catgtaacaa tgttaaatta attataatgg gattgggttt gttatctgtg gtagtatata 7200 tcctagtgtt cctatagtga aataagtagg gttcagccaa agctttcttt gttttgtacc 7260 ttaaattgtt cgattacgtc atcaaaagag atgaaaggta tgtagaacag gttcacgtga 7320 ttaccttttt cttttggctt ggattaatat tcatagtaga actttataaa acgtgtttgt 7380 attgtaggtg gtgtttgtat tatgcttatg actatgtatg gtttgaaaat attttcatta 7440 tacatgaaat tcaactttcc aaataaaagt tctacttcat gtaatccaaa a 7491 <210> 152 <211> 7650

<212> DNA <213> Homo sapians <400> 152 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttqaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 496 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga agggagtaaa ggtatcggga agatatcagg agtaaatctt actcaaaaga ctcacccaat agaggtattt gagccgggag ctgaacatat agttcgccta atgactaaga attggggcga taacgatagc atttttcaag atgtaattga gacaagaggg agagaatatg ctggtttata tgatgacatc tccactcaag gctggtttat tggactgatg tgtgcgattg ctcttctcac actactatta ttaactgttt gctttgtgaa gaggaataga ggtggaaagt actcagttaa agaaaaggaa gatttgcatc cagacccaga aattcagtca gtaaaagatg aaacctttgg tgaatacagt gacagtgatg aaaagcctct caaaggaagc cttcggtccc ttaataggga tatgcagcct actgaaagtg ctgacagctt agtcgaatac ggagagggag accatggtct cttcagtgaa gatggatcat ttattggtgc ctacgctgga tctaaggaga agggatctgt tgaaagcaat ggaagttcta cagcaacttt tccccttcgg gcataaacac aacatatgta agcaacgcta ctggttcacc ccaaccttcc atatttatct gttcaaagga gcaagaactt tcatatagga atagaaacat gctggccgaa gatttcatcc agaagtcaac atcctgcaat tatgttgaaa agagtagtac tttcttcaaa atataaaatg ccaagcactt caggcctatg ttttgcttat attgttttca ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta gatacacctc aactaaatcc aaagtcccca ttcagtatat tccatatttg cctgatttta ctattcggtg tgtttgcata gatgttgcta cttggtgggt ttttctccgt atgcacattg gtatacagtc tctgagaact ggcttggtga ctttgcttca ctacaggtta aaagaccata agcaaactgg ttatttaaaa tgtaaaaagg aatatgaaag tcttattaaa acacttcatt gaaaatatac agtctaaatt tattatttaa attttactag caaaagtctt aggtgaacaa tcaactagta tttgttgagc tcctatttgc ccagagatgg tcatatttaa acagaagtat acgtttttca gtttcaacat gaattttttt atttctgtca gttatgacat ccacgagcat cactttttgt gtctgttttt ttttttttct tggactaaat tcaactgcat ggaagcggtg gtcagaaggt tgttttatac gagaacaggc agaaagtgcc cattgttcag gattctaata gctacatcta cttaatatct tcatttctaa attgactgct tttacctttt tctcatgttt atataatggt atgcttgcat atatttcatg aatacattgt acatattatg ttaatattta cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat gtttgtacag ctagaatata ttagtaagat actgtttttc gtcattccag agctacaact aataacacga ggttccaaag ctgaagactt tgtataaagt atttgggttt tgttcttgta ttgctttctt tcaacagttt caaaataaaa tatcatacaa atattgaggg aaatgttttc atatttttca aaataggttt ttattgttga atgtacatct accccagccc ctcaaaagaa aaactgttta catagaaatt cctacacata cgtttgcgta tatgttattt taaacatctt tgtggtgaga attttttccc cgatattctc cttctgtcaa agtcagaaca aattcaggga atttattttc tggcagttgt gctccagtcc ttttaaaatt gtacatgaac atgttttaga aacaatatgg aggatgatgc atacatgtcg gtcaagttca gcgctcgaca ttttatggaa agattttttt aaccttacca cgaaatactt aactactgtt taagtgaatt gacttatttc actttagttt ttgaactgtg attattggta tactgttata tcctcaactt ggatttatgg taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct ttgtcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 497 atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat 6360 tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga 6420 tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc 6480 gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga 6540 ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt 6600 gggaaaatcc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag 6660 gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 aataaaagtt ctacttcatg taatccaaaa 7650 <210> 153 <211> 7491

<212> DNA <213> Homo sapians <400> 153 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaattc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaagca aaagaaaatt atggcaagac 1200 tttgaaaata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 498 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga agggaaatat gctggtttat atgatgacat ctccactcaa ggctggttta ttggactgat gtgtgcgatt gctcttctca cactactatt attaactgtt tgctttgtga agaggaatag aggtggaaag tactcagtta aagaaaagga agatttgcat ccagacccag aaattcagtc agtaaaagat gaaacctttg gtgaatacag tgacagtgat gaaaagcctc tcaaaggaag ccttcggtcc cttaataggg atatgcagcc tactgaaagt gctgacagct tagtcgaata cggagaggga gaccatggtc tcttcagtga agatggatca tttattggtg cctacgctgg atctaaggag aagggatctg ttgaaagcaa tggaagttct acagcaactt ttccccttcg ggcataaaca caacatatgt aagcaacgct actggttcac cccaaccttc catatttatc tgttcaaagg agcaagaact ttcatatagg aatagaaaca tgctggccga agatttcatc cagaagtcaa catcctgcaa ttatgttgaa aagagtagta ctttcttcaa aatataaaat gccaagcact tcaggcctat gttttgctta tattgttttc aggtgctcaa aatgcaaaac acaaaacaaa tcctgcattt agatacacct caactaaatc caaagtcccc attcagtata ttccatattt gcctgatttt actattcggt gtgtttgcat agatgttgct acttggtggg tttttctccg tatgcacatt ggtatacagt ctctgagaac tggcttggtg actttgcttc actacaggtt aaaagaccat aagcaaactg gttatttaaa atgtaaaaag gaatatgaaa gtcttattaa aacacttcat tgaaaatata cagtctaaat ttattattta aattttacta gcaaaagtct taggtgaaca atcaactagt atttgttgag ctcctatttg cccagagatg gtcatattta aacagaagta tacgtttttc agtttcaaca tgaatttttt tatttctgtc agttatgaca tccacgagca tcactttttg tgtctgtttt tttttttttc ttggactaaa ttcaactgca tggaagcggt ggtcagaagg ttgttttata cgagaacagg cagaaagtgc ccattgttca ggattctaat agctacatct acttaatatc ttcatttcta aattgactgc ttttaccttt ttctcatgtt tatataatgg tatgcttgca tatatttcat gaatacattg tacatattat gttaatattt acacaattta aaatatagat gtgttttatt ttgaagtgag aaaatgaaca ttaacaggca tgtttgtaca gctagaatat attagtaaga tactgttttt cgtcattcca gagctacaac taataacacg aggttccaaa gctgaagact ttgtataaag tatttgggtt ttgttcttgt attgctttct ttcaacagtt tcaaaataaa atatcataca aatattgagg gaaatgtttt catatttttc aaaataggtt tttattgttg aatgtacatc taccccagcc cctcaaaaga aaaactgttt acatagaaat tcctacacat acgtttgcgt atatgttatt ttaaacatct ttgtggtgag aattttttcc ccgatattct ccttctgtca aagtcagaac aaattcaggg aatttatttt ctggcagttg tgctccagtc cttttaaaat tgtacatgaa catgttttag aaacaatatg gaggatgatg catacatgtc ggtcaagttc agcgctcgac attttatgga aagatttttt taaccttacc acgaaatact taactactgt ttaagtgaat tgacttattt cactttagtt tttgaactgt gattattggt atactgttat atcctcaact tggatttatg gtaacccctt ttagttcatg gagaccaaaa tttggggtat ttataatagt cagcgcagga atgcacatgg aatatctact tgtccttttg aacctcacga gtcatccaga atgtatagac aggaaaagca tgtcttattt aaaactgtaa tttatgggct 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2 94 0 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 499 caggatctga ccgcagtccc gggagtaagc atttcaaagg gggaaggcag tgtggtccct 5580 accctgtgtg aatgtgagga tgtagacatc catcagtgca actcgagctc catcctcctc 5640 cgatttctaa ggctccagtt ttctggaggg acagtcatca tgttttgatt tatctgggag 5700 aaaactgtgg tgcacagctt gtgaggaggg caaggttgtg acgttcgagc ttagttctgg 5760 tgttattctg tctcctcttc tttgtcatca gccaaaacgt ggtttttaaa gagagtcatg 5820 caggttagaa ataatgtcaa aaatatttag gaatttaata acctttaagt cagaaactaa 5880 aacaaatact gaaatattag ctcttcctac acttcgtgtt cccctttagc tgcctgaaaa 5940 tcaagattgc tcotactcag atcttctgag tggctaaaac ttatggatat gaaaaatgag 6000 attgaatgat gactatgctt tgctatcatt gttacctttc ctcaatacta tttggcaact 6060 actgggactc ttcagcacaa aaggaataga tctatgattg accctgattt taattgtgaa 6120 attatatgat tcatatattt tatgaatcag aataaccttc aaataaaata aatctaagtc 6180 ggttaaaatg gatttcatga ttttccctca gaaaatgagt aacggagtcc acggcgtgca 6240 atggtaatta taaattggtg atgcttgttt gcaaattgcc cactcgtgat aagtcaacag 6300 ccaatattta aaactttgtt cgttactggc tttaccctaa ctttctctag tctactgtca 6360 atatcatttt aatgtaattg attgtatata gtctcaagaa tggttggtgg gcatgagttc 6420 ctagagaact gtccaagggt tgggaaaatc caaattctct tcctggctcc agcactgatt 6480 ttgtacataa acattaggca ggttgcttaa cctttttatt tcaaactctc tcaactctaa 6540 agtgctaata ataatctcag ttaccttatc tttgtcacag ggtgttcttt tttatgaaga 6600 aaaatttgaa aatgataaaa gctaagatgc cttctaactt cataagcaaa cctttaacta 6660 attatgtatc tgaaagtcac ccccacatac caactcaact tttttcctgt gaacacataa 6720 atatattttt atagaaaaac aaatctacat aaaataaatc tactgtttag tgagcagtat 6780 gacttgtaca tgccattgaa aattattaat cagaagaaaa ttaagcaggg tctttgctat 6840 acaaaagtgt tttccactaa ttttgcatgc gtatttataa gaaaaatgtg aatttggtgg 6900 ttttattcta tcggtataaa ggcatcgata ttttagatgc acccgtgttt gtaaaaatgt 6960 agagcacaat ggaattatgc tggaagtctc aaataatatt tttttcctat tttatactca 7020 tggaagagat aagctaaaga ggggacaata atgagaaatg ttggtgtgct tttctaagca 7080 tttaaaacat aattgccaat tgaaacccta aatatgttta cataccatta agatatgatt 7140 catgtaacaa tgttaaatta attataatgg gattgggttt gttatctgtg gtagtatata 7200 tcctagtgtt cctatagtga aataagtagg gttcagccaa agctttcttt gttttgtacc 7260 ttaaattgtt cgattacgtc atcaaaagag atgaaaggta tgtagaacag gttcacgtga 7320 ttaccttttt cttttggctt ggattaatat tcatagtaga actttataaa acgtgtttgt 7380 attgtaggtg gtgtttgtat tatgcttatg actatgtatg gtttgaaaat attttcatta 7440 tacatgaaat tcaactttcc aaataaaagt tctacttcat gtaatccaaa a 7491 <210> 154

<211> 1171 <212> PRT <213> Homo sapians <400> 154

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 500

Pro Leu His He Tyr 165 Trp Met Asn He Glu 170 Leu Glu His lie Glu 175 Gin Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys ciy Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys 290 295 300 Glu Asn Tvr Gly T,vs — _ Thr Leu T,VR — _ He Glu Asn Val Ser Tvr - a — Gin ---j- 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Al a Phe Leu His cys Glu Phe Phe 450 455 4 6 0 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu ciy Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala I le Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Giy Giu Ala Phe Giu 565 570 57 5 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 501

Asn He Ser Glu 660 Tyr He Val Glu Phe 665 Glu Gly Asn Lys Glu 670 Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Al a Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 6 9 0 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 7 05 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala lie As n Gin Leu m w Sei? m ι? Pro Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val lie Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn ciy 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin lie Xie Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro lie Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Lys Tyr Ala Gly Leu Tyr Asp Asp He 1025 1030 1035 1040 Ser Thr Gin Gly Trp Phe lie Gly Leu Met cys Ala lie Ala Leu Leu 1045 1050 1055 Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly ciy 1060 1065 1070 Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His Pro Asp Pro Glu He 1075 1080 1085 Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu 1090 1095 1100 Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin Pro 1105 1110 1115 1120 Thr Glu Ser Al a Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His Gly 1125 1130 1135 Leu Phe Ser Glu Asp Gly Ser Phe lie Gly Ala Tyr Ala Gly Ser Lys 1140 1145 1150 502

Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro 1155 1160 1165

Leu Arg Ala 1170 <210> 155 <2 11> 1ΟΠ/1 <212> PRT <213> Homo sapians <400> 155

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lvs -i — Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 2 6 0 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro kjJ-&amp;#911; Ser Ar a Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn ciy 370 375 380 Ser Pro Val Asp Asn His Pro Phe Al a Gly Asp Val Val Phe Pro Arg 385 390 395 400 503

Glu He Ser Phe Thr 405 Asn Leu Gin Pro Asn 410 His Thr Ala Val Tyr 415 Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn lie 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe Λ C A j υ 455 4 60 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Al a Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Gys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Al a Ala Asp lie Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys 740 7 4 5 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 one O i J Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 8 3 5 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin lie Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 504

Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val lie Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly r» /- r\ »5u ?QU Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu lie Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn 1 a Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro lie Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin TiVR — — Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val lie Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 156

<211> 1171 <212> PRT <213> Homo sapians <400> 156

Met Giu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 505

Glu Gly His He 100 Ser His Phe Gin Gly 105 Lys Tyr Arg Cys Phe 110 Ala Ser Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala As π Ser T &#906;_θ Lys Gin Z\rwr T.X7C! ‘-‘J. Px?o T,\7Q >.· Leu Leu Leu Pro 245 250 255 Pro Thr Glu Sox* Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Ala Lys 290 295 300 Glu Asn Tyr ciy Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly T.VR — a — Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp r' ι ττ u±y Arg He He He Asp Gly Ala Asn Leu 580 585 590 506

Thr He Ser 595 Asn Val Thr Leu Glu 600 Asp Gin Gly He Tyr 605 Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn lie Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn IT Θ Arg Val 725 730 735 Gin Ala Ser Gin Pro T.V3 “J Glu Μθ t He He Lys Tm Glu ΡΧ&amp;#908; Τ,θπ T.VQ 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Al a Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 89 0 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Al a Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys G1 v --J. T.VB — a — Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Lys Tyr Ala Gly Leu Tyr Asp Asp He 1025 1030 1035 1040 Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys Ala He Ala Leu Leu 1045 1050 1055 Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly Gly 1060 1065 1070 Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His Pro Asp Pro Glu lie 1075 1080 1085 507

Gin Ser Val 1090 Lys Asp Glu Thr Phe 1095 Gly Glu Tyr Ser Asp 1100 Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin Pro 1105 1110 1115 1120 Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His Gly 1125 1130 1135 Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala Tyr Ala Gly Ser Lys 1140 1145 1150 Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro 1155 1160 1165 Leu Arg Ala 1170 <210> 157 <211> 6487

<212> DNA <213> Homo sapians <400> 157 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 508 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacacaac atatgtaagc aacgctactg gttcacccca 2820 accttccata tttatctgtt caaaggagca agaactttca tataggaata gaaacatgct 2880 ggccgaagat ttcatccaga agtcaacatc ctgcaattat gttgaaaaga gtagtacttt 2940 cttcaaaata taaaatgcca agcacttcag gcctatgttt tgcttatatt gttttcaggt 3000 gctcaaaatg caaaacacaa aacaaatcct gcatttagat acacctcaac taaatccaaa 3060 gtccccattc agtatattcc atatttgcct gattttacta ttcggtgtgt ttgcatagat 3120 gttgctactt ggtgggtttt tctccgtatg cacattggta tacagtctct gagaactggc 3180 ttggtgactt tgcttcacta caggttaaaa gaccataagc aaactggtta tttaaaatgt 3240 aaaaaggaat atgaaagtct tattaaaaca cttcattgaa aatatacagt ctaaatttat 3300 tatttaaatt ttactagcaa aagtcttagg tgaacaatca actagtattt gttgagctcc 3360 tatttgccca gagatggtca tatttaaaca gaagtatacg tttttcagtt tcaacatgaa 3420 tttttttatt tctgtcagtt atgacatcca cgagcatcac tttttgtgtc tgtttttttt 3480 tttttcttgg actaaattca actgcatgga agcggtggtc agaaggttgt tttatacgag 3540 aacaggcaga aagtgcccat tgttcaggat tctaatagct acatctactt aatatcttca 3600 tttctaaatt gactgctttt acctttttct catgtttata taatggtatg cttgcatata 3660 tttcatgaat acattgtaca tattatgtta atatttacac aatttaaaat atagatgtgt 3720 tttattttga agtgagaaaa tgaacattaa caggcatgtt tgtacagcta gaatatatta 3780 gtaagatact gtttttcgtc attccagagc tacaactaat aacacgaggt tccaaagctg 3840 aagactttgt ataaagtatt tgggttttgt tcttgtattg ctttctttca acagtttcaa 3900 aataaaatat catacaaata ttgagggaaa tgttttcata tttttcaaaa taggttttta 3960 ttgttgaatg tacatctacc ccagcccctc aaaagaaaaa ctgtttacat agaaattcct 4020 acacatacgt ttgcgtatat gttattttaa acatctttgt ggtgagaatt ttttccccga 4080 tattctcctt ctgtcaaagt cagaacaaat tcagggaatt tattttctgg cagttgtgct 4140 ccagtccttt taaaattgta catgaacatg ttttagaaac aatatggagg atgatgcata 4200 catgtcggtc aagttcagcg ctcgacattt tatggaaaga tttttttaac cttaccacga 4260 aatacttaac tactgtttaa gtgaattgac ttatttcact ttagtttttg aactgtgatt 4320 attggtatac tgttatatcc tcaacttgga tttatggtaa ccccttttag ttcatggaga 4380 ccaaaatttg gggtatttat aatagtcagc gcaggaatgc acatggaata tctacttgtc 4440 cttttgaacc tcacgagtca tccagaatgt atagacagga aaagcatgtc ttatttaaaa 4500 ctgtaattta tgggctcagg atctgaccgc agtcccggga gtaagcattt caaaggggga 4560 aggcagtgtg gtccctaccc tgtgtgaatg tgaggatgta gacatccatc agtgcaactc 4620 gagctccatc ctcctccgat ttctaaggct ccagttttct ggagggacag tcatcatgtt 4680 ttgatttatc tgggagaaaa ctgtggtgca cagcttgtga ggagggcaag gttgtgacgt 4740 tcgagcttag ttctggtgtt attctgtctc ctcttctttg tcatcagcca aaacgtggtt 4800 tttaaagaga gtcatgcagg ttagaaataa tgtcaaaaat atttaggaat ttaataacct 4860 ttaagtcaga aactaaaaca aatactgaaa tattagctct tcctacactt cgtgttcccc 4920 tttagctgcc tgaaaatcaa gattgctcct actcagatct tctgagtggc taaaacttat 4980 ggatatgaaa aatgagattg aatgatgact atgctttgct atcattgtta cctttcctca 5040 atactatttg gcaactactg ggactcttca gcacaaaagg aatagatcta tgattgaccc 5100 tgattttaat tgtgaaatta tatgattcat atattttatg aatcagaata accttcaaat 5160 aaaataaatc taagtcggtt aaaatggatt tcatgatttt ccctcagaaa atgagtaacg 5220 gagtccacgg cgtgcaatgg taattataaa ttggtgatgc ttgtttgcaa attgcccact 5280 cgtgataagt caacagccaa tatttaaaac tttgttcgtt actggcttta ccctaacttt 5340 ctctagtcta ctgtcaatat cattttaatg taattgattg tatatagtct caagaatggt 5400 tggtgggcat gagttcctag agaactgtcc aagggttggg aaaatccaaa ttctcttcct 5460 ggctccagca ctgattttgt acataaacat taggcaggtt gcttaacctt tttatttcaa 5520 actctctcaa ctctaaagtg ctaataataa tctcagttac cttatctttg tcacagggtg 5580 ttctttttta tgaagaaaaa tttgaaaatg ataaaagcta agatgccttc taacttcata 5640 agcaaacctt taactaatta tgtatctgaa agtcaccccc acataccaac tcaacttttt 5700 tcctgtgaac acataaatat atttttatag aaaaacaaat ctacataaaa taaatctact 5760 gtttagtgag cagtatgact tgtacatgcc attgaaaatt attaatcaga agaaaattaa 5820 gcagggtctt tgctatacaa aagtgttttc cactaatttt gcatgcgtat ttataagaaa 5880 aatgtgaatt tggtggtttt attctatcgg tataaaggca tcgatatttt agatgcaccc 5940 gtgtttgtaa aaatgtagag cacaatggaa ttatgctgga agtctcaaat aatatttttt 6000 tcctatttta tactcatgga agagataagc taaagagggg acaataatga gaaatgttgg 6060 tgtgcttttc taagcattta aaacataatt gccaattgaa accctaaata tgtttacata 6120 ccattaagat atgattcatg taacaatgtt aaattaatta taatgggatt gggtttgtta 6180 tctgtggtag tatatatcct agtgttccta tagtgaaata agtagggttc agccaaagct 6240 509 ttctttgttt tgtaccttaa attgttcgat tacgtcatca aaagagatga aaggtatgta 6300 gaacaggttc acgtgattac ctttttcttt tggcttggat taatattcat agtagaactt 6360 tataaaacgt gtttgtattg taggtggtgt ttgtattatg cttatgacta tgtatggttt 6420 gaaaatattt tcattataca tgaaattcaa ctttccaaat aaaagttcta cttcatgtaa 6480 tccaaaa 6487 <210> 158 <211> 7650

<212> DNA <213> Homo sapians <400> 158 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 510 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga agggagtaaa ggtatcggga agatatcagg agtaaatctt actcaaaaga ctcacccaat agaggtattt gagccgggag ctgaacatat agttcgccta atgactaaga attggggcga taacgatagc atttttcaag atgtaattga gacaagaggg agagaatatg ctggtttata tgatgacatc tccactcaag gctggtttat tggactgatg tgtgcgattg ctcttctcac actactatta ttaactgttt gctttgtgaa gaggaataga ggtggaaagt actcagttaa agaaaaggaa gatttgcatc cagacccaga aattcagtca gtaaaagatg aaacctttgg tgaatacagt gacagtgatg aaaagcctct caaaggaagc cttcggtccc ttaataggga tatgcagcct actgaaagtg ctgacagctt agtcgaatac ggagagggag accatggtct cttcagtgaa gatggatcat ttattggtgc ctacgctgga tctaaggaga agggatctgt tgaaagcaat ggaagttcta cagcaacttt tccccttcgg gcataaacac aacatatgta agcaacgcta ctggttcacc ccaaccttcc atatttatct gttcaaagga gcaagaactt tcatatagga atagaaacat gctggccgaa gatttcatcc agaagtcaac atcctgcaat tatgttgaaa agagtagtac tttcttcaaa atataaaatg ccaagcactt caggcctatg ttttgcttat attgttttca ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta gatacacctc aactaaatcc aaagtcccca ttcagtatat tccatatttg cctgatttta ctattcggtg tgtttgcata gatgttgcta cttggtgggt ttttctccgt atgcacattg gtatacagtc tctgagaact ggcttggtga ctttgcttca ctacaggtta aaagaccata agcaaactgg ttatttaaaa tgtaaaaagg aatatgaaag tcttattaaa acacttcatt gaaaatatac agtctaaatt tattatttaa attttactag caaaagtctt aggtgaacaa tcaactagta tttgttgagc tcctatttgc ccagagatgg tcatatttaa acagaagtat acgtttttca gtttcaacat gaattttttt atttctgtca gttatgacat ccacgagcat cactttttgt gtctgttttt ttttttttct tggactaaat tcaactgcat ggaagcggtg gtcagaaggt tgttttatac gagaacaggc agaaagtgcc cattgttcag gattctaata gctacatcta cttaatatct tcatttctaa attgactgct tttacctttt tctcatgttt atataatggt atgcttgcat atatttcatg aatacattgt acatattatg ttaatattta cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat gtttgtacag ctagaatata ttagtaagat actgtttttc gtcattccag agctacaact aataacacga ggttccaaag ctgaagactt tgtataaagt atttgggttt tgttcttgta ttgctttctt tcaacagttt caaaataaaa tatcatacaa atattgaggg aaatgttttc atatttttca aaataggttt ttattgttga atgtacatct accccagccc ctcaaaagaa aaactgttta catagaaatt cctacacata cgtttgcgta tatgttattt taaacatctt tgtggtgaga attttttccc cgatattctc cttctgtcaa agtcagaaca aattcaggga atttattttc tggcagttgt gctccagtcc ttttaaaatt gtacatgaac atgttttaga aacaatatgg aggatgatgc atacatgtcg gtcaagttca gcgctcgaca ttttatggaa agattttttt aaccttacca cgaaatactt aactactgtt taagtgaatt gacttatttc actttagttt ttgaactgtg attattggta tactgttata tcctcaactt ggatttatgg taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct ttgtcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 511 gggaaaatcc gttgcttaac taccttatct ctaagatgcc cccacatacc aatctacata attattaatc tttgcatgcg gcatcgatat ggaagtctca gggacaataa gaaaccctaa ttataatggg ataagtaggg tcaaaagaga gattaatatt atgcttatga aataaaagtt <210> 159 <211> 6487 <212> DNA <213> Homo <400> 159 cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg aatcgtatat agttcaacag tgagtatttt taaggatggc aacattcagg tgcttcaaat tccaaaactc cctcccatgc attagaacac cgcaaacgtg attaaggact taatgactca acccaaactg aggggaaatc gaacaaaatt tttgaagata tttcttggga aaagaagcct tgaaggagaa tccatttgct tcatactgct caatattgat tacagtggtt cgtgtcctgg tgaaaatggc ttgggtagaa tacaaaactt acattgtgaa agatggagaa taatttgacc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag 6660 ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 ctacttcatg taatccaaaa 7650 sapians gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 512 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt gatccatggg gtggacgtta taaacacaac atatgtaagc aacgctactg gttcacccca accttccata tttatctgtt caaaggagca agaactttca tataggaata gaaacatgct ggccgaagat ttcatccaga agtcaacatc ctgcaattat gttgaaaaga gtagtacttt cttcaaaata taaaatgcca agcacttcag gcctatgttt tgcttatatt gttttcaggt gctcaaaatg caaaacacaa aacaaatcct gcatttagat acacctcaac taaatccaaa gtccccattc agtatattcc atatttgcct gattttacta ttcggtgtgt ttgcatagat gttgctactt ggtgggtttt tctccgtatg cacattggta tacagtctct gagaactggc ttggtgactt tgcttcacta caggttaaaa gaccataagc aaactggtta tttaaaatgt aaaaaggaat atgaaagtct tattaaaaca cttcattgaa aatatacagt ctaaatttat tatttaaatt ttactagcaa aagtcttagg tgaacaatca actagtattt gttgagctcc tatttgccca gagatggtca tatttaaaca gaagtatacg tttttcagtt tcaacatgaa tttttttatt tctgtcagtt atgacatcca cgagcatcac tttttgtgtc tgtttttttt tttttcttgg actaaattca actgcatgga agcggtggtc agaaggttgt tttatacgag aacaggcaga aagtgcccat tgttcaggat tctaatagct acatctactt aatatcttca tttctaaatt gactgctttt acctttttct catgtttata taatggtatg cttgcatata tttcatgaat acattgtaca tattatgtta atatttacac aatttaaaat atagatgtgt tttattttga agtgagaaaa tgaacattaa caggcatgtt tgtacagcta gaatatatta gtaagatact gtttttcgtc attccagagc tacaactaat aacacgaggt tccaaagctg aagactttgt ataaagtatt tgggttttgt tcttgtattg ctttctttca acagtttcaa aataaaatat catacaaata ttgagggaaa tgttttcata tttttcaaaa taggttttta ttgttgaatg tacatctacc ccagcccctc aaaagaaaaa ctgtttacat agaaattcct acacatacgt ttgcgtatat gttattttaa acatctttgt ggtgagaatt ttttccccga tattctcctt ctgtcaaagt cagaacaaat tcagggaatt tattttctgg cagttgtgct ccagtccttt taaaattgta catgaacatg ttttagaaac aatatggagg atgatgcata catgtcggtc aagttcagcg ctcgacattt tatggaaaga tttttttaac cttaccacga aatacttaac tactgtttaa gtgaattgac ttatttcact ttagtttttg aactgtgatt attggtatac tgttatatcc tcaacttgga tttatggtaa ccccttttag ttcatggaga ccaaaatttg gggtatttat aatagtcagc gcaggaatgc acatggaata tctacttgtc cttttgaacc tcacgagtca tccagaatgt atagacagga aaagcatgtc ttatttaaaa ctgtaattta tgggctcagg atctgaccgc agtcccggga gtaagcattt caaaggggga aggcagtgtg gtccctaccc tgtgtgaatg tgaggatgta gacatccatc agtgcaactc gagctccatc ctcctccgat ttctaaggct ccagttttct ggagggacag tcatcatgtt ttgatttatc tgggagaaaa ctgtggtgca cagcttgtga ggagggcaag gttgtgacgt tcgagcttag ttctggtgtt attctgtctc ctcttctttg tcatcagcca aaacgtggtt tttaaagaga gtcatgcagg ttagaaataa tgtcaaaaat atttaggaat ttaataacct ttaagtcaga aactaaaaca aatactgaaa tattagctct tcctacactt cgtgttcccc tttagctgcc tgaaaatcaa gattgctcct actcagatct tctgagtggc taaaacttat ggatatgaaa aatgagattg aatgatgact atgctttgct atcattgtta cctttcctca atactatttg gcaactactg ggactcttca gcacaaaagg aatagatcta tgattgaccc tgattttaat tgtgaaatta tatgattcat atattttatg aatcagaata accttcaaat aaaataaatc taagtcggtt aaaatggatt tcatgatttt ccctcagaaa atgagtaacg gagtccacgg cgtgcaatgg taattataaa ttggtgatgc ttgtttgcaa attgcccact cgtgataagt caacagccaa tatttaaaac tttgttcgtt actggcttta ccctaacttt ctctagtcta ctgtcaatat cattttaatg taattgattg tatatagtct caagaatggt tggtgggcat gagttcctag agaactgtcc aagggttggg aaaatccaaa ttctcttcct ggctccagca ctgattttgt acataaacat taggcaggtt gcttaacctt tttatttcaa actctctcaa ctctaaagtg ctaataataa tctcagttac cttatctttg tcacagggtg ttctttttta tgaagaaaaa tttgaaaatg ataaaagcta agatgccttc taacttcata agcaaacctt taactaatta tgtatctgaa agtcaccccc acataccaac tcaacttttt tcctgtgaac acataaatat atttttatag aaaaacaaat ctacataaaa taaatctact gtttagtgag cagtatgact tgtacatgcc attgaaaatt attaatcaga agaaaattaa 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 513 gcagggtctt tgctatacaa aagtgttttc cactaatttt gcatgcgtat ttataagaaa 5880 aatgtgaatt tggtggtttt attctatcgg tataaaggca tcgatatttt agatgcaccc 5940 gtgtttgtaa aaatgtagag cacaatggaa ttatgctgga agtctcaaat aatatttttt 6000 tcctatttta tactcatgga agagataagc taaagagggg acaataatga gaaatgttgg 6060 tgtgcttttc taagcattta aaacataatt gccaattgaa accctaaata tgtttacata 6120 ccattaagat atgattcatg taacaatgtt aaattaatta taatgggatt gggtttgtta 6180 tctgtggtag tatatatcct agtgttccta tagtgaaata agtagggttc agccaaagct 6240 ttctttgttt tgtaccttaa attgttcgat tacgtcatca aaagagatga aaggtatgta 6300 gaacaggttc acgtgattac ctttttcttt tggcttggat taatattcat agtagaactt 6360 tataaaacgt gtttgtattg taggtggtgt ttgtattatg cttatgacta tgtatggttt 6420 gaaaatattt tcattataca tgaaattcaa ctttccaaat aaaagttcta cttcatgtaa 6480 tccaaaa 6487 <210> 160 <211> 893

<212> PRT <213> Homo sapians <4 00> 160

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He lie Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys As n Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 514 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Ary 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 6 2 5 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Giy Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 515 820 825 830 Gly Val Asp Val lie Asn Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser 835 840 845 Pro Gin Pro Ser He Phe lie Cys Ser Lys Glu Gin Glu Leu Ser Tyr 850 855 860 Arg Asn Arg Asn Met Leu Ala Glu Asp Phe He Gin Lys Ser Thr Ser 865 870 875 880 Cys Asn Tyr Val Glu Lys Ser Ser Thr Phe Phe Lys He 885 890 <210> 161 <211> 849

<212> PRT <213> Homo sapians <400> 161

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Λ l . id Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr lie Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 2 8 5 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly Ils Leu Leu Cys 516 355 360 365 Glu Ala Glu dy Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Al a Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr ThX? Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val Il© Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 7 55 760 7 6 5 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val 517 <210> 162 <211> 851

<212> PRT <213> Homo sapians <400> 162

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Al a Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr Tie Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 2 80 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 34 5 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Al a Asn Ala Asn He 518 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 4 7 5 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 57 5 He Asn dy Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 7 2 5 730 73 5 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Ly s 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 7 75 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser 835 840 845 Pro Gin Pro 850 <210> 163 <211> 7329

<212> DNA <213> Homo sapians 519 <400> 163 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggegeegg acagatcgcg ttteggagge ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aategtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tettgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atetataett 840 egeaaaegtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtet cctaccagga caaaggaaat tategetgea cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagect cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagteaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaceaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattaege 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgeaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgetatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgeata tgettgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatetaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagega gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac ttacctgaac agccaacttt 2760 tctaaaggtc atcaaagttg ataaagacac tgccacttta tcttggggac tacctaagaa 2820 attaaatgga aacttaactg gctatctttt gcaatatcag ataataaatg acacctacga 2880 gattggagaa ttaaatgata ttaacattac aactccatca aagcccagct ggcacctctc 2940 aaacctgaat gcaactacca agtacaaatt etaettgagg gettgeaett cacagggctg 3000 tggaaaaccg atcacggagg aaagctccac ettaggagaa gggagtaaag gtatcgggaa 3060 gatatcagga gtaaatetta ctcaaaagac tcacccaata gaggtatttg ageegggage 3120 tgaacatata gttcgcctaa tgactaagaa ttggggcgat aaegatagea tttttcaaga 3180 tgtaattgag acaagaggga gagaatatgc tggtttatat gatgacatct ccactcaagg 3240 ctggtttatt ggactgatgt gtgcgattgc tcttctcaca ctactattat taactgtttg 3300 ctttgtgaag aggaatagag gtggaaagta ctcagttaaa gaaaaggaag atttgcatcc 3360 agacccagaa attcagtcag taaaagatga aacctttggt gaatacagtg acagtgatga 3420 aaagcctctc aaaggaagee ttcggtccct taatagggat atgcagccta ctgaaagtgc 3480 tgacagctta gtcgaatacg gagagggaga ccatggtctc ttcagtgaag atggatcatt 3540 tattggtgcc tacgctggat ctaaggagaa gggatctgtt gaaagcaatg gaagttctac 3600 agcaactttt ccccttcggg cataaacaca acatatgtaa gcaacgctac tggttcaccc 3660 520 caaccttcca tatttatctg ttcaaaggag caagaacttt catataggaa tagaaacatg 3720 ctggccgaag atttcatcca gaagtcaaca tcctgcaatt atgttgaaaa gagtagtact 3780 ttcttcaaaa tataaaatgc caagcacttc aggcctatgt tttgcttata ttgttttcag 3840 gtgctcaaaa tgcaaaacac aaaacaaatc ctgcatttag atacacctca actaaatcca 3900 aagtccccat tcagtatatt ccatatttgc ctgattttac tattcggtgt gtttgcatag 3960 atgttgctac ttggtgggtt tttctccgta tgcacattgg tatacagtct ctgagaactg 4020 gcttggtgac tttgcttcac tacaggttaa aagaccataa gcaaactggt tatttaaaat 4080 gtaaaaagga atatgaaagt cttattaaaa cacttcattg aaaatataca gtctaaattt 4140 attatttaaa ttttactagc aaaagtctta ggtgaacaat caactagtat ttgttgagct 4200 cctatttgcc cagagatggt catatttaaa cagaagtata cgtttttcag tttcaacatg 4260 aattttttta tttctgtcag ttatgacatc cacgagcatc actttttgtg tctgtttttt 4320 tttttttctt ggactaaatt caactgcatg gaagcggtgg tcagaaggtt gttttatacg 4380 agaacaggca gaaagtgccc attgttcagg attctaatag ctacatctac ttaatatctt 4440 catttctaaa ttgactgctt ttaccttttt ctcatgttta tataatggta tgcttgcata 4500 tatttcatga atacattgta catattatgt taatatttac acaatttaaa atatagatgt 4560 gttttatttt gaagtgagaa aatgaacatt aacaggcatg tttgtacagc tagaatatat 4620 tagtaagata ctgtttttcg tcattccaga gctacaacta ataacacgag gttccaaagc 4680 tgaagacttt gtataaagta tttgggtttt gttcttgtat tgctttcttt caacagtttc 4740 aaaataaaat atcatacaaa tattgaggga aatgttttca tatttttcaa aataggtttt 4800 tattgttgaa tgtacatcta ccccagcccc tcaaaagaaa aactgtttac atagaaattc 4860 ctacacatac gtttgcgtat atgttatttt aaacatcttt gtggtgagaa ttttttcccc 4920 gatattctcc ttctgtcaaa gtcagaacaa attcagggaa tttattttct ggcagttgtg 4980 ctccagtcct tttaaaattg tacatgaaca tgttttagaa acaatatgga ggatgatgca 5040 tacatgtcgg tcaagttcag cgctcgacat tttatggaaa gattttttta accttaccac 5100 gaaatactta actactgttt aagtgaattg acttatttca ctttagtttt tgaactgtga 5160 ttattggtat actgttatat cctcaacttg gatttatggt aacccctttt agttcatgga 5220 gaccaaaatt tggggtattt ataatagtca gcgcaggaat gcacatggaa tatctacttg 5280 tccttttgaa cctcacgagt catccagaat gtatagacag gaaaagcatg tcttatttaa 5340 aactgtaatt tatgggctca ggatctgacc gcagtcccgg gagtaagcat ttcaaagggg 5400 gaaggcagtg tggtccctac cctgtgtgaa tgtgaggatg tagacatcca tcagtgcaac 5460 tcgagctcca tcctcctccg atttctaagg ctccagtttt ctggagggac agtcatcatg 5520 ttttgattta tctgggagaa aactgtggtg cacagcttgt gaggagggca aggttgtgac 5580 gttcgagctt agttctggtg ttattctgtc tcctcttctt tgtcatcagc caaaacgtgg 5640 tttttaaaga gagtcatgca ggttagaaat aatgtcaaaa atatttagga atttaataac 5700 ctttaagtca gaaactaaaa caaatactga aatattagct cttcctacac ttcgtgttcc 5760 cctttagctg cctgaaaatc aagattgctc ctactcagat cttctgagtg gctaaaactt 5820 atggatatga aaaatgagat tgaatgatga ctatgctttg ctatcattgt tacctttcct 5880 caatactatt tggcaactac tgggactctt cagcacaaaa ggaatagatc tatgattgac 5940 cctgatttta attgtgaaat tatatgattc atatatttta tgaatcagaa taaccttcaa 6000 ataaaataaa tctaagtcgg ttaaaatgga tttcatgatt ttccctcaga aaatgagtaa 6060 cggagtccac ggcgtgcaat ggtaattata aattggtgat gcttgtttgc aaattgccca 6120 ctcgtgataa gtcaacagcc aatatttaaa actttgttcg ttactggctt taccctaact 6180 ttctctagtc tactgtcaat atcattttaa tgtaattgat tgtatatagt ctcaagaatg 6240 gttggtgggc atgagttcct agagaactgt ccaagggttg ggaaaatcca aattctcttc 6300 ctggctccag cactgatttt gtacataaac attaggcagg ttgcttaacc tttttatttc 6360 aaactctctc aactctaaag tgctaataat aatctcagtt accttatctt tgtcacaggg 6420 tgttcttttt tatgaagaaa aatttgaaaa tgataaaagc taagatgcct tctaacttca 6480 taagcaaacc tttaactaat tatgtatctg aaagtcaccc ccacatacca actcaacttt 6540 tttcctgtga acacataaat atatttttat agaaaaacaa atctacataa aataaatcta 6600 ctgtttagtg agcagtatga cttgtacatg ccattgaaaa ttattaatca gaagaaaatt 6660 aagcagggtc tttgctatac aaaagtgttt tccactaatt ttgcatgcgt atttataaga 6720 aaaatgtgaa tttggtggtt ttattctatc ggtataaagg catcgatatt ttagatgcac 6780 ccgtgtttgt aaaaatgtag agcacaatgg aattatgctg gaagtctcaa ataatatttt 6840 tttcctattt tatactcatg gaagagataa gctaaagagg ggacaataat gagaaatgtt 6900 ggtgtgcttt tctaagcatt taaaacataa ttgccaattg aaaccctaaa tatgtttaca 6960 taccattaag atatgattca tgtaacaatg ttaaattaat tataatggga ttgggtttgt 7020 tatctgtggt agtatatatc ctagtgttcc tatagtgaaa taagtagggt tcagccaaag 7080 ctttctttgt tttgtacctt aaattgttcg attacgtcat caaaagagat gaaaggtatg 7140 tagaacaggt tcacgtgatt acctttttct tttggcttgg attaatattc atagtagaac 7200 tttataaaac gtgtttgtat tgtaggtggt gtttgtatta tgcttatgac tatgtatggt 7260 ttgaaaatat tttcattata catgaaattc aactttccaa ataaaagttc tacttcatgt 7320 aatccaaaa 7329 521 <210> 164 <211> 7650

<212> DNA <213> Homo sapians <400> 164 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc 3000 ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg 3060 agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt 3120 atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca 3180 522 gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc 3240 aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag 3300 ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga 3360 agggagtaaa ggtatcggga agatatcagg agtaaatctt actcaaaaga ctcacccaat 3420 agaggtattt gagccgggag ctgaacatat agttcgccta atgactaaga attggggcga 3480 taacgatagc atttttcaag atgtaattga gacaagaggg agagaatatg ctggtttata 3540 tgatgacatc tccactcaag gctggtttat tggactgatg tgtgcgattg ctcttctcac 3600 actactatta ttaactgttt gctttgtgaa gaggaataga ggtggaaagt actcagttaa 3660 agaaaaggaa gatttgcatc cagacccaga aattcagtca gtaaaagatg aaacctttgg 3720 tgaatacagt gacagtgatg aaaagcctct caaaggaagc cttcggtccc ttaataggga 3780 tatgcagcct actgaaagtg ctgacagctt agtcgaatac ggagagggag accatggtct 3840 cttcagtgaa gatggatcat ttattggtgc ctacgctgga tctaaggaga agggatctgt 3900 tgaaagcaat ggaagttcta cagcaacttt tccccttcgg gcataaacac aacatatgta 3960 agcaacgcta ctggttcacc ccaaccttcc atatttatct gttcaaagga gcaagaactt 4020 tcatatagga atagaaacat gctggccgaa gatttcatcc agaagtcaac atcctgcaat 4080 tatgttgaaa agagtagtac tttcttcaaa atataaaatg ccaagcactt caggcctatg 4140 ttttgcttat attgttttca ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta 4200 gatacacctc aactaaatcc aaagtcccca ttcagtatat tccatatttg cctgatttta 4260 ctattcggtg tgtttgcata gatgttgcta cttggtgggt ttttctccgt atgcacattg 4320 gtatacagtc tctgagaact ggcttggtga ctttgcttca ctacaggtta aaagaccata 4380 agcaaactgg ttatttaaaa tgtaaaaagg aatatgaaag tcttattaaa acacttcatt 4440 gaaaatatac agtctaaatt tattatttaa attttactag caaaagtctt aggtgaacaa 4500 tcaactagta tttgttgagc tcctatttgc ccagagatgg tcatatttaa acagaagtat 4560 acgtttttca gtttcaacat gaattttttt atttctgtca gttatgacat ccacgagcat 4620 cactttttgt gtctgttttt ttttttttct tggactaaat tcaactgcat ggaagcggtg 4680 gtcagaaggt tgttttatac gagaacaggc agaaagtgcc cattgttcag gattctaata 4740 gctacatcta cttaatatct tcatttctaa attgactgct tttacctttt tctcatgttt 4800 atataatggt atgcttgcat atatttcatg aatacattgt acatattatg ttaatattta 4860 cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat 4920 gtttgtacag ctagaatata ttagtaagat actgtttttc gtcattccag agctacaact 4980 aataacacga ggttccaaag ctgaagactt tgtataaagt atttgggttt tgttcttgta 5040 ttgctttctt tcaacagttt caaaataaaa tatcatacaa atattgaggg aaatgttttc 5100 atatttttca aaataggttt ttattgttga atgtacatct accccagccc ctcaaaagaa 5160 aaactgttta catagaaatt cctacacata cgtttgcgta tatgttattt taaacatctt 5220 tgtggtgaga attttttccc cgatattctc cttctgtcaa agtcagaaca aattcaggga 5280 atttattttc tggcagttgt gctccagtcc ttttaaaatt gtacatgaac atgttttaga 5340 aacaatatgg aggatgatgc atacatgtcg gtcaagttca gcgctcgaca ttttatggaa 5400 agattttttt aaccttacca cgaaatactt aactactgtt taagtgaatt gacttatttc 5460 actttagttt ttgaactgtg attattggta tactgttata tcctcaactt ggatttatgg 5520 taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa 5580 tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca 5640 ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg 5700 ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat 5760 gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt 5820 tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg 5880 tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct 5940 ttgtcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa 6000 aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc 6060 tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga 6120 tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt 6180 gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa 6240 aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt 6300 atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat 6360 tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga 6420 tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc 6480 gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga 6540 ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt 6600 gggaaaatcc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag 6660 gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 523 aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 aataaaagtt ctacttcatg taatccaaaa 7650 <210> 165 <211> 7329

<212> DNA <213> Homo sapians <400> 165 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 524 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac ttacctgaac agccaacttt 2760 tctaaaggtc atcaaagttg ataaagacac tgccacttta tcttggggac tacctaagaa 2820 attaaatgga aacttaactg gctatctttt gcaatatcag ataataaatg acacctacga 2880 gattggagaa ttaaatgata ttaacattac aactccatca aagcccagct ggcacctctc 2940 aaacctgaat gcaactacca agtacaaatt ctacttgagg gcttgcactt cacagggctg 3000 tggaaaaccg atcacggagg aaagctccac cttaggagaa gggagtaaag gtatcgggaa 3060 gatatcagga gtaaatctta ctcaaaagac tcacccaata gaggtatttg agccgggagc 3120 tgaacatata gttcgcctaa tgactaagaa ttggggcgat aacgatagca tttttcaaga 3180 tgtaattgag acaagaggga gagaatatgc tggtttatat gatgacatct ccactcaagg 3240 ctggtttatt ggactgatgt gtgcgattgc tcttctcaca ctactattat taactgtttg 3300 ctttgtgaag aggaatagag gtggaaagta ctcagttaaa gaaaaggaag atttgcatcc 3360 agacccagaa attcagtcag taaaagatga aacctttggt gaatacagtg acagtgatga 3420 aaagcctctc aaaggaagcc ttcggtccct taatagggat atgcagccta ctgaaagtgc 3480 tgacagctta gtcgaatacg gagagggaga ccatggtctc ttcagtgaag atggatcatt 3540 tattggtgcc tacgctggat ctaaggagaa gggatctgtt gaaagcaatg gaagttctac 3600 agcaactttt ccccttcggg cataaacaca acatatgtaa gcaacgctac tggttcaccc 3660 caaccttcca tatttatctg ttcaaaggag caagaacttt catataggaa tagaaacatg 3720 ctggccgaag atttcatcca gaagtcaaca tcctgcaatt atgttgaaaa gagtagtact 3780 ttcttcaaaa tataaaatgc caagcacttc aggcctatgt tttgcttata ttgttttcag 3840 gtgctcaaaa tgcaaaacac aaaacaaatc ctgcatttag atacacctca actaaatcca 3900 aagtccccat tcagtatatt ccatatttgc ctgattttac tattcggtgt gtttgcatag 3960 atgttgctac ttggtgggtt tttctccgta tgcacattgg tatacagtct ctgagaactg 4020 gcttggtgac tttgcttcac tacaggttaa aagaccataa gcaaactggt tatttaaaat 4080 gtaaaaagga atatgaaagt cttattaaaa cacttcattg aaaatataca gtctaaattt 4140 attatttaaa ttttactagc aaaagtctta ggtgaacaat caactagtat ttgttgagct 4200 cctatttgcc cagagatggt catatttaaa cagaagtata cgtttttcag tttcaacatg 4260 aattttttta tttctgtcag ttatgacatc cacgagcatc actttttgtg tctgtttttt 4320 tttttttctt ggactaaatt caactgcatg gaagcggtgg tcagaaggtt gttttatacg 4380 agaacaggca gaaagtgccc attgttcagg attctaatag ctacatctac ttaatatctt 4440 catttctaaa ttgactgctt ttaccttttt ctcatgttta tataatggta tgcttgcata 4500 tatttcatga atacattgta catattatgt taatatttac acaatttaaa atatagatgt 4560 gttttatttt gaagtgagaa aatgaacatt aacaggcatg tttgtacagc tagaatatat 4620 tagtaagata ctgtttttcg tcattccaga gctacaacta ataacacgag gttccaaagc 4680 tgaagacttt gtataaagta tttgggtttt gttcttgtat tgctttcttt caacagtttc 4740 aaaataaaat atcatacaaa tattgaggga aatgttttca tatttttcaa aataggtttt 4800 tattgttgaa tgtacatcta ccccagcccc tcaaaagaaa aactgtttac atagaaattc 4860 ctacacatac gtttgcgtat atgttatttt aaacatcttt gtggtgagaa ttttttcccc 4920 gatattctcc ttctgtcaaa gtcagaacaa attcagggaa tttattttct ggcagttgtg 4980 ctccagtcct tttaaaattg tacatgaaca tgttttagaa acaatatgga ggatgatgca 5040 tacatgtcgg tcaagttcag cgctcgacat tttatggaaa gattttttta accttaccac 5100 gaaatactta actactgttt aagtgaattg acttatttca ctttagtttt tgaactgtga 5160 ttattggtat actgttatat cctcaacttg gatttatggt aacccctttt agttcatgga 5220 gaccaaaatt tggggtattt ataatagtca gcgcaggaat gcacatggaa tatctacttg 5280 tccttttgaa cctcacgagt catccagaat gtatagacag gaaaagcatg tcttatttaa 5340 aactgtaatt tatgggctca ggatctgacc gcagtcccgg gagtaagcat ttcaaagggg 5400 gaaggcagtg tggtccctac cctgtgtgaa tgtgaggatg tagacatcca tcagtgcaac 5460 tcgagctcca tcctcctccg atttctaagg ctccagtttt ctggagggac agtcatcatg 5520 ttttgattta tctgggagaa aactgtggtg cacagcttgt gaggagggca aggttgtgac 5580 gttcgagctt agttctggtg ttattctgtc tcctcttctt tgtcatcagc caaaacgtgg 5640 tttttaaaga gagtcatgca ggttagaaat aatgtcaaaa atatttagga atttaataac 5700 ctttaagtca gaaactaaaa caaatactga aatattagct cttcctacac ttcgtgttcc 5760 cctttagctg cctgaaaatc aagattgctc ctactcagat cttctgagtg gctaaaactt 5820 atggatatga aaaatgagat tgaatgatga ctatgctttg ctatcattgt tacctttcct 5880 caatactatt tggcaactac tgggactctt cagcacaaaa ggaatagatc tatgattgac 5940 cctgatttta attgtgaaat tatatgattc atatatttta tgaatcagaa taaccttcaa 6000 ataaaataaa tctaagtcgg ttaaaatgga tttcatgatt ttccctcaga aaatgagtaa 6060 cggagtccac ggcgtgcaat ggtaattata aattggtgat gcttgtttgc aaattgccca 6120 525 ctcgtgataa gtcaacagcc aatatttaaa actttgttcg ttactggctt taccctaact ttctctagtc tactgtcaat atcattttaa tgtaattgat tgtatatagt ctcaagaatg gttggtgggc atgagttcct agagaactgt ccaagggttg ggaaaatcca aattctcttc ctggctccag cactgatttt gtacataaac attaggcagg ttgcttaacc tttttatttc aaactctctc aactctaaag tgctaataat aatctcagtt accttatctt tgtcacaggg tgttcttttt tatgaagaaa aatttgaaaa tgataaaagc taagatgcct tctaacttca taagcaaacc tttaactaat tatgtatctg aaagtcaccc ccacatacca actcaacttt tttcctgtga acacataaat atatttttat agaaaaacaa atctacataa aataaatcta ctgtttagtg agcagtatga cttgtacatg ccattgaaaa ttattaatca gaagaaaatt aagcagggtc tttgctatac aaaagtgttt tccactaatt ttgcatgcgt atttataaga aaaatgtgaa tttggtggtt ttattctatc ggtataaagg catcgatatt ttagatgcac ccgtgtttgt aaaaatgtag agcacaatgg aattatgctg gaagtctcaa ataatatttt tttcctattt tatactcatg gaagagataa gctaaagagg ggacaataat gagaaatgtt ggtgtgcttt tctaagcatt taaaacataa ttgccaattg aaaccctaaa tatgtttaca taccattaag atatgattca tgtaacaatg ttaaattaat tataatggga ttgggtttgt tatctgtggt agtatatatc ctagtgttcc tatagtgaaa taagtagggt tcagccaaag ctttctttgt tttgtacctt aaattgttcg attacgtcat caaaagagat gaaaggtatg tagaacaggt tcacgtgatt acctttttct tttggcttgg attaatattc atagtagaac tttataaaac gtgtttgtat tgtaggtggt gtttgtatta tgcttatgac tatgtatggt ttgaaaatat tttcattata catgaaattc aactttccaa ataaaagttc tacttcatgt aatccaaaa 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7329 <210> 166 <211> 1117

<212> PRT <213> Homo sapians <400> 166

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 526

Pro Thr Glu Ser 260 Gly Ser Glu Ser Ser 265 lie Thr He Leu Lys 270 Gly Glu lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 2 95 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys /-1,. j_y Asn Tyr Arg Cys Th. is Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu iZk 1. u Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Cl n T 1 Q Qqv· Db a Tb v As n Ton Gin Pro As n His Thr Ala Val Tvr Gin \_J -U Vl -V -V ’ V, J- J. liV 4. Iii 4_!\— Vl *· j *- 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr lie Leu Ala Asn Al a As n He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Al a Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arn Z3 Trn - — £- Glu Glu Leu Thx? &amp;amp;Τ-ΓΓ -—3 Val Gin Gly T.vs —j — Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 6 9 0 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 527

Ser Met Glu 755 Gin Asn Gly Pro Gly 760 Leu Glu Tyr Arg Val 765 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Leu Pro Glu Gin Pro Thr Phe Leu Lys 820 82 5 830 Val He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro 835 840 845 Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin lie 850 855 860 lie Asn Asp Thr Tyr Glu He Gly Glu Leu Asn Asp He Asn He Thr 865 870 875 880 Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr 885 890 895 T.VC Φχζτ- T.wa Ph© Φντ· L©u Δ rrr Ala PvC Thi* Ser Gin v m w Lys J x- J X J -L. ‘&#905; j '-j —J 900 905 910 Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He 915 920 925 Gly Lys He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu 930 935 940 Val Phe Glu Pro Gly Ala Glu His He Val Arg Leu Met Thr Lys Asn 945 950 955 960 Trp Gly Asp Asn Asp Ser He Phe Gin Asp Val He Glu Thr Arg Gly 965 970 975 Arg Glu Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe 980 985 990 He Gly Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr 995 1000 1005 Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 1010 1015 1020 Lys Glu Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1025 1030 1035 1040 Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser 1045 1050 1055 Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser 1060 1065 107i 0 Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly 1075 1080 1085 Ser Phe He Gly Ala Tyr Al a Gly Ser Lys Glu Lys Gly Ser Val Glu 1090 1095 1100 Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1105 1110 1115 <210> 167

<211> 1224 <212> PRT <213> Homo sapians <400> 167

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 528

Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lv«S He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyi* Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arn ---J Thr He Val Gin T,VR — ~ Met Pro Met T.vs Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser ciy Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser 71 1 Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala ciy Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Giu Ala Val Val Ser Trp Gin Lys Val Giu Giu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala lie Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 529

Lys His Ser Leu Lys 565 Leu Ser Trp Ser Lys 570 Asp Gly Glu Ala Phe 575 Glu lie Asn Gly Thr Glu Asp Gly Arg He lie He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val m w — — J Ar*rr Sex Gin Pno S©37 Gin Pro Ser His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pno Asp Arg As n Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val Hrs Gly Arg Leu Lys Gly Tyr Gin I1 Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly lie Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 530

Ala Glu His He 1060 Val Arg Leu Met Thr 1065 Lys 1 Asn Trp Gly Asp Asn 1070 Asp Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys ΓΤΚτν x/x Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 ΓΤΝτν xyx Ala Gly Ser Ly s Glu Lys r-1 -«r Ser Val Glu Ser Asn ni Qo-r- Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 168

<211> 1117 <212> PRT <213> Homo sapians <400> 168

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Srn Val Tyr M© t Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 531

Pro Thr Glu Ser 260 Gly Ser Glu Ser Ser 265 He Thr He Leu Lys 270 Gly Glu lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 2 9 5 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu m 77 Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn ciy 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu T 1 Ω CqV Phe Τ&amp;#906;-t v As Π T on m η Pro A.s n His Thr Ala Val Tvr Gin -U J-\-. i—’ -u j. iij. -*· 2 — 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr lie Leu Al a Asn Ala Asn lie 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser IjOu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 67 0 Gly Arg Trp Glu Glu Leu. Thr Arg Val Gin Cl 17 --X Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 6 9 5 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro 1 a Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys 740 745 750 532

Ser Met Glu 755 Gin Asn Gly Pro Gly 760 Leu Glu Tyr Arg Val 765 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Leu Pro Glu Gin Pro Thr Phe Leu Lys 820 825 830 Val He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro 835 840 845 Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He 850 855 860 lie Asn Asp Thr Tyr Glu He Gly Glu Leu Asn Asp lie Asn He Thr 865 870 875 880 Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr 885 890 895 Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys 900 905 910 Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly lie 915 920 925 Gly Lys He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu 930 935 940 Val Phe Glu Pro Gly Ala Glu His lie Val Arg Leu Met Thr Lys Asn 945 950 955 960 Trp Gly Asp Asn Asp Ser lie Phe Gin Asp Val lie Glu Thr Arg Gly 965 970 975 Arg Glu Tyr Ala Gly Leu Tyr Asp Asp lie Ser Thr Gin Gly Trp Phe 980 985 990 He Gly Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr 995 1000 1005 Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 1010 1015 1020 Lys Glu Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1025 1030 1035 1040 Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser 1045 1050 1055 Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser 1060 1065 1070 Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly 1075 1080 1085 Ser Phe lie Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu 1090 1095 1100 Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1105 1110 1115 <210> 169 <211> 7602

<212> DNA <213> Homo sapians gcgcccccgt acagatcgcg atactgcaaa taaggtctca ttgtcttctt ctaatgttcc gttccaacaa caaattgaat cccggctccc tttcggaggc caaatcatag gctgtaaacc cctgaagagc tcctgttaaa tcataaaaca gtgaagctaa ggccggctcg ggcgcaggtg tggaactaag aaaagtgaga aatggagccg attctcaaaa gtcaaaagtc aggaaatcca ggggagaagg ctgtaaactg gggaacttaa ggagacatta cttttacttg gcaattgaaa caagttgcct gaaccaacat cgcccgaggg caaaccataa tttactgttt agattttcat gaagaggact taccatcttc ttcccttcga tttcgtggac 60 120 180 240 300 360 420 480 <400> 169 cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg aatcgtatat agttcaacag tgagtatttt 533 taaggatggc aacattcagg tgcttcaaat tccaaaactc cctcccatgc attagaacac cgcaaacgtg attaaggact caagcaaaga taccatcctc acaggttgat ttatggcaag cacagccagc tcctcgctgg gttatgtgag agttgacaat ccttcaacca ccttgccaat agaaaattac acctgaggca gtatcatatc gtcttactca tattagaaat tatgcttgaa gtcctggagt tattgatgga ctgttcagct tgttccggat gacctgggaa aggaaacaaa cacagttatc cgaagtaggg tccagatagg aaagtgggag ctggaagcca gcgggtgatg actaggatct tacagctcca gtcaacagtt gaaaacaaaa ttcaggacaa aacagtctta aacaccagaa cactgccact tttgcaatat tacaactcca attctacttg caccttagga gactcaccca gaattggggc tgctggttta tgctcttctc gtactcagtt tgaaaccttt ccttaatagg agaccatggt gaagggatct acaacatatg gagcaagaac acatcctgca ttcaggccta atcctgcatt aacccttttt atcccaaacg aaactgggaa ccaaaagaaa aatcctccca atcgaacaag gaagaaaagg attgtacaga aaacccaaac aaaggggaaa tggaacaaaa actttgaaga aatttcttgg acaaagaagc gctgaaggag catccatttg aatcatactg gccaatattg gctacagtgg gtcgtgtcct tatgaaaatg tgttgggtag gctacaaaac ttacattgtg aaagatggag gctaatttga catactgctc ccaccagaaa gctggagctg gaagagcctg ttacctttgg agaagtcagc aatccacaaa cctttgaaat cagggagccc acgcctgctg gggcctgacc gtgatccatg ccaaaggaca agtctgttgg agaaactctg gcctataact ggagtacctg ttatcttggg cagataataa tcaaagccca agggcttgca gaagggagta atagaggtat gataacgata tatgatgaca acactactat aaagaaaagg ggtgaataca gatatgcagc ctcttcagtg gttgaaagca taagcaacgc tttcatatag attatgttga tgttttgctt tagatacacc atttcactga aggggcacat tcgctatgtc aaattgaccc aaggcctccc atgaaagagt acagtcgcaa aaatgccaat tgctgttgcc tcttgctgct ttggtggtga tagagaatgt gaacagccac ctcagagtgc aacctcaacc ctggtgatgt ctgtgtacca atgttgtgga ttgggtacag ggcagaaggt gcacattgca aaaatgctat ttagagtttc aaagcaaatg aagcctttga ccatatctaa tagacagtgc accttcactt accacaacag gaaggtggga ctccatttgt ctagccagcc acataagggt ccatggagca cagtggagtg tctatgcccc ctcagtcagt gggtggacgt gagtacatgg atggaagaac gaatggttcc ctaaaggagc aacagccaac gactacctaa atgacaccta gctggcacct cttcacaggg aaggtatcgg ttgagccggg gcatttttca tctccactca tattaactgt aagatttgca gtgacagtga ctactgaaag aagatggatc atggaagttc tactggttca gaatagaaac aaagagtagt atattgtttt tcaactaaat ccatcggata atctcacttt agaagaaata tcttgaagtg acctttacac atacatgagc tgactactgt gaaactaaca tcccactgag tgagtgtttt cttaccaaag ctcctaccag tcacgatttt tgtgtatagc cacaatcaag tgtcttcccc gtgtgaagcc tgtccgtcca tgctttctta ggaagaagtg gatcaacaga aggaaaaact tcctaagaat tgactcacat aattaatggc tgtaacttta tgccgatata gtctgaaaga caatattagc ggaactgacc gagataccag gtcagaccat tcaagcctct gaatggacca ggaagaagaa ttatgatgtc gactctctat tataaacagt acgtctgaaa acatcccaaa ttccttagat tggtcctgaa ttttctaaag gaaattaaat cgagattgga ctcaaacctg ctgtggaaaa gaagatatca agctgaacat agatgtaatt aggctggttt ttgctttgtg tccagaccca tgaaaagcct tgctgacagc atttattggt tacagcaact ccccaacctt atgctggccg actttcttca caggtgctca ccaaagtccc attccatcga caagggaaat gaatttatag gaggagggag atttattgga caaaagggag tgctttgctg gttaacagtt agtggcagtg gctgaaggct gggagagaaa gacaaaggaa cacgttatag accggaagca tggagagtca agggaaatca tcaaatgtcc ttgatacaaa cattgcgagt aaacccctgg accaccgaag gcagtcacag cctcgtatcc ttgaaacaca acagaagatg gaggaccaag actcaagtaa cagaacagga gagtatattg agagtccaag ttcagggtca catgaaacac caacccaagg ggcctagagt acagtcacaa aaggtccagg tctggagaag acattagtta ggctatcaga gaagtgaaca gcctttagtg agtgagcctt gtcatcaaag ggaaacttaa gaattaaatg aatgcaacta ccgatcacgg ggagtaaatc atagttcgcc gagacaagag attggactga aagaggaata gaaattcagt ctcaaaggaa ttagtcgaat gcctacgctg tttccccttc ccatatttat aagatttcat aaatataaaa aaatgcaaaa cattcagtat acaattcagg accgctgctt ttccaagtgt atccaattgt tgaatattga atctatactt catttccaag caaattccat agtcttcaat tgccaactcc caaaagaaaa attatcgctg tagaagagcc atggcatctt atggctcccc gttttaccaa atggaactat ccaaagatgg tctttgcttc agggcaggcg aagatgctgg ccaatttgga ccaaattgca gtttgaagtt gcaggataat gtatttactg ctgttcttga gtgttcggct ttgaatttga gaaagaaaac tagccgtgaa caccagcagc aaatgattat acagagtgac accacacatt ctatcaatca actatcctga aagttacctg taaattggtg ttctaagatt aatttcattt atatatttca ttgataaaga ctggctatct atattaacat ccaagtacaa aggaaagctc ttactcaaaa taatgactaa ggagagaata tgtgtgcgat gaggtggaaa cagtaaaaga gccttcggtc acggagaggg gatctaagga gggcataaac ctgttcaaag ccagaagtca tgccaagcac cacaaaacaa attccatatt 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 534 tgcctgattt tactattcgg tgtgtttgca tagatgttgc tacttggtgg gtttttctcc 4260 gtatgcacat tggtatacag tctctgagaa ctggcttggt gactttgctt cactacaggt 4320 taaaagacca taagcaaact ggttatttaa aatgtaaaaa ggaatatgaa agtcttatta 4380 aaacacttca ttgaaaatat acagtctaaa tttattattt aaattttact agcaaaagtc 4440 ttaggtgaac aatcaactag tatttgttga gctcctattt gcccagagat ggtcatattt 4500 aaacagaagt atacgttttt cagtttcaac atgaattttt ttatttctgt cagttatgac 4560 atccacgagc atcacttttt gtgtctgttt tttttttttt cttggactaa attcaactgc 4620 atggaagcgg tggtcagaag gttgttttat acgagaacag gcagaaagtg cccattgttc 4680 aggattctaa tagetacatc tacttaatat cttcatttct aaattgactg cttttacctt 4740 tttctcatgt ttatataatg gtatgcttgc atatatttca tgaatacatt gtacatatta 4800 tgttaatatt tacacaattt aaaatataga tgtgttttat tttgaagtga gaaaatgaac 4860 attaacaggc atgtttgtac agctagaata tattagtaag atactgtttt tcgtcattcc 4920 agagctacaa ctaataacac gaggttccaa agctgaagac tttgtataaa gtatttgggt 4980 tttgttcttg tattgctttc tttcaacagt ttcaaaataa aatatcatac aaatattgag 5040 ggaaatgttt tcatattttt caaaataggt ttttattgtt gaatgtacat ctaccccagc 5100 ccctcaaaag aaaaactgtt tacatagaaa ttcctacaca tacgtttgcg tatatgttat 5160 tttaaacatc tttgtggtga gaattttttc cccgatattc tccttctgtc aaagtcagaa 5220 caaattcagg gaatttattt tctggcagtt gtgctccagt ccttttaaaa ttgtacatga 5280 acatgtttta gaaacaatat ggaggatgat gcatacatgt cggtcaagtt cagcgctcga 5340 cattttatgg aaagattttt ttaaccttac cacgaaatac ttaactactg tttaagtgaa 5400 ttgacttatt tcactttagt ttttgaactg tgattattgg tatactgtta tatcctcaac 5460 ttggatttat ggtaacccct tttagttcat ggagaccaaa atttggggta tttataatag 5520 tcagcgcagg aatgcacatg gaatatctac ttgtcctttt gaacctcacg agtcatccag 5580 aatgtataga caggaaaagc atgtcttatt taaaactgta atttatgggc tcaggatctg 5640 accgcagtcc cgggagtaag catttcaaag ggggaaggca gtgtggtccc taccctgtgt 5700 gaatgtgagg atgtagacat ccatcagtgc aactcgagct ccatcctcct ccgatttcta 5760 aggctccagt tttctggagg gacagtcatc atgttttgat ttatctggga gaaaactgtg 5820 gtgcacagct tgtgaggagg gcaaggttgt gacgttcgag cttagttctg gtgttattct 5880 gtctcctctt ctttgtcatc agccaaaacg tggtttttaa agagagtcat gcaggttaga 5940 aataatgtca aaaatattta ggaatttaat aacctttaag tcagaaacta aaacaaatac 6000 tgaaatatta gctcttccta cacttcgtgt tcccctttag ctgcctgaaa atcaagattg 6060 ctcctactca gatcttctga gtggctaaaa cttatggata tgaaaaatga gattgaatga 6120 tgactatgct ttgctatcat tgttaccttt cctcaatact atttggcaac tactgggact 6180 cttcagcaca aaaggaatag atctatgatt gaccctgatt ttaattgtga aattatatga 6240 ttcatatatt ttatgaatca gaataacctt caaataaaat aaatctaagt cggttaaaat 6300 ggatttcatg attttccctc agaaaatgag taacggagtc cacggcgtgc aatggtaatt 6360 ataaattggt gatgcttgtt tgcaaattgc ccactcgtga taagtcaaca gccaatattt 6420 aaaactttgt tcgttactgg ctttacccta actttctcta gtctactgtc aatatcattt 6480 taatgtaatt gattgtatat agtctcaaga atggttggtg ggcatgagtt cctagagaac 6540 tgtccaaggg ttgggaaaat ccaaattctc ttcctggctc cagcactgat tttgtacata 6600 aacattaggc aggttgctta acctttttat ttcaaactct ctcaactcta aagtgctaat 6660 aataatctca gttaccttat ctttgtcaca gggtgttctt ttttatgaag aaaaatttga 6720 aaatgataaa agctaagatg ccttctaact tcataagcaa acctttaact aattatgtat 6780 ctgaaagtca cccccacata ccaactcaac ttttttcctg tgaacacata aatatatttt 6840 tatagaaaaa caaatctaca taaaataaat ctactgttta gtgagcagta tgacttgtac 6900 atgccattga aaattattaa tcagaagaaa attaagcagg gtctttgcta tacaaaagtg 6960 ttttccacta attttgcatg cgtatttata agaaaaatgt gaatttggtg gttttattct 7020 atcggtataa aggcatcgat attttagatg cacccgtgtt tgtaaaaatg tagagcacaa 7080 tggaattatg ctggaagtct caaataatat ttttttccta ttttatactc atggaagaga 7140 taagctaaag aggggacaat aatgagaaat gttggtgtgc ttttctaagc atttaaaaca 7200 taattgccaa ttgaaaccct aaatatgttt acataccatt aagatatgat tcatgtaaca 7260 atgttaaatt aattataatg ggattgggtt tgttatctgt ggtagtatat atcctagtgt 7320 tcctatagtg aaataagtag ggttcagcca aagctttctt tgttttgtac cttaaattgt 7380 tcgattacgt catcaaaaga gatgaaaggt atgtagaaca ggttcacgtg attacctttt 7440 tcttttggct tggattaata ttcatagtag aactttataa aacgtgtttg tattgtaggt 7500 ggtgtttgta ttatgcttat gactatgtat ggtttgaaaa tattttcatt atacatgaaa 7560 ttcaactttc caaataaaag ttctacttca tgtaatccaa aa 7602 <210> 170 <211> 7650 535

<212> DNA <213> Homo sapians <400> 170 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc 3000 ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg 3060 agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt 3120 atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca 3180 gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc 3240 aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag 3300 ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga 3360 agggagtaaa ggtatcggga agatatcagg agtaaatctt actcaaaaga ctcacccaat 3420 agaggtattt gagccgggag ctgaacatat agttcgccta atgactaaga attggggcga 3480 536 taacgatagc atttttcaag atgtaattga gacaagaggg agagaatatg ctggtttata 3540 tgatgacatc tccactcaag gctggtttat tggactgatg tgtgcgattg ctcttctcac 3600 actactatta ttaactgttt gctttgtgaa gaggaataga ggtggaaagt actcagttaa 3660 agaaaaggaa gatttgcatc cagacccaga aattcagtca gtaaaagatg aaacctttgg 3720 tgaatacagt gacagtgatg aaaagcctct caaaggaagc cttcggtccc ttaataggga 3780 tatgcagcct actgaaagtg ctgacagctt agtcgaatac ggagagggag accatggtct 3840 cttcagtgaa gatggatcat ttattggtgc ctacgctgga tctaaggaga agggatctgt 3900 tgaaagcaat ggaagttcta cagcaacttt tccccttcgg gcataaacac aacatatgta 3960 agcaacgcta ctggttcacc ccaaccttcc atatttatct gttcaaagga gcaagaactt 4020 tcatatagga atagaaacat gctggccgaa gatttcatcc agaagtcaac atcctgcaat 4080 tatgttgaaa agagtagtac tttcttcaaa atataaaatg ccaagcactt caggcctatg 4140 ttttgcttat attgttttca ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta 4200 gatacacctc aactaaatcc aaagtcccca ttcagtatat tccatatttg cctgatttta 4260 ctattcggtg tgtttgcata gatgttgcta cttggtgggt ttttctccgt atgcacattg 4320 gtatacagtc tctgagaact ggcttggtga ctttgcttca ctacaggtta aaagaccata 4380 agcaaactgg ttatttaaaa tgtaaaaagg aatatgaaag tcttattaaa acacttcatt 4440 gaaaatatac agtctaaatt tattatttaa attttactag caaaagtctt aggtgaacaa 4500 tcaactagta tttgttgagc tcctatttgc ccagagatgg tcatatttaa acagaagtat 4560 acgtttttca gtttcaacat gaattttttt atttctgtca gttatgacat ccacgagcat 4620 cactttttgt gtctgttttt ttttttttct tggactaaat tcaactgcat ggaagcggtg 4680 gtcagaaggt tgttttatac gagaacaggc agaaagtgcc cattgttcag gattctaata 4740 gctacatcta cttaatatct tcatttctaa attgactgct tttacctttt tctcatgttt 4800 atataatggt atgcttgcat atatttcatg aatacattgt acatattatg ttaatattta 4860 cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat 4920 gtttgtacag ctagaatata ttagtaagat actgtttttc gtcattccag agctacaact 4980 aataacacga ggttccaaag ctgaagactt tgtataaagt atttgggttt tgttcttgta 5040 ttgctttctt tcaacagttt caaaataaaa tatcatacaa atattgaggg aaatgttttc 5100 atatttttca aaataggttt ttattgttga atgtacatct accccagccc ctcaaaagaa 5160 aaactgttta catagaaatt cctacacata cgtttgcgta tatgttattt taaacatctt 5220 tgtggtgaga attttttccc cgatattctc cttctgtcaa agtcagaaca aattcaggga 5280 atttattttc tggcagttgt gctccagtcc ttttaaaatt gtacatgaac atgttttaga 5340 aacaatatgg aggatgatgc atacatgtcg gtcaagttca gcgctcgaca ttttatggaa 5400 agattttttt aaccttacca cgaaatactt aactactgtt taagtgaatt gacttatttc 5460 actttagttt ttgaactgtg attattggta tactgttata tcctcaactt ggatttatgg 5520 taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa 5580 tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca 5640 ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg 5700 ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat 5760 gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt 5820 tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg 5880 tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct 5940 ttgtcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa 6000 aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc 6060 tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga 6120 tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt 6180 gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa 6240 aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt 6300 atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat 6360 tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga 6420 tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc 6480 gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga 6540 ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt 6600 gggaaaatcc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag 6660 gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 537 gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 aataaaagtt ctacttcatg taatccaaaa 7650 <210> 171 <211> 7602

<212> DNA <213> Homo sapians <400> 171 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt caaattccat 960 caagcaaaga aaacccaaac tgctgttgcc tcccactgag agtggcagtg agtcttcaat 1020 taccatcctc aaaggggaaa tcttgctgct tgagtgtttt gctgaaggct tgccaactcc 1080 acaggttgat tggaacaaaa ttggtggtga cttaccaaag gggagagaaa caaaagaaaa 1140 ttatggcaag actttgaaga tagagaatgt ctcctaccag gacaaaggaa attatcgctg 1200 cacagccagc aatttcttgg gaacagccac tcacgatttt cacgttatag tagaagagcc 1260 tcctcgctgg acaaagaagc ctcagagtgc tgtgtatagc accggaagca atggcatctt 1320 gttatgtgag gctgaaggag aacctcaacc cacaatcaag tggagagtca atggctcccc 1380 agttgacaat catccatttg ctggtgatgt tgtcttcccc agggaaatca gttttaccaa 1440 ccttcaacca aatcatactg ctgtgtacca gtgtgaagcc tcaaatgtcc atggaactat 1500 ccttgccaat gccaatattg atgttgtgga tgtccgtcca ttgatacaaa ccaaagatgg 1560 agaaaattac gctacagtgg ttgggtacag tgctttctta cattgcgagt tctttgcttc 1620 acctgaggca gtcgtgtcct ggcagaaggt ggaagaagtg aaacccctgg agggcaggcg 1680 gtatcatatc tatgaaaatg gcacattgca gatcaacaga accaccgaag aagatgctgg 1740 gtcttactca tgttgggtag aaaatgctat aggaaaaact gcagtcacag ccaatttgga 1800 tattagaaat gctacaaaac ttagagtttc tcctaagaat cctcgtatcc ccaaattgca 1860 tatgcttgaa ttacattgtg aaagcaaatg tgactcacat ttgaaacaca gtttgaagtt 1920 gtcctggagt aaagatggag aagcctttga aattaatggc acagaagatg gcaggataat 1980 tattgatgga gctaatttga ccatatctaa tgtaacttta gaggaccaag gtatttactg 2040 ctgttcagct catactgctc tagacagtgc tgccgatata actcaagtaa ctgttcttga 2100 tgttccggat ccaccagaaa accttcactt gtctgaaaga cagaacagga gtgttcggct 2160 gacctgggaa gctggagctg accacaacag caatattagc gagtatattg ttgaatttga 2220 aggaaacaaa gaagagcctg gaaggtggga ggaactgacc agagtccaag gaaagaaaac 2280 cacagttatc ttacctttgg ctccatttgt gagataccag ttcagggtca tagccgtgaa 2340 cgaagtaggg agaagtcagc ctagccagcc gtcagaccat catgaaacac caccagcagc 2400 tccagatagg aatccacaaa acataagggt tcaagcctct caacccaagg aaatgattat 2460 aaagtgggag cctttgaaat ccatggagca gaatggacca ggcctagagt acagagtgac 2520 ctggaagcca cagggagccc cagtggagtg ggaagaagaa acagtcacaa accacacatt 2580 gcgggtgatg acgcctgctg tctatgcccc ttatgatgtc aaggtccagg ctatcaatca 2640 actaggatct gggcctgacc ctcagtcagt gactctctat tctggagaag actatcctga 2700 538 tacagctcca gtgatccatg gggtggacgt tataaacagt acattagtta aagttacctg 2760 gtcaacagtt ccaaaggaca gagtacatgg acgtctgaaa ggctatcaga taaattggtg 2820 gaaaacaaaa agtctgttgg atggaagaac acatcccaaa gaagtgaaca ttctaagatt 2880 ttcaggacaa agaaactctg gaatggttcc ttccttagat gcctttagtg aatttcattt 2940 aacagtctta gcctataact ctaaaggagc tggtcctgaa agtgagcctt atatatttca 3000 aacaccagaa ggagtacctg aacagccaac ttttctaaag gtcatcaaag ttgataaaga 3060 cactgccact ttatcttggg gactacctaa gaaattaaat ggaaacttaa ctggctatct 3120 tttgcaatat cagataataa atgacaccta cgagattgga gaattaaatg atattaacat 3180 tacaactcca tcaaagccca gctggcacct ctcaaacctg aatgcaacta ccaagtacaa 3240 attctacttg agggcttgca cttcacaggg ctgtggaaaa ccgatcacgg aggaaagctc 3300 caccttagga gaagggagta aaggtatcgg gaagatatca ggagtaaatc ttactcaaaa 3360 gactcaccca atagaggtat ttgagccggg agctgaacat atagttcgcc taatgactaa 3420 gaattggggc gataacgata gcatttttca agatgtaatt gagacaagag ggagagaata 3480 tgctggttta tatgatgaca tctccactca aggctggttt attggactga tgtgtgcgat 3540 tgctcttctc acactactat tattaactgt ttgctttgtg aagaggaata gaggtggaaa 3600 gtactcagtt aaagaaaagg aagatttgca tccagaccca gaaattcagt cagtaaaaga 3660 tgaaaccttt ggtgaataca gtgacagtga tgaaaagcct ctcaaaggaa gccttcggtc 3720 ccttaatagg gatatgcagc ctactgaaag tgctgacagc ttagtcgaat acggagaggg 3780 agaccatggt ctcttcagtg aagatggatc atttattggt gcctacgctg gatctaagga 3840 gaagggatct gttgaaagca atggaagttc tacagcaact tttccccttc gggcataaac 3900 acaacatatg taagcaacgc tactggttca ccccaacctt ccatatttat ctgttcaaag 3960 gagcaagaac tttcatatag gaatagaaac atgctggccg aagatttcat ccagaagtca 4020 acatcctgca attatgttga aaagagtagt actttcttca aaatataaaa tgccaagcac 4080 ttcaggccta tgttttgctt atattgtttt caggtgctca aaatgcaaaa cacaaaacaa 4140 atcctgcatt tagatacacc tcaactaaat ccaaagtccc cattcagtat attccatatt 4200 tgcctgattt tactattcgg tgtgtttgca tagatgttgc tacttggtgg gtttttctcc 4260 gtatgcacat tggtatacag tctctgagaa ctggcttggt gactttgctt cactacaggt 4320 taaaagacca taagcaaact ggttatttaa aatgtaaaaa ggaatatgaa agtcttatta 4380 aaacacttca ttgaaaatat acagtctaaa tttattattt aaattttact agcaaaagtc 4440 ttaggtgaac aatcaactag tatttgttga gctcctattt gcccagagat ggtcatattt 4500 aaacagaagt atacgttttt cagtttcaac atgaattttt ttatttctgt cagttatgac 4560 atccacgagc atcacttttt gtgtctgttt tttttttttt cttggactaa attcaactgc 4620 atggaagcgg tggtcagaag gttgttttat acgagaacag gcagaaagtg cccattgttc 4680 aggattctaa tagetacatc tacttaatat cttcatttct aaattgactg cttttacctt 4740 tttctcatgt ttatataatg gtatgcttgc atatatttca tgaatacatt gtacatatta 4800 tgttaatatt tacacaattt aaaatataga tgtgttttat tttgaagtga gaaaatgaac 4860 attaacaggc atgtttgtac agctagaata tattagtaag atactgtttt tcgtcattcc 4920 agagctacaa ctaataacac gaggttccaa agctgaagac tttgtataaa gtatttgggt 4980 tttgttcttg tattgctttc tttcaacagt ttcaaaataa aatatcatac aaatattgag 5040 ggaaatgttt tcatattttt caaaataggt ttttattgtt gaatgtacat ctaccccagc 5100 ccctcaaaag aaaaactgtt tacatagaaa ttcctacaca tacgtttgcg tatatgttat 5160 tttaaacatc tttgtggtga gaattttttc cccgatattc tccttctgtc aaagtcagaa 5220 caaattcagg gaatttattt tctggcagtt gtgctccagt ccttttaaaa ttgtacatga 5280 acatgtttta gaaacaatat ggaggatgat gcatacatgt cggtcaagtt cagcgctcga 5340 cattttatgg aaagattttt ttaaccttac cacgaaatac ttaactactg tttaagtgaa 5400 ttgacttatt tcactttagt ttttgaactg tgattattgg tatactgtta tatcctcaac 5460 ttggatttat ggtaacccct tttagttcat ggagaccaaa atttggggta tttataatag 5520 tcagcgcagg aatgcacatg gaatatctac ttgtcctttt gaacctcacg agtcatccag 5580 aatgtataga caggaaaagc atgtcttatt taaaactgta atttatgggc tcaggatctg 5640 accgcagtcc cgggagtaag catttcaaag ggggaaggca gtgtggtccc taccctgtgt 5700 gaatgtgagg atgtagacat ccatcagtgc aactcgagct ccatcctcct ccgatttcta 5760 aggctccagt tttctggagg gacagtcatc atgttttgat ttatctggga gaaaactgtg 5820 gtgcacagct tgtgaggagg gcaaggttgt gacgttcgag cttagttctg gtgttattct 5880 gtctcctctt ctttgtcatc agccaaaacg tggtttttaa agagagtcat gcaggttaga 5940 aataatgtca aaaatattta ggaatttaat aacctttaag tcagaaacta aaacaaatac 6000 tgaaatatta gctcttccta cacttcgtgt tcccctttag ctgcctgaaa atcaagattg 6060 ctcctactca gatcttctga gtggctaaaa cttatggata tgaaaaatga gattgaatga 6120 tgactatgct ttgctatcat tgttaccttt cctcaatact atttggcaac tactgggact 6180 cttcagcaca aaaggaatag atctatgatt gaccctgatt ttaattgtga aattatatga 6240 ttcatatatt ttatgaatca gaataacctt caaataaaat aaatctaagt cggttaaaat 6300 ggatttcatg attttccctc agaaaatgag taacggagtc cacggcgtgc aatggtaatt 6360 ataaattggt gatgcttgtt tgcaaattgc ccactcgtga taagtcaaca gccaatattt 6420 539 aaaactttgt tcgttactgg ctttacccta actttctcta gtctactgtc aatatcattt taatgtaatt gattgtatat agtctcaaga atggttggtg ggcatgagtt cctagagaac tgtccaaggg ttgggaaaat ccaaattctc ttcctggctc cagcactgat tttgtacata aacattaggc aggttgctta acctttttat ttcaaactct ctcaactcta aagtgctaat aataatctca gttaccttat ctttgtcaca gggtgttctt ttttatgaag aaaaatttga aaatgataaa agctaagatg ccttctaact tcataagcaa acctttaact aattatgtat ctgaaagtca cccccacata ccaactcaac ttttttcctg tgaacacata aatatatttt tatagaaaaa caaatctaca taaaataaat ctactgttta gtgagcagta tgacttgtac atgccattga aaattattaa tcagaagaaa attaagcagg gtctttgcta tacaaaagtg ttttccacta attttgcatg cgtatttata agaaaaatgt gaatttggtg gttttattct atcggtataa aggcatcgat attttagatg cacccgtgtt tgtaaaaatg tagagcacaa tggaattatg ctggaagtct caaataatat ttttttccta ttttatactc atggaagaga taagctaaag aggggacaat aatgagaaat gttggtgtgc ttttctaagc atttaaaaca taattgccaa ttgaaaccct aaatatgttt acataccatt aagatatgat tcatgtaaca atgttaaatt aattataatg ggattgggtt tgttatctgt ggtagtatat atcctagtgt tcctatagtg aaataagtag ggttcagcca aagctttctt tgttttgtac cttaaattgt tcgattacgt catcaaaaga gatgaaaggt atgtagaaca ggttcacgtg attacctttt tcttttggct tggattaata ttcatagtag aactttataa aacgtgtttg tattgtaggt ggtgtttgta ttatgcttat gactatgtat ggtttgaaaa tattttcatt atacataaaa ttcaactttc caaataaaag ttctacttca tgtaatccaa aa 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7602 <210> 172

<211> 1208 <212> PRT <213> Homo sapians <400> 172

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Ser Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 225 230 235 240 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 245 250 255 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 540 260 265 270 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 275 280 285 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 290 295 300 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Ls u Gly Thr Ala Thr 305 310 315 320 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 325 330 335 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 340 345 350 Glu Ala Glu Gly Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 355 360 365 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 370 375 380 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 385 390 395 400 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 4 05 410 415 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 420 4 2 5 430 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 435 440 445 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 450 455 460 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 465 470 475 480 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 485 490 495 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 500 505 510 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 515 520 525 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 530 535 540 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 545 550 555 560 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 565 570 575 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 580 585 590 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 595 600 605 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 610 615 620 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 625 630 635 640 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 645 650 655 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 660 665 670 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val lie Ala 675 680 685 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 690 695 700 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 705 710 715 720 Gin Ala Ser Gin Pro Lys Glu Met lie lie Lys Trp Glu Pro Leu Lys 725 730 735 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 740 745 750 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 541 755 760 765 Thr Leu Arg Val 770 Met Thr Pro Ala Val Tyr Ala 775 Pro Tyr Asp Val Lys 780 Val 785 Gin Ala lie Asn Gin Leu Gly Ser Gly Pro 790 795 Asp Pro Gin Ser Val 800 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr 805 810 Ala Pro Val He His 815 Gly Val Asp Val 820 He Asn Ser Thr Leu val Lys 825 Var Tnr Trp t>er rnr 830 Val Pro Lys Asp 835 Arg Val His Gly Arg Leu Lys 840 Gly Tyr Gin He Asn 845 Trp Trp Lys Thr 850 Lys Ser Leu Leu Asp Gly Arg 855 Thr His Pro Lys Glu 860 Val 865 Asn He Leu Arg Phe Ser Gly Gin Arg Asn 870 875 Ser Gly Met Val Pro 880 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr 885 890 Val Leu Ala Tyr Asn 895 Ser Lys Gly Ala 900 Gly Pro Glu Ser Glu Pro Tyr 905 He Phe Gin Thr Pro 910 Glu Gly Val Pro 915 Glu Gin Pro Thr Phe Leu Lys 920 Val He Lys Val Asp 925 Lys Asp Thr Ala 930 Thr Leu Ser Trp Gly Leu Pro 935 Lys Lys Leu Asn Gly 940 Asn 945 Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He 950 955 He Asn Asp Thr Tyr 960 Glu He Gly Glu Leu Asn Asp He Asn He Thr 965 970 Thr Pro Ser Lys Pro 975 Ser Trp His Leu 980 Ser Asn Leu Asn Ala Thr Thr 985 Lys Tyr Lys Phe Tyr 990 Leu Arg Ala Cys 995 Thr Ser Gin Gly Cys Gly Lys 1000 Pro He Thr Glu Glu 1005 Ser Ser Thr Leu 1010 Gly Glu Gly Ser Lys Gly He 1015 Gly Lys He Ser Gly 1020 Val 1025 Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1030 1035 1040 Ala Glu His He Val Arg Leu Met Thr Lys Asn 1045 1050 Trp Gly Asp Asn Asp 1055 Ser He Phe Gin 106C Asp Val He Glu Thr Arg Gly I 1065 Arg Glu Tyr Ala Gly 1070 Leu Tyr Asp Asp 1075 He Ser Thr Gin Gly Trp Phe 1080 He Gly Leu Met Cys 1085 Ala He Ala Leu 1090 Leu Thr Leu Leu Leu Leu Thr 1095 Val Cys Phe Val Lys 1100 Arg 1105 Asn Arg Giy Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1110 1115 1120 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1125 1130 Thr Phe Gly Glu Tyr 1135 Ser Asp Ser Asp 114C Glu Lys Pro Leu Lys Gly Ser ) 1145 Leu Arg Ser Leu Asn 1150 Arg Asp Met Gin 1155 Pro Thr Glu Ser Ala Asp Ser 1160 Leu Val Glu Tyr Gly 1165 Glu Gly Asp His 1170 Gly Leu Phe Ser Glu Asp Gly 1175 Ser Phe He Gly Ala 1180 Tyr 1185 Thr Ala Gly Ser Ala Thr Phe Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1190 1195 1200 Pro Leu Arg Ala 1205 <210> 173 <211> 1224

<212> PRT 542 <213> Homo sapians <400> 173

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys A. 1. ii He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg lie Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 1 1 c 1 z J ion X X. V 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 2 85 Asp Trp Asn Lys He Giy Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Giy Asp Val Val Phe Pro Arg 385 3 9 0 395 4 0 0 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 543 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala I le Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 C ") c 540 Leu His Met Leu Glu Leu His Cys Glu Ser Ly s Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg He lie He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 7 5 5 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Al a Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 9 6 0 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He lie Asn Asp Thr Tyr 544 965 970 975 Glu lie Gly Glu Leu Asn Asp lie Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005

Leu Arg Ala Cys Thr Ser Gin Gly cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu uly ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val lie Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp lie Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1210 1215 1205

Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 174

<211> 1208 <212> PRT <213> Homo sapians <400> 174

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Al a Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 545 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Ser Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 225 230 235 240 Pro Thr Glu Ser ciy Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 245 250 255 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 260 265 270 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 275 280 285 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 290 295 300 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr one ο ι n &amp;#9633; 1C 320 J v J X V X .1. X His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 325 330 335 Pro Gin Ser Ala Val Tyr Ser Thr ciy Ser Asn Gly lie Leu Leu Cys 340 345 350 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 355 360 365 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 370 375 380 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 385 390 395 400 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 405 410 415 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 420 425 430 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 435 440 445 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 450 455 460 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 465 470 475 480 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 485 490 495 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 500 505 510 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 515 520 525 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 530 535 540 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 545 550 555 560 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 565 570 575 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 580 585 590 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 595 600 605 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 610 615 620 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 625 630 635 640 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 645 650 655 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 546 660 665 670 lie Leu Pro Leu Ala Pro Phe Val 675 680 Arg Tyr Gin Phe Arg Val He Ala 685 Val Asn Glu Val Gly Arg Ser Gin 690 695 Pro Ser Gin Pro Ser Asp His His 700 Glu 705 Thr Pro Pro Ala Ala Pro Asp 710 Arg Asn Pro 715 Gin Asn He Arg Val 720 Gin Ala Ser Gin Pro Lys Glu Met 725 He He Lys 730 Trp Glu Pro Leu Lys 735 Ser Met Glu Gin Asn Gly Pro Gly 740 Leu Glu Tyr 745 Arg Val Thr Trp Lys 750 Pro Gin Gly Ala Pro Val Glu Trp 755 760 Glu Glu Glu Thr Val Thr Asn His 765 Thr Leu Arg Val Met Thr Pro Ala 770 775 Val Tyr Ala Pro Tyr Asp Val Lys 780 Val 785 Gin Ala He Asn Gin Leu Gly 790 Ser Gly Pro 7 9 5 Asp Pro Gin Ser Val 800 Thr Leu Tyr Ser Gly Glu Asp Tyr one OU J Pro Asp Thr Qin Q x v Ala Pro Val He His 815 Gly Val Asp Val He Asn Ser Thr 820 Leu Val Lys 825 Val Thr Trp Ser Thr 830 Val Pro Lys Asp Arg Val His Gly 835 840 Arg Leu Lys Gly Tyr Gin He Asn 845 Trp Trp Lys Thr Lys Ser Leu Leu 850 855 Asp Gly Arg Thr His Pro Lys Glu 860 Val 865 Asn He Leu Arg Phe Ser Gly 870 Gin Arg Asn 875 Ser Gly Met Val Pro 880 Ser Leu Asp Ala Phe Ser Glu Phe 885 His Leu Thr 890 Val Leu Ala Tyr Asn 895 Ser Lys Gly Ala Gly Pro Glu Ser 900 Glu Pro Tyr 905 He Phe Gin Thr Pro 910 Glu Gly Val Pro Glu Gin Pro Thr 915 920 Phe Leu Lys Val lie Lys Val Asp 925 Lys Asp Thr Ala Thr Leu Ser Trp 930 935 Gly Leu Pro Lys Lys Leu Asn Gly 940 Asn 945 Leu Thr Gly Tyr Leu Leu Gin 950 Tyr Gin He 955 He Asn Asp Thr Tyr 960 Glu He Gly Glu Leu Asn Asp He 965 Asn He Thr 970 Thr Pro Ser Lys Pro 975 Ser Trp His Leu Ser Asn Leu Asn 980 Ala Thr Thr 985 Lys Tyr Lys Phe Tyr 990 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys 995 1000 Pro He Thr Glu Glu 1005 Ser Ser Thr Leu Gly Glu Gly Ser 1010 1015 Lys Gly He Gly Lys He Ser Gly 1020 Val Asn Leu Thr Gin Lys Thr His 1025 1030 Pro He Glu Val Phe Glu Pro Gly 1035 1040 Ala Glu His He Val Arg Leu Met 1045 Thr Lys Asn 1050 Trp Gly Asp Asn Asp 1055 Ser He Phe Gin Asp Val He Glu 1060 Thr Arg Gly 1065 Arg Glu Tyr Ala Gly 1070 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe 1075 1080 lie Gly Leu Met Cys 1085 Ala He Ala Leu Leu Thr Leu Leu 1090 1095 Leu Leu Thr Val Cys Phe Val Lys 1100 Arq Asn Arq Glv Gly Lys Tyr Ser 1105 1110 Val Lys Glu Lys Glu Asp Leu His 1115 1120 Pro Asp Pro Glu He Gin Ser Val 1125 Lys Asp Glu 1130 Thr Phe Gly Glu Tyr 1135 Ser Asp Ser Asp Glu Lys Pro Leu 1140 Lys Gly Ser 1145 Leu Arg Ser Leu Asn 1150 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 547 1155 1160 1165

Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe lie Gly Ala 1170 1175 1180 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1185 1190 1195 1200 Thr Ala Thr Phe Pro Leu Arg Ala 1205 <210> 175 <211> 7527

<212> DNA <213> Homo sapians <400> 175 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaaaatt 660 agaacacatc gaacaagatg aaagagtata catgagccaa aagggagatc tatacttcgc 720 aaacgtggaa gaaaaggaca gtcgcaatga ctactgttgc tttgctgcat ttccaagatt 780 aaggactatt gtacagaaaa tgccaatgaa actaacagtt aacagtttaa agcatgctaa 840 tgactcaagt tcatccacag aaattggttc caaggcaaat tccatcaagc aaagaaaacc 900 caaactgctg ttgcctccca ctgagagtgg cagtgagtct tcaattacca tcctcaaagg 960 ggaaatcttg ctgcttgagt gttttgctga aggcttgcca actccacagg ttgattggaa 1020 caaaattggt ggtgacttac caaaggggag agaaacaaaa gaaaattatg gcaagacttt 1080 gaagatagag aatgtctcct accaggacaa aggaaattat cgctgcacag ccagcaattt 1140 cttgggaaca gccactcacg attttcacgt tatagtagaa gagcctcctc gctggacaaa 1200 gaagcctcag agtgctgtgt atagcaccgg aagcaatggc atcttgttat gtgaggctga 1260 aggagaacct caacccacaa tcaagtggag agtcaatggc tccccagttg acaatcatcc 1320 atttgctggt gatgttgtct tccccaggga aatcagtttt accaaccttc aaccaaatca 1380 tactgctgtg taccagtgtg aagcctcaaa tgtccatgga actatccttg ccaatgccaa 1440 tattgatgtt gtggatgtcc gtccattgat acaaaccaaa gatggagaaa attacgctac 1500 agtggttggg tacagtgctt tcttacattg cgagttcttt gcttcacctg aggcagtcgt 1560 gtcctggcag aaggtggaag aagtgaaacc cctggagggc aggcggtatc atatctatga 1620 aaatggcaca ttgcagatca acagaaccac cgaagaagat gctgggtctt actcatgttg 1680 ggtagaaaat gctataggaa aaactgcagt cacagccaat ttggatatta gaaatgctac 1740 aaaacttaga gtttctccta agaatcctcg tatccccaaa ttgcatatgc ttgaattaca 1800 ttgtgaaagc aaatgtgact cacatttgaa acacagtttg aagttgtcct ggagtaaaga 1860 tggagaagcc tttgaaatta atggcacaga agatggcagg ataattattg atggagctaa 1920 tttgaccata tctaatgtaa ctttagagga ccaaggtatt tactgctgtt cagctcatac 1980 tgctctagac agtgctgccg atataactca agtaactgtt cttgatgttc cggatccacc 2040 agaaaacctt cacttgtctg aaagacagaa caggagtgtt cggctgacct gggaagctgg 2100 agctgaccac aacagcaata ttagcgagta tattgttgaa tttgaaggaa acaaagaaga 2160 gcctggaagg tgggaggaac tgaccagagt ccaaggaaag aaaaccacag ttatcttacc 2220 tttggctcca tttgtgagat accagttcag ggtcatagcc gtgaacgaag tagggagaag 2280 tcagcctagc cagccgtcag accatcatga aacaccacca gcagctccag ataggaatcc 2340 acaaaacata agggttcaag cctctcaacc caaggaaatg attataaagt gggagccttt 2400 gaaatccatg gagcagaatg gaccaggcct agagtacaga gtgacctgga agccacaggg 2460 agccccagtg gagtgggaag aagaaacagt cacaaaccac acattgcggg tgatgacgcc 2520 tgctgtctat gccccttatg atgtcaaggt ccaggctatc aatcaactag gatctgggcc 2580 tgaccctcag tcagtgactc tctattctgg agaagactat cctgatacag ctccagtgat 2640 ccatggggtg gacgttataa acagtacatt agttaaagtt acctggtcaa cagttccaaa 2700 ggacagagta catggacgtc tgaaaggcta tcagataaat tggtggaaaa caaaaagtct 2760 gttggatgga agaacacatc ccaaagaagt gaacattcta agattttcag gacaaagaaa 2820 548 ctctggaatg gttccttcct tagatgcctt tagtgaattt catttaacag tcttagccta 2880 taactctaaa ggagctggtc ctgaaagtga gccttatata tttcaaacac cagaaggagt 2940 acctgaacag ccaacttttc taaaggtcat caaagttgat aaagacactg ccactttatc 3000 ttggggacta cctaagaaat taaatggaaa cttaactggc tatcttttgc aatatcagat 3060 aataaatgac acctacgaga ttggagaatt aaatgatatt aacattacaa ctccatcaaa 3120 gcccagctgg cacctctcaa acctgaatgc aactaccaag tacaaattct acttgagggc 3180 ttgcacttca cagggctgtg gaaaaccgat cacggaggaa agctccacct taggagaagg 3240 gagtaaaggt atcgggaaga tatcaggagt aaatcttact caaaagactc acccaataga 3300 ggtatttgag ccgggagctg aacatatagt tcgcctaatg actaagaatt ggggcgataa 3360 cgatagcatt tttcaagatg taattgagac aagagggaga gaatatgctg gtttatatga 3420 tgacatctcc actcaaggct ggtttattgg actgatgtgt gcgattgctc ttctcacact 3480 actattatta actgtttgct ttgtgaagag gaatagaggt ggaaagtact cagttaaaga 3540 aaaggaagat ttgcatccag acccagaaat tcagtcagta aaagatgaaa cctttggtga 3600 atacagtgac agtgatgaaa agcctctcaa aggaagcctt cggtccctta atagggatat 3660 gcagcctact gaaagtgctg acagcttagt cgaatacgga gagggagacc atggtctctt 3720 cagtgaagat ggatcattta ttggtgccta cgctggatct aaggagaagg gatctgttga 3780 aagcaatgga agttctacag caacttttcc ccttcgggca taaacacaac atatgtaagc 3840 aacgctactg gttcacccca accttccata tttatctgtt caaaggagca agaactttca 3900 tataggaata gaaacatgct ggccgaagat ttcatccaga agtcaacatc ctgcaattat 3960 gttgaaaaga gtagtacttt cttcaaaata taaaatgcca agcacttcag gcctatgttt 4020 tgcttatatt gttttcaggt gctcaaaatg caaaacacaa aacaaatcct gcatttagat 4080 acacctcaac taaatccaaa gtccccattc agtatattcc atatttgcct gattttacta 4140 ttcggtgtgt ttgcatagat gttgctactt ggtgggtttt tctccgtatg cacattggta 4200 tacagtctct gagaactggc ttggtgactt tgcttcacta caggttaaaa gaccataagc 4260 aaactggtta tttaaaatgt aaaaaggaat atgaaagtct tattaaaaca cttcattgaa 4320 aatatacagt ctaaatttat tatttaaatt ttactagcaa aagtcttagg tgaacaatca 4380 actagtattt gttgagctcc tatttgccca gagatggtca tatttaaaca gaagtatacg 4440 tttttcagtt tcaacatgaa tttttttatt tctgtcagtt atgacatcca cgagcatcac 4500 tttttgtgtc tgtttttttt tttttcttgg actaaattca actgcatgga agcggtggtc 4560 agaaggttgt tttatacgag aacaggcaga aagtgcccat tgttcaggat tctaatagct 4620 acatctactt aatatcttca tttctaaatt gactgctttt acctttttct catgtttata 4680 taatggtatg cttgcatata tttcatgaat acattgtaca tattatgtta atatttacac 4740 aatttaaaat atagatgtgt tttattttga agtgagaaaa tgaacattaa caggcatgtt 4800 tgtacagcta gaatatatta gtaagatact gtttttcgtc attccagagc tacaactaat 4860 aacacgaggt tccaaagctg aagactttgt ataaagtatt tgggttttgt tcttgtattg 4920 ctttctttca acagtttcaa aataaaatat catacaaata ttgagggaaa tgttttcata 4980 tttttcaaaa taggttttta ttgttgaatg tacatctacc ccagcccctc aaaagaaaaa 5040 ctgtttacat agaaattcct acacatacgt ttgcgtatat gttattttaa acatctttgt 5100 ggtgagaatt ttttccccga tattctcctt ctgtcaaagt cagaacaaat tcagggaatt 5160 tattttctgg cagttgtgct ccagtccttt taaaattgta catgaacatg ttttagaaac 5220 aatatggagg atgatgcata catgtcggtc aagttcagcg ctcgacattt tatggaaaga 5280 tttttttaac cttaccacga aatacttaac tactgtttaa gtgaattgac ttatttcact 5340 ttagtttttg aactgtgatt attggtatac tgttatatcc tcaacttgga tttatggtaa 5400 ccccttttag ttcatggaga ccaaaatttg gggtatttat aatagtcagc gcaggaatgc 5460 acatggaata tctacttgtc cttttgaacc tcacgagtca tccagaatgt atagacagga 5520 aaagcatgtc ttatttaaaa ctgtaattta tgggctcagg atctgaccgc agtcccggga 5580 gtaagcattt caaaggggga aggcagtgtg gtccctaccc tgtgtgaatg tgaggatgta 5640 gacatccatc agtgcaactc gagctccatc ctcctccgat ttctaaggct ccagttttct 5700 ggagggacag tcatcatgtt ttgatttatc tgggagaaaa ctgtggtgca cagcttgtga 5760 ggagggcaag gttgtgacgt tcgagcttag ttctggtgtt attctgtctc ctcttctttg 5820 tcatcagcca aaacgtggtt tttaaagaga gtcatgcagg ttagaaataa tgtcaaaaat 5880 atttaggaat ttaataacct ttaagtcaga aactaaaaca aatactgaaa tattagctct 5940 tcctacactt cgtgttcccc tttagctgcc tgaaaatcaa gattgctcct actcagatct 6000 tctgagtggc taaaacttat ggatatgaaa aatgagattg aatgatgact atgctttgct 6060 atcattgtta cctttcctca atactatttg gcaactactg ggactcttca gcacaaaagg 6120 aatagatcta tgattgaccc tgattttaat tgtgaaatta tatgattcat atattttatg 6180 aatcagaata accttcaaat aaaataaatc taagtcggtt aaaatggatt tcatgatttt 6240 ccctcagaaa atgagtaacg gagtccacgg cgtgcaatgg taattataaa ttggtgatgc 6300 ttgtttgcaa attgcccact cgtgataagt caacagccaa tatttaaaac tttgttcgtt 6360 actggcttta ccctaacttt ctctagtcta ctgtcaatat cattttaatg taattgattg 6420 tatatagtct caagaatggt tggtgggcat gagttcctag agaactgtcc aagggttggg 6480 aaaatccaaa ttctcttcct ggctccagca ctgattttgt acataaacat taggcaggtt 6540 549 gcttaacctt cttatctttg agatgccttc acataccaac ctacataaaa attaatcaga gcatgcgtat tcgatatttt agtctcaaat acaataatga accctaaata taatgggatt agtagggttc aaagagatga taatattcat cttatgacta aaaagttcta <210> 176 <211> 7650 <212> DNA <213> Homo <400> 176 cggaccctgc gaggegeegg tcctgtctta ccaggttaac tcttaccggg aategtatat agttcaacag tgagtatttt taaggatggc aacattcagg tgcttcaaat tccaaaactc cctcccatgc attagaacac egeaaaegtg attaaggact taatgactca acccaaactg aggggaaatc gaacaaaatt tttgaagata tttcttggga aaagaagect tgaaggagaa tccatttgct tcatactgct caatattgat tacagtggtt cgtgtcctgg tgaaaatggc ttgggtagaa tacaaaactt acattgtgaa agatggagaa taatttgacc tactgctcta tttatttcaa actctctcaa ctctaaagtg ctaataataa tctcagttac 6600 tcacagggtg ttctttttta tgaagaaaaa tttgaaaatg ataaaageta 6660 taacttcata agcaaacctt taactaatta tgtatctgaa agtcaccccc 6720 tcaacttttt tcctgtgaac acataaatat atttttatag aaaaacaaat 6780 taaatctact gtttagtgag cagtatgact tgtacatgcc attgaaaatt 6840 agaaaattaa gcagggtctt tgctatacaa aagtgttttc cactaatttt 6900 ttataagaaa aatgtgaatt tggtggtttt attetategg tataaaggca 6960 agatgcaccc gtgtttgtaa aaatgtagag cacaatggaa ttatgctgga 7020 aatatttttt tcctatttta tactcatgga agagataagc taaagagggg 7080 gaaatgttgg tgtgcttttc taagcattta aaacataatt gccaattgaa 7140 tgtttacata ccattaagat atgattcatg taacaatgtt aaattaatta 7200 gggtttgtta tctgtggtag tatatatcct agtgttccta tagtgaaata 7260 agccaaagct ttctttgttt tgtaccttaa attgttcgat taegteatea 7320 aaggtatgta gaacaggttc acgtgattac ctttttcttt tggcttggat 7380 agtagaaett tataaaaegt gtttgtattg taggtggtgt ttgtattatg 7440 tgtatggttt gaaaatattt tcattataca tgaaattcaa ctttccaaat 7500 cttcatgtaa tccaaaa 7527 sapians gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 acagatcgcg ttteggagge ggcgcaggtg ctgtaaactg caaaccataa 120 atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 ccaaaagaaa aaattgaccc tettgaagtg gaggagggag atccaattgt 720 aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 atcgaacaag atgaaagagt atacatgagc caaaagggag atetataett 840 gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 gagaatgtet cctaccagga caaaggaaat tategetgea cagccagcaa 1260 acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 cctcaaccca caatcaagtg gagagteaat ggctccccag ttgacaatca 1440 ggtgatgttg tcttccccag ggaaatcagt tttaceaacc ttcaaccaaa 1500 gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattaege 1620 gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 acattgeaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 aatgetatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 agagtttctc ctaagaatcc tcgtatcccc aaattgeata tgettgaatt 1920 agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 atatetaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 550 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc 3000 ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg 3060 agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt 3120 atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca 3180 gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc 3240 aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag 3300 ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga 3360 agggagtaaa ggtatcggga agatatcagg agtaaatctt actcaaaaga ctcacccaat 3420 agaggtattt gagccgggag ctgaacatat agttcgccta atgactaaga attggggcga 3480 taacgatagc atttttcaag atgtaattga gacaagaggg agagaatatg ctggtttata 3540 tgatgacatc tccactcaag gctggtttat tggactgatg tgtgcgattg ctcttctcac 3600 actactatta ttaactgttt gctttgtgaa gaggaataga ggtggaaagt actcagttaa 3660 agaaaaggaa gatttgcatc cagacccaga aattcagtca gtaaaagatg aaacctttgg 3720 tgaatacagt gacagtgatg aaaagcctct caaaggaagc cttcggtccc ttaataggga 3780 tatgcagcct actgaaagtg ctgacagctt agtcgaatac ggagagggag accatggtct 3840 cttcagtgaa gatggatcat ttattggtgc ctacgctgga tctaaggaga agggatctgt 3900 tgaaagcaat ggaagttcta cagcaacttt tccccttcgg gcataaacac aacatatgta 3960 agcaacgcta ctggttcacc ccaaccttcc atatttatct gttcaaagga gcaagaactt 4020 tcatatagga atagaaacat gctggccgaa gatttcatcc agaagtcaac atcctgcaat 4080 tatgttgaaa agagtagtac tttcttcaaa atataaaatg ccaagcactt caggcctatg 4140 ttttgcttat attgttttca ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta 4200 gatacacctc aactaaatcc aaagtcccca ttcagtatat tccatatttg cctgatttta 4260 ctattcggtg tgtttgcata gatgttgcta cttggtgggt ttttctccgt atgcacattg 4320 gtatacagtc tctgagaact ggcttggtga ctttgcttca ctacaggtta aaagaccata 4380 agcaaactgg ttatttaaaa tgtaaaaagg aatatgaaag tcttattaaa acacttcatt 4440 gaaaatatac agtctaaatt tattatttaa attttactag caaaagtctt aggtgaacaa 4500 tcaactagta tttgttgagc tcctatttgc ccagagatgg tcatatttaa acagaagtat 4560 acgtttttca gtttcaacat gaattttttt atttctgtca gttatgacat ccacgagcat 4620 cactttttgt gtctgttttt ttttttttct tggactaaat tcaactgcat ggaagcggtg 4680 gtcagaaggt tgttttatac gagaacaggc agaaagtgcc cattgttcag gattctaata 4740 gctacatcta cttaatatct tcatttctaa attgactgct tttacctttt tctcatgttt 4800 atataatggt atgcttgcat atatttcatg aatacattgt acatattatg ttaatattta 4860 cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat 4920 gtttgtacag ctagaatata ttagtaagat actgtttttc gtcattccag agctacaact 4980 aataacacga ggttccaaag ctgaagactt tgtataaagt atttgggttt tgttcttgta 5040 ttgctttctt tcaacagttt caaaataaaa tatcatacaa atattgaggg aaatgttttc 5100 atatttttca aaataggttt ttattgttga atgtacatct accccagccc ctcaaaagaa 5160 aaactgttta catagaaatt cctacacata cgtttgcgta tatgttattt taaacatctt 5220 tgtggtgaga attttttccc cgatattctc cttctgtcaa agtcagaaca aattcaggga 5280 atttattttc tggcagttgt gctccagtcc ttttaaaatt gtacatgaac atgttttaga 5340 aacaatatgg aggatgatgc atacatgtcg gtcaagttca gcgctcgaca ttttatggaa 5400 agattttttt aaccttacca cgaaatactt aactactgtt taagtgaatt gacttatttc 5460 actttagttt ttgaactgtg attattggta tactgttata tcctcaactt ggatttatgg 5520 taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa 5580 tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca 5640 ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg 5700 ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat 5760 gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt 5820 tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg 5880 551 tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct 5940 ttgtcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa 6000 aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc 6060 tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga 6120 tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt 6180 gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa 6240 aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt 6300 atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat 6360 tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga 6420 tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc 6480 gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga 6540 ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt 6600 gggaaaatcc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag 6660 gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 aataaaagtt ctacttcatg taatccaaaa 7650 <210> 177 <211> 7527

<212> DNA <213> Homo sapians <400> 177 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaaaatt 660 agaacacatc gaacaagatg aaagagtata catgagccaa aagggagatc tatacttcgc 720 aaacgtggaa gaaaaggaca gtcgcaatga ctactgttgc tttgctgcat ttccaagatt 780 aaggactatt gtacagaaaa tgccaatgaa actaacagtt aacagtttaa agcatgctaa 840 tgactcaagt tcatccacag aaattggttc caaggcaaat tccatcaagc aaagaaaacc 900 caaactgctg ttgcctccca ctgagagtgg cagtgagtct tcaattacca tcctcaaagg 960 ggaaatcttg ctgcttgagt gttttgctga aggcttgcca actccacagg ttgattggaa 1020 caaaattggt ggtgacttac caaaggggag agaaacaaaa gaaaattatg gcaagacttt 1080 gaagatagag aatgtctcct accaggacaa aggaaattat cgctgcacag ccagcaattt 1140 cttgggaaca gccactcacg attttcacgt tatagtagaa gagcctcctc gctggacaaa 1200 gaagcctcag agtgctgtgt atagcaccgg aagcaatggc atcttgttat gtgaggctga 1260 aggagaacct caacccacaa tcaagtggag agtcaatggc tccccagttg acaatcatcc 1320 atttgctggt gatgttgtct tccccaggga aatcagtttt accaaccttc aaccaaatca 1380 552 tactgctgtg taccagtgtg aagcctcaaa tgtccatgga actatccttg ccaatgccaa 1440 tattgatgtt gtggatgtcc gtccattgat acaaaccaaa gatggagaaa attacgctac 1500 agtggttggg tacagtgctt tcttacattg cgagttcttt gcttcacctg aggcagtcgt 1560 gtcctggcag aaggtggaag aagtgaaacc cctggagggc aggcggtatc atatctatga 1620 aaatggcaca ttgcagatca acagaaccac cgaagaagat gctgggtctt actcatgttg 1680 ggtagaaaat gctataggaa aaactgcagt cacagccaat ttggatatta gaaatgctac 1740 aaaacttaga gtttctccta agaatcctcg tatccccaaa ttgcatatgc ttgaattaca 1800 ttgtgaaagc aaatgtgact cacatttgaa acacagtttg aagttgtcct ggagtaaaga 1860 tggagaagcc tttgaaatta atggcacaga agatggcagg ataattattg atggagctaa 1920 tttgaccata tctaatgtaa ctttagagga ccaaggtatt tactgctgtt cagctcatac 1980 tgctctagac agtgctgccg atataactca agtaactgtt cttgatgttc cggatccacc 2040 agaaaacctt cacttgtctg aaagacagaa caggagtgtt cggctgacct gggaagctgg 2100 agctgaccac aacagcaata ttagcgagta tattgttgaa tttgaaggaa acaaagaaga 2160 gcctggaagg tgggaggaac tgaccagagt ccaaggaaag aaaaccacag ttatcttacc 2220 tttggctcca tttgtgagat accagttcag ggtcatagcc gtgaacgaag tagggagaag 2280 tcagcctagc cagccgtcag accatcatga aacaccacca gcagctccag ataggaatcc 2340 acaaaacata agggttcaag cctctcaacc caaggaaatg attataaagt gggagccttt 2400 gaaatccatg gagcagaatg gaccaggcct agagtacaga gtgacctgga agccacaggg 2460 agccccagtg gagtgggaag aagaaacagt cacaaaccac acattgcggg tgatgacgcc 2520 tgctgtctat gccccttatg atgtcaaggt ccaggctatc aatcaactag gatctgggcc 2580 tgaccctcag tcagtgactc tctattctgg agaagactat cctgatacag ctccagtgat 2640 ccatggggtg gacgttataa acagtacatt agttaaagtt acctggtcaa cagttccaaa 2700 ggacagagta catggacgtc tgaaaggcta tcagataaat tggtggaaaa caaaaagtct 2760 gttggatgga agaacacatc ccaaagaagt gaacattcta agattttcag gacaaagaaa 2820 ctctggaatg gttccttcct tagatgcctt tagtgaattt catttaacag tcttagccta 2880 taactctaaa ggagctggtc ctgaaagtga gccttatata tttcaaacac cagaaggagt 2940 acctgaacag ccaacttttc taaaggtcat caaagttgat aaagacactg ccactttatc 3000 ttggggacta cctaagaaat taaatggaaa cttaactggc tatcttttgc aatatcagat 3060 aataaatgac acctacgaga ttggagaatt aaatgatatt aacattacaa ctccatcaaa 3120 gcccagctgg cacctctcaa acctgaatgc aactaccaag tacaaattct acttgagggc 3180 ttgcacttca cagggctgtg gaaaaccgat cacggaggaa agctccacct taggagaagg 3240 gagtaaaggt atcgggaaga tatcaggagt aaatcttact caaaagactc acccaataga 3300 ggtatttgag ccgggagctg aacatatagt tcgcctaatg actaagaatt ggggcgataa 3360 cgatagcatt tttcaagatg taattgagac aagagggaga gaatatgctg gtttatatga 3420 tgacatctcc actcaaggct ggtttattgg actgatgtgt gcgattgctc ttctcacact 3480 actattatta actgtttgct ttgtgaagag gaatagaggt ggaaagtact cagttaaaga 3540 aaaggaagat ttgcatccag acccagaaat tcagtcagta aaagatgaaa cctttggtga 3600 atacagtgac agtgatgaaa agcctctcaa aggaagcctt cggtccctta atagggatat 3660 gcagcctact gaaagtgctg acagcttagt cgaatacgga gagggagacc atggtctctt 3720 cagtgaagat ggatcattta ttggtgccta cgctggatct aaggagaagg gatctgttga 3780 aagcaatgga agttctacag caacttttcc ccttcgggca taaacacaac atatgtaagc 3840 aacgctactg gttcacccca accttccata tttatctgtt caaaggagca agaactttca 3900 tataggaata gaaacatgct ggccgaagat ttcatccaga agtcaacatc ctgcaattat 3960 gttgaaaaga gtagtacttt cttcaaaata taaaatgcca agcacttcag gcctatgttt 4020 tgcttatatt gttttcaggt gctcaaaatg caaaacacaa aacaaatcct gcatttagat 4080 acacctcaac taaatccaaa gtccccattc agtatattcc atatttgcct gattttacta 4140 ttcggtgtgt ttgcatagat gttgctactt ggtgggtttt tctccgtatg cacattggta 4200 tacagtctct gagaactggc ttggtgactt tgcttcacta caggttaaaa gaccataagc 4260 aaactggtta tttaaaatgt aaaaaggaat atgaaagtct tattaaaaca cttcattgaa 4320 aatatacagt ctaaatttat tatttaaatt ttactagcaa aagtcttagg tgaacaatca 4380 actagtattt gttgagctcc tatttgccca gagatggtca tatttaaaca gaagtatacg 4440 tttttcagtt tcaacatgaa tttttttatt tctgtcagtt atgacatcca cgagcatcac 4500 tttttgtgtc tgtttttttt tttttcttgg actaaattca actgcatgga agcggtggtc 4560 agaaggttgt tttatacgag aacaggcaga aagtgcccat tgttcaggat tctaatagct 4620 acatctactt aatatcttca tttctaaatt gactgctttt acctttttct catgtttata 4680 taatggtatg cttgcatata tttcatgaat acattgtaca tattatgtta atatttacac 4740 aatttaaaat atagatgtgt tttattttga agtgagaaaa tgaacattaa caggcatgtt 4800 tgtacagcta gaatatatta gtaagatact gtttttcgtc attccagagc tacaactaat 4860 aacacgaggt tccaaagctg aagactttgt ataaagtatt tgggttttgt tcttgtattg 4920 ctttctttca acagtttcaa aataaaatat catacaaata ttgagggaaa tgttttcata 4980 tttttcaaaa taggttttta ttgttgaatg tacatctacc ccagcccctc aaaagaaaaa 5040 ctgtttacat agaaattcct acacatacgt ttgcgtatat gttattttaa acatctttgt 5100 553 ggtgagaatt ttttccccga tattctcctt ctgtcaaagt cagaacaaat tcagggaatt 5160 tattttctgg cagttgtgct ccagtccttt taaaattgta catgaacatg ttttagaaac 5220 aatatggagg atgatgcata catgtcggtc aagttcagcg ctcgacattt tatggaaaga 5280 tttttttaac cttaccacga aatacttaac tactgtttaa gtgaattgac ttatttcact 5340 ttagtttttg aactgtgatt attggtatac tgttatatcc tcaacttgga tttatggtaa 5400 ccccttttag ttcatggaga ccaaaatttg gggtatttat aatagtcagc gcaggaatgc 5460 acatggaata tctacttgtc cttttgaacc tcacqagtca tccagaatgt atagacagga 5520 aaagcatgtc ttatttaaaa ctgtaattta tgggctcagg atctgaccgc agtcccggga 5580 gtaagcattt caaaggggga aggcagtgtg gtccctaccc tgtgtgaatg tgaggatgta 5640 gacatccatc agtgcaactc gagctccatc ctcctccgat ttctaaggct ccagttttct 5700 ggagggacag tcatcatgtt ttgatttatc tgggagaaaa ctgtggtgca cagcttgtga 5760 ggagggcaag gttgtgacgt tcgagcttag ttctggtgtt attctgtctc ctcttctttg 5820 tcatcagcca aaacgtggtt tttaaagaga gtcatgcagg ttagaaataa tgtcaaaaat 5880 atttaggaat ttaataacct ttaagtcaga aactaaaaca aatactgaaa tattagctct 5940 tcctacactt cgtgttcccc tttagctgcc tgaaaatcaa gattgctcct actcagatct 6000 tctgagtggc taaaacttat ggatatgaaa aatgagattg aatgatgact atgctttgct 6060 atcattgtta cctttcctca atactatttg gcaactactg ggactcttca gcacaaaagg 6120 aatagatcta tgattgaccc tgattttaat tgtgaaatta tatgattcat atattttatg 6180 aatcagaata accttcaaat aaaataaatc taagtcggtt aaaatggatt tcatgatttt 6240 ccctcagaaa atgagtaacg gagtccacgg cgtgcaatgg taattataaa ttggtgatgc 6300 ttgtttgcaa attgcccact cgtgataagt caacagccaa tatttaaaac tttgttcgtt 6360 actggcttta ccctaacttt ctctagtcta ctgtcaatat cattttaatg taattgattg 6420 tatatagtct caagaatggt tggtgggcat gagttcctag agaactgtcc aagggttggg 6480 aaaatccaaa ttctcttcct ggctccagca ctgattttgt acataaacat taggcaggtt 6540 gcttaacctt tttatttcaa actctctcaa ctctaaagtg ctaataataa tctcagttac 6600 cttatctttg tcacagggtg ttctttttta tgaagaaaaa tttgaaaatg ataaaagcta 6660 agatgccttc taacttcata agcaaacctt taactaatta tgtatctgaa agtcaccccc 6720 acataccaac tcaacttttt tcctgtgaac acataaatat atttttatag aaaaacaaat 6780 ctacataaaa taaatctact gtttagtgag cagtatgact tgtacatgcc attgaaaatt 6840 attaatcaga agaaaattaa gcagggtctt tgctatacaa aagtgttttc cactaatttt 6900 gcatgcgtat ttataagaaa aatgtgaatt tggtggtttt attctatcgg tataaaggca 6960 tcgatatttt agatgcaccc gtgtttgtaa aaatgtagag cacaatggaa ttatgctgga 7020 agtctcaaat aatatttttt tcctatttta tactcatgga agagataagc taaagagggg 7080 acaataatga gaaatgttgg tgtgcttttc taagcattta aaacataatt gccaattgaa 7140 accctaaata tgtttacata ccattaagat atgattcatg taacaatgtt aaattaatta 7200 taatgggatt gggtttgtta tctgtggtag tatatatcct agtgttccta tagtgaaata 7260 agtagggttc agccaaagct ttctttgttt tgtaccttaa attgttcgat tacgtcatca 7320 aaagagatga aaggtatgta gaacaggttc acgtgattac ctttttcttt tggcttggat 7380 taatattcat agtagaactt tataaaacgt gtttgtattg taggtggtgt ttgtattatg 7440 cttatgacta tgtatggttt gaaaatattt tcattataca tgaaattcaa ctttccaaat 7500 aaaagttcta cttcatgtaa tccaaaa 7527 <210> 178

<211> 1183 <212> PRT <213> Homo sapians <400> 178

Met Glu Pro Leu Leu Leu Gly Arg dy Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lvs Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 554

Glu Gly His He 100 Ser His Phe Gin Gly 105 Lys Tyr Arg Cys Phe 110 Ala Ser Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 13 0 135 140 Gly Asp Leu Tyr Phe Al a Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser lie Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Ton &amp;#908; vo Tb &amp;#906;- Dm Gin Vs 1 Trn Asn T.WC3 He Cl \r el ι? Τ.ΡΠ j. j~ j. J- 4- Δσρ 245 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Glu 290 295 300 Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly 305 310 315 320 Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr 325 330 335 He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala 340 345 350 Gly Asp Val Val Phe Pro Arg Glu lie Ser Phe Thr Asn Leu Gin Pro 355 360 365 Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr 370 375 380 He Leu Ala Asn Ala Asn He Asp Val Val Asp Val Arg Pro Leu lie 385 390 395 400 Gin Thr Lys Asp Gly Glu Asn Tvr Al a Thr Val Val Gly Tyr Ser Ala 405 410 415 Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp 420 425 430 Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He 435 440 445 Tyr Glu Asn Gly Thr Leu Gin lie Asn Arg Thr Thr Glu Glu Asp Ala 450 455 460 Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val 465 470 475 480 Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro 485 490 495 Lys Asn Pro Arg He Pro Lys Leu His Met Leu Glu Leu His Cys Giu 500 505 510 Ser T.VQ — J Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser 515 520 525 Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He 530 535 540 lie He Asp Gly Ala Asn Leu Thr lie Ser Asn Val Thr Leu Glu Asp 545 550 555 560 Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala Lgu Asp Ser Al a Ala 565 570 575 Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn 580 585 590 555

Leu His Leu 595 Ser Glu Arg Gin Asn 600 Arg Ser Val Arg Leu 605 Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr He Val Glu Phe 610 615 620 Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val 6 2 5 630 635 640 Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg 645 650 655 Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro 660 665 670 Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg 675 680 685 Asn Pro Gin Asn He Arg Val Gin /11. Ser Gin Pro Lys Glu Met He 690 695 700 lie Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu 705 710 715 720 Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu 725 730 735 Glu Glu Thr Val Thr Asn His Thr Leu Ara ----J Val Met Thr Pro Ala Val 740 745 750 Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser 755 760 765 Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro 770 775 780 Asp Thr Ala Pro Val He His Gly Val Asp Val He Asn Ser Thr Leu 785 790 795 800 Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg 805 810 815 Leu Lys Gly Tyr Gin He Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp 820 825 830 Gly Arg Thr His Pro Lys Glu Val Asn He Leu Arg Phe Ser Gly Gin 835 840 845 Arg Asn Ser Gly Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His 850 855 860 Leu Thr Val Leu Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu 865 870 875 880 Pro Tyr I le Phe Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe 885 890 895 Leu Lys Val He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly 900 905 910 Leu Pro Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr 915 920 925 Gin He He Asn Asp Thr Tyr Glu He Gly Glu Leu Asn Asp He Asn 930 935 940 lie Thr Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala 945 950 955 960 Thr Thr Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys 965 970 975 Gly Lys Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys 980 985 990 Gly He Gly Lys lie Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro 995 1000 1005 He Glu Val Phe Glu Pro Gly Ala (στ i. U. His He Val Arg Leu Met Thr 1010 1015 1020 Lys Asn Trp Gly Asp Asn Asp Ser lie Phe Gin Asp Val He Glu Thr 1025 1030 1035 1040 Arg Gly Arg Giu Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly 1045 1050 1055 Trp Phe He Gly Leu Met Cys Ala lie Ala Leu Leu Thr Leu Leu Leu 1060 1065 1070 Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val 1075 1080 1085 556

Lys Glu 1090 Lys Glu Asp Leu His 1095 Pro Asp Pro Glu He 1100 Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys 1105 1110 1115 1120 Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala 1125 1130 1135 Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu 1140 1145 1150 Asp Gly Ser Phe lie Gly Ala J./J. Ala Gly Ser Lys fl ,, O'J. Li Lys Gly Ser 1155 1160 1165 Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1170 1175 1180 <210> 179 <211> 1224 <212> PRT <213> Homo ! sapians <400> 179 Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Al a Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Th.2? Glu Ser Gl &#912;' ° -J Ssx? Glu Ser Ser Τ ]_θ This -j-1 θ Leu T.17C5 •‘"’J Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 557

His Asp Phe His 340 Val He Val Glu Glu 345 Pro Pro Arg Trp Thr 350 Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu dy Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu lie Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn lie 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 p r*c> L©u Glu m ,7 Δ rrt Φν V His τ]_θ Tw Glu As n m 17 Thr* Leu Gin ~-- j Airg — 1 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala lie Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He lie He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Ω1 v --2 Pro m v — — Y Leu Glu Tyr Arg Val Thr Trp T.VR — J. ~ 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu ψγχ; Ser Gly Glu Asp Ty i' Pro Asp Thr Ala Pro Val He His 820 825 830 558

Gly Val Asp 835 Val He Asn Ser Thr 840 Leu Val Lys Val Thr 845 Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr A1 Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu T 1_ θ m χ? 1 Glu Leu As n Δ c r~\ lie As n He Thr Thr Pro Ser T.V« — J. Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr S Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe ciy Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 180 <211> 1183

<212> PRT <213> Homo sapians <400> 180

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 559

Gin Val Pro 35 Thr He He Lys Gin 40 Ser Lys Val Gin Val 45 Ala Phe Pro Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 6 5 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu - x j His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Mgt PlSO Met T.v« Leu Thr Val As π Ser Leu T.XZCS "J His Ala Asn Αςη Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 245 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Glu 290 295 300 Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly 305 310 315 320 Ser Asn dy He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr 325 330 335 He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala 340 345 350 Gly Asp Val Val Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro 355 360 365 Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr 370 375 380 He Leu Ala Asn Ala Asn lie Asp Val Val Asp Val Arg Pro Leu lie 385 390 395 400 Gin Thr Lys Asp Gly Glu Asn Tyr Al a Thr Val Val Gly Tyr Ser Ala 405 410 415 Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp 420 425 430 Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He 435 440 445 Tvr - J. — Glu Asn Gly Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala 450 455 460 Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val 465 470 475 4 80 Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro 485 490 495 Lys Asn Pro Arg He Pro Lys Leu His Met Leu Glu Leu His Cys Glu 500 505 510 Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser Trp S si? 515 520 525 560

Lys Asp 530 Gly Glu Ala Phe Glu 535 He Asn Gly Thr Glu 540 Asp Gly Arg He lie lie Asp Gly Ala Asn Leu Thr He Ser Asn Val Thr Leu Glu Asp 545 550 555 560 Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala Leu Asp Ser Al a Ala 565 570 575 Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn 580 585 590 Leu His Leu Ssr Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu 595 600 605 Ala Gly Ala Asp His Asn Ser Asn lie Ser Glu Tyr lie Val Glu Phe 610 615 620 Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val 625 630 635 640 Gin Gly Lys Lys Thr Thr ci 1 Xie Leu Pro Leu Al a Pro Phe Val Arg 645 650 655 Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro 660 665 670 Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg 675 680 685 Asn Pro Gin Asn lie Arg Val Gin Ala Ser Gin Pro Lys Glu Met He 690 695 700 He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu 705 710 715 720 Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu 725 730 735 Glu Glu Thr Val Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val 740 745 750 Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala lie Asn Gin Leu Gly Ser 755 760 7 65 Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro 770 775 780 Asp Thr Ala Pro Val He His Gly Val Asp Val He Asn Ser Thr Leu 785 790 795 800 Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg 805 810 815 Leu Lys Gly Tyr Gin lie Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp 820 825 830 ciy Arg Thr Hrs Pro Lys Glu Val Asn He Leu Arg Pxis Ser Gly Gin 835 840 845 Arg Asn Ser Gly Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His 850 855 860 Leu Thr Val Leu Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu 865 870 875 880 Pro Tyr lie Phe Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe 885 890 895 Leu Lys Val Xie Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly 900 905 910 Leu Pro Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr 915 920 925 Gin lie He Asn Asp Thr Tyr Glu lie Gly Glu Leu Asn Asp He Asn 930 935 940 He Thr Thr Pro Ser Lys Pr*o Ser Trp His Leu Ser Asn Leu Asn Ala 945 950 955 960 Thr Thr Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys 965 970 975 Gly Lys Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys 980 985 990 Gly He Gly Lys lie Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro 995 1000 1005 He Glu Val Phe Glu Pro Gly Ala Glu His Xie Val Arg Leu Met Thr 1010 1015 1020 561

Lys Asn Trp Gly Asp Asn Asp Ser lie Phe Gin Asp Val He Glu Thr 1025 1030 1035 1040 Arg Gly Arg Glu Tyr 1045 Ala Gly Leu Tyr Asp 105C Asp He Ser Thr Gin 1055 Gly Trp Phe lie Gly Leu 1060 Met Cys Ala He 1065 Ala Leu Leu Thr Leu 107C Leu i Leu Leu Thr Val 1075 Cys Phe I Val Lys Arg 108C Asn 1 Arg Gly Gly Lys 1085 Tyr Ser Val Lys Glu 109C Lys 1 Glu Asp Leu His 1095 Pro Asp Pro Glu He HOC Gin i Ser Val Lys Asp 1105 Glu Thr Phe Gly Glu me Tyr 1 Ser Asp Ser Asp 1115 Glu 1 Lys Pro Leu Lys 1120 Gly Ser Leu Arg Ser 1125 Leu 1 Asn Arg Asp Met 1130 Gin 1 Pro Thr Glu Ser 1135 Ala 1 Asp Ser Leu Val Glu 1140 Tyr Gly Glu Gly 1145 Asp His Gly Leu Phe 1150 Ser 1 Glu Asp Gly Ser 1155 Phe He Gly Ala Tyr 116C Ala 1 Gly Ser Lys Glu 1165 Lys Gly Ser Val Glu 1170 Ser Asn Gly Ser Ser 1175 Thr Ala Thr Phe Pro 1180 Leu 1 Arg Ala <210> 181 <211> 7686

<212> DNA <213> Homo sapians <400> 181 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagataaca tctctcatga 1320 gctcttcact ttacatccag agcctcctcg ctggacaaag aagcctcaga gtgctgtgta 1380 tagcaccgga agcaatggca tcttgttatg tgaggctgaa ggagaacctc aacccacaat 1440 caagtggaga gtcaatggct ccccagttga caatcatcca tttgctggtg atgttgtctt 1500 ccccagggaa atcagtttta ccaaccttca accaaatcat actgctgtgt accagtgtga 1560 agcctcaaat gtccatggaa ctatccttgc caatgccaat attgatgttg tggatgtccg 1620 tccattgata caaaccaaag atggagaaaa ttacgctaca gtggttgggt acagtgcttt 1680 cttacattgc gagttctttg cttcacctga ggcagtcgtg tcctggcaga aggtggaaga 1740 agtgaaaccc ctggagggca ggcggtatca tatctatgaa aatggcacat tgcagatcaa 1800 cagaaccacc gaagaagatg ctgggtctta ctcatgttgg gtagaaaatg ctataggaaa 1860 aactgcagtc acagccaatt tggatattag aaatgctaca aaacttagag tttctcctaa 1920 gaatcctcgt atccccaaat tgcatatgct tgaattacat tgtgaaagca aatgtgactc 1980 acatttgaaa cacagtttga agttgtcctg gagtaaagat ggagaagcct ttgaaattaa 2040 562 tggcacagaa tttagaggac tataactcaa aagacagaac tagcgagtat gaccagagtc ccagttcagg ccatcatgaa ctctcaaccc accaggccta agaaacagtc tgtcaaggtc ctattctgga cagtacatta gaaaggctat caaagaagtg agatgccttt tgaaagtgag aaaggtcatc aaatggaaac tggagaatta cctgaatgca aaaaccgatc atcaggagta acatatagtt aattgagaca gtttattgga tgtgaagagg cccagaaatt gcctctcaaa cagcttagtc tggtgcctac aacttttccc ccttccatat gccgaagatt ttcaaaatat ctcaaaatgc tccccattca ttgctacttg tggtgacttt aaaaggaata atttaaattt atttgcccag ttttttattt ttttcttgga acaggcagaa ttctaaattg ttcatgaata ttattttgaa taagatactg agactttgta ataaaatatc tgttgaatgt cacatacgtt attctccttc cagtcctttt atgtcggtca atacttaact ttggtatact caaaatttgg ttttgaacct tgtaatttat gatggcagga caaggtattt gtaactgttc aggagtgttc attgttgaat caaggaaaga gtcatagccg acaccaccag aaggaaatga gagtacagag acaaaccaca caggctatca gaagactatc gttaaagtta cagataaatt aacattctaa agtgaatttc ccttatatat aaagttgata ttaactggct aatgatatta actaccaagt acggaggaaa aatcttactc cgcctaatga agagggagag ctgatgtgtg aatagaggtg cagtcagtaa ggaagccttc gaatacggag gctggatcta cttcgggcat ttatctgttc tcatccagaa aaaatgccaa aaaacacaaa gtatattcca gtgggttttt gcttcactac tgaaagtctt tactagcaaa agatggtcat ctgtcagtta ctaaattcaa agtgcccatt actgctttta cattgtacat gtgagaaaat tttttcgtca taaagtattt atacaaatat acatctaccc tgcgtatatg tgtcaaagtc aaaattgtac agttcagcgc actgtttaag gttatatcct ggtatttata cacgagtcat gggctcagga taattattga tggagctaat ttgaccatat ctaatgtaac 2100 actgctgttc agctcatact gctctagaca gtgctgccga 2160 ttgatgttcc ggatccacca gaaaaccttc acttgtctga 2220 ggctgacctg ggaagctgga gctgaccaca acagcaatat 2280 ttgaaggaaa caaagaagag cctggaaggt gggaggaact 2340 aaaccacagt tatcttacct ttggctccat ttgtgagata 2400 tgaacgaagt agggagaagt cagcctagcc agccgtcaga 2460 cagctccaga taggaatcca caaaacataa gggttcaagc 2520 ttataaagtg ggagcctttg aaatccatgg agcagaatgg 2580 tgacctggaa gccacaggga gccccagtgg agtgggaaga 2640 cattgcgggt gatgacgcct gctgtctatg ccccttatga 2700 atcaactagg atctgggcct gaccctcagt cagtgactct 2760 ctgatacagc tccagtgatc catggggtgg acgttataaa 2820 cctggtcaac agttccaaag gacagagtac atggacgtct 2880 ggtggaaaac aaaaagtctg ttggatggaa gaacacatcc 2940 gattttcagg acaaagaaac tctggaatgg ttccttcctt 3000 atttaacagt cttagcctat aactctaaag gagctggtcc 3060 ttcaaacacc agaaggagta cctgaacagc caacttttct 3120 aagacactgc cactttatct tggggactac ctaagaaatt 3180 atcttttgca atatcagata ataaatgaca cctacgagat 3240 acattacaac tccatcaaag cccagctggc acctctcaaa 3300 acaaattcta cttgagggct tgcacttcac agggctgtgg 3360 gctccacctt aggagaaggg agtaaaggta tcgggaagat 3420 aaaagactca cccaatagag gtatttgagc cgggagctga 3480 ctaagaattg gggcgataac gatagcattt ttcaagatgt 3540 aatatgctgg tttatatgat gacatctcca ctcaaggctg 3600 cgattgctct tctcacacta ctattattaa ctgtttgctt 3660 gaaagtactc agttaaagaa aaggaagatt tgcatccaga 3720 aagatgaaac ctttggtgaa tacagtgaca gtgatgaaaa 3780 ggtcccttaa tagggatatg cagcctactg aaagtgctga 3840 agggagacca tggtctcttc agtgaagatg gatcatttat 3900 aggagaaggg atctgttgaa agcaatggaa gttctacagc 3960 aaacacaaca tatgtaagca acgctactgg ttcaccccaa 4020 aaaggagcaa gaactttcat ataggaatag aaacatgctg 4080 gtcaacatcc tgcaattatg ttgaaaagag tagtactttc 4140 gcacttcagg cctatgtttt gcttatattg ttttcaggtg 4200 acaaatcctg catttagata cacctcaact aaatccaaag 4260 tatttgcctg attttactat tcggtgtgtt tgcatagatg 4320 ctccgtatgc acattggtat acagtctctg agaactggct 4380 aggttaaaag accataagca aactggttat ttaaaatgta 4440 attaaaacac ttcattgaaa atatacagtc taaatttatt 4500 agtcttaggt gaacaatcaa ctagtatttg ttgagctcct 4560 atttaaacag aagtatacgt ttttcagttt caacatgaat 4620 tgacatccac gagcatcact ttttgtgtct gttttttttt 4680 ctgcatggaa gcggtggtca gaaggttgtt ttatacgaga 4740 gttcaggatt ctaatagcta catctactta atatcttcat 4800 cctttttctc atgtttatat aatggtatgc ttgcatatat 4860 attatgttaa tatttacaca atttaaaata tagatgtgtt 4920 gaacattaac aggcatgttt gtacagctag aatatattag 4980 ttccagagct acaactaata acacgaggtt ccaaagctga 5040 gggttttgtt cttgtattgc tttctttcaa cagtttcaaa 5100 tgagggaaat gttttcatat ttttcaaaat aggtttttat 5160 cagcccctca aaagaaaaac tgtttacata gaaattccta 5220 ttattttaaa catctttgtg gtgagaattt tttccccgat 5280 agaacaaatt cagggaattt attttctggc agttgtgctc 5340 atgaacatgt tttagaaaca atatggagga tgatgcatac 5400 tcgacatttt atggaaagat ttttttaacc ttaccacgaa 5460 tgaattgact tatttcactt tagtttttga actgtgatta 5520 caacttggat ttatggtaac cccttttagt tcatggagac 5580 atagtcagcg caggaatgca catggaatat ctacttgtcc 5640 ccagaatgta tagacaggaa aagcatgtct tatttaaaac 5700 tctgaccgca gtcccgggag taagcatttc aaagggggaa 5760 563 ggcagtgtgg tccctaccct gtgtgaatgt gaggatgtag acatccatca gtgcaactcg 5820 agctccatcc tcctccgatt tctaaggctc cagttttctg gagggacagt catcatgttt 5880 tgatttatct gggagaaaac tgtggtgcac agcttgtgag gagggcaagg ttgtgacgtt 5940 cgagcttagt tctggtgtta ttctgtctcc tcttctttgt catcagccaa aacgtggttt 6000 ttaaagagag tcatgcaggt tagaaataat gtcaaaaata tttaggaatt taataacctt 6060 taagtcagaa actaaaacaa atactgaaat attagctctt cctacacttc gtgttcccct 6120 ttagctgcct gaaaatcaag attgctccta ctcagatctt ctgagtggct aaaacttatg 6180 gatatgaaaa atgagattga atgatgacta tgctttgcta tcattgttac ctttcctcaa 6240 tactatttgg caactactgg gactcttcag cacaaaagga atagatctat gattgaccct 6300 gattttaatt gtgaaattat atgattcata tattttatga atcagaataa ccttcaaata 6360 aaataaatct aagtcggtta aaatggattt catgattttc cctcagaaaa tgagtaacgg 6420 agtccacggc gtgcaatggt aattataaat tggtgatgct tgtttgcaaa ttgcccactc 6480 gtgataagtc aacagccaat atttaaaact ttgttcgtta ctggctttac cctaactttc 6540 tctagtctac tgtcaatatc attttaatgt aattgattgt atatagtctc aagaatggtt 6600 ggtgggcatg agttcctaga gaactgtcca agggttggga aaatccaaat tctcttcctg 6660 gctccagcac tgattttgta cataaacatt aggcaggttg cttaaccttt ttatttcaaa 6720 ctctctcaac tctaaagtgc taataataat ctcagttacc ttatctttgt cacagggtgt 6780 tcttttttat gaagaaaaat ttgaaaatga taaaagctaa gatgccttct aacttcataa 6840 gcaaaccttt aactaattat gtatctgaaa gtcaccccca cataccaact caactttttt 6900 cctgtgaaca cataaatata tttttataga aaaacaaatc tacataaaat aaatctactg 6960 tttagtgagc agtatgactt gtacatgcca ttgaaaatta ttaatcagaa gaaaattaag 7020 cagggtcttt gctatacaaa agtgttttcc actaattttg catgcgtatt tataagaaaa 7080 atgtgaattt ggtggtttta ttctatcggt ataaaggcat cgatatttta gatgcacccg 7140 tgtttgtaaa aatgtagagc acaatggaat tatgctggaa gtctcaaata atattttttt 7200 cctattttat actcatggaa gagataagct aaagagggga caataatgag aaatgttggt 7260 gtgcttttct aagcatttaa aacataattg ccaattgaaa ccctaaatat gtttacatac 7320 cattaagata tgattcatgt aacaatgtta aattaattat aatgggattg ggtttgttat 7380 ctgtggtagt atatatccta gtgttcctat agtgaaataa gtagggttca gccaaagctt 7440 tctttgtttt gtaccttaaa ttgttcgatt acgtcatcaa aagagatgaa aggtatgtag 7500 aacaggttca catgattacc tttttctttt ggcttggatt aatattcata gtagaacttt 7560 ataaaacgtg tttgtattgt aggtggtgtt tgtattatgc ttatgactat gtatggtttg 7620 aaaatatttt cattatacat gaaattcaac tttccaaata aaagttctac ttcatgtaat 7680 ccaaaa 7686 <210> 182 <211> 7650

<212> DNA <213> Homo sapians <400> 182 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 564 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 ttgggtagaa aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 tacaaaactt agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 acattgtgaa agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 agatggagaa gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 taatttgacc atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 tactgctcta gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 accagaaaac cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 tggagctgac cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 agagcctgga aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 acctttggct ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 aagtcagcct agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 tccacaaaac ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 tttgaaatcc atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gggagcccca gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 gcctgctgtc tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 gcctgaccct cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gatccatggg gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 aaaggacaga gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 tctgttggat ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 aaactctgga atggttcctt ccttagatgc ctttagtgaa tttcatttaa cagtcttagc 3000 ctataactct aaaggagctg gtcctgaaag tgagccttat atatttcaaa caccagaagg 3060 agtacctgaa cagccaactt ttctaaaggt catcaaagtt gataaagaca ctgccacttt 3120 atcttgggga ctacctaaga aattaaatgg aaacttaact ggctatcttt tgcaatatca 3180 gataataaat gacacctacg agattggaga attaaatgat attaacatta caactccatc 3240 aaagcccagc tggcacctct caaacctgaa tgcaactacc aagtacaaat tctacttgag 3300 ggcttgcact tcacagggct gtggaaaacc gatcacggag gaaagctcca ccttaggaga 3360 agggagtaaa ggtatcggga agatatcagg agtaaatctt actcaaaaga ctcacccaat 3420 agaggtattt gagccgggag ctgaacatat agttcgccta atgactaaga attggggcga 3480 taacgatagc atttttcaag atgtaattga gacaagaggg agagaatatg ctggtttata 3540 tgatgacatc tccactcaag gctggtttat tggactgatg tgtgcgattg ctcttctcac 3600 actactatta ttaactgttt gctttgtgaa gaggaataga ggtggaaagt actcagttaa 3660 agaaaaggaa gatttgcatc cagacccaga aattcagtca gtaaaagatg aaacctttgg 3720 tgaatacagt gacagtgatg aaaagcctct caaaggaagc cttcggtccc ttaataggga 3780 tatgcagcct actgaaagtg ctgacagctt agtcgaatac ggagagggag accatggtct 3840 cttcagtgaa gatggatcat ttattggtgc ctacgctgga tctaaggaga agggatctgt 3900 tgaaagcaat ggaagttcta cagcaacttt tccccttcgg gcataaacac aacatatgta 3960 agcaacgcta ctggttcacc ccaaccttcc atatttatct gttcaaagga gcaagaactt 4020 tcatatagga atagaaacat gctggccgaa gatttcatcc agaagtcaac atcctgcaat 4080 tatgttgaaa agagtagtac tttcttcaaa atataaaatg ccaagcactt caggcctatg 4140 ttttgcttat attgttttca ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta 4200 gatacacctc aactaaatcc aaagtcccca ttcagtatat tccatatttg cctgatttta 4260 ctattcggtg tgtttgcata gatgttgcta cttggtgggt ttttctccgt atgcacattg 4320 gtatacagtc tctgagaact ggcttggtga ctttgcttca ctacaggtta aaagaccata 4380 agcaaactgg ttatttaaaa tgtaaaaagg aatatgaaag tcttattaaa acacttcatt 4440 gaaaatatac agtctaaatt tattatttaa attttactag caaaagtctt aggtgaacaa 4500 tcaactagta tttgttgagc tcctatttgc ccagagatgg tcatatttaa acagaagtat 4560 acgtttttca gtttcaacat gaattttttt atttctgtca gttatgacat ccacgagcat 4620 cactttttgt gtctgttttt ttttttttct tggactaaat tcaactgcat ggaagcggtg 4680 gtcagaaggt tgttttatac gagaacaggc agaaagtgcc cattgttcag gattctaata 4740 gctacatcta cttaatatct tcatttctaa attgactgct tttacctttt tctcatgttt 4800 atataatggt atgcttgcat atatttcatg aatacattgt acatattatg ttaatattta 4860 cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat 4920 565 gtttgtacag aataacacga ttgctttctt atatttttca aaactgttta tgtggtgaga atttattttc aacaatatgg agattttttt actttagttt taaccccttt tgcacatgga ggaaaagcat ggagtaagca gtagacatcc tctggaggga tgaggagggc ttgtcatcag aatatttagg tcttcctaca tcttctgagt gctatcattg aggaatagat atgaatcaga tttccctcag tgcttgtttg gttactggct ttgtatatag gggaaaatcc gttgcttaac taccttatct ctaagatgcc cccacatacc aatctacata attattaatc tttgcatgcg gcatcgatat ggaagtctca gggacaataa gaaaccctaa ttataatggg ataagtaggg tcaaaagaqa gattaatatt atgcttatga aataaaagtt ctagaatata ggttccaaag tcaacagttt aaataggttt catagaaatt attttttccc tggcagttgt aggatgatgc aaccttacca ttgaactgtg tagttcatgg atatctactt gtcttattta tttcaaaggg atcagtgcaa cagtcatcat aaggttgtga ccaaaacgtg aatttaataa cttcgtgttc ggctaaaact ttacctttcc ctatgattga ataaccttca aaaatgagta caaattgccc ttaccctaac tctcaagaat aaattctctt ctttttattt ttgtcacagg ttctaacttc aactcaactt aaataaatct agaagaaaat tatttataag tttagatgca aataatattt tgagaaatgt atatgtttac attgggtttg ttcagccaaa tgaaaggtat catagtagaa ctatgtatgg ctacttcatg ttagtaagat ctgaagactt caaaataaaa ttattgttga cctacacata cgatattctc gctccagtcc atacatgtcg cgaaatactt attattggta agaccaaaat gtccttttga aaactgtaat ggaaggcagt ctcgagctcc gttttgattt cgttcgagct gtttttaaag cctttaagtc ccctttagct tatggatatg tcaatactat ccctgatttt aataaaataa acggagtcca actcgtgata tttctctagt ggttggtggg cctggctcca caaactctct gtgttctttt ataagcaaac ttttcctgtg actgtttagt taagcagggt aaaaatgtga cccgtgtttg ttttcctatt tggtgtgctt ataccattaa ttatctgtgg gctttctttg gtagaacagg ctttataaaa tttgaaaata taatccaaaa actgtttttc tgtataaagt tatcatacaa atgtacatct cgtttgcgta cttctgtcaa ttttaaaatt gtcaagttca aactactgtt tactgttata ttggggtatt acctcacgag ttatgggctc gtggtcccta atcctcctcc atctgggaga tagttctggt agagtcatgc agaaactaaa gcctgaaaat aaaaatgaga ttggcaacta aattgtgaaa atctaagtcg cggcgtgcaa agtcaacagc ctactgtcaa catgagttcc gcactgattt caactctaaa ttatgaagaa ctttaactaa aacacataaa gagcagtatg ctttgctata atttggtggt taaaaatgta ttatactcat ttctaagcat gatatgattc tagtatatat ttttgtacct ttcacgtgat cgtgtttgta ttttcattat gtcattccag atttgggttt atattgaggg accccagccc tatgttattt agtcagaaca gtacatgaac gcgctcgaca taagtgaatt tcctcaactt tataatagtc tcatccagaa aggatctgac ccctgtgtga gatttctaag aaactgtggt gttattctgt aggttagaaa acaaatactg caagattgct ttgaatgatg ctgggactct ttatatgatt gttaaaatgg tggtaattat caatatttaa tatcatttta tagagaactg tgtacataaa gtgctaataa aaatttgaaa ttatgtatct tatattttta acttgtacat caaaagtgtt tttattctat gagcacaatg ggaagagata ttaaaacata atgtaacaat cctagtgttc taaattgttc tacctttttc ttgtaggtgg acatgaaatt agctacaact tgttcttgta aaatgttttc ctcaaaagaa taaacatctt aattcaggga atgttttaga ttttatggaa gacttatttc ggatttatgg agcgcaggaa tgtatagaca cgcagtcccg atgtgaggat gctccagttt gcacagcttg ctcctcttct taatgtcaaa aaatattagc cctactcaga actatgcttt tcagcacaaa catatatttt atttcatgat aaattggtga aactttgttc atgtaattga tccaagggtt cattaggcag taatctcagt atgataaaag gaaagtcacc tagaaaaaca gcaattgaaa ttccactaat cggtataaag gaattatgct agctaaagag attgccaatt gttaaattaa ctatagtgaa gattacgtca ttttggcttg tgtttgtatt caactttcca 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7650 <210> 183 <211> 7686 <212> DNA <213> Homo <400> 183 cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg aatcgtatat agttcaacag sapians gcgcccccgt acagatcgcg atactgcaaa taaggtctca ttgtcttctt ctaatgttcc gttccaacaa cccggctccc tttcggaggc caaatcatag gctgtaaacc cctgaagagc tcctgttaaa tcataaaaca ggccggctcg ggcgcaggtg tggaactaag aaaagtgaga aatggagccg attctcaaaa gtcaaaagtc ggggagaagg ctgtaaactg gggaacttaa ggagacatta cttttacttg gcaattgaaa caagttgcct cgcccgaggg caaaccataa tttactgttt agattttcat gaagaggact taccatcttc ttcccttcga 60 120 180 240 300 360 420 566 tgagtatttt caaattgaat gtgaagctaa aggaaatcca taaggatggc aacccttttt atttcactga ccatcggata aacattcagg atcccaaacg aggggcacat atctcacttt tgcttcaaat aaactgggaa tcgctatgtc agaagaaata tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg cctcccatgc aatcctccca aaggcctccc acctttacac attagaacac atcgaacaag atgaaagagt atacatgagc cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt attaaggact attgtacaga aaatgccaat gaaactaaca taatgactca agttcatcca cagaaattgg ttccaaggca acccaaactg ctgttgcctc ccactgagag tggcagtgag aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg gaacaaaatt ggtggtgact taccaaaggg gagagaaaca tttgaagata gagaatgtct cctaccagga caaaggaaat tttcttggga acagccactc acgattttca cgttatagta gctcttcact ttacatccag agcctcctcg ctggacaaag tagcaccgga agcaatggca tcttgttatg tgaggctgaa caagtggaga gtcaatggct ccccagttga caatcatcca ccccagggaa atcagtttta ccaaccttca accaaatcat agcctcaaat gtccatggaa ctatccttgc caatgccaat tccattgata caaaccaaag atggagaaaa ttacgctaca cttacattgc gagttctttg cttcacctga ggcagtcgtg agtgaaaccc ctggagggca ggcggtatca tatctatgaa cagaaccacc gaagaagatg ctgggtctta ctcatgttgg aactgcagtc acagccaatt tggatattag aaatgctaca gaatcctcgt atccccaaat tgcatatgct tgaattacat acatttgaaa cacagtttga agttgtcctg gagtaaagat tggcacagaa gatggcagga taattattga tggagctaat tttagaggac caaggtattt actgctgttc agctcatact tataactcaa gtaactgttc ttgatgttcc ggatccacca aagacagaac aggagtgttc ggctgacctg ggaagctgga tagcgagtat attgttgaat ttgaaggaaa caaagaagag gaccagagtc caaggaaaga aaaccacagt tatcttacct ccagttcagg gtcatagccg tgaacgaagt agggagaagt ccatcatgaa acaccaccag cagctccaga taggaatcca ctctcaaccc aaggaaatga ttataaagtg ggagcctttg accaggccta gagtacagag tgacctggaa gccacaggga agaaacagtc acaaaccaca cattgcgggt gatgacgcct tgtcaaggtc caggctatca atcaactagg atctgggcct ctattctgga gaagactatc ctgatacagc tccagtgatc cagtacatta gttaaagtta cctggtcaac agttccaaag gaaaggctat cagataaatt ggtggaaaac aaaaagtctg caaagaagtg aacattctaa gattttcagg acaaagaaac agatgccttt agtgaatttc atttaacagt cttagcctat tgaaagtgag ccttatatat ttcaaacacc agaaggagta aaaggtcatc aaagttgata aagacactgc cactttatct aaatggaaac ttaactggct atcttttgca atatcagata tggagaatta aatgatatta acattacaac tccatcaaag cctgaatgca actaccaagt acaaattcta cttgagggct aaaaccgatc acggaggaaa gctccacctt aggagaaggg atcaggagta aatcttactc aaaagactca cccaatagag acatatagtt cgcctaatga ctaagaattg gggcgataac aattgagaca agagggagag aatatgctgg tttatatgat gtttattgga ctgatgtgtg cgattgctct tctcacacta tgtgaagagg aatagaggtg gaaagtactc agttaaagaa cccagaaatt cagtcagtaa aagatgaaac ctttggtgaa gcctctcaaa ggaagccttc ggtcccttaa tagggatatg cagcttagtc gaatacggag agggagacca tggtctcttc tggtgcctac gctggatcta aggagaaggg atctgttgaa aacttttccc cttcgggcat aaacacaaca tatgtaagca ccttccatat ttatctgttc aaaggagcaa gaactttcat gccgaagatt tcatccagaa gtcaacatcc tgcaattatg gaaccaacat attccatcga caagggaaat gaatttatag gaggagggag atttattgga caaaagggag tgctttgctg gttaacagtt aattccatca tcttcaatta ccaactccac aaagaaaatt tatcgctgca gaagataaca aagcctcaga ggagaacctc tttgctggtg actgctgtgt attgatgttg gtggttgggt tcctggcaga aatggcacat gtagaaaatg aaacttagag tgtgaaagca ggagaagcct ttgaccatat gctctagaca gaaaaccttc gctgaccaca cctggaaggt ttggctccat cagcctagcc caaaacataa aaatccatgg gccccagtgg gctgtctatg gaccctcagt catggggtgg gacagagtac ttggatggaa tctggaatgg aactctaaag cctgaacagc tggggactac ataaatgaca cccagctggc tgcacttcac agtaaaggta gtatttgagc gatagcattt gacatctcca ctattattaa aaggaagatt tacagtgaca cagcctactg agtgaagatg agcaatggaa acgctactgg ataggaatag ttgaaaagag tttcgtggac acaattcagg accgctgctt ttccaagtgt atccaattgt tgaatattga atctatactt catttccaag taaagcatgc agcaaagaaa ccatcctcaa aggttgattg atggcaagac cagccagcaa tctctcatga gtgctgtgta aacccacaat atgttgtctt accagtgtga tggatgtccg acagtgcttt aggtggaaga tgcagatcaa ctataggaaa tttctcctaa aatgtgactc ttgaaattaa ctaatgtaac gtgctgccga acttgtctga acagcaatat gggaggaact ttgtgagata agccgtcaga gggttcaagc agcagaatgg agtgggaaga ccccttatga cagtgactct acgttataaa atggacgtct gaacacatcc ttccttcctt gagctggtcc caacttttct ctaagaaatt cctacgagat acctctcaaa agggctgtgg tcgggaagat cgggagctga ttcaagatgt ctcaaggctg ctgtttgctt tgcatccaga gtgatgaaaa aaagtgctga gatcatttat gttctacagc ttcaccccaa aaacatgctg tagtactttc 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 567 ttcaaaatat aaaatgccaa gcacttcagg cctatgtttt gcttatattg ttttcaggtg ctcaaaatgc aaaacacaaa acaaatcctg catttagata cacctcaact aaatccaaag tccccattca gtatattcca tatttgcctg attttactat tcggtgtgtt tgcatagatg ttgctacttg gtgggttttt ctccgtatgc acattggtat acagtctctg agaactggct tggtgacttt gcttcactac aggttaaaag accataagca aactggttat ttaaaatgta aaaaggaata tgaaagtctt attaaaacac ttcattgaaa atatacagtc taaatttatt atttaaattt tactagcaaa agtcttaggt gaacaatcaa ctagtatttg ttgagctcct atttgcccag agatggtcat atttaaacag aagtatacgt ttttcagttt caacatgaat ttttttattt ctgtcagtta tgacatccac gagcatcact ttttgtgtct gttttttttt ttttcttgga ctaaattcaa ctgcatggaa gcggtggtca gaaggttgtt ttatacgaga acaggcagaa agtgcccatt gttcaggatt ctaatagcta catctactta atatcttcat ttctaaattg actgctttta cctttttctc atgtttatat aatggtatgc ttgcatatat ttcatgaata cattgtacat attatgttaa tatttacaca atttaaaata tagatgtgtt ttattttgaa gtgagaaaat gaacattaac aggcatgttt gtacagctag aatatattag taagatactg tttttcgtca ttccagagct acaactaata acacgaggtt ccaaagctga agactttgta taaagtattt gggttttgtt cttgtattgc tttctttcaa cagtttcaaa ataaaatatc atacaaatat tgagggaaat gttttcatat ttttcaaaat aggtttttat tgttgaatgt acatctaccc cagcccctca aaagaaaaac tgtttacata gaaattccta cacatacgtt tgcgtatatg ttattttaaa catctttgtg gtgagaattt tttccccgat attctccttc tgtcaaagtc agaacaaatt cagggaattt attttctggc agttgtgctc cagtcctttt aaaattgtac atgaacatgt tttagaaaca atatggagga tgatgcatac atgtcggtca agttcagcgc tcgacatttt atggaaagat ttttttaacc ttaccacgaa atacttaact actgtttaag tgaattgact tatttcactt tagtttttga actgtgatta ttggtatact gttatatcct caacttggat ttatggtaac cccttttagt tcatggagac caaaatttgg ggtatttata atagtcagcg caggaatgca catggaatat ctacttgtcc ttttgaacct cacgagtcat ccagaatgta tagacaggaa aagcatgtct tatttaaaac tgtaatttat gggctcagga tctgaccgca gtcccgggag taagcatttc aaagggggaa ggcagtgtgg tccctaccct gtgtgaatgt gaggatgtag acatccatca gtgcaactcg agctccatcc tcctccgatt tctaaggctc cagttttctg gagggacagt catcatgttt tgatttatct gggagaaaac tgtqgtgcac aacttgtgag gagggcaagg ttgtgacgtt cgagcttagt tctggtgtta ttctgtctcc tcttctttgt catcagccaa aacgtggttt ttaaagagag tcatgcaggt tagaaataat gtcaaaaata tttaggaatt taataacctt taagtcagaa actaaaacaa atactgaaat attagctctt cctacacttc gtgttcccct ttagctgcct gaaaatcaag attgctccta ctcagatctt ctgagtggct aaaacttatg gatatgaaaa atgagattga atgatgacta tgctttgcta tcattgttac ctttcctcaa tactatttgg caactactgg gactcttcag cacaaaagga atagatctat gattgaccct gattttaatt gtgaaattat atgattcata tattttatga atcagaataa ccttcaaata aaataaatct aagtcggtta aaatggattt catgattttc cctcagaaaa tgagtaacgg agtccacggc gtgcaatggt aattataaat tggtgatgct tgtttgcaaa ttgcccactc gtgataagtc aacagccaat atttaaaact ttgttcgtta ctggctttac cctaactttc tctagtctac tgtcaatatc attttaatgt aattgattgt atatagtctc aagaatggtt ggtgggcatg agttcctaga gaactgtcca agggttggga aaatccaaat tctcttcctg gctccagcac tgattttgta cataaacatt aggcaggttg cttaaccttt ttatttcaaa ctctctcaac tctaaagtgc taataataat ctcagttacc ttatctttgt cacagggtgt tcttttttat gaagaaaaat ttgaaaatga taaaagctaa gatgccttct aacttcataa gcaaaccttt aactaattat gtatctgaaa gtcaccccca cataccaact caactttttt cctgtgaaca cataaatata tttttataga aaaacaaatc tacataaaat aaatctactg tttagtgagc agtatgactt gtacatgcca ttgaaaatta ttaatcagaa gaaaattaag cagggtcttt gctatacaaa agtgttttcc actaattttg catgcgtatt tataagaaaa atgtgaattt ggtggtttta ttctatcggt ataaaggcat cgatatttta gatgcacccg tgtttgtaaa aatgtagagc acaatggaat tatgctggaa gtctcaaata atattttttt cctattttat actcatggaa gagataagct aaagagggga caataatgag aaatgttggt gtgcttttct aagcatttaa aacataattg ccaattgaaa ccctaaatat gtttacatac cattaagata tgattcatgt aacaatgtta aattaattat aatgggattg ggtttgttat ctgtggtagt atatatccta gtgttcctat agtgaaataa gtagggttca gccaaagctt tctttgtttt gtaccttaaa ttgttcgatt acgtcatcaa aagagatgaa aggtatgtag aacaggttca cgtgattacc tttttctttt ggcttggatt aatattcata gtagaacttt ataaaacgtg tttgtattgt aggtggtgtt tgtattatgc ttatgactat gtatggtttg aaaatatttt cattatacat gaaattcaac tttccaaata aaagttctac ttcatgtaat ccaaaa 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7620 7680 7686 568 <210> 184 <211> 1236

<212> PRT <213> Homo sapians <400> 184

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu ciy His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His lie Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 2 4 5 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Asp Asn He Ser His Glu Leu Phe 340 345 350 Thr Leu His Pro Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala 355 360 365 Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu Cys Glu Ala Glu Gly 370 375 380 Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp 385 390 395 400 Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe 405 410 415 Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser 420 425 430 Asn Val His Gly Thr He Leu Ala Asn Ala Asn He Asp Val Val Asp 569 435 440 445 Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val 450 455 460 Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu 465 470 475 4 80 Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly 485 490 495 Arg Arg Tyr His He Tyr Glu Asn ciy Thr Leu Gin He Asn Arg Thr 500 505 510 Thr Glu Glu Asp Ala Gly Ser Tyr Ser Gys Trp Val Glu Asn Ala lie 515 520 525 Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys 530 535 540 Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys Leu His Met Leu 545 550 555 560 Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu 565 570 575 Lys Leu Ser Trp Ser Lys Asp ciy Glu Ala Phe Glu He Asn Gly Thr 580 585 590 Glu Asp θ&amp;#943;γ Arg He He He Asp Gly Ala Asn Leu Thr He Ser Asn 595 600 605 Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala 610 615 620 Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro 625 630 635 640 Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val 645 650 655 Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu 660 665 670 Tyr Tie Val Glu Phe Glu m iz 2 As n T.VC Glu Glu &amp;#908;τ/Λ X X. Gly Trp 7-1,-, VJXU 675 680 685 Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu 690 695 700 Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val 705 710 715 720 Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro 725 730 735 Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin 740 745 750 Pro Lys Glu Met lie lie Lys Trp Glu Pro Leu Lys Ser Met Glu Gin 755 760 765 Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala 770 775 780 Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val 785 790 795 800 Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He 805 810 815 Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser 820 825 830 Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val lie His Gly Val Asp Val 835 840 845 lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp 850 855 860 Arg Val His Gly Arg Leu Lys Gly Tyr Gin lie Asn Trp Trp Lys Thr 865 870 875 8 80 Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu Val Asn He Leu 885 890 895 Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro Ser Leu Asp Ala 900 905 910 Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn Ser Lys Gly Ala 915 920 925 Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro Glu Gly Val Pro 570

Glu 930 Gin Pro Thr Phe Leu 935 Lys Val He Lys Val 940 Asp Lys Asp Thr Ala 945 Thr Leu Ser Trp Gly 950 Leu Pro Lys Lys Leu 955 Asn Gly Asn Leu Thr 960 Gly Tyr Leu Leu Gin 965 Tyr Gin lie He Asn 970 Asp Thr Tyr Glu He 975 Gly Glu Leu Asn Asp 9 80 He Asn He Thr Thr 985 Pro Ser Lys Pro Ser 990 Trp His Leu Ser Asn 995 Leu Asn Ala Thr Thr 100C Lys 1 Tyr Lys Phe Tyr 1005 Leu Arg Ala Cys Thr 101C Ser 1 Gin Gly Cys Gly 1015 Lys Pro He Thr Glu 102C Glu 1 Ser Ser Thr Leu 1025 Gly Glu Gly Ser Lys 1030 Gly 1 He Gly Lys He 1035 Ser dy Val Asn Leu 1040 Thr Gin Lys Thr His 1045 Pro He Glu Val Phe 105C Glu 1 Pro Gly Ala Glu 1055 His He Val Arg Leu 1060 Met Thr Lys Asn Trp 1065 Gly Asp Asn Asp Ser 1070 He 1 Phe Gin Asp Val 1075 lie 1 Glu Thr Arg Gly 108C Arg 1 Glu Tyr Ala Gly 1085 Leu Tyr Asp Asp lie 109C Ser 1 Thr Gin Gly Trp 1095 Phe He Gly Leu Met HOC Cys Ala He Ala Leu 1105 Leu 1 Thr Leu Leu Leu 1110 Leu Thr Val Cys Phe 1115 Val » Lys Arg Asn Arg 1120 Gly Gly Lys Tyr Ser 1125 Val > Lys Glu Lys Glu 1130 Asp 1 Leu His Pro Asp 1135 Pro Glu He Gin Ser 1140 Val 1 Lys Asp Glu Thr 1145 Phe Gly Glu Tyr Ser 1150 Asp 1 Ser Asp Glu Lys 1155 Pro Leu T.v« —j. — \r Ser 1160 Lgu. 1 Δ rrf ger Leu Asn 1165 Δ r-z-r 1 Asp vie t Gin Pro 1170 Thr 1 Glu Ser Ala Asp 1175 Ser Leu Val Glu Tyr 1180 Gly 1 Glu Gly Asp His 1185 Gly Leu Phe Ser Glu 1190 Asp 1 Gly Ser Phe He 1195 Gly Ala Tyr Ala Gly 1200 Ser Lys Glu Lys Gly 1205 Ser Val Glu Ser Asn 1210 Gly 1 Ser Ser Thr Ala 1215 Thr Phe Pro Leu Arg 1235 1220 AT a. 1225 1230 <210> 185

<211> 1224 <212> PRT <213> Homo sapians <400> 185

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 3 5 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 571 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys ciy Leu Pro 145 150 155 16 0 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His lie Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr lie Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu ciy Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr m v — — J Ser Asn m ι? X Is Leu Leu 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Giy Thr He Leu Ala Asn Ala Asn lie 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu ciy Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys CQA 3 u v 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie lie He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly lie Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 572 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn lie Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 7 7 5 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala lie Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val H1S Gly Arg Leu Lys Gly Tyr' Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val lie Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn lie Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 , 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His lie Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 > 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 573 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr ciy 1170 1175 , 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Al a 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 186 <211> 1236

<212> PRT <213> Homo sapians <400> 186

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 T5 l~i x"\ X lit A r, vs Γ1Ο r· 1 ,, Tyr Phe r> 1 ~ VJ-Lli He Glu Cys m. u •Λ &#906; _ 2A±d Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Giy lie Ala Met Ser Glu G lu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His Xie Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys ciy Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 574 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Asp Asn He Ser His Glu Leu Phe 340 345 350 Thr Leu His Pro Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala 355 360 365 Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly 370 375 380 Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly Ser Pro Val Asp 385 390 395 400 Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe 405 410 415 Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser 420 425 430 Asn Val His Gly Thr He Leu Ala Asn Ala Asn He Asp Val Val Asp 435 440 445 Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val 450 455 460 Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe Al a Ser Pro Glu 465 470 475 480 Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly 485 490 495 Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr 500 505 510 Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He 515 520 525 Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys 530 535 540 T.pn Δ r*rr Val Ssi? Pro T VC J\s n Pro Δ v- — He Dv-z-k T t r c* T ΓΜ1 U 1 r. M-A T z-x 1 ΛΧ y -j x J- xj_y O ±JC u. 11J.O i'icz 1— i—J L4. 545 550 555 560 Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu 565 570 575 Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr 580 585 590 Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu Thr He Ser Asn 595 600 605 Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser Ala His Thr Al a 610 615 620 Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val Leu Asp Val Pro 625 630 635 640 Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val 645 650 655 Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn lie Ser Glu 660 665 670 Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu 675 680 685 Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu 690 695 700 Ala Pro Phe Val Arg Tyr Gin Phe Arg Val lie Ala Val Asn Glu Val 705 710 715 720 Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro 725 730 7 35 Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin 740 745 750 Pro Lys Glu Met lie lie Lys Trp Glu Pro Leu Lys Ser Met Glu Gin 755 760 765 Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala 770 775 780 Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val 785 790 795 800 Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala lie 575

805 810 815 Asn Gin Leu Gly Ser Gly Pro Asp 820 Pro Gin Ser Val Thr Leu 825 830 Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala 835 840 Pro Val He His Gly Val 845 Asp Val lie Asn 850 Ser Thr Leu Val Lys Val 855 Thr Trp Ser Thr Val Pro ο z n Q v v Lys Asp Arg Val 865 His Giy Arg Leu Lys Gly 870 Tyr Gin lie Asn Trp Trp 875 Lys Thr 880 Lys Ser Leu Leu Asp Gly Arg Thr 885 His Pro Lys Glu Val Asn 890 He Leu 895 Arg Phe Ser Gly Gin Arg Asn Ser 900 Gly Met Val Pro Ser Leu 905 910 Asp Ala Phe Ser Glu Phe His Leu Thr Val 915 920 Leu Ala Tyr Asn Ser Lys 925 Giy Ala Gly Pro 930 Glu Ser Glu Pro Tyr He 935 Phe Gin Thr Pro Glu Gly 940 Val Pro Glu Gin 945 Pro Thr Phe Leu Lys Val 950 He Lys Val Asp Lys Asp 955 Thr Ala 960 Thr Leu Ser Trp Gly Leu Pro Lys 965 Lys Leu Asn Gly Asn Leu 970 Thr Gly 975 Tyr Leu Leu Gin Tyr Gin He He 980 Asn Asp Thr Tyr Glu He 985 990 Gly Glu Leu Asn Asp He Asn He Thr Thr 995 100C Pro Ser Lys Pro Ser Trp ) 1005 His Leu Ser Asn 101C Leu Asn Ala Thr Thr Lys I 1015 Tyr Lys Phe Tyr Leu Arg 1020 Ala Cys Thr Ser 1025 Gin Gly Cys Gly Lys Pro 1030 He Thr Glu Glu Ser Ser 1035 Thr Leu 1040 Gly Glu Gly Ser Lys Gly He Gly 1045 Lys He Ser Gly Val Asn 1050 Leu. Thr 1055 Gin Lys Thr His Pro He Glu Val 1060 Phe Glu Pro Gly Ala Glu 1065 107C His He 1 Val Arg Leu Met Thr Lys Asn Trp 1075 108C Gly Asp Asn Asp Ser He ι 1085 Phe Gin Asp Val 1090 He Glu Thr Arg Gly Arg > 1095 Glu Tyr Ala Gly Leu Tyr 1100 Asp Asp He Ser “i inc; J_ _L V D Thr Gin Gly Trp Phe Xie 1110 Gly Leu Met Cys Ala lie 1115 Ala Leu 1120 Leu Thr Leu Leu Leu Leu Thr Val 1125 Cys Phe Val Lys Arg Asn 1130 Arg Gly 1135 Gly Lys Tyr Ser Val Lys Glu Lys 1140 Glu Asp Leu His Pro Asp 1145 115C Pro Glu I He Gin Ser Val Lys Asp Glu Thr 1155 116C Phe Gly Glu Tyr Ser Asp ι 1165 Ser Asp Glu Lys 1170 Pro Leu Lys Gly Ser Leu 1175 Arg Ser Leu Asn Arg Asp 1180 Met Gin Pro Thr 1185 Glu Ser Ala Asp Ser Leu 1190 Val Glu Tyr Gly Glu Gly 1195 Asp His 1200 Gly Leu Phe Ser Glu Asp Gly Ser 1205 Phe lie Gly Ala Tyr Ala 1210 Gly Ser 1215 Lys Glu Pro Leu Lys Gly Ser Val Glu Ser 1220 Arg Ala 1235 Asn Gly Ser Ser Thr Ala 1225 123C Thr Phe I <210> 187 <211> 7563

<212> DNA <213> Homo sapians 576 <400> 187 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaaaatt 660 agaacacatc gaacaagatg aaagagtata catgagccaa aagggagatc tatacttcgc 720 aaacgtggaa gaaaaggaca gtcgcaatga ctactgttgc tttgctgcat ttccaagatt 780 aaggactatt gtacagaaaa tgccaatgaa actaacagtt aacagtttaa agcatgctaa 840 tgactcaagt tcatccacag aaattggttc caaggcaaat tccatcaagc aaagaaaacc 900 caaactgctg ttgcctccca ctgagagtgg cagtgagtct tcaattacca tcctcaaagg 960 ggaaatcttg ctgcttgagt gttttgctga aggcttgcca actccacagg ttgattggaa 1020 caaaattggt ggtgacttac caaaggggag agaaacaaaa gaaaattatg gcaagacttt 1080 gaagatagag aatgtctcct accaggacaa aggaaattat cgctgcacag ccagcaattt 1140 cttgggaaca, gccactcacg attttcacgt tatagtagaa gataacatct ctcatgagct 1200 cttcacttta catccagagc ctcctcgctg gacaaagaag cctcagagtg ctgtgtatag 1260 caccggaagc aatggcatct tgttatgtga ggctgaagga gaacctcaac ccacaatcaa 1320 gtggagagtc aatggctccc cagttgacaa tcatccattt gctggtgatg ttgtcttccc 1380 cagggaaatc agttttacca accttcaacc aaatcatact gctgtgtacc agtgtgaagc 1440 ctcaaatgtc catggaacta tccttgccaa tgccaatatt gatgttgtgg atgtccgtcc 1500 attgatacaa accaaagatg gagaaaatta cgctacagtg gttgggtaca gtgctttctt 1560 acattgcgag ttctttgctt cacctgaggc agtcgtgtcc tggcagaagg tggaagaagt 1620 gaaacccctg gagggcaggc ggtatcatat ctatgaaaat ggcacattgc agatcaacag 1680 aaccaccgaa gaagatgctg qgtcttactc atgttgggta gaaaatgcta taggaaaaac 1740 tgcagtcaca gccaatttgg atattagaaa tgctacaaaa cttagagttt ctcctaagaa 1800 tcctcgtatc cccaaattgc atatgcttga attacattgt gaaagcaaat gtgactcaca 1860 tttgaaacac agtttgaagt tgtcctggag taaagatgga gaagcctttg aaattaatgg 1920 cacagaagat ggcaggataa ttattgatgg agctaatttg accatatcta atgtaacttt 1980 agaggaccaa ggtatttact gctgttcagc tcatactgct ctagacagtg ctgccgatat 2040 aactcaagta actgttcttg atgttccgga tccaccagaa aaccttcact tgtctgaaag 2100 acagaacagg agtgttcggc tgacctggga agctggagct gaccacaaca gcaatattag 2160 cgagtatatt gttgaatttg aaggaaacaa agaagagcct ggaaggtggg aggaactgac 2220 cagagtccaa ggaaagaaaa ccacagttat cttacctttg gctccatttg tgagatacca 2280 gttcagggtc atagccgtga acgaagtagg gagaagtcag cctagccagc cgtcagacca 2340 tcatgaaaca ccaccagcag ctccagatag gaatccacaa aacataaggg ttcaagcctc 2400 tcaacccaag gaaatgatta taaagtggga gcctttgaaa tccatggagc agaatggacc 2460 aggcctagag tacagagtga cctggaagcc acagggagcc ccagtggagt gggaagaaga 2520 aacagtcaca aaccacacat tgcgggtgat gacgcctgct gtctatgccc cttatgatgt 2580 caaggtccag gctatcaatc aactaggatc tgggcctgac cctcagtcag tgactctcta 2640 ttctggagaa gactatcctg atacagctcc agtgatccat ggggtggacg ttataaacag 2700 tacattagtt aaagttacct ggtcaacagt tccaaaggac agagtacatg gacgtctgaa 2760 aggctatcag ataaattggt ggaaaacaaa aagtctgttg gatggaagaa cacatcccaa 2820 agaagtgaac attctaagat tttcaggaca aagaaactct ggaatggttc cttccttaga 2880 tgcctttagt gaatttcatt taacagtctt agcctataac tctaaaggag ctggtcctga 2940 aagtgagcct tatatatttc aaacaccaga aggagtacct gaacagccaa cttttctaaa 3000 ggtcatcaaa gttgataaag acactgccac tttatcttgg ggactaccta agaaattaaa 3060 tggaaactta actggctatc ttttgcaata tcagataata aatgacacct acgagattgg 3120 agaattaaat gatattaaca ttacaactcc atcaaagccc agctggcacc tctcaaacct 3180 gaatgcaact accaagtaca aattctactt gagggcttgc acttcacagg gctgtggaaa 3240 accgatcacg gaggaaagct ccaccttagg agaagggagt aaaggtatcg ggaagatatc 3300 aggagtaaat cttactcaaa agactcaccc aatagaggta tttgagccgg gagctgaaca 3360 tatagttcgc ctaatgacta agaattgggg cgataacgat agcatttttc aagatgtaat 3420 tgagacaaga gggagagaat atgctggttt atatgatgac atctccactc aaggctggtt 3480 tattggactg atgtgtgcga ttgctcttct cacactacta ttattaactg tttgctttgt 3540 gaagaggaat agaggtggaa agtactcagt taaagaaaag gaagatttgc atccagaccc 3600 agaaattcag tcagtaaaag atgaaacctt tggtgaatac agtgacagtg atgaaaagcc 3660 577 tctcaaagga agccttcggt cccttaatag ggatatgcag cctactgaaa gtgctgacag cttagtcgaa tacggagagg gagaccatgg tctcttcagt gaagatggat catttattgg tgcctacgct ggatctaagg agaagggatc tgttgaaagc aatggaagtt ctacagcaac ttttcccctt cgggcataaa cacaacatat gtaagcaacg ctactggttc accccaacct tccatattta tctgttcaaa ggagcaagaa ctttcatata ggaatagaaa catgctggcc gaagatttca tccagaagtc aacatcctgc aattatgttg aaaagagtag tactttcttc aaaatataaa atgccaagca cttcaggcct atgttttgct tatattgttt tcaggtgctc aaaatgcaaa acacaaaaca aatcctgcat ttagatacac ctcaactaaa tccaaagtcc ccattcagta tattccatat ttgcctgatt ttactattcg gtgtgtttgc atagatgttg ctacttggtg ggtttttctc cgtatgcaca ttggtataca gtctctgaga actggcttgg tgactttgct tcactacagg ttaaaagacc ataagcaaac tggttattta aaatgtaaaa aggaatatga aagtcttatt aaaacacttc attgaaaata tacagtctaa atttattatt taaattttac tagcaaaagt cttaggtgaa caatcaacta gtatttgttg agctcctatt tgcccagaga tggtcatatt taaacagaag tatacgtttt tcagtttcaa catgaatttt tttatttctg tcagttatga catccacgag catcactttt tgtgtctgtt tttttttttt tcttggacta aattcaactg catggaagcg gtggtcagaa ggttgtttta tacgagaaca ggcagaaagt gcccattgtt caggattcta atagctacat ctacttaata tcttcatttc taaattgact gcttttacct ttttctcatg tttatataat ggtatgcttg catatatttc atgaatacat tgtacatatt atgttaatat ttacacaatt taaaatatag atgtgtttta ttttgaagtg agaaaatgaa cattaacagg catgtttgta cagctagaat atattagtaa gatactgttt ttcgtcattc cagagctaca actaataaca cgaggttcca aagctgaaga ctttgtataa agtatttggg ttttgttctt gtattgcttt ctttcaacag tttcaaaata aaatatcata caaatattga gggaaatgtt ttcatatttt tcaaaatagg tttttattgt tgaatgtaca tctaccccag cccctcaaaa gaaaaactgt ttacatagaa attcctacac atacgtttgc gtatatgtta ttttaaacat ctttgtggtg agaatttttt ccccgatatt ctccttctgt caaagtcaga acaaattcag ggaatttatt ttctggcagt tgtgctccag tccttttaaa attgtacatg aacatgtttt agaaacaata tggaggatga tgcatacatg tcggtcaagt tcagcgctcg acattttatg gaaagatttt tttaacctta ccacgaaata cttaactact gtttaagtga attgacttat ttcactttag tttttgaact gtgattattg gtatactgtt atatcctcaa cttggattta tggtaacccc ttttagttca tggagaccaa aatttggggt atttataata gtcagcgcag gaatgcacat ggaatatcta cttgtccttt tgaacctcac gagtcatcca gaatgtatag acaggaaaag catgtcttat ttaaaactgt aatttatggg ctcaggatct gaccgcagtc ccgggagtaa gcatttcaaa gggggaaggc agtgtggtcc ctaccctgtg tgaatgtgag gatgtagaca tccatcagtg caactcgagc tccatcctcc tccgatttct aaggctccag ttttctggag ggacagtcat catgttttga tttatctggg agaaaactgt ggtgcacagc ttgtgaggag ggcaaggttg tgacgttcga gcttagttct ggtgttattc tgtctcctct tctttgtcat cagccaaaac gtggttttta aagagagtca tgcaggttag aaataatgtc aaaaatattt aggaatttaa taacctttaa gtcagaaact aaaacaaata ctgaaatatt agctcttcct acacttcgtg ttccccttta gctgcctgaa aatcaagatt gctcctactc agatcttctg agtggctaaa acttatggat atgaaaaatg agattgaatg atgactatgc tttgctatca ttgttacctt tcctcaatac tatttggcaa ctactgggac tcttcagcac aaaaggaata gatctatgat tgaccctgat tttaattgtg aaattatatg attcatatat tttatgaatc agaataacct tcaaataaaa taaatctaag tcggttaaaa tggatttcat gattttccct cagaaaatga gtaacggagt ccacggcgtg caatggtaat tataaattgg tgatgcttgt ttgcaaattg cccactcgtg ataagtcaac agccaatatt taaaactttg ttcgttactg gctttaccct aactttctct agtctactgt caatatcatt ttaatgtaat tgattgtata tagtctcaag aatggttggt gggcatgagt tcctagagaa ctgtccaagg gttgggaaaa tccaaattct cttcctggct ccagcactga ttttgtacat aaacattagg caggttgctt aaccttttta tttcaaactc tctcaactct aaagtgctaa taataatctc agttacctta tctttgtcac agggtgttct tttttatgaa gaaaaatttg aaaatgataa aagctaagat gccttctaac ttcataagca aacctttaac taattatgta tctgaaagtc acccccacat accaactcaa cttttttcct gtgaacacat aaatatattt ttatagaaaa acaaatctac ataaaataaa tctactgttt agtgagcagt atgacttgta catgccattg aaaattatta atcagaagaa aattaagcag ggtctttgct atacaaaagt gttttccact aattttgcat gcgtatttat aagaaaaatg tgaatttggt ggttttattc tatcggtata aaggcatcga tattttagat gcacccgtgt ttgtaaaaat gtagagcaca atggaattat gctggaagtc tcaaataata tttttttcct attttatact catggaagag ataagctaaa gaggggacaa taatgagaaa tgttggtgtg cttttctaag catttaaaac ataattgcca attgaaaccc taaatatgtt tacataccat taagatatga ttcatgtaac aatgttaaat taattataat gggattgggt ttgttatctg tggtagtata tatcctagtg ttcctatagt gaaataagta gggttcagcc aaagctttct ttgttttgta ccttaaattg ttcgattacg tcatcaaaag agatgaaagg tatgtagaac 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 578 aggttcacgt aaacgtgttt atattttcat aaa <210> 188 <211> 7650 <212> DNA <213> Homo <400> 188 cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg aatcgtatat agttcaacag tgagtatttt taaggatggc aacattcagg tgcttcaaat tccaaaactc cctcccatgc attagaacac cgcaaacgtg attaaggact taatgactca acccaaactg aggggaaatc gaacaaaatt tttgaagata tttcttggga aaagaagcct tgaaggagaa tccatttgct tcatactgct caatattgat tacagtggtt cgtgtcctgg tgaaaatggc ttgggtagaa tacaaaactt acattgtgaa agatggagaa taatttgacc tactgctcta accagaaaac tggagctgac agagcctgga acctttggct aagtcagcct tccacaaaac tttgaaatcc gggagcccca gcctgctgtc gcctgaccct gatccatggg aaaggacaga tctgttggat gattaccttt ttcttttggc ttggattaat attcatagta gaactttata 7440 gtattgtagg tggtgtttgt attatgctta tgactatgta tggtttgaaa 7500 tatacatgaa attcaacttt ccaaataaaa gttctacttc atgtaatcca 7560 7563 sapians gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 aatgctatag gaaaaactgc agtcacagcc aatttggata ttagaaatgc 1860 agagtttctc ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt 1920 agcaaatgtg actcacattt gaaacacagt ttgaagttgt cctggagtaa 1980 gcctttgaaa ttaatggcac agaagatggc aggataatta ttgatggagc 2040 atatctaatg taactttaga ggaccaaggt atttactgct gttcagctca 2100 gacagtgctg ccgatataac tcaagtaact gttcttgatg ttccggatcc 2160 cttcacttgt ctgaaagaca gaacaggagt gttcggctga cctgggaagc 2220 cacaacagca atattagcga gtatattgtt gaatttgaag gaaacaaaga 2280 aggtgggagg aactgaccag agtccaagga aagaaaacca cagttatctt 2340 ccatttgtga gataccagtt cagggtcata gccgtgaacg aagtagggag 2400 agccagccgt cagaccatca tgaaacacca ccagcagctc cagataggaa 2460 ataagggttc aagcctctca acccaaggaa atgattataa agtgggagcc 2520 atggagcaga atggaccagg cctagagtac agagtgacct ggaagccaca 2580 gtggagtggg aagaagaaac agtcacaaac cacacattgc gggtgatgac 2640 tatgcccctt atgatgtcaa ggtccaggct atcaatcaac taggatctgg 2700 cagtcagtga ctctctattc tggagaagac tatcctgata cagctccagt 2760 gtggacgtta taaacagtac attagttaaa gttacctggt caacagttcc 2820 gtacatggac gtctgaaagg ctatcagata aattggtgga aaacaaaaag 2880 ggaagaacac atcccaaaga agtgaacatt ctaagatttt caggacaaag 2940 579 aaactctgga ctataactct agtacctgaa atcttgggga gataataaat aaagcccagc ggcttgcact agggagtaaa agaggtattt taacgatagc tgatgacatc actactatta agaaaaggaa tgaatacagt tatgcagcct cttcagtgaa tgaaagcaat agcaacgcta tcatatagga tatgttgaaa ttttgcttat gatacacctc ctattcggtg gtatacagtc agcaaactgg gaaaatatac tcaactagta acgtttttca cactttttgt gtcagaaggt gctacatcta atataatggt cacaatttaa gtttgtacag aataacacga ttgctttctt atatttttca aaactgttta tgtggtgaga atttattttc aacaatatgg agattttttt actttagttt taaccccttt tgcacatgga ggaaaagcat ggagtaagca gtagacatcc tctggaggga tgaggagggc ttgtcatcag aatatttagg tcttcctaca tcttctgagt gctatcattg aggaatagat atgaatcaga tttccctcag tgcttgtttg gttactggct ttgtatatag gggaaaatcc atggttcctt aaaggagctg cagccaactt ctacctaaga gacacctacg tggcacctct tcacagggct ggtatcggga gagccgggag atttttcaag tccactcaag ttaactgttt gatttgcatc gacagtgatg actgaaagtg gatggatcat ggaagttcta ctggttcacc atagaaacat agagtagtac attgttttca aactaaatcc tgtttgcata tctgagaact ttatttaaaa agtctaaatt tttgttgagc gtttcaacat gtctgttttt tgttttatac cttaatatct atgcttgcat aatatagatg ctagaatata ggttccaaag tcaacagttt aaataggttt catagaaatt attttttccc tggcagttgt aggatgatgc aaccttacca ttgaactgtg tagttcatgg atatctactt gtcttattta tttcaaaggg atcagtgcaa cagtcatcat aaggttgtga ccaaaacgtg aatttaataa cttcgtgttc ggctaaaact ttacctttcc ctatgattga ataaccttca aaaatgagta caaattgccc ttaccctaac tctcaagaat aaattctctt ccttagatgc gtcctgaaag ttctaaaggt aattaaatgg agattggaga caaacctgaa gtggaaaacc agatatcagg ctgaacatat atgtaattga gctggtttat gctttgtgaa cagacccaga aaaagcctct ctgacagctt ttattggtgc cagcaacttt ccaaccttcc gctggccgaa tttcttcaaa ggtgctcaaa aaagtcccca gatgttgcta ggcttggtga tgtaaaaagg tattatttaa tcctatttgc gaattttttt ttttttttct gagaacaggc tcatttctaa atatttcatg tgttttattt ttagtaagat ctgaagactt caaaataaaa ttattgttga cctacacata cgatattctc gctccagtcc atacatgtcg cgaaatactt attattggta agaccaaaat gtccttttga aaactgtaat ggaaggcagt ctcgagctcc gttttgattt cgttcgagct gtttttaaag cctttaagtc ccctttagct tatggatatg tcaatactat ccctgatttt aataaaataa acggagtcca actcgtgata tttctctagt ggttggtggg cctggctcca ctttagtgaa tgagccttat catcaaagtt aaacttaact attaaatgat tgcaactacc gatcacggag agtaaatctt agttcgccta gacaagaggg tggactgatg gaggaataga aattcagtca caaaggaagc agtcgaatac ctacgctgga tccccttcgg atatttatct gatttcatcc atataaaatg atgcaaaaca ttcagtatat cttggtgggt ctttgcttca aatatgaaag attttactag ccagagatgg atttctgtca tggactaaat agaaagtgcc attgactgct aatacattgt tgaagtgaga actgtttttc tgtataaagt tatcatacaa atgtacatct cgtttgcgta cttctgtcaa ttttaaaatt gtcaagttca aactactgtt tactqttata ttggggtatt acctcacgag ttatgggctc gtggtcccta atcctcctcc atctgggaga tagttctggt agagtcatgc agaaactaaa gcctgaaaat aaaaatgaga ttggcaacta aattgtgaaa atctaagtcg cggcgtgcaa agtcaacagc ctactgtcaa catgagttcc gcactgattt tttcatttaa atatttcaaa gataaagaca ggctatcttt attaacatta aagtacaaat gaaagctcca actcaaaaga atgactaaga agagaatatg tgtgcgattg ggtggaaagt gtaaaagatg cttcggtccc ggagagggag tctaaggaga gcataaacac gttcaaagga agaagtcaac ccaagcactt caaaacaaat tccatatttg ttttctccgt ctacaggtta tcttattaaa caaaagtctt tcatatttaa gttatgacat tcaactgcat cattgttcag tttacctttt acatattatg aaatgaacat gtcattccag atttgggttt atattgaggg accccagccc tatgttattt agtcagaaca gtacatgaac gcgctcgaca taagtgaatt tcctcaactt tataatagtc tcatccagaa aggatctgac ccctgtgtga gatttctaag aaactgtggt gttattctgt aggttagaaa acaaatactg caagattgct ttgaatgatg ctgggactct ttatatgatt gttaaaatgg tggtaattat caatatttaa tatcatttta tagagaactg tgtacataaa cagtcttagc caccagaagg ctgccacttt tgcaatatca caactccatc tctacttgag ccttaggaga ctcacccaat attggggcga ctggtttata ctcttctcac actcagttaa aaacctttgg ttaataggga accatggtct agggatctgt aacatatgta gcaagaactt atcctgcaat caggcctatg cctgcattta cctgatttta atgcacattg aaagaccata acacttcatt aggtgaacaa acagaagtat ccacgagcat ggaagcggtg gattctaata tctcatgttt ttaatattta taacaggcat agctacaact tgttcttgta aaatgttttc ctcaaaagaa taaacatctt aattcaggga atgttttaga ttttatggaa gacttatttc ggatttatgg agcgcaggaa tgtatagaca cgcagtcccg atgtgaggat gctccagttt gcacagcttg ctcctcttct taatgtcaaa aaatattagc cctactcaga actatgcttt tcagcacaaa catatatttt atttcatgat aaattggtga aactttgttc atgtaattga tccaagggtt cattaggcag 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 580 gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 aataaaagtt ctacttcatg taatccaaaa 7650 <210> 189 <211> 7563

<212> DNA <213> Homo sapians <400> 189 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaaaatt 660 agaacacatc gaacaagatg aaagagtata catgagccaa aagggagatc tatacttcgc 720 aaacgtggaa gaaaaggaca gtcgcaatga ctactqttgc tttgctgcat ttccaagatt 780 aaggactatt gtacagaaaa tgccaatgaa actaacagtt aacagtttaa agcatgctaa 840 tgactcaagt tcatccacag aaattggttc caaggcaaat tccatcaagc aaagaaaacc 900 caaactgctg ttgcctccca ctgagagtgg cagtgagtct tcaattacca tcctcaaagg 960 ggaaatcttg ctgcttgagt gttttgctga aggcttgcca actccacagg ttgattggaa 1020 caaaattggt ggtgacttac caaaggggag agaaacaaaa gaaaattatg gcaagacttt 1080 gaagatagag aatgtctcct accaggacaa aggaaattat cgctgcacag ccagcaattt 1140 cttgggaaca gccactcacg attttcacgt tatagtagaa gataacatct ctcatgagct 1200 cttcacttta catccagagc ctcctcgctg gacaaagaag cctcagagtg ctgtgtatag 1260 caccggaagc aatggcatct tgttatgtga ggctgaagga gaacctcaac ccacaatcaa 1320 gtggagagtc aatggctccc cagttgacaa tcatccattt gctggtgatg ttgtcttccc 1380 cagggaaatc agttttacca accttcaacc aaatcatact gctgtgtacc agtgtgaagc 1440 ctcaaatgtc catggaacta tccttgccaa tgccaatatt gatgttgtgg atgtccgtcc 1500 attgatacaa accaaagatg gagaaaatta cgctacagtg gttgggtaca gtgctttctt 1560 acattgcgag ttctttgctt cacctgaggc agtcgtgtcc tggcagaagg tggaagaagt 1620 gaaacccctg gagggcaggc ggtatcatat ctatgaaaat ggcacattgc agatcaacag 1680 aaccaccgaa gaagatgctg ggtcttactc atgttgggta gaaaatgcta taggaaaaac 1740 tgcagtcaca gccaatttgg atattagaaa tgctacaaaa cttagagttt ctcctaagaa 1800 tcctcgtatc cccaaattgc atatgcttga attacattgt gaaagcaaat gtgactcaca 1860 tttgaaacac agtttgaagt tgtcctggag taaagatgga gaagcctttg aaattaatgg 1920 cacagaagat ggcaggataa ttattgatgg agctaatttg accatatcta atgtaacttt 1980 agaggaccaa ggtatttact gctgttcagc tcatactgct ctagacagtg ctgccgatat 2040 aactcaagta actgttcttg atgttccgga tccaccagaa aaccttcact tgtctgaaag 2100 acagaacagg agtgttcggc tgacctggga agctggagct gaccacaaca gcaatattag 2160 581 cgagtatatt gttgaatttg aaggaaacaa agaagagcct ggaaggtggg aggaactgac 2220 cagagtccaa ggaaagaaaa ccacagttat cttacctttg gctccatttg tgagatacca 2280 gttcagggtc atagccgtga acgaagtagg gagaagtcag cctagccagc cgtcagacca 2340 tcatgaaaca ccaccagcag ctccagatag gaatccacaa aacataaggg ttcaagcctc 2400 tcaacccaag gaaatgatta taaagtggga gcctttgaaa tccatggagc agaatggacc 2460 aggcctagag tacagagtga cctggaagcc acagggagcc ccagtggagt gggaagaaga 2520 aacagtcaca aaccacacat tgcgggtgat gacgcctgct gtctatgccc cttatgatgt 2580 caaggtccag gctatcaatc aactaggatc tgggcctgac cctcagtcag tgactctcta 2640 ttctggagaa gactatcctg atacagctcc agtgatccat ggggtggacg ttataaacag 2700 tacattagtt aaagttacct ggtcaacagt tccaaaggac agagtacatg gacgtctgaa 2760 aggctatcag ataaattggt ggaaaacaaa aagtctgttg gatggaagaa cacatcccaa 2820 agaagtgaac attctaagat tttcaggaca aagaaactct ggaatggttc cttccttaga 2880 tgcctttagt gaatttcatt taacagtctt agcctataac tctaaaggag ctggtcctga 2940 aagtgagcct tatatatttc aaacaccaga aggagtacct gaacagccaa cttttctaaa 3000 ggtcatcaaa gttgataaag acactgccac tttatcttgg ggactaccta agaaattaaa 3060 tggaaactta actggctatc ttttgcaata tcagataata aatgacacct acgagattgg 3120 agaattaaat gatattaaca ttacaactcc atcaaagccc agctggcacc tctcaaacct 3180 gaatgcaact accaagtaca aattctactt gagggcttgc acttcacagg gctgtggaaa 3240 accgatcacg gaggaaagct ccaccttagg agaagggagt aaaggtatcg ggaagatatc 3300 aggagtaaat cttactcaaa agactcaccc aatagaggta tttgagccgg gagctgaaca 3360 tatagttcgc ctaatgacta agaattgggg cgataacgat agcatttttc aagatgtaat 3420 tgagacaaga gggagagaat atgctggttt atatgatgac atctccactc aaggctggtt 3480 tattggactg atgtgtgcga ttgctcttct cacactacta ttattaactg tttgctttgt 3540 gaagaggaat agaggtggaa agtactcagt taaagaaaag gaagatttgc atccagaccc 3600 agaaattcag tcagtaaaag atgaaacctt tggtgaatac agtgacagtg atgaaaagcc 3660 tctcaaagga agccttcggt cccttaatag ggatatgcag cctactgaaa gtgctgacag 3720 cttagtcgaa tacggagagg gagaccatgg tctcttcagt gaagatggat catttattgg 3780 tgcctacgct ggatctaagg agaagggatc tgttgaaagc aatggaagtt ctacagcaac 3840 ttttcccctt cgggcataaa cacaacatat gtaagcaacg ctactggttc accccaacct 3900 tccatattta tctgttcaaa ggagcaagaa ctttcatata ggaatagaaa catgctggcc 3960 gaagatttca tccagaagtc aacatcctgc aattatgttg aaaagagtag tactttcttc 4020 aaaatataaa atgccaagca cttcaggcct atgttttgct tatattgttt tcaggtgctc 4080 aaaatgcaaa acacaaaaca aatcctgcat ttagatacac ctcaactaaa tccaaagtcc 4140 ccattcagta tattccatat ttgcctgatt ttactattcg gtgtgtttgc atagatgttg 4200 ctacttggtg ggtttttctc cgtatgcaca ttggtataca gtctctgaga actggcttgg 4260 tgactttgct tcactacagg ttaaaagacc ataagcaaac tggttattta aaatgtaaaa 4320 aggaatatga aagtcttatt aaaacacttc attgaaaata tacagtctaa atttattatt 4380 taaattttac tagcaaaagt cttaggtgaa caatcaacta gtatttgttg agctcctatt 4440 tgcccagaga tggtcatatt taaacagaag tatacgtttt tcagtttcaa catgaatttt 4500 tttatttctg tcagttatga catccacgag catcactttt tgtgtctgtt tttttttttt 4560 tcttggacta aattcaactg catggaagcg gtggtcagaa ggttgtttta tacgagaaca 4620 ggcagaaagt gcccattgtt caggattcta atagctacat ctacttaata tcttcatttc 4680 taaattgact gcttttacct ttttctcatg tttatataat ggtatgcttg catatatttc 4740 atgaatacat tgtacatatt atgttaatat ttacacaatt taaaatatag atgtgtttta 4800 ttttgaagtg agaaaatgaa cattaacagg catgtttgta cagctagaat atattagtaa 4860 gatactgttt ttcgtcattc cagagctaca actaataaca cgaggttcca aagctgaaga 4920 ctttgtataa agtatttggg ttttgttctt gtattgcttt ctttcaacag tttcaaaata 4980 aaatatcata caaatattga gggaaatgtt ttcatatttt tcaaaatagg tttttattgt 5040 tgaatgtaca tctaccccag cccctcaaaa gaaaaactgt ttacatagaa attcctacac 5100 atacgtttgc gtatatgtta ttttaaacat ctttgtggtg agaatttttt ccccgatatt 5160 ctccttctgt caaagtcaga acaaattcag ggaatttatt ttctggcagt tgtgctccag 5220 tccttttaaa attgtacatg aacatgtttt agaaacaata tggaggatga tgcatacatg 5280 tcggtcaagt tcagcgctcg acattttatg gaaagatttt tttaacctta ccacgaaata 5340 cttaactact gtttaagtga attgacttat ttcactttag tttttgaact gtgattattg 5400 gtatactgtt atatcctcaa cttggattta tggtaacccc ttttagttca tggagaccaa 5460 aatttggggt atttataata gtcagcgcag gaatgcacat ggaatatcta cttgtccttt 5520 tgaacctcac gagtcatcca gaatgtatag acaggaaaag catgtcttat ttaaaactgt 5580 aatttatggg ctcaggatct gaccgcagtc ccgggagtaa gcatttcaaa gggggaaggc 5640 agtgtggtcc ctaccctgtg tgaatgtgag gatgtagaca tccatcagtg caactcgagc 5700 tccatcctcc tccgatttct aaggctccag ttttctggag ggacagtcat catgttttga 5760 tttatctggg agaaaactgt ggtgcacagc ttgtgaggag ggcaaggttg tgacgttcga 5820 gcttagttct ggtgttattc tgtctcctct tctttgtcat cagccaaaac gtggttttta 5880 582 aagagagtca tgcaggttag aaataatgtc aaaaatattt aggaatttaa taacctttaa gtcagaaact aaaacaaata ctgaaatatt agctcttcct acacttcgtg ttccccttta gctgcctgaa aatcaagatt gctcctactc agatcttctg agtggctaaa acttatggat atgaaaaatg agattgaatg atgactatgc tttgctatca ttgttacctt tcctcaatac tatttggcaa ctactgggac tcttcagcac aaaaggaata gatctatgat tgaccctgat tttaattgtg aaattatatg attcatatat tttatgaatc agaataacct tcaaataaaa taaatctaag tcggttaaaa tggatttcat gattttccct cagaaaatga gtaacggagt ccacggcgtg caatggtaat tataaattgg tgatgcttgt ttgcaaattg cccactcgtg ataagtcaac agccaatatt taaaactttg ttcgttactg gctttaccct aactttctct agtctactgt caatatcatt ttaatgtaat tgattgtata tagtctcaag aatggttggt gggcatgagt tcctagagaa ctgtccaagg gttgggaaaa tccaaattct cttcctggct ccagcactga ttttgtacat aaacattagg caggttgctt aaccttttta tttcaaactc tctcaactct aaagtgctaa taataatctc agttacctta tctttgtcac agggtgttct tttttatgaa gaaaaatttg aaaatgataa aagctaagat gccttctaac ttcataagca aacctttaac taattatgta tctgaaagtc acccccacat accaactcaa cttttttcct gtgaacacat aaatatattt ttatagaaaa acaaatctac ataaaataaa tctactgttt agtgagcagt atgacttgta catgccattg aaaattatta atcagaagaa aattaagcag ggtctttgct atacaaaagt gttttccact aattttgcat gcgtatttat aagaaaaatg tgaatttggt ggttttattc tatcggtata aaggcatcga tattttagat gcacccgtgt ttgtaaaaat gtagagcaca atggaattat gctggaagtc tcaaataata tttttttcct attttatact catggaagag ataagctaaa gaggggacaa taatgagaaa tgttggtgtg cttttctaag catttaaaac ataattgcca attgaaaccc taaatatgtt tacataccat taagatatga ttcatgtaac aatgttaaat taattataat gggattgggt ttgttatctg tggtagtata tatcctagtg ttcctatagt gaaataagta gggttcagcc aaagctttct ttgttttgta ccttaaattg ttcgattacg tcatcaaaag agatgaaagg tatgtagaac aggttcacgt gattaccttt ttcttttggc ttggattaat attcatagta gaactttata aaacgtgttt gtattgtagg tggtgtttgt attatgctta tgactatgta tggtttgaaa atattttcat tatacatgaa attcaacttt ccaaataaaa gttctacttc atgtaatcca aaa 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7563 <210> 190

<211> 1195 <212> PRT <213> Homo sapians <400> 190

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp ciy Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Lys Leu Glu His lie Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr lie Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 583

Ser Ser Ser 195 Thr Glu He Gly Ser 200 Lys Ala Asn Ser He 205 Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr I le Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Al a Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 245 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys lie 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu ciy Thr Ala Thr His Asp Phe His Val lie Val Glu Asp 290 295 300 Asn He Ser His Glu Leu Phe Thr Leu His Pro Glu Pro Pro Arg Trp 305 310 315 320 Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly lie 325 330 335 Leu Leu cys Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg 340 345 350 Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val 355 360 365 Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala 370 375 380 Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn 385 390 395 400 Ala Asn lie Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp 405 410 415 Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys λ ο n z. V A Π C “1Z, J A Ο Λ O U Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu 435 440 445 Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly 450 455 460 Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser 465 470 475 480 Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu 485 490 495 Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg 500 505 510 lie Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp 515 520 525 Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu 530 535 540 Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly 545 550 555 560 Ala Asn Leu Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr 565 570 5 7 5 cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin 580 585 590 Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser 595 600 605 Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp 610 615 62 0 His Asn Ser Asn He Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys 625 630 635 640 Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys 645 650 655 Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg 660 665 670 Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser 675 680 685 584

Asp His 690 His Glu Thr Pro Pro 695 Ala Ala Pro Asp Arg 700 Asn Pro Gin Asn lie Arg Val Gin Ala Ser Gin Pro Lys Glu Met lie lie Lys Trp Glu 705 710 715 720 Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val TOC I i. 3 730 735 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Η Λ A I tt V 745 750 Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr 755 760 765 Asp Val Lys Val Gin Ala He Asn Gin Leu Giy Ser Gly Pro Asp Pro 770 775 780 Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro 785 790 795 800 Val He His Giy Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr 805 810 815 Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr 820 825 830 Gin lie Asn Trp Trp Lys Thr Lys Ssr Leu Leu Asp Gly Arg Thr His 835 840 845 Pro Lys Glu Val Asn He Leu Arg Phe Ser Giy Gin Arg Asn Ser Gly 850 855 860 Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu 865 870 875 880 Ala Tyr Asn Ser Lys Giy Ala Gly Pro Glu Ser Glu Pro Tyr He Phe 885 890 895 Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val lie 900 905 910 Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys 915 920 925 Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn 930 935 940 Asp Thr Tyr Glu lie Gly Glu Leu Asn Asp lie Asn lie Thr Thr Pro 945 950 955 960 Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr 965 970 975 Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He 980 985 990 Thr Glu Glu Ser υθχ Leu Gly U X Ll Gly Ser Lys Giy He Gly Lys 995 1000 1005 lie Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro lie Glu Val Phe 1010 1015 1020 Glu Pro Gly Ala Glu His lie Val Arg Leu Met Thr Lys Asn Trp ciy 10 2 5 1030 1035 1040 Asp Asn Asp Ser Tie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu 1045 1050 1055 Tyr Ala Gly Leu Tyr Asp Asp lie Ser Thr Gin Gly Trp Phe lie Gly 1060 1065 1070 Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys 1075 1080 1085 Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu 1090 1095 1100 Asp Leu His Pro Asp Pro Glu He Gin Ssx? Val Lys Asp Π 11 &amp;#908; J. u Thr Phe 1105 1110 1115 1120 Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg 1125 1130 1135 Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Al 3 Asp Ser Leu Val 1140 1145 1150 Glu Tyr Giy Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe 1155 1160 1165 He Gly Al 3 Tyr Al 3 Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn 1170 1175 1180 585

Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1185 1190 1195 <210> 191 <211> 1224

<212> PRT <213> Homo sapians <400> 191

Met Glu Pro Leu Leu Leu Giy Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr I le lie Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 1 A R 1 rt Λ 1 c rt 1 C. A _L I -J J. k> X _> -J X V V Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Giy Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 586

Cys Glu Ala Ser 420 Asn Val His Gly Thr 425 lie Leu Ala Asn Ala 430 Asn He Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Giy Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie lie He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser r λ c υ j r c λ o &amp;#9633; υ 655 Asn He Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Tro Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val lie His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 587

Ser Lys Gly 915 Ala Gly Pro Glu Ser 920 Glu Pro Tyr He Phe 925 Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Giy Leu Pro Lys Lys Leu Asn Giy 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn A.sp Thi? Tyr 965 970 975 Glu He ciy Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 9 9 0 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Giy Ser Lys Giy He Giy Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro lie Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu Hrs He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Giy Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr AX 3 Gly Ser Lys Glu Lys Gly Ser Val GXu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 192

<211> 1195 <212> PRT <213> Homo sapians <400> 192

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Τ7-» 1 ναι Pro Thr τ π lie τ 1 x x-te Lys 'JXH Sex Lys Val Gin V al Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 588

Asn Lys Leu 115 Gly He Al a Met Ser 120 Glu Glu He Glu Phe 125 lie Val Pro Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Al a Ala Phe Pro Arg Leu Arg Thr lie Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys lie Gly Gly Asp Leu 245 250 255 Pro Lys Gly Arg Glu Thr Lys G lu Asn Tyr Gly Lys Thr •&amp;#973;β&amp;#971; Lys lie 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Asp 290 295 300 Asn He Ser His Glu Leu Phe Thr Leu His Pro Glu Pro Pro Arg Trp 305 310 315 320 Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He 325 330 335 Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg 340 345 350 Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val 355 360 365 Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala 370 375 380 Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn 385 390 395 400 Ala Asn He Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp 405 410 415 Ciy Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys 420 425 430 Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu 435 440 445 Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn ciy 450 455 460 Thr Leu Gin lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser 465 470 475 480 Cys Trp Val Glu Asn Ala He ciy Lys Thr Ala Val Thr Ala Asn Leu 485 490 495 Asp lie Arg Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg 500 505 510 lie Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp 515 520 525 Ser His Leu Τ,ν&lt;5 His Ser Leu Lys Leu Ser Trp Ser Lys &amp;#902; /-ll ,., oxy Glu 530 535 540 Ala Phe Glu lie Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly 545 550 555 560 Ala Asn Leu Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr 565 570 575 Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin 580 585 590 Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser 595 600 605 589

Glu Arg 610 Gin Asn Arg Ser Val 615 Arg Leu Thr Trp Glu 620 Ala Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys 625 630 635 640 Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys 645 650 655 Thr Thr Val He Leu Pro Leu Al a Pro Phe Val Arg Tyr Gin Phe Arg 660 665 670 Val He Ala val Asn Glu Val ciy Arg Ser Gin Pro Ser Gin Pro Ser 675 680 685 Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro G 1 i"i Asn 690 695 700 lie Arg Val Gin Ala Ser Gin Pro Lys Glu Met He lie Lys Trp Glu 705 710 715 720 Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val 725 730 735 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val 740 745 750 Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr 755 760 765 Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser Giy Pro Asp Pro 770 775 780 Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro 785 790 795 800 Val lie His Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr 805 810 815 Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr 820 825 830 Gin He Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His 835 840 845 Pro Lys Glu Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly 850 855 860 Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu 865 870 875 880 Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe 885 890 895 Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He 900 905 910 Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys uy s 915 920 925 Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn 930 935 940 Asp Thr Tyr Glu He Giy Glu Leu Asn Asp He Asn He Thr Thr Pro 945 950 955 960 Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr 965 970 975 Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He 980 985 990 Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys 995 1000 1005 He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro lie Glu Val Phe 1010 1015 1020 Glu Pro Gly Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly 1025 1030 1035 1040 Asp Asn Asp Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu 1045 1050 1055 Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe lie Gly 1060 1065 1070 Leu Met Cys Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Gys 1075 1080 1085 Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu 1090 1095 1100 590

Asp Leu His Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe 1105 1110 1115 112 Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg 1125 1130 1135 Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val 1140 1145 1150 Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe 1155 1160 1165 lie Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn 1170 1175 1180 Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1185 1190 1195 <210> 193 <211> 7570

<212> DNA <213> Homo sapians <400> 193 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcagttt ccaggttaac taaggtctca 120 gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt 180 cctgaagagc aatggagccg cttttacttg gaagaggact aatcgtatat ctaatgttcc 240 tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa 300 tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat 360 gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt 420 atttcactga ccatcggata attccatcga acaattcagg aacattcagg atcccaaacg 480 aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa 540 tcgctatgtc agaagaaata gaatttatag ttccaagtgt tccaaaactc ccaaaagaaa 600 aaattgaccc tcttgaagtg gaggagggag atccaattgt cctcccatgc aatcctccca 660 aaggcctccc acctttacac atttattgga tgaatattga attagaacac atcgaacaag 720 atgaaagagt atacatgagc caaaagggag atctatactt cgcaaacgtg gaagaaaagg 780 acagtcgcaa tgactactgt tgctttgctg catttccaag attaaggact attgtacaga 840 aaatgccaat gaaactaaca gttaacagtt taaagcatgc taatgactca agttcatcca 900 cagaaattgg ttccaaggca aattccatca agcaaagaaa acccaaactg ctgttgcctc 960 ccactgagag tggcagtgag tcttcaatta ccatcctcaa aggggaaatc ttgctgcttg 1020 agtgttttgc tgaaggcttg ccaactccac aggttgattg gaacaaaatt ggtggtgact 1080 taccaaaggg gagagaaaca aaagaaaatt atggcaagac tttgaagata gagaatgtct 1140 cctaccagga caaaggaaat tatcgctgca cagccagcaa tttcttggga acagccactc 1200 acgattttca cgttatagta gaagagcctc ctcgctggac aaagaagcct cagagtgctg 1260 tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc tgaaggagaa cctcaaccca 1320 caatcaagtg gagagtcaat ggctccccag ttgacaatca tccatttgct ggtgatgttg 1380 tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa tcatactgct gtgtaccagt 1440 gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc caatattgat gttgtggatg 1500 tccgtccatt gatacaaacc aaagatggag aaaattacgc tacagtggtt gggtacagtg 1560 ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt cgtgtcctgg cagaaggtgg 1620 aagaagtgaa acccctggag ggcaggcggt atcatatcta tgaaaatggc acattgcaga 1680 tcaacagaac caccgaagaa gatgctgggt cttactcatg ttgggtagaa aatgctatag 1740 gaaaaactgc agtcacagcc aatttggata ttagaaatgc tacaaaactt agagtttctc 1800 ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt acattgtgaa agcaaatgtg 1860 actcacattt gaaacacagt ttgaagttgt cctggagtaa agatggagaa gcctttgaaa 1920 ttaatggcac agaagatggc aggataatta ttgatggagc taatttgacc atatctaatg 1980 taactttaga ggaccaaggt atttactgct gttcagctca tactgctcta gacagtgctg 2040 ccgatataac tcaagtaact gttcttgatg ttccggatcc accagaaaac cttcacttgt 2100 ctgaaagaca gaacaggagt gttcggctga cctgggaagc tggagctgac cacaacagca 2160 atattagcga gtatattgtt gaatttgaag gaaacaaaga agagcctgga aggtgggagg 2220 aactgaccag agtccaagga aagaaaacca cagttatctt acctttggct ccatttgtga 2280 gataccagtt cagggtcata gccgtgaacg aagtagggag aagtcagcct agccagccgt 2340 cagaccatca tgaaacacca ccagcagctc cagataggaa tccacaaaac ataagggttc 2400 aagcctctca acccaaggaa atgattataa agtgggagcc tttgaaatcc atggagcaga 2460 atggaccagg cctagagtac agagtgacct ggaagccaca gggagcccca gtggagtggg 2520 591 aagaagaaac atgatgtcaa ctctctattc taaacagtac gtctgaaagg atcccaaaga ccttagatgc gtcctgaaag ttctaaaggt aattaaatgg agattggaga caaacctgaa gtggaaaacc agatatcagg ctgaacatat atgtaattga gctggtttat gctttgtgaa cagacccaga aaaagcctct ctgacagctt ttattggtgc cagcaacttt ccaaccttcc gctggccgaa tttcttcaaa ggtgctcaaa aaagtcccca gatgttgcta ggcttggtga tgtaaaaagg tattatttaa tcctatttgc gaattttttt ttttttttct gagaacaggc tcatttctaa atatttcatg tgttttattt ttagtaagat ctgaagactt caaaataaaa ttattgttga cctacacata cgatattctc gctccagtcc atacatgtcg cgaaatactt attattggta agaccaaaat gtccttttga aaactgtaat ggaaggcagt ctcgagctcc gttttgattt cgttcgagct gtttttaaag cctttaagtc ccctttagct tatggatatg tcaatactat ccctgatttt agtcacaaac cacacattgc gggtgatgac gcctgctgtc tatgcccctt ggtccaggct atcaatcaac taggatctgg gcctgaccct cagtcagtga tggagaagac tatcctgata cagctccagt gatccatggg gtggacgtta attagttaaa gttacctggt caacagttcc aaaggacaga gtacatggac ctatcagata aattggtgga aaacaaaaag tctgttggat ggaagaacac agtgaacatt ctaagatttt caggacaaag aaactctgga atggttcctt ctttagtgaa tttcatttaa cagtcttagc ctataactct aaaggagctg tgagccttat atatttcaaa caccagaagg agtacctgaa cagccaactt catcaaagtt gataaagaca ctgccacttt atcttgggga ctacctaaga aaacttaact ggctatcttt tgcaatatca gataataaat gacacctacg attaaatgat attaacatta caactccatc aaagcccagc tggcacctct tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct gatcacggag gaaagctcca ccttaggaga agggagtaaa ggtatcggga agtaaatctt actcaaaaga ctcacccaat agaggtattt gagccgggag agttcgccta atgactaaga attggggcga taacgatagc atttttcaag gacaagaggg agagaatatg ctggtttata tgatgacatc tccactcaag tggactgatg tgtgcgattg ctcttctcac actactatta ttaactgttt gaggaataga ggtggaaagt actcagttaa agaaaaggaa gatttgcatc aattcagtca gtaaaagatg aaacctttgg tgaatacagt gacagtgatg caaaggaagc cttcggtccc ttaataggga tatgcagcct actgaaagtg agtcgaatac ggagagggag accatggtct cttcagtgaa gatggatcat ctacgctgga tctaaggaga agggatctgt tgaaagcaat ggaagttcta tccccttcgg gcataaacac aacatatgta agcaacgcta ctggttcacc atatttatct gttcaaagga gcaagaactt tcatatagga atagaaacat gatttcatcc agaagtcaac atcctgcaat tatgttgaaa agagtagtac atataaaatg ccaagcactt caggcctatg ttttgcttat attgttttca atgcaaaaca caaaacaaat cctgcattta gatacacctc aactaaatcc ttcagtatat tccatatttg cctgatttta ctattcggtg tgtttgcata cttggtgggt ttttctccgt atgcacattg gtatacagtc tctgagaact ctttgcttca ctacaggtta aaagaccata agcaaactgg ttatttaaaa aatatgaaag tcttattaaa acacttcatt gaaaatatac agtctaaatt attttactag caaaagtctt aggtgaacaa tcaactagta tttgttgagc ccagagatgg tcatatttaa acagaagtat acgtttttca gtttcaacat atttctgtca gttatgacat ccacgagcat cactttttgt gtctgttttt tggactaaat tcaactgcat ggaagcggtg gtcagaaggt tgttttatac agaaagtgcc cattgttcag gattctaata gctacatcta cttaatatct attgactgct tttacctttt tctcatgttt atataatggt atgcttgcat aatacattgt acatattatg ttaatattta cacaatttaa aatatagatg tgaagtgaga aaatgaacat taacaggcat gtttgtacag ctagaatata actgtttttc gtcattccag agctacaact aataacacga ggttccaaag tgtataaagt atttgggttt tgttcttgta ttgctttctt tcaacagttt tatcatacaa atattgaggg aaatgttttc atatttttca aaataggttt atgtacatct accccagccc ctcaaaagaa aaactgttta catagaaatt cgtttgcgta tatgttattt taaacatctt tgtggtgaga attttttccc cttctgtcaa agtcagaaca aattcaggga atttattttc tggcagttgt ttttaaaatt gtacatgaac atgttttaga aacaatatgg aggatgatgc gtcaagttca gcgctcgaca ttttatggaa agattttttt aaccttacca aactactgtt taagtgaatt gacttatttc actttagttt ttgaactgtg tactgttata tcctcaactt ggatttatgg taaccccttt tagttcatgg ttggggtatt tataatagtc agcgcaggaa tgcacatgga atatctactt acctcacgag tcatccagaa tgtatagaca ggaaaagcat gtcttattta ttatgggctc aggatctgac cgcagtcccg ggagtaagca tttcaaaggg gtggtcccta ccctgtgtga atgtgaggat gtagacatcc atcagtgcaa atcctcctcc gatttctaag gctccagttt tctggaggga cagtcatcat atctgggaga aaactgtggt gcacagcttg tgaggagggc aaggttgtga tagttctggt gttattctgt ctcctcttct ttgtcatcag ccaaaacgtg agagtcatgc aggttagaaa taatgtcaaa aatatttagg aatttaataa agaaactaaa acaaatactg aaatattagc tcttcctaca cttcgtgttc gcctgaaaat caagattgct cctactcaga tcttctgagt ggctaaaact aaaaatgaga ttgaatgatg actatgcttt gctatcattg ttacctttcc ttggcaacta ctgggactct tcagcacaaa aggaatagat ctatgattga aattgtgaaa ttatatgatt catatatttt atgaatcaga ataaccttca 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 592 aataaaataa atctaagtcg gttaaaatgg atttcatgat tttccctcag aaaatgagta 6300 acggagtcca cggcgtgcaa tggtaattat aaattggtga tgcttgtttg caaattgccc 6360 actcgtgata agtcaacagc caatatttaa aactttgttc gttactggct ttaccctaac 6420 tttctctagt ctactgtcaa tatcatttta atgtaattga ttgtatatag tctcaagaat 6480 ggttggtggg catgagttcc tagagaactg tccaagggtt gggaaaatcc aaattctctt 6540 cctggctcca gcactgattt tgtacataaa cattaggcag gttgcttaac ctttttattt 6600 caaactctct caactctaaa qtqctaataa taatctcagt taccttatct ttqtcacaqq 6660 gtgttctttt ttatgaagaa aaatttgaaa atgataaaag ctaagatgcc ttctaacttc 6720 ataagcaaac ctttaactaa ttatgtatct gaaagtcacc cccacatacc aactcaactt 6780 ttttcctgtg aacacataaa tatattttta tagaaaaaca aatctacata aaataaatct 6840 actgtttagt gagcagtatg acttgtacat gccattgaaa attattaatc agaagaaaat 6900 taagcagggt ctttgctata caaaagtgtt ttccactaat tttgcatgcg tatttataag 6960 aaaaatgtga atttggtggt tttattctat cggtataaag gcatcgatat tttagatgca 7020 cccgtgtttg taaaaatgta gagcacaatg gaattatgct ggaagtctca aataatattt 7080 ttttcctatt ttatactcat ggaagagata agctaaagag gggacaataa tgagaaatgt 7140 tggtgtgctt ttctaagcat ttaaaacata attgccaatt gaaaccctaa atatgtttac 7200 ataccattaa gatatgattc atgtaacaat gttaaattaa ttataatggg attgggtttg 7260 ttatctgtgg tagtatatat cctagtgttc ctatagtgaa ataagtaggg ttcagccaaa 7320 gctttctttg ttttgtacct taaattgttc gattacgtca tcaaaagaga tgaaaggtat 7380 gtagaacagg ttcacgtgat tacctttttc ttttggcttg gattaatatt catagtagaa 7440 ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt atgcttatga ctatgtatgg 7500 tttgaaaata ttttcattat acatgaaatt caactttcca aataaaagtt ctacttcatg 7560 taatccaaaa 7570 <210> 194 <211> 7650

<212> DNA <213> Homo sapians <400> 194 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcaggtg ctgtaaactg caaaccataa 120 tcctgtctta atactgcaaa caaatcatag tggaactaag gggaacttaa tttactgttt 180 ccaggttaac taaggtctca gctgtaaacc aaaagtgaga ggagacatta agattttcat 240 tcttaccggg ttgtcttctt cctgaagagc aatggagccg cttttacttg gaagaggact 300 aatcgtatat ctaatgttcc tcctgttaaa attctcaaaa gcaattgaaa taccatcttc 360 agttcaacag gttccaacaa tcataaaaca gtcaaaagtc caagttgcct ttcccttcga 420 tgagtatttt caaattgaat gtgaagctaa aggaaatcca gaaccaacat tttcgtggac 480 taaggatggc aacccttttt atttcactga ccatcggata attccatcga acaattcagg 540 aacattcagg atcccaaacg aggggcacat atctcacttt caagggaaat accgctgctt 600 tgcttcaaat aaactgggaa tcgctatgtc agaagaaata gaatttatag ttccaagtgt 660 tccaaaactc ccaaaagaaa aaattgaccc tcttgaagtg gaggagggag atccaattgt 720 cctcccatgc aatcctccca aaggcctccc acctttacac atttattgga tgaatattga 780 attagaacac atcgaacaag atgaaagagt atacatgagc caaaagggag atctatactt 840 cgcaaacgtg gaagaaaagg acagtcgcaa tgactactgt tgctttgctg catttccaag 900 attaaggact attgtacaga aaatgccaat gaaactaaca gttaacagtt taaagcatgc 960 taatgactca agttcatcca cagaaattgg ttccaaggca aattccatca agcaaagaaa 1020 acccaaactg ctgttgcctc ccactgagag tggcagtgag tcttcaatta ccatcctcaa 1080 aggggaaatc ttgctgcttg agtgttttgc tgaaggcttg ccaactccac aggttgattg 1140 gaacaaaatt ggtggtgact taccaaaggg gagagaaaca aaagaaaatt atggcaagac 1200 tttgaagata gagaatgtct cctaccagga caaaggaaat tatcgctgca cagccagcaa 1260 tttcttggga acagccactc acgattttca cgttatagta gaagagcctc ctcgctggac 1320 aaagaagcct cagagtgctg tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc 1380 tgaaggagaa cctcaaccca caatcaagtg gagagtcaat ggctccccag ttgacaatca 1440 tccatttgct ggtgatgttg tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa 1500 tcatactgct gtgtaccagt gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc 1560 caatattgat gttgtggatg tccgtccatt gatacaaacc aaagatggag aaaattacgc 1620 tacagtggtt gggtacagtg ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt 1680 cgtgtcctgg cagaaggtgg aagaagtgaa acccctggag ggcaggcggt atcatatcta 1740 tgaaaatggc acattgcaga tcaacagaac caccgaagaa gatgctgggt cttactcatg 1800 593 ttgggtagaa tacaaaactt acattgtgaa agatggagaa taatttgacc tactgctcta accagaaaac tggagctgac agagcctgga acctttggct aagtcagcct tccacaaaac tttgaaatcc gggagcccca -gcctgctgtc gcctgaccct gatccatggg aaaggacaga tctgttggat aaactctgga ctataactct agtacctgaa atcttgggga gataataaat aaagcccagc ggcttgcact agggagtaaa agaggtattt taacgatagc tgatgacatc actactatta agaaaaggaa tgaatacagt tatgcagcct cttcagtgaa tgaaagcaat agcaacgcta tcatatagga tatgttgaaa ttttgcttat gatacacctc ctattcggtg gtatacagtc agcaaactgg gaaaatatac tcaactagta acgtttttca cactttttgt gtcagaaggt gctacatcta atataatggt cacaatttaa gtttgtacag aataacacga ttgctttctt atatttttca aaactgttta tgtggtgaga atttattttc aacaatatgg agattttttt actttagttt aatgctatag agagtttctc agcaaatgtg gcctttgaaa atatctaatg gacagtgctg cttcacttgt cacaacagca aggtgggagg ccatttgtga agccagccgt ataagggttc atggagcaga gtggagtggg tatgcccctt cagtcagtga gtggacgtta gtacatggac ggaagaacac atggttcctt aaaggagctg cagccaactt ctacctaaga gacacctacg tggcacctct tcacagggct ggtatcggga gagccgggag atttttcaag tccactcaag ttaactgttt gatttgcatc gacagtgatg actgaaagtg gatggatcat ggaagttcta ctggttcacc atagaaacat agagtagtac attgttttca aactaaatcc tgtttgcata tctgagaact ttatttaaaa agtctaaatt tttgttgagc gtttcaacat gtctgttttt tgttttatac cttaatatct atgcttgcat aatatagatg ctagaatata ggttccaaag tcaacagttt aaataggttt catagaaatt attttttccc tggcagttgt aggatgatgc aaccttacca ttgaactgtg gaaaaactgc ctaagaatcc actcacattt ttaatggcac taactttaga ccgatataac ctgaaagaca atattagcga aactgaccag gataccagtt cagaccatca aagcctctca atggaccagg aagaagaaac atgatgtcaa ctctctattc taaacagtac gtctgaaagg atcccaaaga ccttagatgc gtcctgaaag ttctaaaggt aattaaatgg agattggaga caaacctgaa gtggaaaacc agatatcagg ctgaacatat atgtaattga gctggtttat gctttgtgaa cagacccaga aaaagcctct ctgacagctt ttattggtgc cagcaacttt ccaaccttcc gctggccgaa tttcttcaaa ggtgctcaaa aaagtcccca gatgttgcta ggcttggtga tgtaaaaagg tattatttaa tcctatttgc gaattttttt ttttttttct gagaacaggc tcatttctaa atatttcatg tgttttattt ttagtaagat ctgaagactt caaaataaaa ttattgttga cctacacata cgatattctc gctccagtcc atacatgtcg cgaaatactt attattggta agtcacagcc tcgtatcccc gaaacacagt agaagatggc ggaccaaggt tcaagtaact gaacaggagt gtatattgtt agtccaagga cagggtcata tgaaacacca acccaaggaa cctagagtac agtcacaaac ggtccaggct tggagaagac attagttaaa ctatcagata agtgaacatt ctttagtgaa tgagccttat catcaaagtt aaacttaact attaaatgat tgcaactacc gatcacggag agtaaatctt agttcgccta gacaagaggg tggactgatg gaggaataga aattcagtca caaaggaagc agtcgaatac ctacgctgga tccccttcgg atatttatct gatttcatcc atataaaatg atgcaaaaca ttcagtatat cttggtgggt ctttgcttca aatatgaaag attttactag ccagagatgg atttctgtca tggactaaat agaaagtgcc attgactgct aatacattgt tgaagtgaga actgtttttc tgtataaagt tatcatacaa atgtacatct cgtttgcgta cttctgtcaa ttttaaaatt gtcaagttca aactactgtt tactgttata aatttggata aaattgcata ttgaagttgt aggataatta atttactgct gttcttgatg gttcggctga gaatttgaag aagaaaacca gccgtgaacg ccagcagctc atgattataa agagtgacct cacacattgc atcaatcaac tatcctgata gttacctggt aattggtgga ctaagatttt tttcatttaa atatttcaaa gataaagaca ggctatcttt attaacatta aagtacaaat gaaagctcca actcaaaaga atgactaaga agagaatatg tgtgcgattg ggtggaaagt gtaaaagatg cttcggtccc ggagagggag tctaaggaga gcataaacac gttcaaagga agaagtcaac ccaagcactt caaaacaaat tccatatttg ttttctccgt ctacaggtta tcttattaaa caaaagtctt tcatatttaa gttatgacat tcaactgcat cattgttcag tttacctttt acatattatg aaatgaacat gtcattccag atttgggttt atattgaggg accccagccc tatgttattt agtcagaaca gtacatgaac gcgctcgaca taagtgaatt tcctcaactt ttagaaatgc tgcttgaatt cctggagtaa ttgatggagc gttcagctca ttccggatcc cctgggaagc gaaacaaaga cagttatctt aagtagggag cagataggaa agtgggagcc ggaagccaca gggtgatgac taggatctgg cagctccagt caacagttcc aaacaaaaag caggacaaag cagtcttagc caccagaagg ctgccacttt tgcaatatca caactccatc tctacttgag ccttaggaga ctcacccaat attggggcga ctggtttata ctcttctcac actcagttaa aaacctttgg ttaataggga accatggtct agggatctgt aacatatgta gcaagaactt atcctgcaat caggcctatg cctgcattta cctgatttta atgcacattg aaagaccata acacttcatt aggtgaacaa acagaagtat ccacgagcat ggaagcggtg gattctaata tctcatgttt ttaatattta taacaggcat agctacaact tgttcttgta aaatgttttc ctcaaaagaa taaacatctt aattcaggga atgttttaga ttttatggaa gacttatttc ggatttatgg 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 594 taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa 5580 tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca 5640 ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg 5700 ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat 5760 gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt 5820 tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg 5880 tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct 5940 ttytcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa 6000 aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc 6060 tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga 6120 tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt 6180 gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa 6240 aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt 6300 atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat 6360 tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga 6420 tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc 6480 gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga 6540 ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt 6600 gggaaaatcc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag 6660 gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt 6720 taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag 6780 ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc 6840 cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca 6900 aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa 6960 attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat 7020 tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag 7080 gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct 7140 ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag 7200 gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt 7260 gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa 7320 ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa 7380 ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca 7440 tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg 7500 gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt 7560 atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca 7620 aataaaagtt ctacttcatg taatccaaaa 7650 <210> 195 <211> 7570

<212> DNA <213> Homo sapians <400> 195 cggaccctgc gcgcccccgt cccggctccc ggccggctcg ggggagaagg cgcccgaggg 60 gaggcgccgg acagatcgcg tttcggaggc ggcgcagttt ccaggttaac taaggtctca 120 gctgtaaacc aaaagtgaga ggagacatta agattttcat tcttaccggg ttgtcttctt 180 cctgaagagc aatggagccg cttttacttg gaagaggact aatcgtatat ctaatgttcc 240 tcctgttaaa attctcaaaa gcaattgaaa taccatcttc agttcaacag gttccaacaa 300 tcataaaaca gtcaaaagtc caagttgcct ttcccttcga tgagtatttt caaattgaat 360 gtgaagctaa aggaaatcca gaaccaacat tttcgtggac taaggatggc aacccttttt 420 atttcactga ccatcggata attccatcga acaattcagg aacattcagg atcccaaacg 480 aggggcacat atctcacttt caagggaaat accgctgctt tgcttcaaat aaactgggaa 540 tcgctatgtc agaagaaata gaatttatag ttccaagtgt tccaaaactc ccaaaagaaa 600 aaattgaccc tcttgaagtg gaggagggag atccaattgt cctcccatgc aatcctccca 660 aaggcctccc acctttacac atttattgga tgaatattga attagaacac atcgaacaag 720 atgaaagagt atacatgagc caaaagggag atctatactt cgcaaacgtg gaagaaaagg 780 acagtcgcaa tgactactgt tgctttgctg catttccaag attaaggact attgtacaga 840 aaatgccaat gaaactaaca gttaacagtt taaagcatgc taatgactca agttcatcca 900 cagaaattgg ttccaaggca aattccatca agcaaagaaa acccaaactg ctgttgcctc 960 ccactgagag tggcagtgag tcttcaatta ccatcctcaa aggggaaatc ttgctgcttg 1020 595 agtgttttgc tgaaggcttg ccaactccac aggttgattg gaacaaaatt ggtggtgact 1080 taccaaaggg gagagaaaca aaagaaaatt atggcaagac tttgaagata gagaatgtct 1140 cctaccagga caaaggaaat tatcgctgca cagccagcaa tttcttggga acagccactc 1200 acgattttca cgttatagta gaagagcctc ctcgctggac aaagaagcct cagagtgctg 1260 tgtatagcac cggaagcaat ggcatcttgt tatgtgaggc tgaaggagaa cctcaaccca 1320 caatcaagtg gagagtcaat ggctccccag ttgacaatca tccatttgct ggtgatgttg 1380 tcttccccag ggaaatcagt tttaccaacc ttcaaccaaa tcatactgct gtgtaccagt 1440 gtgaagcctc aaatgtccat ggaactatcc ttgccaatgc caatattgat gttgtggatg 1500 tccgtccatt gatacaaacc aaagatggag aaaattacgc tacagtggtt gggtacagtg 1560 ctttcttaca ttgcgagttc tttgcttcac ctgaggcagt cgtgtcctgg cagaaggtgg 1620 aagaagtgaa acccctggag ggcaggcggt atcatatcta tgaaaatggc acattgcaga 1680 tcaacagaac caccgaagaa gatgctgggt cttactcatg ttgggtagaa aatgctatag 1740 gaaaaactgc agtcacagcc aatttggata ttagaaatgc tacaaaactt agagtttctc 1800 ctaagaatcc tcgtatcccc aaattgcata tgcttgaatt acattgtgaa agcaaatgtg 1860 actcacattt gaaacacagt ttgaagttgt cctggagtaa agatggagaa gcctttgaaa 1920 ttaatggcac agaagatggc aggataatta ttgatggagc taatttgacc atatctaatg 1980 taactttaga ggaccaaggt atttactgct gttcagctca tactgctcta gacagtgctg 2040 ccgatataac tcaagtaact gttcttgatg ttccggatcc accagaaaac cttcacttgt 2100 ctgaaagaca gaacaggagt gttcggctga cctgggaagc tggagctgac cacaacagca 2160 atattagcga gtatattgtt gaatttgaag gaaacaaaga agagcctgga aggtgggagg 2220 aactgaccag agtccaagga aagaaaacca cagttatctt acctttggct ccatttgtga 2280 gataccagtt cagggtcata gccgtgaacg aagtagggag aagtcagcct agccagccgt 2340 cagaccatca tgaaacacca ccagcagctc cagataggaa tccacaaaac ataagggttc 2400 aagcctctca acccaaggaa atgattataa agtgggagcc tttgaaatcc atggagcaga 2460 atggaccagg cctagagtac agagtgacct ggaagccaca gggagcccca gtggagtggg 2520 aagaagaaac agtcacaaac cacacattgc gggtgatgac gcctgctgtc tatgcccctt 2580 atgatgtcaa ggtccaggct atcaatcaac taggatctgg gcctgaccct cagtcagtga 2640 ctctctattc tggagaagac tatcctgata cagctccagt gatccatggg gtggacgtta 2700 taaacagtac attagttaaa gttacctggt caacagttcc aaaggacaga gtacatggac 2760 gtctgaaagg ctatcagata aattggtgga aaacaaaaag tctgttggat ggaagaacac 2820 atcccaaaga agtgaacatt ctaagatttt caggacaaag aaactctgga atggttcctt 2880 ccttagatgc ctttagtgaa tttcatttaa cagtcttagc ctataactct aaaggagctg 2940 gtcctgaaag tgagccttat atatttcaaa caccagaagg agtacctgaa cagccaactt 3000 ttctaaaggt catcaaagtt gataaagaca ctgccacttt atcttgggga ctacctaaga 3060 aattaaatgg aaacttaact ggctatcttt tgcaatatca gataataaat gacacctacg 3120 agattggaga attaaatgat attaacatta caactccatc aaagcccagc tggcacctct 3180 caaacctgaa tgcaactacc aagtacaaat tctacttgag ggcttgcact tcacagggct 3240 gtggaaaacc gatcacggag gaaagctcca ccttaggaga agggagtaaa ggtatcggga 3300 agatatcagg agtaaatctt actcaaaaga ctcacccaat agaggtattt gagccgggag 3360 ctgaacatat agttcgccta atgactaaga attggggcga taacgatagc atttttcaag 3420 atgtaattga gacaagaggg agagaatatg ctggtttata tgatgacatc tccactcaag 3480 gctggtttat tggactgatg tgtgcgattg ctcttctcac actactatta ttaactgttt 3540 gctttgtgaa gaggaataga ggtggaaagt actcagttaa agaaaaggaa gatttgcatc 3600 cagacccaga aattcagtca gtaaaagatg aaacctttgg tgaatacagt gacagtgatg 3660 aaaagcctct caaaggaagc cttcggtccc ttaataggga tatgcagcct actgaaagtg 3720 ctgacagctt agtcgaatac ggagagggag accatggtct cttcagtgaa gatggatcat 3780 ttattggtgc ctacgctgga tctaaggaga agggatctgt tgaaagcaat ggaagttcta 3840 cagcaacttt tccccttcgg gcataaacac aacatatgta agcaacgcta ctggttcacc 3900 ccaaccttcc atatttatct gttcaaagga gcaagaactt tcatatagga atagaaacat 3960 gctggccgaa gatttcatcc agaagtcaac atcctgcaat tatgttgaaa agagtagtac 4020 tttcttcaaa atataaaatg ccaagcactt caggcctatg ttttgcttat attgttttca 4080 ggtgctcaaa atgcaaaaca caaaacaaat cctgcattta gatacacctc aactaaatcc 4140 aaagtcccca ttcagtatat tccatatttg cctgatttta ctattcggtg tgtttgcata 4200 gatgttgcta cttggtgggt ttttctccgt atgcacattg gtatacagtc tctgagaact 4260 ggcttggtga ctttgcttca ctacaggtta aaagaccata agcaaactgg ttatttaaaa 4320 tgtaaaaagg aatatgaaag tcttattaaa acacttcatt gaaaatatac agtctaaatt 4380 tattatttaa attttactag caaaagtctt aggtgaacaa tcaactagta tttgttgagc 4440 tcctatttgc ccagagatgg tcatatttaa acagaagtat acgtttttca gtttcaacat 4500 gaattttttt atttctgtca gttatgacat ccacgagcat cactttttgt gtctgttttt 4560 ttttttttct tggactaaat tcaactgcat ggaagcggtg gtcagaaggt tgttttatac 4620 gagaacaggc agaaagtgcc cattgttcag gattctaata gctacatcta cttaatatct 4680 tcatttctaa attgactgct tttacctttt tctcatgttt atataatggt atgcttgcat 4740 596 atatttcatg aatacattgt acatattatg ttaatattta cacaatttaa aatatagatg tgttttattt tgaagtgaga aaatgaacat taacaggcat gtttgtacag ctagaatata ttagtaagat actgtttttc gtcattccag agctacaact aataacacga ggttccaaag ctgaagactt tgtataaagt atttgggttt tgttcttgta ttgctttctt tcaacagttt caaaataaaa tatcatacaa atattgaggg aaatgttttc atatttttca aaataggttt ttattgttga atgtacatct accccagccc ctcaaaagaa aaactgttta catagaaatt cctacacata cgtttgcgta tatgttattt taaacatctt tgtggtgaga attttttccc cgatattctc cttctgtcaa agtcagaaca aattcaggga atttattttc tggcagttgt gctccagtcc ttttaaaatt gtacatgaac atgttttaga aacaatatgg aggatgatgc atacatgtcg gtcaagttca gcgctcgaca ttttatggaa agattttttt aaccttacca cgaaatactt aactactgtt taagtgaatt gacttatttc actttagttt ttgaactgtg attattggta tactgttata tcctcaactt ggatttatgg taaccccttt tagttcatgg agaccaaaat ttggggtatt tataatagtc agcgcaggaa tgcacatgga atatctactt gtccttttga acctcacgag tcatccagaa tgtatagaca ggaaaagcat gtcttattta aaactgtaat ttatgggctc aggatctgac cgcagtcccg ggagtaagca tttcaaaggg ggaaggcagt gtggtcccta ccctgtgtga atgtgaggat gtagacatcc atcagtgcaa ctcgagctcc atcctcctcc gatttctaag gctccagttt tctggaggga cagtcatcat gttttgattt atctgggaga aaactgtggt gcacagcttg tgaggagggc aaggttgtga cgttcgagct tagttctggt gttattctgt ctcctcttct ttgtcatcag ccaaaacgtg gtttttaaag agagtcatgc aggttagaaa taatgtcaaa aatatttagg aatttaataa cctttaagtc agaaactaaa acaaatactg aaatattagc tcttcctaca cttcgtgttc ccctttagct gcctgaaaat caagattgct cctactcaga tcttctgagt ggctaaaact tatggatatg aaaaatgaga ttgaatgatg actatgcttt gctatcattg ttacctttcc tcaatactat ttggcaacta ctgggactct tcagcacaaa aggaatagat ctatgattga ccctgatttt aattgtgaaa ttatatgatt catatatttt atgaatcaga ataaccttca aataaaataa atctaagtcg gttaaaatgg atttcatgat tttccctcag aaaatgagta acggagtcca cggcgtgcaa tggtaattat aaattggtga tgcttgtttg caaattgccc actcgtgata agtcaacagc caatatttaa aactttgttc gttactggct ttaccctaac tttctctagt ctactgtcaa tatcatttta atgtaattga ttgtatatag tctcaagaat ggttggtggg catgagttcc tagagaactg tccaagggtt gggaaaatcc aaattctctt cctggctcca gcactgattt tgtacataaa cattaggcag gttgcttaac ctttttattt caaactctct caactctaaa gtgctaataa taatctcagt taccttatct ttgtcacagg gtgttctttt ttatgaagaa aaatttgaaa atgataaaag ctaagatgcc ttctaacttc ataagcaaac ctttaactaa ttatgtatct gaaagtcacc cccacatacc aactcaactt ttttcctgtg aacacataaa tatattttta tagaaaaaca aatctacata aaataaatct actgtttagt gagcagtatg acttgtacat gccattgaaa attattaatc agaagaaaat taagcagggt ctttgctata caaaagtgtt ttccactaat tttgcatgcg tatttataag aaaaatgtga atttggtggt tttattctat cggtataaag gcatcgatat tttagatgca cccgtgtttg taaaaatgta gagcacaatg gaattatgct ggaagtctca aataatattt ttttcctatt ttatactcat ggaagagata agctaaagag gggacaataa tgagaaatgt tggtgtgctt ttctaagcat ttaaaacata attgccaatt gaaaccctaa atatgtttac ataccattaa gatatgattc atgtaacaat gttaaattaa ttataatggg attgggtttg ttatctgtgg tagtatatat cctagtgttc ctatagtgaa ataagtaggg ttcagccaaa gctttctttg ttttgtacct taaattgttc gattacgtca tcaaaagaga tgaaaggtat gtagaacagg ttcacgtgat tacctttttc ttttggcttg gattaatatt catagtagaa ctttataaaa cgtgtttgta ttgtaggtgg tgtttgtatt atgcttatga ctatgtatgg tttgaaaata ttttcattat acatgaaatt caactttcca aataaaagtt ctacttcatg taatccaaaa 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 7260 7320 7380 7440 7500 7560 7570 <210> 196 <211> 1224

<212> PRT <213> Homo sapians <400> 196

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 597 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser As n Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He AT a Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu dy Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 3 2 5 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His cys Glu Phe Phe 450 /ICC 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg lie Pro Lys 598 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr cys cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Al a Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 6 85 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val lie Al a 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Al a Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn Hrs 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Al a He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 82 0 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Giy Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala ciy Pro Glu Ser Glu Pro Tyr lie Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 Q K A J V 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He lie Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys II© Ser Gly 599 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser lie Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 , 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 , 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 197 <211> 1224 xT τ nam "" z. x z. c xx x <213> Homo sapians <400> 197

Met 1 Glu Pro Leu Leu 5 Leu Gly Arg Gly Leu 10 He Val Tyr Leu Met 15 Phe Leu Leu Leu Lys Phe Ser Lys Al a He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He I le Lvs Gin Ser Lys Val Gin Val Ala Phe Pro 3 5 40 45 Phe Asp Glu Tyr Phe Gin He Glu cys Glu Al a Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 600 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Giy Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser 1. ti Val Tyr Ser Thr Giy Ser Asn Gly lie Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Giy Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 4 4 5 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 7\ &#906; o Cc-v- nl ,·, 7\ &#906; o Up &#906; Cz^v- ΓΡν-ν-, m „ T χ τ c? Val Glu Glu Val T ve zi j_ Cl L J_ nxu V Cl X v Ci a. kJCJ- \jr ii 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr I le Ser Asn Val Thr Leu Glu Asp Gin Gly Xie Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 6 60 6 6 5 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Giy Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 601 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Al a He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Giy Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Giy Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Giy Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Giy Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val lie Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr ai v --J. Tvr ~ x — Leu Leu Gin Tvr J ·*- Gin He He Asn Thr j-2 j. 965 970 975 Glu lie Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 1005 Leu Arg Al a Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Giy 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 1080 1085 Leu Tyr Asp Asp He Ser Thr Gin Giy Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1Σ 6 5 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Giy 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 602 1220 <210> 198 <211> 1224

<212> PRT <213> Homo sapians <400> 198

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Al a lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe lie Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro lie Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Γ&#906;ν- T IJ -J -1 τ' m»»t- m-χ-—. 7\ -. v. Tl ~ Γ&#906;,Ι T -^11 /-1 1 11 U 4 —1 Π ,1 fly XT X O XJCU 11X0 xxc x y x xxp rxc u nsii X -LC ox u XJC u OX U. 11X0 X X o ο x ix O X Xi 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Al a Asn Asp Ser Ser Ser Ser Thr Glu lie ciy 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu cys 355 360 365 Glu Ala Glu ciy Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 603 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn ciy Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 7\ r-. T 1 x-i Oz-X-V- r* 1 ,, ΓΠττν Tl « &#910;7-» 1 ,-1,, nk /-χ Pl „ 7-1., &#902; c ri Τ ττο ill ,, Glu Pro non xxc kJCl kJ x u. χ x tJ v α. x _L Ci XT UC kJ X U. kJX^ no li -UJ' J kJ X Cl 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 7 2 5 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Giy Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys ciy Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 604 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu lie Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 1000 i 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 108C ι 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 116C I 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1170 1175 1180 Glu Gly Asp His Giy Leu Phe Ser Glu Asp Gly Ser Phe lie Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 199

<211> 1224 <212> PRT <213> Homo sapians <400> 199

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin lie Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He I le Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Giy His He Ser His Phe Gin Gly Lys Tyr Arg cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 605 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr lie Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 2 2 5 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr lie Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu' Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 &#904;) V Gin Cqv 7\ &#906; o Λ7= &#906; mt, -v- r> &#906; 7\ τ T Λ Leu Leu Cys X J- '-Z V ui xy j. DCL X HX. uxy CCl Λ511 foiy X 1C 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Al a Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Giy Thr He Leu Ala Asn Ala Asn Xie 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Al a Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Giy Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg lie lie He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 606 610 615 620 Leu 625 Asp Val Pro Asp Pro Pro Glu Asn 630 Leu His Leu Ser Glu Arg Gin 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu 645 Ala Gly Ala Asp His Asn Ser 650 655 Asn He Ser Glu Tyr He Val Glu Phe 660 665 Glu Gly Asn Lys Glu Glu Pro 67 0 Gly Arg Trp Glu Glu Leu Thr Arg Val 675 680 Gin Gly Lys Lys Thr Thr Val 685 lie Leu 690 Pro Leu Ala Pro Phe Val Arg 695 Tyr Gin Phe Arg Val He Ala 700 Val 705 Asn Glu Val Gly Arg Ser Gin Pro 710 Ser Gin Pro Ser Asp His His 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg 725 Asn Pro Gin Asn He Arg Val 730 735 Gin Ala Ser Gin Pro Lys Glu Met He 740 745 He Lys Trp Glu Pro Leu Lys 750 Ser Met Glu Gin Asn Gly Pro Gly Leu 755 760 Glu Tyr Arg Val Thr Trp Lys 765 Pro Gin 770 Gly Ala Pro Val Glu Trp Glu 775 Glu Glu Thr Val Thr Asn His 780 Thr 785 Leu Arg Val Met Thr Pro Ala Val 790 Tyr Ala Pro Tyr Asp Val Lys 795 800 Val Gin Ala He Asn Gin Leu Gly Ser 805 Gly Pro Asp Pro Gin Ser Val 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro 820 825 Asp Thr Ala Pro Val He His 830 Gly Val Asp Val He Asn Ser Thr Leu 835 840 Val Lys Val Thr Trp Ser Thr 845 Val Pro 850 Lys Asp Arg Val His Gly Arg 855 Leu Lys Gly Tyr Gin He Asn 860 Trp 865 Trp Lys Thr Lys Ser Leu Leu Asp 870 Gly Arg Thr His Pro Lys Glu 875 880 Val Asn He Leu Arg Phe Ser Gly Gin 885 Arg Asn Ser Gly Met Val Pro 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His 900 905 Leu Thr Val Leu Ala Tyr Asn 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu 915 920 Pro Tyr He Phe Gin Thr Pro 925 Glu Gly 930 Val Pro Glu Gin Pro Thr Phe 935 Leu Lys Val He Lys Val Asp 940 Lys 945 Asp Thr Ala Thr Leu Ser Trp Gly 950 Leu Pro Lys Lys Leu Asn Gly 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr 965 Gin He lie Asn Asp Thr Tyr 970 975 Glu He Gly Glu Leu Asn Asp He Asn 980 985 He Thr Thr Pro Ser Lys Pro 990 Ser Trp His Leu Ser Asn Leu Asn Ala 995 1000 Thr Thr Lys Tyr Lys Phe Tyr 1005 Leu Arg 101C Ala Cys Thr Ser Gin Gly Cys ι 1015 Gly Lys Pro He Thr Glu Glu 1020 Ser Ser 1025 Thr Leu Gly Glu Gly Ser Lys 1030 Gly He Gly Lys He Ser Gly 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro 1045 He Glu Val Phe Glu Pro Gly 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr 1075 1080 Arg Gly Arg Glu Tyr Ala Gly 1085 Leu Tyr 109C Asp Asp He Ser Thr Gin Gly ι 1095 Trp Phe He Gly Leu Met Cys 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 607 1105 1110 1115 1120

Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135

Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150

Ser Asp Ser Asp Glu Lys Pro Le-u Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165

Arg Asp Met 1170 Gin Pro Thr Glu 1175 Ser Al a Asp Ser Leu Val 1180 Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 120 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn ciy Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 <210> 200 <211> 1171 <212> PRT <213> Homo sapians <400> 200 Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 τ»Κ λ 71 r~, —. /-’ll. ΓΠ,τ-μ- Τ&#906; K Λ r> 1 Tl 7-1,, Γττη 7-1 ,, 7\ 1 o T 117- r*1 tr Aon Glu me kJ X U χγχ. XT liC kJXli xxc VI J- Ul O VI J- Ul nxu XJ y o Pro 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He lie Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Gly Lys Tyr Arg cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu lie Glu Phe He Val Pro 115 120 125 Ser V a 1 Pro Lys Phe Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn lie Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu lie Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 2 55 Pro Thr Glu Ser ciy Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 2 85 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Giu Ala Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 608 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 3 6 0 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 3 75 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn lie 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 LSU Hxs Met Lsu Glu Lsu Hxs Γ*Χ7«3 "-J Glu Ser T.X7C5 "J Pvcj '-J Δ cjn xr Ssx Hxs Τ·θ&#971; 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 7 2 5 730 735 Gin Ala Ser Gin Pro Lys Glu Met He lie Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 7 5 5 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 7 7 5 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 609 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr 820 Pro Asp Thr Ala Pro Val 825 830 He His Gly Val Asp 835 Val He Asn Ser Thr 840 Leu Val Lys Val Thr Trp 845 Ser Thr Val Pro Lys 850 Asp Arg Val His Gly 855 Arg Leu Lys Gly Tyr Gin 860 He Asn Trp Trp Lys 865 Thr Lys Ser Leu Leu 870 Asp Gly Arg Thr His Pro 875 Lys Glu 880 Val Asn lie Leu Arg Phe Ser Gly 885 Gin Arg Asn Ser Gly Met 890 Val Pro 895 Ser Leu Asp Ala Phe Ser Glu Phe 900 His Leu Thr Val Leu Ala 905 910 Tyr Asn Ser Lys Gly 915 Ala Gly Pro Glu Ser 920 Glu Pro Tyr He Phe Gin 925 Thr Pro Glu Gly Val 930 Pro Glu Gin Pro Thr 935 Phe Leu Lys Val He Lys 940 Val Asp Lys Asp Thr 945 Ala Thr Leu Ser Trp 950 Gly Leu Pro Lys Lys Leu 955 Asn Gly 960 Asn Leu Thr Gly Tyr Leu Leu Gin 965 Tyr Gin He He Asn Asp 970 Thr Tyr 975 Glu He Gly Glu Leu Asn Asp lie 980 Asn He Thr Thr Pro Ser 985 990 Lys Pro Ser Trp His 995 Leu Ser Asn Leu Asn 100C Ala Thr Thr Lys Tyr Lys ) 1005 Phe Tyr Leu Arg Ala 1010 Cys Thr Ser Gin Gly 1015 Cys Gly Lys Pro He Thr 1020 Glu Glu Ser Ser Thr 1025 Leu Gly Glu Gly Lys 1030 Tyr Ala Gly Leu Tyr Asp 1035 Asp He 1040 Ser Thr Gin Gly Trp Phe He Gly 1045 Leu Met Cys Ala He Ala 1050 Leu Le u. 1055 Thr Leu Leu Leu Leu Thr Val Cys 1060 Phe Val Lys Arg Asn Arg Gly Gly 1065 1070 Lys Tyr Ser 1075 Val Lys Glu Lys Glu Asp Leu His Pro Asp Pro > 1080 1085 Glu He Gin Ser Val 1090 Lys Asp Glu Thr Phe 1095 Gly Glu Tyr Ser Asp Ser 1100 Asp Glu Lys Pro Leu 1105 Lys Gly Ser Leu Arg 1110 Ser Leu Asn Arg Asp Met 1115 Gin Pro 1120 Thr Glu Ser Ala Asp Ser Leu Val 1125 Glu Tyr Gly Glu Gly Asp 1130 His Gly 1135 Leu Phe Ser Glu Asp Gly Ser Phe 1140 He Gly Ala Tyr Ala Gly Ser Lys 1145 1150 Glu Lys Gly 1155 Leu Arg Ala 1170 Ser Val Glu Ser Asn Gly Ser Ser Thr Ala Thr > 1160 1165 Phe Pro <210> 201 <211> 893

<212> PRT <213> Homo sapians <400> 201

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He V a 1 Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 610 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyi; Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Ly s Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser lie Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 m-v-v-x &#902; Ο ΤΛ T TTO Tl r> r 1 ,, π,, A c*< Leu Pro τ _ _ — rl,, a rr Glu Thr T.va nop non -LJ_y O _l j_ «j j__y mo XX J, S VJX.J iix y ‘-‘J 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Al a Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Al a Val Tyr Ser Thr Gly Ser Asn Gly Tie Leu Leu cys 355 360 3 6 5 Glu Ala Glu dy Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu 1.χ Asn Ala Asn lie 420 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His lie Tyr Glu Asn Gly Thr Leu Gin 485 490 495 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 611 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 lie Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 610 615 62 0 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 6 4 0 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 __ T TT«. &#906; tut J_ η &#906; m •η &#906; _ m TTx. 1 i nr LibU ναι ivl© L ml rlu ZA-Lct veil -y- rlu iyr- Η&#970;ψ v ax j_iy 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Thr Thr Tyr Val Ser Asn Ala Thr Gly Ser 835 840 845 Pro Gin Pro Ser He Phe He Cys Ser Lys Glu Gin Glu Leu Ser Tyr 850 855 860 Arg Asn Arg Asn Met Leu Ala Glu Asp Phe lie Gin Lys Ser Thr Ser 865 870 875 880 Cys Asn Tyr Val Glu Lys Ser Ser Thr Phe Phe Lys He 885 890 <210> 202

<211> 1117 <212> PRT <213> Homo sapians <400> 202

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Al a Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 612 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys lie Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Giy Ser Glu Ser Ser He Thr He Leu Lys Giy Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu m. kjxy Thr Ala ml, -v, X 11X 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu lie Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Giy Thr He Leu Ala Asn Ala As n He 420 425 430 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 460 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp lie Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 535 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg lie He He Asp Gly Ala Asn Leu 613 580 585 590 Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Al a Asp He Thr Gin Val Thr Val 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala ciy Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 6 9 0 6 95 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn lie Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr T,©U Tvr m ,7 Glu Δ c r> Lsu jvr, Ol 1-1 m vi Om ΦΗ r PhS T <=11 Tire - j - — —jr J- J- XU -I- Vi XU J_ ii V XU J. ii J_ XJC IA iUJ 820 825 830 Val I Τ Θ Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro 835 840 845 Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Glri He 850 855 860 He Asn Asp Thr Tyr Glu lie Gly Glu Leu Asn Asp He Asn He Thr 865 870 875 880 Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr 885 890 895 Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly cys Gly Lys 900 905 910 Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He 915 920 925 Gly Lys He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro He Glu 930 935 940 Val Phe Glu Pro Gly Ala Glu His He Val Arg Leu Met Thr Lys Asn 945 950 955 960 Trp Gly Asp Asn Asp Ser He Phe Gin Asp Val lie Glu Thr Arg Gly 965 970 975 Arg Glu Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe 980 985 990 He Gly Leu Met Cys Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr 995 1000 1005 Val Cys Phe Val Lys Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu 1010 1015 1020 Lys Glu Asp Leu His Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu 1025 1030 1035 1040 Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser 1045 1050 1055 Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser 1060 1065 1070 Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly 614 1075 1080 1085

Ser Phe lie Gly Ala Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu 1090 1095 1100

Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1105 1110 1115 <210> 203

<211> 1208 <212> PRT <213> Homo sapians <400> 203

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro lie Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Ser Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 225 2 3 0 2 3 5 240 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr lie Leu Lys Gly Glu 245 250 255 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 260 265 270 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 275 280 285 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 290 295 300 Lys Gly Asn Tyr Arg cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 305 310 315 320 His Asp Phe His Val lie Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 325 330 335 Pro Gin Ser Al a Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu Cys 340 345 350 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 355 360 365 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 370 375 380 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 615 385 390 395 400 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 405 410 415 Asp Val Val Asp Val Arg Pro Leu lie Gin Thr Lys Asp Gly Glu Asn 420 425 430 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 435 440 445 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 450 455 460 Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin 465 470 475 480 lie Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 485 490 495 Glu Asn Ala lie Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 500 505 510 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 515 520 525 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 530 535 540 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 545 550 555 560 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 565 570 575 Thr lie Ser Asn Val Thr Leu Glu Asp Gin Giy He Tyr Cys Cys Ser 580 585 590 Ala His Thr Ala Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val 595 600 605 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 610 615 620 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 625 630 635 640 Asn lie Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 645 650 655 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 660 665 670 He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 675 680 685 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin- Pro Ser Asp His His 690 695 700 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 705 710 715 720 Gin Ala Ser Gin Pro Lys Glu Met lie He Lys Trp Glu Pro Leu Lys 725 730 735 Ser Met Glu Gin Asn Giy Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 740 745 750 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 755 760 765 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 770 775 780 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 785 790 795 800 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 805 810 815 Gly Val Asp Val lie Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 820 825 830 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin lie Asn 835 840 845 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 850 855 860 Val Asn lie Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 865 870 875 880 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 616 885 890 895 Ser Lys Giy Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 900 905 910 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 915 920 925 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 930 935 940 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 945 950 955 960 Glu lie Gly Glu Leu Asn Asp lie Asn He Thr Thr Pro Ser Lys Pro 965 970 975 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 980 985 990 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro lie Thr Glu Glu 995 1000 1005 Ser Ser Thr Leu c-ly Glu Gly Ser Lys Gly lie Gly Lys He Ser Gly 1010 1015 1020 Val Asn Leu Thr Gin Lys Thr His Pro lie Glu Val Phe Glu Pro Gly 1025 1030 1035 1040 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Giy Asp Asn Asp 1045 1050 1055 Ser He Phe Gin Asp Val He Glu Thr Arg Giy Arg Glu Tyr Ala Gly 1060 1065 1070 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe He Gly Leu Met Cys 1075 1080 1085 Ala lie Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 1090 1095 1100 Arg Asn Arg Gly Giy Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1105 1110 1115 1120 Pro Asp Pro Glu He Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1125 1130 1135 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1140 1145 1150 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr Gly 1155 1160 1165 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1170 1175 1180 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1185 1190 1195 1200 Thr Ala Thr Phe Pro Leu Arg Ala 1205 <210> 204

<211> 1183 <212> PRT <213> Homo sapians <400> 204

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu lie Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 617 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser lie Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Giy Gly Asp Leu 245 250 255 Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Glu 290 295 300 Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala Val Tyr Ser Thr Gly 305 310 315 320 Ser Asn Gly He Leu Leu Cys Glu Ala Glu Giy Glu Pro Gin Pro Thr 325 330 335 He Lys Trp Arg T T - &#906; V di Asn Gly Ser Pro Val Asp Asn Hi.s Pro Til·, ~ xriic; A &#906; -rix a 340 345 350 Gly Asp Val Val Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro 355 360 365 Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr 370 375 380 He Leu Ala Asn Ala Asn He Asp Val Val Asp Val Arg Pro Leu He 385 390 395 400 Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Al a 405 410 415 Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp 420 425 430 Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His lie 435 440 445 Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala 450 455 460 Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He Gly Lys Thr Ala Val 465 470 475 480 Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val Ser Pro 485 490 495 Lys Asn Pro Arg He Pro Lys Leu His Met Leu Glu Leu His Cys Glu 500 505 510 Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser 515 520 525 Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp θ&#943;γ Arg He 530 535 540 He He Asp Gly Ala Asn Leu Thr I le Ser Asn Val Thr Leu Glu Asp 545 550 555 560 Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala 565 570 575 Asp He Thr Gin Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn 580 585 590 Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu 618 595 600 605 Ala Gly Ala Asp His Asn Ser Asn He Ser Glu Tyr lie Val Glu Phe 610 615 620 Glu Gly Asn Lys Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val 625 630 635 640 Gin Gly Lys Lys Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg 6 4 5 650 655 Tyr Gin Phe Arg Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro 660 665 670 Ser Gin Pro Ser Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg 675 680 685 Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin Pro Lys Glu Met He 690 695 700 lie Lys Trp Glu Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu 705 710 715 720 Glu Tyr Arg Val Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu 725 730 735 Glu Glu Thr Val Thr Asn His Thr Leu Arg Val Met Thr Pro Ala Val 740 745 750 Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser 755 760 765 Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro 770 775 780 Asp Thr Ala Pro Val He His Gly Val Asp Val He Asn Ser Thr Leu 785 790 795 800 Val Lys Val Thr Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg 805 810 815 Leu Lys Gly Tyr Gin He Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp 820 825 830 771 17 Δ Thr U ι o Pro T x r c? Glu Val Asn lie Ls u Δτγτ Phs Ser m ι? Gin “*- e il J-O J -J j. j. 835 840 845 Arg Asn Ser Gly Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His 850 855 860 Leu Thr Val Leu Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu 865 870 875 880 Pro Tyr He Phe Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe 885 890 895 Leu Lys Val He Lys Val Asp Lys Asp Thr Ala Thr Leu Ser Trp ciy 900 905 910 Leu Pro Lys Lys Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr 915 920 925 Gin He lie Asn Asp Thr Tyr Glu lie Gly Glu Leu Asn Asp lie Asn 930 935 940 lie Thr Thr Pro Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala 945 950 955 960 Thr Thr Lys Tyr Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys 965 970 975 Gly Lys Pro He Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys 980 985 990 Gly He Gly Lys He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro 995 1000 1005 He Glu Val Phe Glu Pro Gly Al a. Glu His He Val Arg Leu Met Thr 1010 1015 1020 Lys Asn Trp Gly Asp Asn Asp Ser lie Phe Gin Asp Val He Glu Thr 1025 1030 1035 1040 Arg Gly Arg Glu Tyr Ala Gly Leu Tyr Asp Asp He Ser Thr Gin Gly 1045 1050 1055 Trp Phe He Gly Leu Met Cys Ala lie Ala Leu Leu Thr Leu Leu Leu 1060 1065 1070 Leu Thr Val Cys Phe Val Lys Arg Asn Arg Gly ciy Lys Tyr Ser Val 1075 1080 1085 Lys Glu Lys Glu Asp Leu His Pro Asp Pro Glu lie Gin Ser Val Lys 619 1090 1095 1100 Asp Glu Thr Phe Gly Glu Tyr Ser Asp Ser Asp Glu Lys Pro Leu Lys 1105 1110 1115 112 Gly Ser Leu Arg Ser Leu Asn Arg Asp Met Gin Pro Thr Glu Ser Ala 1125 1130 1135 Asp Ser Leu Val Glu Tyr Gly Glu Gly Asp His Gly Leu Phe Ser Glu 114 0 1145 1150 Asp Gly Ser Phe lie Gly Ala Tyr Ala Gly Ser Ly s Glu Lys Gly Ser 1155 1160 1165 Val Glu Ser Asn Gly Ser Ser Thr Ala Thr Phe Pro Leu Arg Ala 1170 1175 1180 <210> 205 <211> 1236 <212> PRT <213> Homo &#943; sapians <400> 205 Met Glu Pro Leu Leu Leu Giy Arg Giy Leu He Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 τ 1 ~ τ 1 — T-l — Λ n — r' 1 ,, mkv. τ»κ —k Λ -v- z-r τ &#906; z- &#908; -v r-> 7\ ·»-. niS M.rg X 1C X xc riu &#9633; ΘΓ m3 n nS n OCJ. kjxy 111X rue nx y X xc rx kj noil 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu Gly Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys ciy Leu Pro 145 150 155 160 Pro Leu His lie Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys ciy Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Ala Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser lie Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 He Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys lie Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys lie Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Asp Asn He Ser His Glu Leu Phe 620 340 345 350 Thr Leu His Pro Glu Pro Pro Arg Trp Thr Lys Lys Pro Gin Ser Ala 355 360 365 Val Tyr Ser Thr Gly Ser Asn Gly lie Leu Leu cys Glu Ala Glu Gly 370 375 380 Glu Pro Gin Pro Thr lie Lys Trp Arg Val Asn Gly Ser Pro Val Asp 385 390 395 400 Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe 405 410 415 Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser 420 425 430 Asn Val His Giy Thr lie Leu Ala Asn Ala Asn He Asp Val Val Asp 435 440 445 Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val 450 455 460 Val Gly Tyr Ser Ala Phe Leu His cys Glu Phe Phe Ala Ser Pro Glu 465 470 4 7 5 480 Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly 485 490 495 Arg Arg Tyr His He Tyr Glu Asn Gly Thr Leu Gin lie Asn Arg Thr 500 505 510 Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val Glu Asn Ala He 515 520 525 Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys 530 535 540 Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys Leu His Met Leu 545 550 555 560 Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu 565 570 575 Leu m r- Asp /-1,, 7\ 1 -. /-1,, Tl 7\ ι-, -yi /- 1 TT ml·- v i_iy s OCX -LJ-jJ OC1 ny’S ciy ex u λχ a. sr lie ex u x xc noil dX y X 111 580 585 590 Glu Asp Gly Arg lie lie He Asp Gly Ala Asn Leu Thr lie Ser Asn 595 600 605 Val Thr Leu Glu Asp Gin Gly He Tyr Cys Cys Ser Ala His Thr Ala 610 615 620 Leu Asp Ser Ala Ala Asp lie Thr Gin Val Thr Val Leu Asp Val Pro 625 630 635 640 Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin Asn Arg Ser Val 645 650 655 Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser Asn He Ser Glu 660 665 670 Tyr lie Val Glu Phe Glu Giy Asn Lys Glu Glu Pro Gly Arg Trp Glu 675 680 685 Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val Tie Leu Pro Leu 690 695 700 Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala Val Asn Glu Val 705 710 715 720 Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His Glu Thr Pro Pro 725 730 735 Al a Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val Gin Ala Ser Gin 740 745 750 Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys Ser Met Glu Gin 755 760 765 Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys Pro Gin Giy Ala 770 775 780 Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg Val 785 790 795 800 Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys Val Gin Ala He 805 810 815 Asn Gin Leu Giy Ser Gly Pro Asp Pro Gin Ser Val Thr Leu Tyr Ser 820 825 830 Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His Gly Val Asp Val 621 835 840 845 He Asn Ser Thr Leu 850 Val Lys Val Thr Trp Ser Thr 855 860 Val Pro Lys Asp Arg 865 Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 870 875 Trp Trp Lys Thr 880 Lys Ser Leu Leu Asp 885 Gly Arg Thr His Pro Lys Glu 890 Val Asn He Leu 895 Arg Phe Ser Gly Gin 900 Arg Asn Ser Gly Met Val Pro 905 Ser Leu Asp Ala 910 Phe Ser Glu Phe His 915 Leu Thr Val Leu Ala Tyr Asn 920 Ser Lys Gly Ala 925 Gly Pro Glu Ser Glu 930 Pro Tyr He Phe Gin Thr Pro 935 940 Glu Gly Val Pro Glu 945 Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 950 955 Lys Asp Thr Ala 960 Thr Leu Ser Trp Gly 965 Leu Pro Lys Lys Leu Asn Gly 970 Asn Leu Thr Gly 975 Tyr Leu Leu Gin Tyr 980 Gin He He Asn Asp Thr Tyr 985 Glu He Gly Glu 990 Leu Asn Asp He Asn 995 He Thr Thr Pro Ser Lys Pro 1000 Ser Trp His Leu 1005 Ser Asn Leu Asn Ala 1010 Thr Thr Lys Tyr Lys Phe Tyr 1015 102C Leu Arg Ala Cys 1 Thr 1025 Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1030 1035 Ser Ser Thr Leu 1040 Gly Glu Gly Ser Lys 1045 Gly He Gly Lys He Ser Gly . 1050 Val Asn Leu Thr 1055 Gin Lys Thr His Pro 1060 He Glu Val Phe Glu Pro Gly 1065 Ala Glu His He 1070 Val Arg Leu Met Thr 1075 Lys Asn Ti’p Gly Asp Asn Asp 1080 Ser lie Phe Gin 1085 Asp Val lie Glu Thr 1090 Arg Gly Arg Glu Tyr Ala Gly 1095 110C Leu Tyr Asp Asp 1 He 1105 Ser Thr Gin Gly I Trp Phe He Gly Leu Met Cys 1110 1115 Ala He Ala Leu 1120 Leu Thr Leu Leu Leu 1125 Leu Thr Val Cys Phe Val Lys , 1130 Arg Asn Arg Gly 1135 Gly Lys Tyr Ser Val 1140 Lys Glu Lys Glu Asp Leu His 1145 Pro Asp Pro Glu 1150 He Gin Ser Val Lys 1155 Asp Glu Thr Phe Gly Glu Tyr 1160 Ser Asp Ser Asp 1165 Glu Lys Pro Leu Lys 1170 Gly Ser Leu Arg Ser Leu Asn 1175 118 C Arg Asp Met Gin 1 Pro 1185 Thr Glu Ser Ala 1 Asp Ser Leu Val Glu Tyr Gly 1190 1195 Glu Gly Asp His 1200 Gly Leu Phe Ser Glu 1205 Asp Gly Ser Phe He Gly Ala > 1210 Tyr Ala Gly Ser 1215 Lys Pro Glu Lys Gly Ser 1220 Leu Arg Ala 1235 Val Glu Ser Asn Gly Ser Ser 1225 Thr Ala Thr Phe 1230 <210> 206 <211> 1195

<212> PRT <213> Homo sapians <400> 206

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 15 10 15

Leu Leu Leu Lys Phe Ser Lys Ala He Glu He Pro Ser Ser Val Gin 622 20 25 30 Gin Val Pro Thr He He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 5 5 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg He He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His lie Ser His Phe Gin Giy Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly He Ala Met Ser Glu Glu He Glu Phe He Val Pro 115 120 125 Lys Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser Gin Lys 130 135 140 Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg Asn Asp 145 150 155 160 Tyr Cys Cys Phe Al a Ala Phe Pro Arg Leu Arg Thr He Val Gin Lys 165 170 175 Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn Asp Ser 180 185 190 Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys Gin Arg 195 200 205 Lys Pro Lys Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu Ser Ser 210 215 220 lie Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe Ala Glu 225 230 235 240 Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly Asp Leu 245 250 255 Pro Lys Giy Arg Giu Thr Lys Giu Asn Tyr Gly Lys Thr Leu Lys He 260 265 270 Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr Ala Ser 275 280 285 Asn Phe Leu Gly Thr Ala Thr His Asp Phe His Val He Val Glu Asp 290 295 300 Asn He Ser His Glu Leu Phe Thr Leu His Pro Glu Pro Pro Arg Trp 305 310 315 320 Thr Lys Lys Pro Gin Ser Al a Val Tyr Ser Thr Gly Ser Asn Gly Xie 325 330 335 Leu Leu cys Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg 340 345 350 Val Asn Gly Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val 355 360 365 Phe Pro Arg Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala 370 375 380 Val Tyr Gin Cys Glu Ala Ser Asn Val His Gly Thr He Leu Al a Asn 385 390 395 400 Ala Asn He Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp 405 410 415 Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys 420 425 430 Glu Phe Phe Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu 435 440 445 Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr His He Tyr Glu Asn Gly 450 455 460 Thr Leu Gin He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser 465 470 475 4 80 Cys Trp Val Glu Asn Ala He Giy Lys Thr Ala Val Thr Ala Asn Leu 485 490 495 Asp lie Arg Asn 1 a Thr Ly s Leu Arg Val Ser Pro Lys Asn Pro Arg 500 505 510 He Pro Lys Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp 623 515 520 525 Ser His Leu Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu 530 535 540 Ala Phe Glu He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly 545 550 555 560 Ala Asn Leu Thr He Ser Asn Val Thr Leu Glu Asp Gin Gly He Tyr 565 570 5 7 5 Cys Cys Ser Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin 580 585 590 Val Thr Val Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser 595 600 605 Glu Arg Gin Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp 610 615 620 His Asn Ser Asn He Ser Glu Tyr lie Val Glu Phe Glu Gly Asn Lys 625 630 635 640 Glu Glu Pro Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys 645 650 655 Thr Thr Val He Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg 660 665 670 Val He Ala Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser 675 680 685 Asp His His Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn 690 695 700 lie Arg Val Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu 705 710 715 720 Pro Leu Lys Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val 725 730 735 Thr Trp Lys Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val 740 745 750 Thr Asn His Thr Leu Arg Val Met Thr' Pro Ala Val Tyr Ala Pro Tyr 755 760 765 Asp Val Lys Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro 770 775 780 Gin Ser Val Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro 785 790 795 800 Val He His Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr 805 810 815 Trp Ser Thr Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr 820 825 830 Gin He Asn Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His 835 840 845 Pro Lys Glu Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly 850 855 860 Met Val Pro Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu 865 870 875 880 Ala Tyr Asn Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe 885 890 895 Gin Thr Pro Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He 900 905 910 Lys Val Asp Lys Asp Thr 311. xx Thr Leu Ser Trp Gly Leu Pro Lys Lys 915 920 925 Leu Asn Gly Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn 930 935 940 Asp Thr Tyr Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro 945 950 955 960 Ser Lys Pro Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr 965 970 975 Lys Phe Tyr Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He 980 985 990 Thr Glu Glu Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys 995 1000 1005 He Ser Gly Val Asn Leu Thr Gin Lys Thr His Pro lie Glu Val Phe 624 1010 1015 1020

Glu Pro Gly Ala Glu His lie Val Arg Leu Met Thr Lys Asn Trp Gly 1025 Asp » Asn Asp Ser He 1030 Phe Gin Asp Val He 1035 Glu Thr Arg Gly Arg 1040 Glu Tyr Ala Gly Leu 1045 Tyr Asp Asp He Ser 1050 Thr Gin Gly Trp Phe 1055 He Gly Leu Met Cys 1060 Ala &#943; He Ala Leu Leu 1065 Thr Leu Leu Leu Leu 1070 Thr Val Cys Phe Val 1075 Lys 1 Arg Asn Arg Gly 1080 Gly Lys Tyr Ser Val 1085 Lys Glu Lys Glu Asp 109C Leu 1 His Pro Asp Pro 1095 Glu 1 He Gin Ser Val HOC Lys 1 Asp Glu Thr Phe 1105 Gly Glu Tyr Ser Asp 1110 Ser Asp Glu Lys Pro 1115 Leu i Lys Gly Ser Leu 1120 Arg Ser Leu Asn Arg 1125 Asp 1 Met Gin Pro Thr 1130 Glu 1 Ser Ala Asp Ser 1135 Leu Val Glu Tyr Gly 1140 Glu 1 Gly Asp His Gly 1145 Leu Phe Ser Glu Asp 1150 Gly 1 Ser Phe He Gly 1155 Ala 1 Tyr Ala Gly Ser 1160 Lys 1 Glu Lys Gly Ser 1165 Val 1 Glu Ser Asn Gly 1170 Ser 1 Ser Thr Ala Thr 1175 Phe Pro Leu Arg Ala 1180 1185 1190 1195 <210> 207 <211> 7651

<212> DNA <213> Homo sapians <220>

<221> CDS <222> (272 ).(3946) <400> 207 cggaccctgc gaggcgccgg tcctgtctta ccaggttaac tcttaccggg gcgcccccgt acagatcgcg atactgcaaa taaggtctca ttgtcttctt cccggctccc tttcggaggc caaatcatag gctgtaaacc cctgaagagc aga gga eta ate gta tat eta atg Arg Gly Leu 10 He Val Tyr Leu Met 15 gca att gaa ata cca tet tea gtt Ala He 25 Glu He Pro Ser Ser 30 Val cag tea aaa gtc caa gtt gcc ttt Gin 40 Ser Lys Val Gin Val 45 Ala Phe ggccggctcg ggggagaagg ggcgcaggtg ctgtaaactg tggaactaag gggaacttaa aaaagtgaga ggagacatta a atg gag ccg ctt tta Met Glu Pro Leu Leu 1 5 ttc etc ctg tta aaa ttc Phe Leu Leu Leu Lys Phe 20 cgcccgaggg 60 caaaccataa 120 tttactgttt 180 agattttcat 240 ctt gga 292 Leu Gly tea aaa 340 Ser Lys caa cag gtt cca aca ate Gin Gin Val Pro Thr lie 35 ata aaa 388 He Lys ccc ttc gat gag tat ttt Pro Phe Asp Glu Tyr Phe 50 caa att 436 Gin He 55 gaa Glu tgt Cys gaa Glu get Ala aaa Lys 60 gga Gly aat Asn cca Pro gaa Glu cca Pro 65 aca Thr ttt Phe teg Ser tgg Trp act Thr 70 aag Lys 484 gat ggc aac cct ttt tat ttc act gac cat egg ata att cca teg aac 532 Asp Gly Asn Pro Phe Tyr Phe Thr Asp His Arg lie He Pro Ser Asn 75 80 85 625 aat Asn tea Ser gga Gly 90 aca Thr ttc Phe agg Arg ate He cca Pro 95 aac Asn gag Glu ggg Gly cac His ata He 100 tet Ser cac His ttt Phe 580 caa ggg aaa tac ege tgc ttt get tea aat aaa ctg gga ate get atg 628 Gin Gly Lys Tyr Arg Cys Phe Ala Ser Asn Lys Leu Gly He Ala Met 105 110 115 tea gaa gaa ata gaa ttt ata gtt cca agt gtt cca aaa etc cca aaa 676 Ser Glu Glu He Glu Phe He Val Pro Ser Val Pro Lys Leu Pro Lys 120 125 130 135 gaa 9.6.9 att gac cct ett CJ99 gtg gag gag gga gat cca att gtc etc 724 Glu Lys He Asp Pro Leu Glu Val Glu Glu Gly Asp Pro lie Val Leu 140 145 150 cca tgc aat cct ccc aaa ggc etc cca cct tta cac att tat tgg atg 772 Pro Cys Asn Pro Pro Lys dy Leu Pro Pro Leu His He Tyr Trp Met 155 160 165 aat att gaa tta gaa cac ate gaa caa gat gaa aga gta tac atg age 820 Asn lie Glu Leu Glu His He Glu Gin Asp Glu Arg Val Tyr Met Ser 170 175 180 caa aag gga gat cta tac ttc gca aac gtg gaa gaa aag gac agt ege 868 Gin Lys Gly Asp Leu Tyr Phe Ala Asn Val Glu Glu Lys Asp Ser Arg 185 190 195 tta n 1 r aat gac tac tgt tgc ttt get gca ttt cca ag a agg act att y t a y j. υ Asn Asp Tyr Cys Cys Phe Ala Ala Phe Pro Arg Leu Arg Thr lie Val 200 205 210 215 cag aaa atg cca atg aaa cta aca gtt aac agt tta aag cat get aat 964 Gin Lys Met Pro Met Lys Leu Thr Val Asn Ser Leu Lys His Ala Asn 220 225 230 g ac tea agt tea tcc aca gaa. att ggt tcc aag gca a i. tcc ate aag 1012 Asp Ser Ser Ser Ser Thr Glu He Gly Ser Lys Ala Asn Ser He Lys 235 240 245 caa aga 999 ccc aaa ctg ctg ttg cct ccc act gag agt ggc agt gag 1060 Gin Arg Lys Pro Lv<2 'a. Leu Leu Leu Pro Pro Thr Glu Ser Gly Ser Glu 250 255 260 tet tea att acc ate etc aaa ggg gaa ate ttg ctg ett gag tgt ttt 1108 Ser Ser He Thr He Leu Lys Gly Glu He Leu Leu Leu Glu Cys Phe 265 270 275 get gaa ggc ttg cca act cca cag gtt gat tgg aac aaa att ggt ggt 1156 Ala Glu Gly Leu Pro Thr Pro Gin Val Asp Trp Asn Lys He Gly Gly 280 285 290 295 gac tta cca aag ggg aga gaa aca aaa gaa aat tat ggc aag act ttg 1204 Asp Leu Pro Lys Gly Arg Glu Thr Lys Glu Asn Tyr Gly Lys Thr Leu 3 0 0 305 310 aag ata gag aat gtc tcc tac cag gac aaa gga aat tat ege tgc aca 1252 Lys He Glu Asn Val Ser Tyr Gin Asp Lys Gly Asn Tyr Arg Cys Thr 315 320 325 gcc age aat ttc ttg gga aca gcc act cac gat ttt cac gtt ata gta 1300 626

Ala Ser Asn 330 Phe Leu Gly Thr Ala 335 Thr His Asp Phe His 340 Val He Val gaa gag cct cct ege tgg aca aag aag cct cag agt get gtg tat age 1348 Glu Glu Pro Pro Arg Trp Thr Lys Lys Pro G1 n Ser Ala Val Tyr Ser 345 350 355 acc gga age aat ggc ate ttg tta tgt gag get gaa gga gaa cct caa 1396 Thr Gly Ser Asn Gly He Leu Leu Cys Glu Ala Glu Gly Glu Pro Gin 360 365 370 375 ccc aca ate aag tgg aga gtc aat ggc tcc cca gtt gac aat cat cca 1444 Pro Thr He Lys Trp Arg Val Asn Gly Ser Pro Val Asp Asn His Pro 380 385 390 ttt get ggt gat gtt gtc ttc ccc agg gaa ate agt ttt acc aac ett 1492 Phe Ala Gly Asp Val Val Phe Pro Arg Glu He Ser Phe Thr Asn Leu 395 400 405 caa cca aat cat act get gtg tac cag tgt gaa gcc tea aat gtc cat 1540 Gin Pro Asn His Thr Ala Val Tyr Gin Cys Glu Ala Ser Asn val His 410 415 420 gga act ate ett gcc aat gee aat att gat gtt gtg gat gtc cgt cca 1588 Gly Thr He Leu Al a Asn Ala Asn lie Asp Val Val Asp Val Arg Pro 425 430 435 ttg ata caa acc aaa gat gga gaa aat tac get aca gtg gtt ggg tac 1636 Leu lie Gin Thr Lys Asp Gly Glu Asn Tyr Ala Thr Val Val Gly Tyr 440 4 4 5 a r n 4 r 5 re _/ \j agt get ttc tta cat tgc gag ttc ttt get tea cct gag gca gtc gtg 1684 Ser Ala Phe Leu His Cys Glu Phe Phe Ala Ser Pro Glu Ala Val Val 460 465 470 tcc tgg cag aag gtg gaa gaa gtg aaa ccc ctg gag ggc agg egg tat 1732 Ser Trp Gin Lys Val Glu Glu Val Lys Pro Leu Glu Gly Arg Arg Tyr 475 480 485 cat ate tat gaa aat ggc aca ttg cag ate aac aga acc acc gaa gaa 1780 His He Tyr Glu Asn Gly Thr Leu Gin He Asn Arg Thr Thr Glu Glu 490 495 500 gat get ggg tct tac tea tgt tgg gta gaa aat get ata gga aaa act 1828 Asp Ala Gly Ser Tyr Ser cys Trp Val Glu Asn Ala lie Gly Lys Thr 505 510 515 gca gtc aca gcc aat ttg gat att aga aat get aca aaa ett aga gtt 1876 Ala Val Thr Ala Asn Leu Asp He Arg Asn Ala Thr Lys Leu Arg Val 520 525 530 535 tct cct aag aat cct cgt ate ccc aaa ttg cat atg ett gaa tta cat 1924 Ser Pro Lys Asn Pro Arg lie Pro Lys Leu His Met Leu Glu Leu His 540 545 550 tgt gaa age aaa tgt gac tea cat ttg aaa cac agt ttg aag ttg tcc 1972 Cys Glu Ser Lys Cys Asp Ser His Leu Lys His Ser Leu Lys Leu Ser 555 560 565 tgg agt aaa gat gga gaa gcc ttt gaa att aat ggc aca gaa gat ggc 2020 Trp Ser Lys Asp Gly Glu Ala Phe Glu He Asn Gly Thr Glu Asp Gly 570 575 580 627 2068 agg ata att att gat gga Arg lie He He Asp Gly 585 get aat ttg acc ata Ala Asn Leu Thr He 590 tct aat gta act tta Ser Asn Val Thr Leu 595 gag gac caa ggt att tac Glu Asp Gin Gly He Tyr 600 605 tgc tgt tea get Cys Cys Ser Ala c at His 610 act get eta gac Thr Ala Leu Asp agt

Ser 615 2116 get gcc gat ata Ala Ala Asp He act caa gta act gtt ett gat Thr Gin Val Thr Val Leu Asp 620 625 gtt ccg gat cca cca Val Pro Asp Pro Pro 630 2164 gaa aac ett cac ttg tct Glu Asn Leu His Leu Ser 635 gaa aga cag aac agg Glu Arg Gin Asn Arg 640 agt gtt egg ctg acc Ser Val Arg Leu Thr 645 2212 tgg gaa get gga get gac Trp Glu Ala Gly Ala Asp 650 cac aac age aat att His Asn Ser Asn He 655 age gag tat att gtt Ser Glu Tyr lie Val 660 2260 gaa ttt gaa gga aac aaa Glu Phe Glu Gly Asn Lys 665 gaa gag cct gga agg Glu Glu Pro Gly Arg 670 tgg gag gaa ctg acc Trp Glu Glu Leu Thr 675 2308 aga gtc caa gga aag aaa Arg Val Gin Gly Lys Lys 680 685 acc aca gtt ate Thr Thr Val He tta

Leu 690 cct ttg get cca Pro Leu Ala Pro ttt

Phe 695 2356 gtg aga tac cag Val Arg Tyr Gin ttc agg gtc ata gcc gtg aac Phe Arg Val lie Ala Val Asn 700 705 gaa gta ggg aaa aat Glu Val Gly Arg Ser 710 2404 cag cct age cag ccg tea gac cat cat gaa aca Gin Pro Ser Gin Pro Ser Asp His His Glu Thr 715 720 cca cca gca get cca Pro Pro Ala Ala Pro 725 2452 gat agg aat cca caa aac ata agg gtt caa gcc Asp Arg Asn Pro Asn iiG Arg Var Gin Ala 730 735 tct caa ccc aag gaa Ser Gin Pro Lys Glu 740 2500 atg att ata aag tgg gag cct ttg aaa tcc atg Met He He Lys Trp Glu Pro Leu Lys Ser Met 745 750 gag cag aat gga cca Glu Gin Asn Gly Pro 755 2548 ggc eta Gly Leu 760 gag tac Glu Tyr aga gtg Arg Val 7 65 acc tgg aag cca Thr Trp Lys Pro cag

Gin 770 gga gcc cca gtg Gly Ala Pro Val gag

Glu 775 2596 tgg gaa gaa gaa aca gtc aca aac cac aca ttg egg Trp Glu Glu Glu Thr Val Thr Asn His Thr Leu Arg 780 785 gtg atg aeg Val Met Thr 790 cct

Pro 2644 get gtc tat gcc cct tat Ala Val Tyr Ala Pro Tyr 795 gat gtc aag gtc cag get ate aat caa eta Asp Val Lys Val Gin Ala He Asn Gin Leu 800 805 2692 gga tct ggg cct gac cct Gly Ser Gly Pro Asp Pro 810 cag tea gtg act etc tat

Gin Ser Val Thr Leu Tyr tct gga gaa Ser Gly Glu 820 gac

Asp 2740 tat cct gat aca get cca gtg ate cat ggg gtg gac gtt ata aac agt 2788 628

Tyr Pro 825 Asp Thr Ala Pro Val 830 He His Gly Val Asp 835 Val He Asn Ser aca tta gtt aaa gtt acc tgg tea aca gtt cca aag gac aga gta cat 2836 Thr 840 Leu Val Lys Val Thr 845 Trp Ser Thr Val Pro 850 Lys Asp Arg Val His 855 gga cgt ctg aaa ggc tat cag ata aat tgg tgg aaa aca aaa agt ctg 2884 Gly Arg Leu Lys Gly 860 Tyr Gin He Asn Trp 865 Trp Lys Thr Lys Ser 870 Leu ttg gat gga aga aca cat ccc aaa gaa gtg aac att eta aga ttt tea 2932 Leu Asp Gly Arg 875 Thr His Pro Lys Glu 880 Val Asn He Leu Arg 885 Phe Ser gga caa aga aac tet gga atg gtt cct tcc tta gat gcc ttt agt gaa 2980 Gly Gin Arg 890 Asn Ser Gly Met Val 895 Pro Ser Leu Asp Ala 900 Phe Ser Glu ttt cat tta aca gtc tta gcc tat aac tet aaa gga get ggt cct gaa 3028 Phe His 905 Leu Thr Val Leu Ala 910 Tyr Asn Ser Lys Gly 915 Al a Gly Pro Glu agt gag cct tat ata ttt caa aca cca gaa gga gta cct gaa cag cca 3076 Ser 920 Glu Pro Tyr He Phe 925 Gin Thr Pro Glu Gly 930 Val Pro Glu Gin Pro 935 act ttt eta aag gtc ate aaa gtt gat aaa gac act gcc act tta tet 3124 Thr Phe Leu Lys Val 940 He Lys Val Asp Lys 945 Asp Thr Ala Thr Leu 950 Ser tgg gga eta cct aag aaa tta aat gga aac tta act ggc tat ctt ttg 3172 Trp Gly Leu Pro 955 Lys Lys Leu Asn Gly 9 6 0 Asn Leu Thr Gly Tyr 965 Leu Leu caa tat cag ata ata aat gac acc tac gag att gga gaa tta aat gat 3220 Gin Tyr Gin 970 He He Asn Asp Thr 975 Tyr Glu He Gly Glu 980 Leu Asn Asp att CicLC att aca act cca tea aag ccc age tgg cac etc tea aac ctg 3268 lie Asn 985 He Thr Thr Pro Ser 99C Lys ι Pro Ser Trp His 995 Leu Ser Asn Leu S-St gca act acc aag tac aaa ttc tac ttg agg get tgc act tea cag 3316 Asn 100C Ala ) Thr Thr Lys Tyr Lys 1005 Phe Tyr Leu Arg 101C Ala 1 Cys Thr Ser Gin 1015 ggc tgt gga aaa ccg ate aeg gag gaa age tcc acc tta gga gaa ggg 3364 Gly Cys Gly Lys Pro 1020 He 1 Thr Glu Glu Ser Ser 1025 Thr Leu Gly Glu 103C Gly 1 agt aaa ggt ate ggg aag ata tea gga gta aat ctt act caa aag act 3412 Ser Lvc &#905; ~ dy He 1035 Gly Lys He Ser Gly 104C T7a 1 V 0.4. 1 Asn Thr Gin 1045 Lys Thr cac cca ata gag gta ttt gag ccg gga get gaa cat ata gtt ege eta 3460 His Pro He 1050 Glu Val Phe Glu Pro 1055 Gly Ala Glu His He 106C Val 1 Arg Leu atg act aag aat tgg ggc gat ssc gat age att ttt caa gat gta att 3508 Met Thr Lys Asn Trp Gly Asp Asn Asp Ser lie Phe Gin Asp Val lie 1065 1070 1075 629 gag aca Glu Thr 1080 aga Arg ggg Gly aga Arg gaa tat Glu Tyr 1085 get Ala ggt Gly tta Leu tat gat Tyr Asp 1090 gac Asp ate lie tcc Ser act Thr 1095 3556 caa ggc tgg ttt att gga ctg atg tgt geg att get ett etc aca eta 3604 Gin Gly Trp Phe lie Gly Leu 1100 Met cys Ala He Ala 1105 Leu Leu Thr 111C Leu ) eta tta tta act gtt tgc ttt gtg aag agg aat aga ggt gga aag tac 3652 Leu Leu Leu Thr 1115 Val Cys Phe Val Lys 1120 Arg 1 Asn Arg Gly Giy 1125 Lys Tyr tea gtt aaa gaa aag gaa gat ttg cat cca gac cca gaa att cag tea 3700 Ser Val Lys 1130 Glu 1 Lys Glu Asp Leu His 1135 Pro Asp Pro Glu 114C He 1 Gin Ser gta aaa gat gaa acc ttt ggt gaa tac agt gac agt gat gaa aag cct 3748 Val Lys Asp 1145 Glu Thr Phe Gly 115C Glu 1 Tyr Ser Asp Ser Asp 1155 Glu Lys Pro etc aaa gga age ett egg tcc ett aat agg gat atg cag cct act gaa 3796 Leu Lys 1160 Gly Ser Leu Arg Ser 1165 Leu Asn Arg Asp Met 1170 Gin Pro Thr Glu 1175 agt get gac age tta gtc gaa tac gga gag gga gac cat ggt etc ttc 3844 Ser Ala Asp Ser Leu 1180 Val Glu Tyr Gly Glu 1185 Gly Asp His Gly Leu 1190 Phe 1 agt gaa gat gga tea ttt att ggt gcc tac get gga tet aag gag aag 3892 Ser Glu Asp Gly 1195 Ser Phe He Gly Ala 1200 Tyr 1 Ala Gly Ser Lys 1205 Glu 1 Lys gga tet gtt gaa age aat gga agt tet aca gca act ttt ccc ett egg 3940 Gly Ser Val 1210 Glu Ser Asn Gly Ser 1215 Ser Thr Ala Thr Phe 1220 Pro 1 Leu Arg gca taa acacaacata tgtaagcaac gctactggtt caccccaacc ttccatattt 3996 Ala * atctgttcaa aggagcaaga actttcatat aggaatagaa acatgctggc cgaagatttc 4056 atccagaagt caacatcctg caattatgtt gaaaagagta gtactttctt caaaatataa 4116 aatgccaagc acttcaggcc tatgttttgc ttatattgtt ttcaggtgct caaaatgcaa 4176 aacacaaaac aaatcctgca tttagataca cctcaactaa atccaaagtc cccattcagt 4236 atattccata tttgcctgat tttactattc ggtgtgtttg catagatgtt gctacttggt 4296 gggtttttct ccgtatgcac attggtatac agtctctgag aactggcttg gtgactttgc 4356 ttcactacag gttaaaagac cataagcaaa ctggttattt aaaatgtaaa aaggaatatg 4416 aaagtcttat taaaacactt cattgaaaat atacagtcta aatttattat ttaaatttta 4476 ctagcaaaag tcttaggtga acaatcaact agtatttgtt gagctcctat ttgcccagag 4536 atggtcatat ttaaacagaa gtatacgttt ttcagtttca acatgaattt ttttatttct 4596 gtcagttatg acatccacga gcatcacttt ttgtgtctgt tttttttttt tttcttggac 4656 taaattcaac tgcatggaag cggtggtcag aaggttgttt tatacgagaa caggcagaaa 4716 gtgcccattg ttcaggattc taatagctac atctacttaa tatcttcatt tctaaattga 4776 ctgcttttac ctttttctca tgtttatata atggtatgct tgcatatatt tcatgaatac 4836 attgtacata ttatgttaat atttacacaa tttaaaatat agatgtgttt tattttgaag 4896 tgagaaaatg aacattaaca ggcatgtttg tacagctaga atatattagt aagatactgt 4956 ttttcgtcat tccagagcta caactaataa cacgaggttc caaagctgaa gactttgtat 5016 aaagtatttg ggttttgttc ttgtattgct ttctttcaac agtttcaaaa taaaatatca 5076 tacaaatatt gagggaaatg ttttcatatt tttcaaaata ggtttttatt gttgaatgta 5136 catctacccc agcccctcaa aagaaaaact gtttacatag aaattcctac acatacgttt 5196 gcgtatatgt tattttaaac atctttgtgg tgagaatttt ttccccgata ttctccttct 5256 630 gtcaaagtca gaacaaattc agggaattta ttttctggca gttgtgctcc agtcctttta aaattgtaca tgaacatgtt ttagaaacaa tatggaggat gatgcataca tgtcggtcaa gttcagcgct cgacatttta tggaaagatt tttttaacct taccacgaaa tacttaacta ctgtttaagt gaattgactt atttcacttt agtttttgaa ctgtgattat tggtatactg ttatatcctc aacttggatt tatggtaacc ccttttagtt catggagacc aaaatttggg gtatttataa tagtcagcgc aggaatgcac atggaatatc tacttgtcct tttgaacctc acgagtcatc cagaatgtat agacaggaaa agcatgtctt atttaaaact gtaatttatg ggctcaggat ctgaccgcag tcccgggagt aagcatttca aagggggaag gcagtgtggt ccctaccctg tgtgaatgtg aggatgtaga catccatcag tgcaactcga gctccatcct cctccgattt ctaaggctcc agttttctgg agggacagtc atcatgtttt gatttatctg ggagaaaact gtggtgcaca gcttgtgagg agggcaaggt tgtgacgttc gagcttagtt ctggtgttat tctgtctcct cttctttgtc atcagccaaa acgtggtttt taaagagagt catgcaggtt agaaataatg tcaaaaatat ttaggaattt aataaccttt aagtcagaaa ctaaaacaaa tactgaaata ttagctcttc ctacacttcg tgttcccctt tagctgcctg aaaatcaaga ttgctcctac tcagatcttc tgagtggcta aaacttatgg atatgaaaaa tgagattgaa tgatgactat gctttgctat cattgttacc tttcctcaat actatttggc aactactggg actcttcagc acaaaaggaa tagatctatg attgaccctg attttaattg tgaaattata tgattcatat attttatgaa tcagaataac cttcaaataa aataaatcta agtcggttaa aatggatttc atgattttcc ctcagaaaat gagtaacgga gtccacggcg tgcaatggta attataaatt ggtgatgctt gtttgcaaat tgcccactcg tgataagtca acagccaata tttaaaactt tgttcgttac tggctttacc ctaactttct ctagtctact gtcaatatca ttttaatgta attgattgta tatagtctca agaatggttg gtgggcatga gttcctagag aactgtccaa gggttgggaa aatccaaatt ctcttcctgg ctccagcact gattttgtac ataaacatta ggcaggttgc ttaacctttt tatttcaaac tctctcaact ctaaagtgct aataataatc tcagttacct tatctttgtc acagggtgtt cttttttatg aagaaaaatt tgaaaatgat aaaagctaag atgccttcta acttcataag caaaccttta actaattatg tatctgaaag tcacccccac ataccaactc aacttttttc ctgtgaacac ataaatatat ttttatagaa aaacaaatct acataaaata aatctactgt ttagtgagca gtatgacttg tacatgccat tgaaaattat taatcagaag aaaattaagc agggtctttg ctatacaaaa gtgttttcca ctaattttgc atgcgtattt ataagaaaaa tgtgaatttg gtggttttat tctatcggta taaaggcatc gatattttag atgcacccgt gtttgtaaaa atgtagagca caatggaatt atgctggaag tctcaaataa tatttttttc ctattttata ctcatggaag agataagcta aagaggggac aataatgaga aatgttggtg tgcttttcta agcatttaaa acataattgc caattgaaac cctaaatatg tttacatacc attaagatat gattcatgta acaatgttaa attaattata atgggattgg gtttgttatc tgtggtagta tatatcctag tgttcctata gtgaaataag tagggttcag ccaaagcttt ctttgttttg taccttaaat tgttcgatta cgtcatcaaa agagatgaaa ggtatgtaga acaggttcac gtgattacct ttttcttttg gcttggatta atattcatag tagaacttta taaaacgtgt ttgtattgta ggtggtgttt gtattatgct tatgactatg tatggtttga aaatattttc attatacatg aaattcaact ttccaaataa aagttctact tcatgtaatc caaaa <210> 208 <211> 1224

<212> PRT <213> Homo sapians 5316 5376 5436 5496 5556 5616 5676 5736 5796 5856 5916 5976 6036 6096 6156 6216 6276 6336 6396 6456 6516 6576 6636 6696 6756 6816 6876 6936 6996 7056 7116 7176 7236 7296 7356 7416 7476 7536 7596 7651 <400> 208

Met Glu Pro Leu Leu Leu Gly Arg Gly Leu lie Val Tyr Leu Met Phe 1 5 10 15 Leu Leu Leu Lys Phe Ser Lys Ala lie Glu He Pro Ser Ser Val Gin 20 25 30 Gin Val Pro Thr lie He Lys Gin Ser Lys Val Gin Val Ala Phe Pro 35 40 45 Phe Asp Glu Tyr Phe Gin He Glu Cys Glu Ala Lys Gly Asn Pro Glu 50 55 60 Pro Thr Phe Ser Trp Thr Lys Asp Gly Asn Pro Phe Tyr Phe Thr Asp 65 70 75 80 His Arg lie He Pro Ser Asn Asn Ser Gly Thr Phe Arg He Pro Asn 85 90 95 Glu Gly His He Ser His Phe Gin Gly Lys Tyr Arg Cys Phe Ala Ser 100 105 110 Asn Lys Leu Gly lie Ala Met Ser Glu Glu He Glu Phe He Val Pro 631 115 120 125 Ser Val Pro Lys Leu Pro Lys Glu Lys He Asp Pro Leu Glu Val Glu 130 135 140 Glu ciy Asp Pro He Val Leu Pro Cys Asn Pro Pro Lys Gly Leu Pro 145 150 155 160 Pro Leu His He Tyr Trp Met Asn He Glu Leu Glu His He Glu Gin 165 170 175 Asp Glu Arg Val Tyr Met Ser Gin Lys Gly Asp Leu Tyr Phe Ala Asn 180 185 190 Val Glu Glu Lys Asp Ser Arg Asn Asp Tyr Cys Cys Phe Ala Ala Phe 195 200 205 Pro Arg Leu Arg Thr He Val Gin Lys Met Pro Met Lys Leu Thr Val 210 215 220 Asn Ser Leu Lys His Al a Asn Asp Ser Ser Ser Ser Thr Glu He Gly 225 230 235 240 Ser Lys Ala Asn Ser He Lys Gin Arg Lys Pro Lys Leu Leu Leu Pro 245 250 255 Pro Thr Glu Ser Gly Ser Glu Ser Ser He Thr He Leu Lys Gly Glu 260 265 270 lie Leu Leu Leu Glu Cys Phe Ala Glu Gly Leu Pro Thr Pro Gin Val 275 280 285 Asp Trp Asn Lys He Gly Gly Asp Leu Pro Lys Gly Arg Glu Thr Lys 290 295 300 Glu Asn Tyr Gly Lys Thr Leu Lys He Glu Asn Val Ser Tyr Gin Asp 305 310 315 320 Lys Gly Asn Tyr Arg Cys Thr Ala Ser Asn Phe Leu Gly Thr Ala Thr 325 330 335 His Asp Phe His Val He Val Glu Glu Pro Pro Arg Trp Thr Lys Lys 340 345 350 Pro Gin Ser Ala Val Tyr Ser Thr Gly Ser Asn Gly He Leu Leu fVB — -L ~ 355 360 365 Glu Ala Glu Gly Glu Pro Gin Pro Thr He Lys Trp Arg Val Asn Gly 370 375 380 Ser Pro Val Asp Asn His Pro Phe Ala Gly Asp Val Val Phe Pro Arg 385 390 395 400 Glu He Ser Phe Thr Asn Leu Gin Pro Asn His Thr Ala Val Tyr Gin 405 410 415 Cys Glu Ala Ser Asn Val His Gly Thr He Leu Ala Asn Ala Asn He 4 2 0 425 430 Asp Val Val Asp Val Arg Pro Leu He Gin Thr Lys Asp Gly Glu Asn 435 440 445 Tyr Ala Thr Val Val Gly Tyr Ser Ala Phe Leu His Cys Glu Phe Phe 450 455 4 60 Ala Ser Pro Glu Ala Val Val Ser Trp Gin Lys Val Glu Glu Val Lys 465 470 475 480 Pro Leu Glu Gly Arg Arg Tyr Hrs He Tyr Glu Asn Gly Thr Leu Gin 485 490 495 He Asn Arg Thr Thr Glu Glu Asp Ala Gly Ser Tyr Ser Cys Trp Val 500 505 510 Glu Asn Ala He Gly Lys Thr Ala Val Thr Ala Asn Leu Asp He Arg 515 520 525 Asn Ala Thr Lys Leu Arg Val Ser Pro Lys Asn Pro Arg He Pro Lys 530 53 5 540 Leu His Met Leu Glu Leu His Cys Glu Ser Lys Cys Asp Ser His Leu 545 550 555 560 Lys His Ser Leu Lys Leu Ser Trp Ser Lys Asp Gly Glu Ala Phe Glu 565 570 575 He Asn Gly Thr Glu Asp Gly Arg He He He Asp Gly Ala Asn Leu 580 585 590 Thr He Ser Asn Val Thr Lsu Glu Asp Gin Gly He Tyr Cys Cys Ser 595 600 605 Ala His Thr Ala Leu Asp Ser Ala Ala Asp He Thr Gin Val Thr Val 632 610 615 620 Leu Asp Val Pro Asp Pro Pro Glu Asn Leu His Leu Ser Glu Arg Gin 625 630 635 640 Asn Arg Ser Val Arg Leu Thr Trp Glu Ala Gly Ala Asp His Asn Ser 645 650 655 Asn He Ser Glu Tyr He Val Glu Phe Glu Gly Asn Lys Glu Glu Pro 660 665 670 Gly Arg Trp Glu Glu Leu Thr Arg Val Gin Gly Lys Lys Thr Thr Val 675 680 685 lie Leu Pro Leu Ala Pro Phe Val Arg Tyr Gin Phe Arg Val He Ala 690 695 700 Val Asn Glu Val Gly Arg Ser Gin Pro Ser Gin Pro Ser Asp His His 705 710 715 720 Glu Thr Pro Pro Ala Ala Pro Asp Arg Asn Pro Gin Asn He Arg Val 725 730 735 Gin Ala Ser Gin Pro Lys Glu Met He He Lys Trp Glu Pro Leu Lys 740 745 750 Ser Met Glu Gin Asn Gly Pro Gly Leu Glu Tyr Arg Val Thr Trp Lys 755 760 765 Pro Gin Gly Ala Pro Val Glu Trp Glu Glu Glu Thr Val Thr Asn His 770 775 780 Thr Leu Arg Val Met Thr Pro Ala Val Tyr Ala Pro Tyr Asp Val Lys 785 790 795 800 Val Gin Ala He Asn Gin Leu Gly Ser Gly Pro Asp Pro Gin Ser Val 805 810 815 Thr Leu Tyr Ser Gly Glu Asp Tyr Pro Asp Thr Ala Pro Val He His 820 825 830 Gly Val Asp Val He Asn Ser Thr Leu Val Lys Val Thr Trp Ser Thr 835 840 845 Val Pro Lys Asp Arg Val His Gly Arg Leu Lys Gly Tyr Gin He Asn 850 855 860 Trp Trp Lys Thr Lys Ser Leu Leu Asp Gly Arg Thr His Pro Lys Glu 865 870 875 880 Val Asn He Leu Arg Phe Ser Gly Gin Arg Asn Ser Gly Met Val Pro 885 890 895 Ser Leu Asp Ala Phe Ser Glu Phe His Leu Thr Val Leu Ala Tyr Asn 900 905 910 Ser Lys Gly Ala Gly Pro Glu Ser Glu Pro Tyr He Phe Gin Thr Pro 915 920 925 Glu Gly Val Pro Glu Gin Pro Thr Phe Leu Lys Val He Lys Val Asp 930 935 940 Lys Asp Thr Ala Thr Leu Ser Trp Gly Leu Pro Lys Lys Leu Asn Gly 945 950 955 960 Asn Leu Thr Gly Tyr Leu Leu Gin Tyr Gin He He Asn Asp Thr Tyr 965 970 975 Glu He Gly Glu Leu Asn Asp He Asn He Thr Thr Pro Ser Lys Pro 980 985 990 Ser Trp His Leu Ser Asn Leu Asn Ala Thr Thr Lys Tyr Lys Phe Tyr 995 100C I 1005 Leu Arg Ala Cys Thr Ser Gin Gly Cys Gly Lys Pro He Thr Glu Glu 1010 1015 1020 Ser Ser Thr Leu Gly Glu Gly Ser Lys Gly He Gly Lys He Ser Gly 1025 1030 1035 1040 Val Asn Leu Thr Gin Lys Thr His Pro He Glu Val Phe Glu Pro Gly 1045 1050 1055 Ala Glu His He Val Arg Leu Met Thr Lys Asn Trp Gly Asp Asn Asp 1060 1065 1070 Ser He Phe Gin Asp Val He Glu Thr Arg Gly Arg Glu Tyr Ala Gly 1075 108C I 1085 Leu Tyr Asp Asp He Ser Thr Gin Gly Trp Phe lie Gly Leu Met Cys 1090 1095 1100 Ala He Ala Leu Leu Thr Leu Leu Leu Leu Thr Val Cys Phe Val Lys 633 1105 1110 1115 1120 Arg Asn Arg Gly Gly Lys Tyr Ser Val Lys Glu Lys Glu Asp Leu His 1125 1130 1135 Pro Asp Pro Glu lie Gin Ser Val Lys Asp Glu Thr Phe Gly Glu Tyr 1140 1145 1150 Ser Asp Ser Asp Glu Lys Pro Leu Lys Gly Ser Leu Arg Ser Leu Asn 1155 1160 1165 Arg Asp Met Gin Pro Thr Glu Ser Ala Asp Ser Leu Val Glu Tyr ciy 1170 1175 1180 Glu Gly Asp His Gly Leu Phe Ser Glu Asp Gly Ser Phe He Gly Ala 1185 1190 1195 1200 Tyr Ala Gly Ser Lys Glu Lys Gly Ser Val Glu Ser Asn Gly Ser Ser 1205 1210 1215 Thr Ala Thr Phe Pro Leu Arg Ala 1220 634 WHAT IS CLAIMED IS: 1. An isolated antibody or fragment thereof that immunospecifically binds to an epitope on a 282P1G3 protein encoded by the polypeptide sequence set forth in SEQ ID NO:3. 2. The antibody or fragment thereof of claim 1, wherein said antibody is a monoclonal antibody. 3. A hybridoma that produces the antibody of claim 2. 4. The antibody or fragment thereof of claim 1, wherein the monoclonal antibody is a recombinant protein. 5. The antibody or fragment thereof of claim 1, wherein the monoclonal antibody is comprised of a single chain monoclonal antibody. 6. The antibody or fragment thereof according to any one of claims 1, 2, 4 or 5, wherein said fragment is an Fab, F(ab')2, Fv or Sfv fragment. 7. The antibody or fragment thereof according to claim 1, wherein said antibody is a human antibody. 8. The antibody or fragment thereof of any one of claims 1, 2, 4, 5, 6 or 7, wherein said antibody or fragment thereof is labelled with an agent. 9. The antibody or fragment thereof of claim 8, wherein the agent is selected from the group consisting of radioactive isotopes, chemotherapeutic agents and toxins. 10. The antibody or fragment thereof of claim 9, wherein the radioactive isotope is selected from the group consisting of 91At, 11I, 113I, 90Y, 66Re, 68Re, 33Sm, 92Bi, 32P and a radioactive isotope of Lu. 11. The antibody or fragment thereof of claim 9, wherein the chemotherapeutic agent is selected from the group consisting of taxol, actinomycin, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, gelonin, and calicheamicin. 635 12. The antibody or fragment thereof of claim 9, wherein the toxin is selected from the group consisting of diphtheria toxin, enomycin, phenomycin, Pseudomonas exotoxin (PE) A, PE40, abrin, abrin A chain, mitogellin, modeccin A chain, and alpha-sarcin. 13. The antibody or fragment thereof of any one of claims 1, 2, and 4 to 12, wherein the antibody or fragment thereof further comprises a pharmaceutically acceptable carrier. 14. A vector comprising a polynucleotide encoding a single chain monoclonal antibody according to claims 4 or 5.

For the Applicant

WOLFF, BREGMAN AND GOLLER by: 636