JP2003259872A - Human esophageal carcinoma antigenic peptide and method for diagnosing esophageal carcinoma - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an esophageal carcinoma antigenic peptide useful for diagnosing the esophageal carcinoma, to provide an antibody to the antigenic peptide, and to provide methods for diagnosing the esophageal carcinoma. <P>SOLUTION: This human esophageal carcinoma antigenic peptide is expressed by a polynucleotide comprising any one of ten kinds of specified base sequences (refer to the specification). The method for diagnosing the human esophageal carcinoma comprising testing whether any antibody which bonds to the antigenic peptide exists in serum of an examinee or not, the antibody which bonds to the antigenic peptide, and the other method for diagnosing the human esophageal carcinoma comprising testing whether any antigenic peptide which bonds to the antibody exists in a living sample of the examinee or not are provided in the specification, respectively. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an antigen peptide for human esophageal cancer and a method for diagnosing esophageal cancer. More specifically, the invention of this application relates to 10 novel antigenic peptides expressed in human esophageal cancer cells, and a method for highly accurately diagnosing esophageal cancer using at least one of these peptides.

[0002]

2. Description of the Related Art Esophageal cancer is a malignant tumor that often occurs in men after the age of 40. Although the cause is unknown,
Specific factors in eating habits (for example, preference for hot and cold foods and stimulative foods, short-term meals, etc.), or factors such as alcohol and smoking are cited as the incentives.

The most frequently occurring sites are in the middle of the chest, followed by the lower chest, the upper chest, the abdominal esophagus, and the cervical esophagus. Invasion of adjacent organs early, metastasis to regional lymph nodes, especially metastasis to tracheal lymph nodes, etc. affects prognosis, generalized weakness due to dysphagia at the end stage of esophageal cancer, perforation of tracheobronchial and aortic cancer Often die from.

For the treatment of esophageal cancer, it is detected early, the excision of the carcinoma by radical surgery and the regional lymph node dissection are adequately performed, and further the surgical results are improved by both radiation therapy and chemotherapy. Is being done.

Therefore, as a countermeasure against esophageal cancer, early detection of carcinoma is the most important issue, and direct diagnosis such as esophageal angiography, esophageal fiber, and biopsy examination is mainly performed. However, these direct diagnoses are often performed on patients who are aware of some signs of discomfort in the esophagus or chest. The initial symptoms of esophageal cancer are dysphagia, posterior sternal pain, and regurgitation, but in general, many cases of esophageal cancer have already progressed at the time of detection, and further early detection is required.

Therefore, a molecular biological diagnosis method using a protein marker for esophageal cancer has been proposed. Since this method does not require large-scale equipment and the burden on the subjects is small, it can be widely applied to many subjects without subjective symptoms.

[0007] For example, as a protein marker for esophageal cancer, those described in Japanese Patent Publication No. 2000-511536 or α-fe
toprotein, CEA, SCC, CYFR21-1, microglobulin, isof
errin etc. are known.

[0008] Furthermore, a SEREX method (serological identification of antigens) for screening a protein prepared from mRNA of tumor cells of a cancer-bearing patient with autologous serum of the patient
by recombinant expression cloning) was reported (Pro
Natl. Acad. Sci. USA 92: 11810-11813, 1995; US Pat. No. 5698396), cancer antigens recognized by IgG antibody in malignant melanoma, renal cancer, esophageal cancer, colon cancer, lung cancer, etc., It has also been reported that it was isolated by the SEREX method (Int. J.
Cancer 72: 965-971, 1997; Cancer Res. 58: 1034-104.
1, 1998; Int. J. Cancer 29: 652-658, 1998; Int. J.
Oncol. 14: 703-708, 1999; Cancer Res. 56: 4766-4772,
1996; Hum. Mol. Genet 6: 33-39, 1997). In addition,
2001-333782 discloses a malignant melanoma antigen protein identified by the SEREX method, a DNA sequence encoding the same, and a method for diagnosing malignant melanoma using these.

[0009]

[Problems to be Solved by the Invention] Molecular biological diagnosis using an antigen protein marker is less burdensome on the subject than imaging of the esophagus and biopsy examination, and the examination procedure is simple. It is possible to diagnose many subjects who do not have it, and it is expected to contribute greatly to the early detection of esophageal cancer. However, in order to further improve the diagnostic accuracy, it is essential to prepare more antigen protein markers and use them in combination.

The invention of this application has been made in view of the above-mentioned circumstances, and an object thereof is to provide a plurality of novel antigen peptides effective for the diagnosis of esophageal cancer.

It is another object of the invention of this application to provide an antibody against the above-mentioned antigenic peptide and a method for esophageal cancer diagnosis using the same.

[0012]

This application discloses, as a first invention for solving the above-mentioned problems, SEQ ID NOS: 1, 3,
Provided is a human esophageal cancer antigen peptide in which a polynucleotide consisting of the nucleotide sequences of 5, 7, 9, 11, 13, 15, 17, and 19 is expressed.

This application is the second invention, SEQ ID NO:
Provided is a polynucleotide comprising each nucleotide sequence of 1, 3, 5, 7, 9, 11, 13, 15, 17 and 19 or a partial continuous sequence thereof.

This application is based on the second invention as the third invention.
Provided are recombinant expression vectors, each carrying a polynucleotide of the invention.

This application provides the third invention as the fourth invention.
Provided is a transformed cell with each recombinant expression vector of the invention.

[0016] This application is directed to the first invention as the fifth invention.
Antibodies that bind the antigenic peptides of the invention are provided.

This application provides the first invention as the sixth invention.
Provided are labeled antibodies that bind to the antigenic peptides of the invention.

As a seventh invention, this application tests whether or not an antibody that binds to the antigenic peptide of the first invention is present in the serum of a subject, and one or more types of the antibody are present in the serum. The present invention provides a method for diagnosing human esophageal cancer, characterized by determining that the subject is an esophageal cancer patient or a person at high risk of esophageal cancer.

In the diagnostic method of the seventh invention, it is a preferred embodiment to test the binding between the antibody of the subject serum and the antigen peptide on a plate on which one or more kinds of the antigen peptides of the first invention are immobilized. I am sorry.

As an eighth invention, this application tests whether or not an antigenic peptide that binds to the antibody of the fifth invention or the labeled antibody of the sixth invention is present in a biological sample of a subject, Provided is a method for diagnosing human esophageal cancer, which comprises determining a subject having one or more kinds of the antigen peptides in a sample as an esophageal cancer patient or a high risk patient of esophageal cancer.

In the diagnostic method of the eighth invention, one of preferred embodiments is to test the binding between the antibody and the antigen peptide on a plate on which one or more of the antibodies of the fifth invention are immobilized.

The present invention provides, as a ninth invention, at least the following elements: (1) one or more of the antigenic peptides of the first invention; and (2) a labeled antibody that specifically binds to serum antibodies. The present invention provides an esophageal cancer diagnosis kit.

This application provides, as a tenth invention, at least the following elements: (1) a plate on which one or more kinds of the antigen peptides of the first invention are immobilized; and (2) a specific binding to an antibody in serum. The present invention provides a diagnostic kit for esophageal cancer, which comprises a labeled antibody.

This application provides, as an eleventh invention, an esophageal cancer diagnosis kit comprising at least one kind of the labeled antibody of the sixth invention.

The present application provides, as a twelfth invention, at least the following elements: (1) one or more kinds of the antibody of the fifth invention; and (2) the above-mentioned antibody which binds to the same antigenic peptide as the antibody of (1). Sixth
An esophageal cancer diagnostic kit comprising the labeled antibody of the invention.

This application provides, as a thirteenth invention, at least the following elements: (1) a plate on which one or more kinds of the antibody of the fifth invention is immobilized; and (2) an immobilization on the plate of (1) above. An esophageal cancer diagnosis kit comprising the labeled antibody of the sixth invention, which binds to the same antigenic peptide as the above antibody.

That is, the invention of this application is based on the above-mentioned SERE.
Based on method X, a cDNA library was created from mRNA isolated from human esophageal cancer-derived cultured cell T.Tn strain, and among the peptides expressed from each cDNA, antibodies in multiple esophageal cancer patient sera and The 10 species that react were identified and completed.

The invention of this application is based on the novel antigen peptide as described above and the polynucleotide encoding the same. Regarding the base sequences and amino acid sequences shown in SEQ ID NOs: 1-18, respectively, addition or deletion of one or more bases, substitution with another base, or one or more amino acid residues based on these base mutations It also includes additions, deletions and substitutions with other amino acids.

The term "antibody in serum" means an antibody IgG that is present in the serum of patients with esophageal cancer and binds to the antigenic peptide of the first invention. The “antibody” of the fifth invention and the “labeled antibody” of the sixth invention mean a polyclonal antibody or a monoclonal antibody prepared by using the antigen peptide of the first invention as an immunogen.

Hereinafter, embodiments of each invention will be described in detail.

[0031]

BEST MODE FOR CARRYING OUT THE INVENTION The esophageal cancer antigen polypeptide of the first invention comprises SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, and 1.
It is 10 kinds of peptides that express 10 kinds of polynucleotides each consisting of 9 nucleotide sequences. As shown in Table 1, the polynucleotides encoding these 10 peptides are 9
The species is a known cDNA and one species is an unknown cDNA. In addition,
There is no known protein that encodes a cDNA as an antigen protein for an esophageal cancer antibody.

[0032]

[Table 1]

Although the translation regions of the two species are unknown, as will be described later, when these polynucleotides whose translation regions are unknown are also expressed in the host-vector system, they bind to serum antibodies derived from patients with esophageal cancer. A peptide expressed from a polynucleotide whose translation region is unknown because it expresses a peptide having sex is also included in the antigenic polypeptide of the first invention. The cDNA for which the translation region has been determined is
It has the amino acid sequences of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14 and 16.

The antigenic peptide of the first invention is the second peptide, respectively.
The polynucleotide of the invention (ie, SEQ ID NOs: 1, 3,
It can be used in the diagnosis of esophageal cancer of the sixth invention as an expression product of 10 kinds of polynucleotides each consisting of the nucleotide sequences of 5, 7, 9, 11, 13, 15, 17, and 19. For example, a recombinant expression vector (the third
From the invention), RNA is prepared by in vitro transcription, and in vitro translation is performed using this as a template to express the peptide in vitro. In addition, a recombinant expression vector is introduced into a prokaryotic cell such as Escherichia coli or Bacillus subtilis or a eukaryotic cell such as yeast, insect cell or mammalian cell to obtain a transformed cell (fourth
If the invention) is prepared, the peptide encoded by the polynucleotide can be expressed from this transformed cell.

When the antigenic peptide is expressed by in vitro translation, the above polynucleotide is inserted into a vector having an RNA polymerase promoter to prepare a recombinant expression vector, and this vector is treated with an RNA polymerase corresponding to the promoter. When added to an in vitro translation system such as a rabbit reticulocyte lysate or wheat germ extract containing the antigen peptide, the antigen peptide can be produced in vitro. RNA polymerase promoters include T7, T3, S
P6 etc. can be illustrated. Vectors containing these RNA polymerase promoters include pKA1, pCDM8, pT3 / T7
18, pT7 / 319, pBluescript II, etc. can be exemplified.

When the antigenic peptide is expressed in a microorganism such as Escherichia coli, the above polynucleotide is recombined into an expression vector having an origin capable of replicating in the microorganism, a promoter, a ribosome binding site, a DNA cloning site, a terminator and the like. When an expression vector is prepared, host cells are transformed with this expression vector, and the resulting transformant is cultured, the antigen peptide encoded by this polynucleotide can be expressed from a microorganism. At this time, it can be expressed as a fusion protein with another protein. Expression vectors for E. coli include pUC system, pBluescript II, pET expression system, pG
EX expression system etc. can be illustrated.

When the antigenic peptide is expressed in eukaryotic cells, the polynucleotide is inserted into an expression vector for eukaryotic cells having a promoter, splicing region, poly (A) addition site, etc. to prepare a recombinant vector. If prepared and introduced into a eukaryotic cell, the antigen peptide can be expressed in the transformed eukaryotic cell. As an expression vector,
pKA1, pCDM8, pSVK3, pMSG, pSVL, pBK-CMV, pBK-RSV,
Examples include EBV vector, pRS, pcDNA3, pMSG, pYES2 and the like. In addition, pIND / V5-His, pFLAG-CMV-2, pEGFP-N1, pE
If GFP-C1 etc. is used as an expression vector, His tag, F
The antigen peptide can be expressed as a fusion protein to which various tags such as LAG tag, myc tag, HA tag and GFP are added. As eukaryotic cells, monkey kidney cells COS7, mammalian cultured cells such as Chinese hamster ovary cells CHO, budding yeast, fission yeast, silkworm cells, Xenopus egg cells, etc. are generally used, but can express the antigenic peptide of the present invention. Any eukaryotic cell may be used as long as it is one. To introduce the expression vector into eukaryotic cells, known methods such as electroporation, calcium phosphate method, liposome method, and DEAE dextran method can be used.

After the antigen peptide of the first invention is expressed in prokaryotic cells or eukaryotic cells, the desired peptide can be isolated and purified from the culture by a combination of known separation procedures. For example, treatment with denaturing agents such as urea and surfactants, ultrasonic treatment, enzymatic digestion, salting out and solvent precipitation methods, dialysis, centrifugation, ultrafiltration, gel filtration, SDS-PAGE,
Isoelectric focusing, ion exchange chromatography, hydrophobic chromatography, affinity chromatography, reverse phase chromatography and the like can be mentioned.

The recombinant antigen peptide obtained by the above method includes a fusion protein with any other protein. For example, a fusion protein with glutatin-S-transferase (GST) or green fluorescent protein (GFP) can be exemplified. Furthermore, the peptide expressed in the transformed cell may be subjected to various modifications in the cell after being translated. Therefore, the modified peptide is also the first
Included within the scope of antigenic peptides of the invention. Examples of such post-translational modification include elimination of N-terminal methionine, N-terminal acetylation, sugar chain addition, limited degradation by intracellular protease, myristoylation, isoprenylation, phosphorylation and the like.

The second invention is based on the nucleotide sequences of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17 and 19 which encode the antigenic peptide of the first invention, or a partial continuous sequence thereof. Is a polynucleotide. Here, the “partially continuous sequence” is a base sequence that covers the region (ORF or CDS region) encoding the antigen peptide in each base sequence.

SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17
Or, the nucleotide sequence of 19 is a cDNA prepared from total mRNA isolated from a cultured cell T.Tn strain derived from human esophageal cancer.
CDNA identified from the library. Therefore, these cDNAs can be obtained by a known method (Mol. Cell Biol. 2, 161-170, 1982; J. Gene 25, 26 from human esophageal cancer-derived cell T.Tn strain).
3-269, 1983; Gene, 150, 243-250, 1994) for cD
Synthesized NA, SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17
Alternatively, it can be obtained by a method of isolating each cDNA using a probe DNA prepared based on each nucleotide sequence of 19. Alternatively, each cDNA can also be obtained by an RT-PCR method in which a primer set is prepared based on each nucleotide sequence and the mRNA isolated from the T.Tn cell line is used as a template. The obtained cDNA is, for example, PCR (Polym
erase chain reaction) method, NASBN (Nucleic acid sequ)
ence based amplification) method, TMA (Transcription-m
ediated amplification) method and SDA (Strand Displac)
It can be amplified by a commonly used gene amplification method such as ement amplification method.

The antibody of the fifth invention is a polyclonal antibody or a monoclonal antibody, and a whole molecule capable of binding to an epitope of the antigenic peptide of the first invention, and
Fab, F (ab ') ₂ , Fv fragments and the like are all included. Such an antibody is, for example, in the case of a polyclonal antibody, after immunizing an animal with an antigen peptide or a partial fragment thereof as an immunogen,
It can be obtained from serum. Alternatively, it can be prepared by introducing the expression vector for eukaryotic cells into the muscle or skin of an animal by injection or gene gun, and then collecting serum. As animals, mice, rats, rabbits, goats, chickens and the like are used.

Further, the monoclonal antibody is prepared by a known method for producing a monoclonal antibody ("Monoclonal antibody", written by Kamei Nagasou and Hirokuji Terada, Hirokawa Shoten, 1990; "Monoclonal Ant.
ibody "James W. Goding, third edition, Academic Pre
ss, 1996), for example, by the following procedure. 1: Preparation of Hybridoma Cell Group Immunizing a mammal with an immunogen containing each of the antigenic peptides of the first invention or a partial fragment thereof, and appropriately boosting the animal as necessary to sufficiently sensitize the animal. . Then from this animal antibody-producing cells (lymphocytes or spleen cells)
To extract fused cells of the myeloma (myeloma) cell line. A hybridoma cell group can be obtained by selecting and culturing a plurality of cells each producing the desired monoclonal antibody from these fused cell lines. Hereinafter, each step will be described in detail. a) Preparation of immunogen For example, the antigen peptide expressed by in vitro transcription from the recombinant expression vector of the third invention or the antigen peptide expressed from the transformed cell of the fourth invention can be used as the immunogen. Alternatively, a partial fragment (10-20 amino acids)
In the case of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14 and 18
It may be a synthetic peptide prepared based on the amino acid sequence of. These immunogens can also be used in the form of fusion proteins with other proteins (eg glutathione-S-transferase: GST). The use of such a fusion protein is particularly preferable because it facilitates and ensures the isolation of the target protein from the expression product of the host-vector system, and the hybridoma cell screening step described below. b) Immunization of animals As the animals to be immunized, mammals used in known hybridoma production methods can be used. Specifically, for example, mouse, rat, goat, sheep, cow, horse and the like. However, from the viewpoint of easy availability of myeloma cells to be fused with the extracted antibody-producing cells, it is preferable to use mice or rats as the immunized animals. Also,
There are no particular restrictions on the strains of mouse and rat actually used, and in the case of mice, for example, strains A, AKR, BALB, etc.
/ c, BDP, BA, CE, C3H, 57BL, C57BR, C57L, DBA, FL,
HTH, HT1, LP, NZB, NZW, RF, RIII, SJL, SWR, WB, 12
If 9 etc. are also rats, for example, Low, Lewis
s, Spraque, Daweley, ACI, BN, Fischer and the like can be used. Of these, the BALB / c strain is particularly preferable for mice and the low strain for rats is particularly preferable as the immunized animals, considering the fusion compatibility with myeloma cells described below. In addition,
The age of immunization of these mice or rats is preferably 5 to 12 weeks.

Immunization of animals can be carried out by administering the solution of the immunogen intradermally or intraperitoneally to the animals. The administration schedule of the immunogen varies depending on the type of animal to be immunized, individual difference, etc.
The administration interval is preferably 1 to 2 weeks. The dose of the antigen varies depending on the type of animal, individual difference, etc.
-100 μg / μl. c) Cell fusion 1 to 5 days after the final immunization day of the above administration schedule, spleen cells or lymphocytes containing antibody-producing cells are aseptically removed from the immunized animal. Isolation of antibody-producing cells from these spleen cells or lymphocytes can be performed according to a known method.

Next, the antibody-producing cells and myeloma cells are fused. This myeloma cell is not particularly limited and can be appropriately selected and used from known cell lines. However, considering the convenience of selecting hybridomas from fused cells, the selection procedure for HGPR has been established.
T (Hpoxanthine-guanine phosphoribosyl transferas
e) It is preferable to use a defective strain. That is, mouse-derived X63-Ag8 (X63), NS1-Ag4 / 1 (NS-1), P3X63-Ag8.Ul (P3
Ul), X63-Ag8.653 (X63.653), SP2 / 0-Ag14 (SP2 / 0), MPC1
1-45.6TG1.7 (45.6TG), FO, S149 / 5XXO, BU.1, etc., 210.RSY3.Ag.1.2.3 (Y3) from rat, U266AR (SK from human)
O-007), GM1500 / GTG-A12 (GM1500), UC729-6, LICR-LOW
-HMy2 (HMy2), 8226AR / NIP4-1 (NP41) etc.

The fusion of the antibody-producing cells and the myeloma cells can be appropriately carried out according to a known method under conditions that do not extremely reduce the cell viability. As such a method, for example, a chemical method of mixing antibody-producing cells and myeloma cells in a high-concentration polymer solution such as polyethylene glycol, a physical method of utilizing electrical stimulation, or the like can be used.

The selection of fused cells and non-fused cells is carried out, for example, by
It is preferable to carry out by a known HAT (hypoxanthine / aminopterin / thymidine) selection method. This method is effective when obtaining fused cells using HGPRT-deficient myeloma cells that cannot survive in the presence of aminopterin. That is, by culturing the unfused cells and the fused cells in HAT medium, only the fused cells having resistance to aminopterin can be selectively allowed to survive and proliferate. d) Screening of hybridoma The screening of hybridoma cells producing the desired monoclonal antibody is carried out by a known enzyme immunoassay (EI
A: Enzyme Immunoassay), radioimmunoassay (RIA: Ra
dio Immunoassay), fluorescent antibody method and the like. When the fusion protein is used as an immunogen,
Hybridoma cells can be more reliably screened by performing the above-mentioned screening methods together for a protein that is a fusion partner.

By such screening, a group of hybridoma cells each producing a monoclonal antibody that specifically binds to the antigenic peptide can be obtained.

The hybridoma cells after screening are cloned by a known method such as a methylcellulose method, a soft agarose method, and a limiting dilution method, and used for antibody production.

The hybridoma cells obtained by the method described above can be stored in a frozen state in liquid nitrogen or in a freezer at -80 ° C or lower. 2: Acquisition and purification of monoclonal antibody By culturing the hybridoma cell prepared in the above 1 by a known method, a monoclonal antibody that specifically binds to the antigen peptide can be obtained.

The culture may be carried out, for example, in a medium of the same composition used in the above-mentioned cloning method, or in order to produce a large amount of monoclonal antibody, hybridoma cells are injected intraperitoneally into a mouse and the ascites fluid is injected. The monoclonal antibody may be collected from

The monoclonal antibody thus obtained can be purified by, for example, ammonium sulfate salting out method, gel filtration method, ion exchange chromatography method, affinity chromatography method and the like.

The labeled antibody of the sixth invention of this application is the same polyclonal antibody or monoclonal antibody as the antibody of the fifth invention, and is an antibody labeled with a labeling substance. As the labeling substance, an enzyme, a radioisotope or a fluorescent dye can be used. The enzyme is turnover
There is no particular limitation as long as it satisfies the conditions such as large number, stability even when bound to an antibody, and specifically coloring a substrate, and an enzyme used for a usual EIA, for example, Peroxidase, β-galactosidase, alkaline phosphatase, glucose oxidase, acetylcholinesterase, glucose-6-phosphorylation dehydrogenase, malate dehydrogenase and the like can also be used. In addition, enzyme inhibitors, coenzymes and the like can also be used. The binding between these enzymes and the antibody can be performed by a known method using a crosslinking agent such as a maleimide compound. As the substrate, a known substance can be used depending on the type of enzyme used. For example, when peroxidase is used as the enzyme, 3,3 ′, 5,5′-tetramethylbenzidine can be used, and when alkaline phosphatase is used as the enzyme, paranitrophenol or the like can be used. As a radioisotope, ¹²⁵ I
Those used in ordinary RIA such as ³ H and ³ H can be used. As the fluorescent dye, those used in ordinary fluorescent antibody methods such as fluorescein isothiocyanate (FITC) and tetramethylrhodamine isothiocyanate (TRITC) can be used.

The method for diagnosing human esophageal cancer according to the seventh aspect of the present invention tests whether or not there is at least one antibody that binds to the antigenic peptide according to the first aspect of the present invention in the serum of a subject, and the presence of the antibody in the serum Subject to be determined to be an esophageal cancer patient or a high risk person of esophageal cancer. That is, the antigenic peptide of the first invention is
Since it was identified as a peptide that binds to antibodies (IgG) in the sera of multiple patients with esophageal cancer, one of the antibodies that binds to these antigenic peptides by reacting with the sera of subjects
A serum containing more than one type can be determined as a serum of an esophageal cancer patient or an esophageal cancer high-risk patient. At this time, it is preferable to determine the binding of serum peptides to preferably 3 or more, and more preferably 5 or more antigenic peptides.

For specific diagnosis, for example, a subject serum is brought into contact with the antigen peptide expressed by the transformed cell of the fourth invention, and the antigen peptide and the IgG antibody in the subject serum are reacted in a liquid phase. Furthermore, a labeled IgG antibody that specifically binds to the IgG antibody in serum may be reacted to detect the signal of the labeled IgG antibody. As the labeling substance of the labeled IgG antibody, an enzyme, a radioisotope or a fluorescent dye as exemplified in the labeling enzyme of the sixth invention can be used. When using an enzyme, add a substrate that decomposes and develops color by enzymatic action, determine the enzymatic activity by optically measuring the amount of substrate degradation, convert this to the amount of bound antibody, and compare with the standard value. The amount of antibody is calculated from When a radioisotope is used, the radiation dose emitted by the radioisotope is measured with a scintillation counter or the like. When a fluorescent dye is used, the amount of fluorescence may be measured by a measuring device combined with a fluorescent microscope.

For detection of the signal, Western blot analysis as shown in the examples can be adopted. Alternatively, the conjugate of the antigen peptide + the antibody in serum + the labeled IgG antibody is separated by a known separation means (chromatography method, salting out method, alcohol precipitation method, enzyme method, solid phase method, etc.), and the labeled IgG antibody is isolated. May be detected.

The diagnostic kit of the ninth invention is provided so as to enable such a diagnostic method to be carried out easily and in a wide range.

In the diagnostic method of the seventh invention, one or more kinds of antigenic peptides can be immobilized on a plate, and the binding of the test subject serum to the antibody can be tested on this substrate. By immobilizing the antigen peptide on the substrate,
Unbound labeled binding molecule can be easily removed. The diagnostic kit of the tenth aspect of the invention is provided so as to enable such a diagnostic method to be carried out easily and in a wide range.

The diagnostic method of the eighth invention of this application tests whether or not an antigenic peptide that binds to the antibody of the fifth invention is present in a biological sample of a subject, and the antigenic peptide is 1 in the sample. Subjects with more than one type are determined to be patients with esophageal cancer or those at high risk of esophageal cancer. That is, since the antibody of the fifth invention is an antibody that specifically binds to the antigenic peptide expressed in esophageal cancer cells, a biological sample containing one or more types of antigenic peptides that bind to this antibody is used in an esophageal cancer patient. Alternatively, it can be determined as a sample of a patient at high risk of esophageal cancer. At that time, it is preferable to determine the binding to the antigenic peptide in the sample for preferably 3 or more types of antibodies, and more preferably 5 or more types of antibodies. The biological sample may be blood or blood cells (mononuclear cells, etc.).

One aspect of the diagnostic method of the eighth invention is a method of binding an antibody and an antigen peptide in a liquid phase system. For example, the labeled antibody of the sixth invention and a biological sample are brought into contact with each other to bind the labeled antibody and the antigen peptide, and the conjugate is separated by the same method as in the seventh invention,
Labeled signal is detected in a similar manner. As a method that enables simple and wide-ranging implementation of such a diagnostic method,
A diagnostic kit of the eleventh invention is provided.

Another method for diagnosing in a liquid phase system is to bring the antibody (primary antibody) of the fifth invention into contact with a biological sample to bind the primary antibody and the antigen peptide, and to bind the conjugate of the sixth invention. A labeled antibody (secondary antibody) is allowed to bind, and the labeled signal in the ternary conjugate is detected. Alternatively, in order to further enhance the signal, an unlabeled secondary antibody may be first bound to the antibody + antigen peptide conjugate, and the labeling substance may be bound to this secondary antibody. Such binding of the labeling substance to the secondary antibody can be carried out, for example, by biotinylating the secondary antibody and avidinizing the labeling substance. Alternatively, an antibody (tertiary antibody) that recognizes a partial region (for example, Fc region) of the secondary antibody may be labeled, and this tertiary antibody may be bound to the secondary antibody.
Both the primary antibody and the secondary antibody may be monoclonal antibodies, or one of the primary antibody and the secondary antibody may be a polyclonal antibody. Separation of the conjugate from the liquid phase and detection of the signal can be performed in the same manner as in the seventh aspect. Further, the diagnostic kit of the twelfth invention is provided so as to enable such a diagnostic method to be carried out easily and in a wide range.

Another aspect of the diagnostic method of the eighth invention is:
A method for testing the binding between the antibody of the fifth invention and an antigen peptide in a solid phase system. This solid phase method is a preferable method for detecting an extremely small amount of antigenic peptide and simplifying the operation. That is, this solid-phase method is such that the antibody (primary antibody) of the fifth invention is immobilized on a resin plate or the like, the immobilized antibody is allowed to bind to the antigen peptide, and the unbound peptide is washed off and then left on the plate. In this method, a labeled antibody (secondary antibody) is bound to the antibody + antigen peptide conjugate and the signal of the second antibody is detected. This method
This is the so-called “sandwich method”, and when an enzyme is used as a marker, “ELISA (enzyme
The method is widely used as "linked immunosorbent assay)". Both the primary antibody and the secondary antibody may be monoclonal antibodies, or either one of the primary antibody and the secondary antibody may be a polyclonal antibody. The signal can be detected in the same manner as in the seventh aspect. In addition, the thirteenth aspect is provided as a method that enables simple and wide-ranging implementation of such a diagnostic method.
A diagnostic kit of the invention is provided.

The diagnostic kit of the ninth to thirteenth inventions is the same as the seventh invention.
And a reagent kit for performing the diagnostic method of the eighth invention. Various types of such kits are commercially available according to the type of test component, and the diagnostic kit of the present invention also includes the antigen peptide of the first invention, the antibody of the fifth invention, and / or the kit of the sixth invention. It can be constituted by each element used in publicly known kits except that a labeled antibody is used.

Hereinafter, the invention of this application will be described in more detail and specifically with reference to Examples, but the invention of this application is not limited by the following examples.

[0065]

[Example] 1. Preparation of cDNA library T.Tn strain, a cultured cell derived from human esophageal cancer, was
The cells were cultured in DMEM medium containing 10% fetal bovine serum supplemented with μg / ml). This cell line T.Tn from guanidinium-thiocyan
ate-phenol-chloroform extraction method
g) was isolated, and oligo-dT (Oligotex-dT30 super, TAKARA
Poly (A) selection was performed twice to purify mRNA. Using this obtained mRNA (5.7 μg), T.Tn strain
A cDNA library was constructed. Single-stranded cDNA was synthesized using Xho I linker primer and 5-methyl dCTP.
A double-stranded cDNA having a blunt end was synthesized from this single-stranded cDNA by T4 DNA polymerase, and a linker containing a restriction enzyme site (Eco RI / λZAP II) was added to both ends of this double-stranded cDNA. Transfer the cDNA fragment to the bacteriophage (St
ratagene) and consists of 1.8 × 10 ⁶ clones
A cDNA library was created. 2. Screening of cDNA library E. coli XL1-Blue was infected with each phage vector of the cDNA library of the T.Tn strain prepared above, and plaques were formed on an NZY agarose plate. Expression was induced in each infected Escherichia coli by treatment with 10 mM IPTG to express the peptide encoded by each cDNA. Transfer this peptide to a nitrocellulose membrane (NitroBind: Osmonics), and
[TBS containing 0.5% Tween 20 (10 mM Tris-HCl, 150 mM
NaCl; pH 7.5)] to remove the adsorbed bacteriophage by washing the membrane with TBS-Twee containing 1% albumin.
Nonspecific reaction was suppressed at n. This filter was reacted with sera of 16 esophageal cancer patients diluted 2000 times at room temperature for 2 hours each.

Serum was isolated from a patient, stored at -80 ° C, and immediately before use, TBS-Tween containing 1% by weight of albumin.
(Contains 0.5% polyoxyethylenesorbitan monolaurate
Tween) solution was used and the final dilution was made 500 times.
The diluted serum was mixed with E. coli lysate at a ratio of 1: 5, left at 4 ° C. for 8 hours, centrifuged at 15,000 rpm for 20 minutes, and the supernatant was collected. In addition, untreated serum was diluted 2000 times before use.

Blot the serum and the expressed peptide above.
Reaction with the nitrocellulose membrane at room temperature for 10 to 20 hours.
The peptide to which the antibody in the serum reacted was identified. Sanawa
Then, as a secondary antibody, alkaline phosphate diluted 5000 times
Anatase-labeled anti-human IgG-F (ab ') ₂Goat antibody (Jachson)
Nitroblue tetrazolium (Wako)
And 5-Bromo-4-Chloro-3-indolylphosphate (Wako)
Detect the labeling signal by the enzyme color reaction used and develop color
Colonies matching the positive reaction site are agarose plate
Collect from above, SM buffer (100 mM NaCl, 10 mM MgSO 4_Four,
It was dissolved in 50 mM Tris-HCl; pH 7.5). Positive color reaction
In the same manner as above until the colonies are united, the secondary,
Repeated the third screening, Ig in serum of 16 patients
Screening phage clones that react with G,
165 positive clones were isolated. 3. Identification of new antigen From the 165 positive clones obtained, PCR
PCR product was amplified and the resulting PCR product was used for Big Dye DNA Se
quencing Kit (ABI) and ABI Prism (PerkinElmer)
And sequenced using. Check using existing database
As a result of searching, 163 types of antigens derived from existing genes, unknown inheritance
There were two types of offspring-derived antigens. Some of the known genes are
3 types of oncogene-related genes, and cancer suppressor-related genes
Two gene types were included. Also, like keratin19,
What has already been established as a tumor marker for squamous cell carcinoma
, BLCAP, BST2, E (sp19), etc.
It also included the reported genes.

Excluding these antigenic peptides, which are the expression products of cancer-related genes, 10 novel antigenic peptides reactive with serum antibodies of all 16 patients were identified. these
The cDNA sequences encoding the 10 novel antigen peptides are SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17 and 19 respectively.
It has each base sequence of. In addition, SEQ ID NOS: 1, 3, 5,
The nucleotide sequences of 7, 9, 11, 13, and 15 have the amino acid sequences of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14 and 16, respectively.

FIG. 1-10 shows the results of Western blot analysis for examining the binding reaction between these 10 novel antigen peptides and the antibody in the serum of each patient. In FIG. 1-10, the arrow indicates the polypeptide specifically reacted with the antibody in the patient serum. Introduced because it was detected in E. coli extract treated with IPTG and not in untreated E. coli extract
It can be confirmed that the polypeptide is derived from cDNA.

[0070]

INDUSTRIAL APPLICABILITY As described in detail above, the invention of this application provides 10 novel antigen peptides useful as diagnostic markers for esophageal cancer. This makes it possible to improve the accuracy of diagnosis of esophageal cancer.

[0071]

[Sequence list]                                SEQUENCE LISTING <110> Japan Science and Technology Corporation <120> Antigenic peptides for carcinoma of the esophagus and diagnosis of  the carcinoma <130> NP02057-YS <140> <141> <160> 18 <170> PatentIn Ver. 2.1 <210> 1 <211> 2527 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (95) .. (2248) <400> 1 gggaggtcgg ggctgcgggc gctcgctggt ggcggacccg gaggctgctg cggcgccggg 60 gctccgtggc ctggattgaa tccgatcggg agcc atg agc gtg gac aaa gct gag 115                                       Met Ser Val Asp Lys Ala Glu                                         1 5 cta tgc ggg tct ctg ctc acc tgg tta cag acg ttc cac gtt ccg tct 163 Leu Cys Gly Ser Leu Leu Thr Trp Leu Gln Thr Phe His Val Pro Ser          10 15 20 ccc tgt gcc agc cct cag gac ctg agc agc ggc ctt gcc gta gcc tat 211 Pro Cys Ala Ser Pro Gln Asp Leu Ser Ser Gly Leu Ala Val Ala Tyr      25 30 35 gtg ctg aac cag ata gac ccc tcc tgg ttc aac gag gca tgg ctc cag 259 Val Leu Asn Gln Ile Asp Pro Ser Trp Phe Asn Glu Ala Trp Leu Gln  40 45 50 55 ggc atc tcg gaa gat cca ggt ccc aac tgg aag ctg aag gtc agc aat 307 Gly Ile Ser Glu Asp Pro Gly Pro Asn Trp Lys Leu Lys Val Ser Asn                  60 65 70 ctg aag atg gtc tta cgg agc cta gta gag tac tcc cag gat gtc ctg 355 Leu Lys Met Val Leu Arg Ser Leu Val Glu Tyr Ser Gln Asp Val Leu              75 80 85 gcg cat cct gtg tca gaa gag cat ctc cca gat gtg agc ctc att gga 403 Ala His Pro Val Ser Glu Glu His Leu Pro Asp Val Ser Leu Ile Gly          90 95 100 gag ttc tca gac ccg gca gag ctc ggc aag ctg ctt cag ctg gtg ctg 451 Glu Phe Ser Asp Pro Ala Glu Leu Gly Lys Leu Leu Gln Leu Val Leu     105 110 115 ggc tgt gcc atc agt tgc gag aaa aag cag gac cac atc cag aga atc 499 Gly Cys Ala Ile Ser Cys Glu Lys Lys Gln Asp His Ile Gln Arg Ile 120 125 130 135 atg acg ctg gaa gaa tcg gtt cag cat gtg gtg atg gaa gcc atc caa 547 Met Thr Leu Glu Glu Ser Val Gln His Val Val Met Glu Ala Ile Gln                 140 145 150 gag ctc atg acc aaa gac act cct gac tcc ctg tca cca gag acg tat 595 Glu Leu Met Thr Lys Asp Thr Pro Asp Ser Leu Ser Pro Glu Thr Tyr             155 160 165 ggc aac ttt gac agc cag tcc cgc agg tac tat ttc cta agt gag gag 643 Gly Asn Phe Asp Ser Gln Ser Arg Arg Tyr Tyr Phe Leu Ser Glu Glu         170 175 180 gct gag gag ggg gac gaa tta cag cag cgc tgt ctg gat ctg gag cgg 691 Ala Glu Glu Gly Asp Glu Leu Gln Gln Arg Cys Leu Asp Leu Glu Arg     185 190 195 cag ctg atg ctc ctg tca gag gag aag cag agc ctg gcg caa gag aat 739 Gln Leu Met Leu Leu Ser Glu Glu Lys Gln Ser Leu Ala Gln Glu Asn 200 205 210 215 gca ggg ctg cgg gag cgg atg ggc cgg cct gaa ggc gag ggt acc cca 787 Ala Gly Leu Arg Glu Arg Met Gly Arg Pro Glu Gly Glu Gly Thr Pro                 220 225 230 ggt ctc act gcc aag aag ctg ctg ctg ctg caa tcc cag ctg gag cag 835 Gly Leu Thr Ala Lys Lys Leu Leu Leu Leu Gln Ser Gln Leu Glu Gln             235 240 245 ttg cag gag gag aac ttc agg ctg gag agt ggc agg gag gat gag cgc 883 Leu Gln Glu Glu Asn Phe Arg Leu Glu Ser Gly Arg Glu Asp Glu Arg         250 255 260 ctg cgc tgt gcc gag ctg gag agg gag gtt gcg gag ctg cag cac cgg 931 Leu Arg Cys Ala Glu Leu Glu Arg Glu Val Ala Glu Leu Gln His Arg     265 270 275 aac cag gcg ctg act agc ctg gcc cag gag gca cag gcc ctg aag gat 979 Asn Gln Ala Leu Thr Ser Leu Ala Gln Glu Ala Gln Ala Leu Lys Asp 280 285 290 295 gag atg gat gaa cta cgg cag tct tcg gag cgt gct ggg cag ctg gag 1027 Glu Met Asp Glu Leu Arg Gln Ser Ser Glu Arg Ala Gly Gln Leu Glu                 300 305 310 gcc acg ctg acc agt tgc cgg cgc cgc ttg ggc gag ctg agg gag ctg 1075 Ala Thr Leu Thr Ser Cys Arg Arg Arg Leu Gly Glu Leu Arg Glu Leu             315 320 325 cgg cgg cag gtg cgg cag ctg gag gaa cgc aac gcc ggc cac gcc gag 1123 Arg Arg Gln Val Arg Gln Leu Glu Glu Arg Asn Ala Gly His Ala Glu         330 335 340 cgc acg cga caa ctg gag gat gag cta cgc cga gcg ggc tcc ctg cgc 1171 Arg Thr Arg Gln Leu Glu Asp Glu Leu Arg Arg Ala Gly Ser Leu Arg     345 350 355 gcc cag ctg gag gcg cag cgg cgg cag gtg cag gaa ctg cag ggc cag 1219 Ala Gln Leu Glu Ala Gln Arg Arg Gln Val Gln Glu Leu Gln Gly Gln 360 365 370 375 cgg cag gag gag gcc atg aag gcc gag aaa tgg cta ttt gaa tgc cgc 1267 Arg Gln Glu Glu Ala Met Lys Ala Glu Lys Trp Leu Phe Glu Cys Arg                 380 385 390 aac ctg gag gaa aag tat gag tcg gtg aca aag gag aag gag cgg ctg 1315 Asn Leu Glu Glu Lys Tyr Glu Ser Val Thr Lys Glu Lys Glu Arg Leu             395 400 405 ttg gcg gag cgg gac tcc ttg cgg gag gcc aat gag gag ctg cgc tgc 1363 Leu Ala Glu Arg Asp Ser Leu Arg Glu Ala Asn Glu Glu Leu Arg Cys         410 415 420 gcc cag ctg cag ccg cgg ggg ttg acc cag gcc gat ccc tca ctg gat 1411 Ala Gln Leu Gln Pro Arg Gly Leu Thr Gln Ala Asp Pro Ser Leu Asp     425 430 435 ccc acc tcc aca ccc gtg gat aac tta gcc gca gag atc ctg cct gcg 1459 Pro Thr Ser Thr Pro Val Asp Asn Leu Ala Ala Glu Ile Leu Pro Ala 440 445 450 455 gag ctc agg gag acg ctc ctg cgg ctt cag ctg gag aac aag cgg ctg 1507 Glu Leu Arg Glu Thr Leu Leu Arg Leu Gln Leu Glu Asn Lys Arg Leu                 460 465 470 tgc agg cag gag gcg gcc gac cgg gag cgg cag gag gag ctg cag cgc 1555 Cys Arg Gln Glu Ala Ala Asp Arg Glu Arg Gln Glu Glu Leu Gln Arg             475 480 485 cac ctg gag gat gcc aac cgc gcg cgc cac ggg ttg gag acg cag cac 1603 His Leu Glu Asp Ala Asn Arg Ala Arg His Gly Leu Glu Thr Gln His         490 495 500 cgg ctg aac cag cag cag cta tcc gag ctg cgg gcc cag gtg gag gac 1651 Arg Leu Asn Gln Gln Gln Leu Ser Glu Leu Arg Ala Gln Val Glu Asp     505 510 515 ctg cag aaa gcc ctg cag gag cag ggg ggc aag act gaa gat tcc att 1699 Leu Gln Lys Ala Leu Gln Glu Gln Gly Gly Lys Thr Glu Asp Ser Ile 520 525 530 535 ttg ctg aaa agg aag ctg gag gaa cat ttg cag aag ctt cat gag gca 1747 Leu Leu Lys Arg Lys Leu Glu Glu His Leu Gln Lys Leu His Glu Ala                 540 545 550 gat ctg gag ttg cag agg aag cgg gag tac att gag gag ctg gag cca 1795 Asp Leu Glu Leu Gln Arg Lys Arg Glu Tyr Ile Glu Glu Leu Glu Pro             555 560 565 ccc act gac agc agc aca gcc cgg cgg atc gag gag ctg cag cat aac 1843 Pro Thr Asp Ser Ser Thr Ala Arg Arg Ile Glu Glu Leu Gln His Asn         570 575 580 ttg cag aag aag gac gcg gac ttg cgg gcc atg gag gag cga tac cgc 1891 Leu Gln Lys Lys Asp Ala Asp Leu Arg Ala Met Glu Glu Arg Tyr Arg     585 590 595 cgc tac gtg gac aag gcc cgc atg gtc atg cag acc atg gaa ccc aag 1939 Arg Tyr Val Asp Lys Ala Arg Met Val Met Gln Thr Met Glu Pro Lys 600 605 610 615 cag cgg cca gct gcg ggg gca cct cca gaa ctc cat tcc ctg agg aca 1987 Gln Arg Pro Ala Ala Gly Ala Pro Pro Glu Leu His Ser Leu Arg Thr                 620 625 630 cag ctc cga gaa cgg gat gtc cgc atc cga cac ctg gag atg gac ttt 2035 Gln Leu Arg Glu Arg Asp Val Arg Ile Arg His Leu Glu Met Asp Phe             635 640 645 gag aaa agc cga agt cag cgg gag cag gaa gaa aag ctg ctc atc agt 2083 Glu Lys Ser Arg Ser Gln Arg Glu Gln Glu Glu Lys Leu Leu Ile Ser         650 655 660 gcc tgg tat aat atg ggc atg gcc ttg cag cag cga gct ggg gag gag 2131 Ala Trp Tyr Asn Met Gly Met Ala Leu Gln Gln Arg Ala Gly Glu Glu     665 670 675 cgg gcg cct gcc cat gcc cag tca ttc ctg gca cag cag cgg ctg gca 2179 Arg Ala Pro Ala His Ala Gln Ser Phe Leu Ala Gln Gln Arg Leu Ala 680 685 690 695 acc aat tct cgc cgt gga ccc ttg gga cgc ctg gca tct ctg aac ctt 2227 Thr Asn Ser Arg Arg Gly Pro Leu Gly Arg Leu Ala Ser Leu Asn Leu                 700 705 710 cgc ccc act gac aag cac tga cagacctcac aatcaagcca gcctgggctc 2278 Arg Pro Thr Asp Lys His             715 cacccaccct ggcttcctcc agctcacatg gcgcccagca ctgggcttca gccaggtgct 2338 cgagagcttt gaggccatga tctctgctct tccctctccc agattggtgg ggagggaggg 2398 cgggaggtag atataggcct gttcttttta gcaatgtgat tcttgttgtt gattctctct 2458 ctggagttca tgtgctgcct caggagactc tgattttata tttgagaaaa ataaaggcgt 2518 tcaatctgc 2527 <210> 2 <211> 717 <212> PRT <213> Homo sapiens <400> 2 Met Ser Val Asp Lys Ala Glu Leu Cys Gly Ser Leu Leu Thr Trp Leu   1 5 10 15 Gln Thr Phe His Val Pro Ser Pro Cys Ala Ser Pro Gln Asp Leu Ser              20 25 30 Ser Gly Leu Ala Val Ala Tyr Val Leu Asn Gln Ile Asp Pro Ser Trp          35 40 45 Phe Asn Glu Ala Trp Leu Gln Gly Ile Ser Glu Asp Pro Gly Pro Asn      50 55 60 Trp Lys Leu Lys Val Ser Asn Leu Lys Met Val Leu Arg Ser Leu Val  65 70 75 80 Glu Tyr Ser Gln Asp Val Leu Ala His Pro Val Ser Glu Glu His Leu                  85 90 95 Pro Asp Val Ser Leu Ile Gly Glu Phe Ser Asp Pro Ala Glu Leu Gly             100 105 110 Lys Leu Leu Gln Leu Val Leu Gly Cys Ala Ile Ser Cys Glu Lys Lys         115 120 125 Gln Asp His Ile Gln Arg Ile Met Thr Leu Glu Glu Ser Val Gln His     130 135 140 Val Val Met Glu Ala Ile Gln Glu Leu Met Thr Lys Asp Thr Pro Asp 145 150 155 160 Ser Leu Ser Pro Glu Thr Tyr Gly Asn Phe Asp Ser Gln Ser Arg Arg                 165 170 175 Tyr Tyr Phe Leu Ser Glu Glu Ala Glu Glu Gly Asp Glu Leu Gln Gln             180 185 190 Arg Cys Leu Asp Leu Glu Arg Gln Leu Met Leu Leu Ser Glu Glu Lys         195 200 205 Gln Ser Leu Ala Gln Glu Asn Ala Gly Leu Arg Glu Arg Met Gly Arg     210 215 220 Pro Glu Gly Glu Gly Thr Pro Gly Leu Thr Ala Lys Lys Leu Leu Leu 225 230 235 240 Leu Gln Ser Gln Leu Glu Gln Leu Gln Glu Glu Asn Phe Arg Leu Glu                 245 250 255 Ser Gly Arg Glu Asp Glu Arg Leu Arg Cys Ala Glu Leu Glu Arg Glu             260 265 270 Val Ala Glu Leu Gln His Arg Asn Gln Ala Leu Thr Ser Leu Ala Gln         275 280 285 Glu Ala Gln Ala Leu Lys Asp Glu Met Asp Glu Leu Arg Gln Ser Ser     290 295 300 Glu Arg Ala Gly Gln Leu Glu Ala Thr Leu Thr Ser Cys Arg Arg Arg 305 310 315 320 Leu Gly Glu Leu Arg Glu Leu Arg Arg Gln Val Arg Gln Leu Glu Glu                 325 330 335 Arg Asn Ala Gly His Ala Glu Arg Thr Arg Gln Leu Glu Asp Glu Leu             340 345 350 Arg Arg Ala Gly Ser Leu Arg Ala Gln Leu Glu Ala Gln Arg Arg Gln         355 360 365 Val Gln Glu Leu Gln Gly Gln Arg Gln Glu Glu Ala Met Lys Ala Glu     370 375 380 Lys Trp Leu Phe Glu Cys Arg Asn Leu Glu Glu Lys Tyr Glu Ser Val 385 390 395 400 Thr Lys Glu Lys Glu Arg Leu Leu Ala Glu Arg Asp Ser Leu Arg Glu                 405 410 415 Ala Asn Glu Glu Leu Arg Cys Ala Gln Leu Gln Pro Arg Gly Leu Thr             420 425 430 Gln Ala Asp Pro Ser Leu Asp Pro Thr Ser Thr Pro Val Asp Asn Leu         435 440 445 Ala Ala Glu Ile Leu Pro Ala Glu Leu Arg Glu Thr Leu Leu Arg Leu     450 455 460 Gln Leu Glu Asn Lys Arg Leu Cys Arg Gln Glu Ala Ala Asp Arg Glu 465 470 475 480 Arg Gln Glu Glu Leu Gln Arg His Leu Glu Asp Ala Asn Arg Ala Arg                 485 490 495 His Gly Leu Glu Thr Gln His Arg Leu Asn Gln Gln Gln Leu Ser Glu             500 505 510 Leu Arg Ala Gln Val Glu Asp Leu Gln Lys Ala Leu Gln Glu Gln Gly         515 520 525 Gly Lys Thr Glu Asp Ser Ile Leu Leu Lys Arg Lys Leu Glu Glu His     530 535 540 Leu Gln Lys Leu His Glu Ala Asp Leu Glu Leu Gln Arg Lys Arg Glu 545 550 555 560 Tyr Ile Glu Glu Leu Glu Pro Pro Thr Asp Ser Ser Thr Ala Arg Arg                 565 570 575 Ile Glu Glu Leu Gln His Asn Leu Gln Lys Lys Asp Ala Asp Leu Arg             580 585 590 Ala Met Glu Glu Arg Tyr Arg Arg Tyr Val Asp Lys Ala Arg Met Val         595 600 605 Met Gln Thr Met Glu Pro Lys Gln Arg Pro Ala Ala Gly Ala Pro Pro     610 615 620 Glu Leu His Ser Leu Arg Thr Gln Leu Arg Glu Arg Asp Val Arg Ile 625 630 635 640 Arg His Leu Glu Met Asp Phe Glu Lys Ser Arg Ser Gln Arg Glu Gln                 645 650 655 Glu Glu Lys Leu Leu Ile Ser Ala Trp Tyr Asn Met Gly Met Ala Leu             660 665 670 Gln Gln Arg Ala Gly Glu Glu Arg Ala Pro Ala His Ala Gln Ser Phe         675 680 685 Leu Ala Gln Gln Arg Leu Ala Thr Asn Ser Arg Arg Gly Pro Leu Gly     690 695 700 Arg Leu Ala Ser Leu Asn Leu Arg Pro Thr Asp Lys His 705 710 715 <210> 3 <211> 5676 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (658) .. (4056) <400> 3 ggatccttga gggcactggt gcgactttca ggtgaggtct tagcagatga aagcggctgg 60 ctgtggcccg cgccagtagt gctttctgct ccgcactcgc cgtgagccag gtgtgcaacc 120 ggatttgggg cgagggtcgc gctggctacc tcgcatgcgc agagccggaa gcccgctgac 180 cggactacag ctcccagaag agccttgtgg aggccgcaga cgcgaagccg ctggcgccat 240 cttgaaatct gatcctccat ccccgaggct ttgcgtctgc gcggccggcc gctgctgctc 300 cgggagccca gtctgctaaa aggggaggac gttgaggacg cggcggctgg cgggagagac 360 agctggggag agacatggca gggtcggagc gcggcctgcg cctctgtcac tcagcatcct 420 cttaggcgtt tccacgcccg ccccctgccc gaggggcggg gctgacggct ctggtacccg 480 gagtcggcgc gcggggcagg ggcgcgcccc tgcagagtgg ggaccccact gggctgtgcc 540 atgctgaccg gagaccaccg aggcgggaga cagagcgcgg cgaagagcca ttgagtggtc 600 acccagtagc cgccgccgcc gccgcctcgg gaagcttgcc acccgctagg agggaag 657 atg aag gag att tgc agg atc tgt gcc cga gag ctg tgt gga aac cag 705 Met Lys Glu Ile Cys Arg Ile Cys Ala Arg Glu Leu Cys Gly Asn Gln   1 5 10 15 cgg cgc tgg atc ttc cac acg gcg tcc aag ctc aat ctc cag gtt ctg 753 Arg Arg Trp Ile Phe His Thr Ala Ser Lys Leu Asn Leu Gln Val Leu              20 25 30 ctt tcg cac gtc ttg ggc aag gat gtc ccc cgc gat ggc aaa gcc gag 801 Leu Ser His Val Leu Gly Lys Asp Val Pro Arg Asp Gly Lys Ala Glu          35 40 45 ttc gct tgc agc aag tgt gct ttc atg ctt gat cga atc tat cga ttc 849 Phe Ala Cys Ser Lys Cys Ala Phe Met Leu Asp Arg Ile Tyr Arg Phe      50 55 60 gac aca gtt att gcc cgg att gaa gcg ctt tct att gag cgc ttg caa 897 Asp Thr Val Ile Ala Arg Ile Glu Ala Leu Ser Ile Glu Arg Leu Gln  65 70 75 80 aag ctg cta ctg gag aag gat cgc ctc aag ttc tgc att gcc agt atg 945 Lys Leu Leu Leu Glu Lys Asp Arg Leu Lys Phe Cys Ile Ala Ser Met                  85 90 95 tat cgg aag aat aac gat gac tct ggc gcg gag atc aag gcg ggg aat 993 Tyr Arg Lys Asn Asn Asp Asp Ser Gly Ala Glu Ile Lys Ala Gly Asn             100 105 110 ggg acg gtt gac atg tcc gtc tta ccc gat gcg aga tac tct gca ctg 1041 Gly Thr Val Asp Met Ser Val Leu Pro Asp Ala Arg Tyr Ser Ala Leu         115 120 125 ctc cag gag gac ttc gcc tat tca ggg ttt gag tgc tgg gtg gag aat 1089 Leu Gln Glu Asp Phe Ala Tyr Ser Gly Phe Glu Cys Trp Val Glu Asn     130 135 140 gag gat cag atc cag gag cca cac agc tgc cat ggt tca gaa ggc cct 1137 Glu Asp Gln Ile Gln Glu Pro His Ser Cys His Gly Ser Glu Gly Pro 145 150 155 160 gga aac cga ccc agg aga tgc cgt ggt tgt gcc gct ttg cgg gtt gct 1185 Gly Asn Arg Pro Arg Arg Cys Arg Gly Cys Ala Ala Leu Arg Val Ala                 165 170 175 gat tct gac tat gaa gcc att tgt aag gta cct cga aag gtg gcc aga 1233 Asp Ser Asp Tyr Glu Ala Ile Cys Lys Val Pro Arg Lys Val Ala Arg             180 185 190 agt atc tcc tgc ggc cct tct agc agg tgg tcg acc agc att tgc act 1281 Ser Ile Ser Cys Gly Pro Ser Ser Arg Trp Ser Thr Ser Ile Cys Thr         195 200 205 gaa gaa cca gcg ttg tct gag gtt ggg cca ccc gac tta gca agc aca 1329 Glu Glu Pro Ala Leu Ser Glu Val Gly Pro Pro Asp Leu Ala Ser Thr     210 215 220 aag gta ccc cca gat gga gaa agc atg gag gaa gag acg cct ggt tcc 1377 Lys Val Pro Pro Asp Gly Glu Ser Met Glu Glu Glu Thr Pro Gly Ser 225 230 235 240 tct gtg gaa tct ttg gat gca agc gtc cag gct agc cct cca caa cag 1425 Ser Val Glu Ser Leu Asp Ala Ser Val Gln Ala Ser Pro Pro Gln Gln                 245 250 255 aaa gat gag gag act gag aga agt gca aag gaa ctt gga aag tgt gac 1473 Lys Asp Glu Glu Thr Glu Arg Ser Ala Lys Glu Leu Gly Lys Cys Asp             260 265 270 tgt tgt tca gat gat cag gct ccg cag cat ggg tgt aat cac aag ctg 1521 Cys Cys Ser Asp Asp Gln Ala Pro Gln His Gly Cys Asn His Lys Leu         275 280 285 gaa tta gct ctt agc atg att aaa ggt ctt gat tat aag ccc atc cag 1569 Glu Leu Ala Leu Ser Met Ile Lys Gly Leu Asp Tyr Lys Pro Ile Gln     290 295 300 agc ccc cga ggg agc agg ctt ccg att cca gtg aaa tcc agc cta cct 1617 Ser Pro Arg Gly Ser Arg Leu Pro Ile Pro Val Lys Ser Ser Leu Pro 305 310 315 320 gga gcc aag cct ggc cct agc atg aca gat gga gtt agt tcc ggt ttc 1665 Gly Ala Lys Pro Gly Pro Ser Met Thr Asp Gly Val Ser Ser Gly Phe                 325 330 335 ctt aac agg tct ttg aaa ccc ctt tac aag aca cct gtg agt tat ccc 1713 Leu Asn Arg Ser Leu Lys Pro Leu Tyr Lys Thr Pro Val Ser Tyr Pro             340 345 350 ttg gag ctt tca gac ctg cag gag ctg tgg gat gat ctc tgt gaa gat 1761 Leu Glu Leu Ser Asp Leu Gln Glu Leu Trp Asp Asp Leu Cys Glu Asp         355 360 365 tat ttg ccg ctc cgg gtc cag ccc atg act gaa gag ttg ctg aaa caa 1809 Tyr Leu Pro Leu Arg Val Gln Pro Met Thr Glu Glu Leu Leu Lys Gln     370 375 380 caa aag ctg aat tca cat gag acc act ata act cag cag tct gta tct 1857 Gln Lys Leu Asn Ser His Glu Thr Thr Ile Thr Gln Gln Ser Val Ser 385 390 395 400 gat tcc cac ttg gca gaa ctc cag gaa aaa atc cag caa aca gag gcc 1905 Asp Ser His Leu Ala Glu Leu Gln Glu Lys Ile Gln Gln Thr Glu Ala                 405 410 415 acc aac aag att ctt caa gag aaa ctt aat gaa atg agc tat gaa cta 1953 Thr Asn Lys Ile Leu Gln Glu Lys Leu Asn Glu Met Ser Tyr Glu Leu             420 425 430 aag tgt gct cag gag tcg tct caa aag caa gat ggt aca att cag aac 2001 Lys Cys Ala Gln Glu Ser Ser Gln Lys Gln Asp Gly Thr Ile Gln Asn         435 440 445 ctc aag gaa act ctg aaa agc agg gaa cgt gag act gag gag ttg tac 2049 Leu Lys Glu Thr Leu Lys Ser Arg Glu Arg Glu Thr Glu Glu Leu Tyr     450 455 460 cag gta att gaa ggt caa aat gac aca atg gca aag ctt cga gaa atg 2097 Gln Val Ile Glu Gly Gln Asn Asp Thr Met Ala Lys Leu Arg Glu Met 465 470 475 480 ctg cac caa agc cag ctt gga caa ctt cac agc tca gag ggt act tct 2145 Leu His Gln Ser Gln Leu Gly Gln Leu His Ser Ser Glu Gly Thr Ser                 485 490 495 cca gct cag caa cag gta gct ctg ctt gat ctt cag agt gct tta ttc 2193 Pro Ala Gln Gln Gln Val Ala Leu Leu Asp Leu Gln Ser Ala Leu Phe             500 505 510 tgc agc caa ctt gaa ata cag aag ctc cag agg gtg gta cga cag aaa 2241 Cys Ser Gln Leu Glu Ile Gln Lys Leu Gln Arg Val Val Arg Gln Lys         515 520 525 gag cgc caa ctg gct gat gcc aaa caa tgt gtg caa ttt gta gag gct 2289 Glu Arg Gln Leu Ala Asp Ala Lys Gln Cys Val Gln Phe Val Glu Ala     530 535 540 gca gca cac gag agt gaa cag cag aaa gag gct tct tgg aaa cat aac 2337 Ala Ala His Glu Ser Glu Gln Gln Lys Glu Ala Ser Trp Lys His Asn 545 550 555 560 cag gaa ttg cga aaa gcc ttg cag cag cta caa gaa gaa ttg cag aat 2385 Gln Glu Leu Arg Lys Ala Leu Gln Gln Leu Gln Glu Glu Leu Gln Asn                 565 570 575 aag agc caa cag ctt cgt gcc tgg gag gct gaa aaa tac aat gag att 2433 Lys Ser Gln Gln Leu Arg Ala Trp Glu Ala Glu Lys Tyr Asn Glu Ile             580 585 590 cga acc cag gaa caa aac atc cag cac cta aac cat agt ctg agt cac 2481 Arg Thr Gln Glu Gln Asn Ile Gln His Leu Asn His Ser Leu Ser His         595 600 605 aag gag cag ttg ctt cag gaa ttt cgg gag ctc cta cag tat cga gat 2529 Lys Glu Gln Leu Leu Gln Glu Phe Arg Glu Leu Leu Gln Tyr Arg Asp     610 615 620 aac tca gac aaa acc ctt gaa gca aat gaa atg ttg ctt gag aaa ctt 2577 Asn Ser Asp Lys Thr Leu Glu Ala Asn Glu Met Leu Leu Glu Lys Leu 625 630 635 640 cgc cag cga ata cat gat aaa gct gtt gct ctg gag cgg gct ata gat 2625 Arg Gln Arg Ile His Asp Lys Ala Val Ala Leu Glu Arg Ala Ile Asp                 645 650 655 gaa aaa ttc tct gct cta gaa gag aaa gaa aaa gaa ctg cgc cag ctt 2673 Glu Lys Phe Ser Ala Leu Glu Glu Lys Glu Lys Glu Leu Arg Gln Leu             660 665 670 cgt ctt gct gtg aga gag cga gat cat gac tta gag aga ctg cgc gat 2721 Arg Leu Ala Val Arg Glu Arg Asp His Asp Leu Glu Arg Leu Arg Asp         675 680 685 gtc ctc tcc tcc aat gaa gct act atg caa agt atg gag agt ctc ctg 2769 Val Leu Ser Ser Asn Glu Ala Thr Met Gln Ser Met Glu Ser Leu Leu     690 695 700 agg gcc aaa ggc ctg gaa gtg gaa cag tta tct act acc tgt caa aac 2817 Arg Ala Lys Gly Leu Glu Val Glu Gln Leu Ser Thr Thr Cys Gln Asn 705 710 715 720 ctc cag tgg ctg aaa gaa gaa atg gaa acc aaa ttt agc cgt tgg cag 2865 Leu Gln Trp Leu Lys Glu Glu Met Glu Thr Lys Phe Ser Arg Trp Gln                 725 730 735 aag gaa caa gag agt atc att cag cag tta cag acg tct ctt cat gat 2913 Lys Glu Gln Glu Ser Ile Ile Gln Gln Leu Gln Thr Ser Leu His Asp             740 745 750 agg aac aaa gaa gtg gag gat ctt agt gca aca ctg ctc tgc aaa ctt 2961 Arg Asn Lys Glu Val Glu Asp Leu Ser Ala Thr Leu Leu Cys Lys Leu         755 760 765 gga cca ggg cag agt gag ata gca gag gag ctg tgc cag cgt cta cag 3009 Gly Pro Gly Gln Ser Glu Ile Ala Glu Glu Leu Cys Gln Arg Leu Gln     770 775 780 cga aag gaa agg atg ctg cag gac ctt cta agt gat cga aat aaa caa 3057 Arg Lys Glu Arg Met Leu Gln Asp Leu Leu Ser Asp Arg Asn Lys Gln 785 790 795 800 gtg ctg gaa cat gaa atg gag att caa ggc ctg ctt cag tct gtg agc 3105 Val Leu Glu His Glu Met Glu Ile Gln Gly Leu Leu Gln Ser Val Ser                 805 810 815 acc agg gag cag gaa agc caa gct gct gca gag aag ttg gtg caa gcc 3153 Thr Arg Glu Gln Glu Ser Gln Ala Ala Ala Glu Lys Leu Val Gln Ala             820 825 830 tta atg gaa aga aat tca gaa tta cag gcc ctg cgc caa tat tta gga 3201 Leu Met Glu Arg Asn Ser Glu Leu Gln Ala Leu Arg Gln Tyr Leu Gly         835 840 845 ggg aga gac tcc ctg atg tcc caa gca ccc atc tct aac caa caa gct 3249 Gly Arg Asp Ser Leu Met Ser Gln Ala Pro Ile Ser Asn Gln Gln Ala     850 855 860 gaa gtt acc ccc act ggc cgt ctt gga aaa cag act gat caa ggt tca 3297 Glu Val Thr Pro Thr Gly Arg Leu Gly Lys Gln Thr Asp Gln Gly Ser 865 870 875 880 atg cag ata cct tcc aga gat gat agc act tca ttg act gcc aaa gag 3345 Met Gln Ile Pro Ser Arg Asp Asp Ser Thr Ser Leu Thr Ala Lys Glu                 885 890 895 gat gtc agc ata ccc aga tcc aca tta gga gac ttg gac aca gtt gca 3393 Asp Val Ser Ile Pro Arg Ser Thr Leu Gly Asp Leu Asp Thr Val Ala             900 905 910 ggg ctg gaa aaa gaa ctg agt aat gcc aaa gag gaa ctt gaa ctc atg 3441 Gly Leu Glu Lys Glu Leu Ser Asn Ala Lys Glu Glu Leu Glu Leu Met         915 920 925 gct aaa aaa gaa aga gaa agt cag atg gaa ctt tct gct cta cag tcc 3489 Ala Lys Lys Glu Arg Glu Ser Gln Met Glu Leu Ser Ala Leu Gln Ser     930 935 940 atg atg gct gtg cag gaa gaa gag ctg cag gtg cag gct gct gat atg 3537 Met Met Ala Val Gln Glu Glu Glu Leu Gln Val Gln Ala Ala Asp Met 945 950 955 960 gag tct ctg acc agg aac ata cag att aaa gaa gat ctc ata aag gac 3585 Glu Ser Leu Thr Arg Asn Ile Gln Ile Lys Glu Asp Leu Ile Lys Asp                 965 970 975 ctg caa atg caa ctg gtt gat cct gaa gac ata cca gct atg gaa cgc 3633 Leu Gln Met Gln Leu Val Asp Pro Glu Asp Ile Pro Ala Met Glu Arg             980 985 990 ctg acc cag gaa gtc tta ctt ctt cgg gaa aaa gtt gct tca gta gaa 3681 Leu Thr Gln Glu Val Leu Leu Leu Arg Glu Lys Val Ala Ser Val Glu         995 1000 1005 tcc cag ggt caa gaa att tca gga aac cga aga caa cag ttg ctg ctg 3729 Ser Gln Gly Gln Glu Ile Ser Gly Asn Arg Arg Gln Gln Leu Leu Leu    1010 1015 1020 atg cta gaa gga cta gta gat gaa cgg agt cgg ctc aat gag gcc tta 3777 Met Leu Glu Gly Leu Val Asp Glu Arg Ser Arg Leu Asn Glu Ala Leu 1025 1030 1035 1040 caa gca gag aga cag ctc tat agc agt ctg gtg aag ttc cat gcc cat 3825 Gln Ala Glu Arg Gln Leu Tyr Ser Ser Leu Val Lys Phe His Ala His                1045 1050 1055 cca gag agc tct gag aga gac cga act ctg cag gtg gaa ctg gaa ggg 3873 Pro Glu Ser Ser Glu Arg Asp Arg Thr Leu Gln Val Glu Leu Glu Gly            1060 1065 1070 gct cag gtg tta cgc agt cgg cta gaa gaa gtt ctt gga aga agc ttg 3921 Ala Gln Val Leu Arg Ser Arg Leu Glu Glu Val Leu Gly Arg Ser Leu        1075 1080 1085 gag cgc tta aac agg ctg gag acc ctg gcc gcc att gga ggt gca gct 3969 Glu Arg Leu Asn Arg Leu Glu Thr Leu Ala Ala Ile Gly Gly Ala Ala    1090 1095 1100 gca ggg gat gac acc gaa gat aca agc act gag ttc act gac agt att 4017 Ala Gly Asp Asp Thr Glu Asp Thr Ser Thr Glu Phe Thr Asp Ser Ile 1105 1110 1115 1120 gag gag gag gct gca cac cat agt cac cag caa cta tag cttcagaagc 4066 Glu Glu Glu Ala Ala His His Ser His Gln Gln Leu                1125 1130 atttttactt gcaagacgat ggacacattc cccttgggct ttttgtaact gaaacgcacc 4126 acagaagaca gggagtcatc gaagggctgc tcggggaggt ggcagggcgg aggacctgct 4186 tgggaagaaa ctccaagaag attggaatgc ttccaaagca agaatctttc tcagtgaaat 4246 ctcattatac aaagagaacc ttatgcaacc tgacaaacca ctgaggtcat ggtgactcag 4306 tgatcagcag atggtacttc aacagcaatc ccctgtcaaa cctcagaact tgaggctgaa 4366 acattgcttc cacccaccat cagtgaagat gtaactagca tgttacaaga gtgaataatc 4426 tggacttcag agattaagtc accaatagtg atctcacaag cactcaccgg aactcctata 4486 atgtctccac tttgtccatg ccatttagca atctcatctc ctaaatggac tgtgcctatg 4546 attcttaagg agaaagtgaa tcattggtag atatcctgca caagcagctg gactttccag 4606 taatagcttt cttggggcta ttaggaaaat taaacaagaa atgaggcttt ctgggtctgc 4666 ctgtatgtct tctgcataag acaaagaaga gacatcgaat caaccaataa gaagagccca 4726 aataagcatc ctcaaatctt ttgggatttg gcacttgggg acatgagtag ttgtctggga 4786 tacgtcatat tctcaacagt ttctttgtag tagtaggatc accttcttat aataggatca 4846 ccttcttgtt gctatagctg tacccgacct tcccttctcc cttgagtgct tgcatgagct 4906 ccacttttcc ttttgcttga acagcttctc ctgagtcctc cttaccgatg gttgtgactt 4966 taattatata catctctgtc cctccagaca gatccctctg tcctcactct ctgatttcat 5026 tgaggatctt gggtgagaga gagggacctg caggatgaac aaatgtctac tctaagacag 5086 ctagattggg aggttggctg gtcactgatg gttataatga ctgtgggaca ggattaactt 5146 cagaataaat gaacaggaga cacagatatg aagaaagttt ctgattgata tggtctgaag 5206 tactcctggt attgcaagtc atttgctcta attctcaatt gtaggcaaac tgatttgtaa 5266 atttgcttct tcagccttct ttcctgtagc ctagcatgga gaatctgacc agaccccatt 5326 ttgagaaggt cagcctacac tggaatgaac tttttacatt agggcatttg tatttccctc 5386 acaatacttg ccacattact tggcatagga gagatgctta gtgtaattat aagttaacaa 5446 gcctttggat cagggcttga ctcatgatag acaaagtata tgcctgctgg atggaagaat 5506 ctcttgggcg agcaccattt ttctttccat cacctttcct tgaaaatata tcttcagctt 5566 tgggtaggag gaatcttggt gtatgaaatc attgcaaatt tacttcatct tttctggagt 5626 ttgaagttgt gactctcctg ctaccaatta aataaagctt actttgccat 5676 <210> 4 <211> 1132 <212> PRT <213> Homo sapiens <400> 4 Met Lys Glu Ile Cys Arg Ile Cys Ala Arg Glu Leu Cys Gly Asn Gln   1 5 10 15 Arg Arg Trp Ile Phe His Thr Ala Ser Lys Leu Asn Leu Gln Val Leu              20 25 30 Leu Ser His Val Leu Gly Lys Asp Val Pro Arg Asp Gly Lys Ala Glu          35 40 45 Phe Ala Cys Ser Lys Cys Ala Phe Met Leu Asp Arg Ile Tyr Arg Phe      50 55 60 Asp Thr Val Ile Ala Arg Ile Glu Ala Leu Ser Ile Glu Arg Leu Gln  65 70 75 80 Lys Leu Leu Leu Glu Lys Asp Arg Leu Lys Phe Cys Ile Ala Ser Met                  85 90 95 Tyr Arg Lys Asn Asn Asp Asp Ser Gly Ala Glu Ile Lys Ala Gly Asn             100 105 110 Gly Thr Val Asp Met Ser Val Leu Pro Asp Ala Arg Tyr Ser Ala Leu         115 120 125 Leu Gln Glu Asp Phe Ala Tyr Ser Gly Phe Glu Cys Trp Val Glu Asn     130 135 140 Glu Asp Gln Ile Gln Glu Pro His Ser Cys His Gly Ser Glu Gly Pro 145 150 155 160 Gly Asn Arg Pro Arg Arg Cys Arg Gly Cys Ala Ala Leu Arg Val Ala                 165 170 175 Asp Ser Asp Tyr Glu Ala Ile Cys Lys Val Pro Arg Lys Val Ala Arg             180 185 190 Ser Ile Ser Cys Gly Pro Ser Ser Arg Trp Ser Thr Ser Ile Cys Thr         195 200 205 Glu Glu Pro Ala Leu Ser Glu Val Gly Pro Pro Asp Leu Ala Ser Thr     210 215 220 Lys Val Pro Pro Asp Gly Glu Ser Met Glu Glu Glu Thr Pro Gly Ser 225 230 235 240 Ser Val Glu Ser Leu Asp Ala Ser Val Gln Ala Ser Pro Pro Gln Gln                 245 250 255 Lys Asp Glu Glu Thr Glu Arg Ser Ala Lys Glu Leu Gly Lys Cys Asp             260 265 270 Cys Cys Ser Asp Asp Gln Ala Pro Gln His Gly Cys Asn His Lys Leu         275 280 285 Glu Leu Ala Leu Ser Met Ile Lys Gly Leu Asp Tyr Lys Pro Ile Gln     290 295 300 Ser Pro Arg Gly Ser Arg Leu Pro Ile Pro Val Lys Ser Ser Leu Pro 305 310 315 320 Gly Ala Lys Pro Gly Pro Ser Met Thr Asp Gly Val Ser Ser Gly Phe                 325 330 335 Leu Asn Arg Ser Leu Lys Pro Leu Tyr Lys Thr Pro Val Ser Tyr Pro             340 345 350 Leu Glu Leu Ser Asp Leu Gln Glu Leu Trp Asp Asp Leu Cys Glu Asp         355 360 365 Tyr Leu Pro Leu Arg Val Gln Pro Met Thr Glu Glu Leu Leu Lys Gln     370 375 380 Gln Lys Leu Asn Ser His Glu Thr Thr Ile Thr Gln Gln Ser Val Ser 385 390 395 400 Asp Ser His Leu Ala Glu Leu Gln Glu Lys Ile Gln Gln Thr Glu Ala                 405 410 415 Thr Asn Lys Ile Leu Gln Glu Lys Leu Asn Glu Met Ser Tyr Glu Leu             420 425 430 Lys Cys Ala Gln Glu Ser Ser Gln Lys Gln Asp Gly Thr Ile Gln Asn         435 440 445 Leu Lys Glu Thr Leu Lys Ser Arg Glu Arg Glu Thr Glu Glu Leu Tyr     450 455 460 Gln Val Ile Glu Gly Gln Asn Asp Thr Met Ala Lys Leu Arg Glu Met 465 470 475 480 Leu His Gln Ser Gln Leu Gly Gln Leu His Ser Ser Glu Gly Thr Ser                 485 490 495 Pro Ala Gln Gln Gln Val Ala Leu Leu Asp Leu Gln Ser Ala Leu Phe             500 505 510 Cys Ser Gln Leu Glu Ile Gln Lys Leu Gln Arg Val Val Arg Gln Lys         515 520 525 Glu Arg Gln Leu Ala Asp Ala Lys Gln Cys Val Gln Phe Val Glu Ala     530 535 540 Ala Ala His Glu Ser Glu Gln Gln Lys Glu Ala Ser Trp Lys His Asn 545 550 555 560 Gln Glu Leu Arg Lys Ala Leu Gln Gln Leu Gln Glu Glu Leu Gln Asn                 565 570 575 Lys Ser Gln Gln Leu Arg Ala Trp Glu Ala Glu Lys Tyr Asn Glu Ile             580 585 590 Arg Thr Gln Glu Gln Asn Ile Gln His Leu Asn His Ser Leu Ser His         595 600 605 Lys Glu Gln Leu Leu Gln Glu Phe Arg Glu Leu Leu Gln Tyr Arg Asp     610 615 620 Asn Ser Asp Lys Thr Leu Glu Ala Asn Glu Met Leu Leu Glu Lys Leu 625 630 635 640 Arg Gln Arg Ile His Asp Lys Ala Val Ala Leu Glu Arg Ala Ile Asp                 645 650 655 Glu Lys Phe Ser Ala Leu Glu Glu Lys Glu Lys Glu Leu Arg Gln Leu             660 665 670 Arg Leu Ala Val Arg Glu Arg Asp His Asp Leu Glu Arg Leu Arg Asp         675 680 685 Val Leu Ser Ser Asn Glu Ala Thr Met Gln Ser Met Glu Ser Leu Leu     690 695 700 Arg Ala Lys Gly Leu Glu Val Glu Gln Leu Ser Thr Thr Cys Gln Asn 705 710 715 720 Leu Gln Trp Leu Lys Glu Glu Met Glu Thr Lys Phe Ser Arg Trp Gln                 725 730 735 Lys Glu Gln Glu Ser Ile Ile Gln Gln Leu Gln Thr Ser Leu His Asp             740 745 750 Arg Asn Lys Glu Val Glu Asp Leu Ser Ala Thr Leu Leu Cys Lys Leu         755 760 765 Gly Pro Gly Gln Ser Glu Ile Ala Glu Glu Leu Cys Gln Arg Leu Gln     770 775 780 Arg Lys Glu Arg Met Leu Gln Asp Leu Leu Ser Asp Arg Asn Lys Gln 785 790 795 800 Val Leu Glu His Glu Met Glu Ile Gln Gly Leu Leu Gln Ser Val Ser                 805 810 815 Thr Arg Glu Gln Glu Ser Gln Ala Ala Ala Glu Lys Leu Val Gln Ala             820 825 830 Leu Met Glu Arg Asn Ser Glu Leu Gln Ala Leu Arg Gln Tyr Leu Gly         835 840 845 Gly Arg Asp Ser Leu Met Ser Gln Ala Pro Ile Ser Asn Gln Gln Ala     850 855 860 Glu Val Thr Pro Thr Gly Arg Leu Gly Lys Gln Thr Asp Gln Gly Ser 865 870 875 880 Met Gln Ile Pro Ser Arg Asp Asp Ser Thr Ser Leu Thr Ala Lys Glu                 885 890 895 Asp Val Ser Ile Pro Arg Ser Thr Leu Gly Asp Leu Asp Thr Val Ala             900 905 910 Gly Leu Glu Lys Glu Leu Ser Asn Ala Lys Glu Glu Leu Glu Leu Met         915 920 925 Ala Lys Lys Glu Arg Glu Ser Gln Met Glu Leu Ser Ala Leu Gln Ser     930 935 940 Met Met Ala Val Gln Glu Glu Glu Leu Gln Val Gln Ala Ala Asp Met 945 950 955 960 Glu Ser Leu Thr Arg Asn Ile Gln Ile Lys Glu Asp Leu Ile Lys Asp                 965 970 975 Leu Gln Met Gln Leu Val Asp Pro Glu Asp Ile Pro Ala Met Glu Arg             980 985 990 Leu Thr Gln Glu Val Leu Leu Leu Arg Glu Lys Val Ala Ser Val Glu         995 1000 1005 Ser Gln Gly Gln Glu Ile Ser Gly Asn Arg Arg Gln Gln Leu Leu Leu    1010 1015 1020 Met Leu Glu Gly Leu Val Asp Glu Arg Ser Arg Leu Asn Glu Ala Leu 1025 1030 1035 1040 Gln Ala Glu Arg Gln Leu Tyr Ser Ser Leu Val Lys Phe His Ala His                1045 1050 1055 Pro Glu Ser Ser Glu Arg Asp Arg Thr Leu Gln Val Glu Leu Glu Gly            1060 1065 1070 Ala Gln Val Leu Arg Ser Arg Leu Glu Glu Val Leu Gly Arg Ser Leu        1075 1080 1085 Glu Arg Leu Asn Arg Leu Glu Thr Leu Ala Ala Ile Gly Gly Ala Ala    1090 1095 1100 Ala Gly Asp Asp Thr Glu Asp Thr Ser Thr Glu Phe Thr Asp Ser Ile 1105 1110 1115 1120 Glu Glu Glu Ala Ala His His Ser His Gln Gln Leu                1125 1130 <210> 5 <211> 3028 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (123) .. (1571) <400> 5 gaacgggtgc ctcagtgtcc ttcccctccc ctcgcctggc ctcgccgtcc tctccccgca 60 gccggaccgg aactatgtga tcccggaagt tccggggcct ttgctgtgtg ggataaacag 120 ta atg gcg gag gct gca act ccc gga aca aca gcc aca aca tca gga 167    Met Ala Glu Ala Ala Thr Pro Gly Thr Thr Ala Thr Thr Ser Gly      1 5 10 15 gca gga gcg gca gcg gcg acg gcg gca gca gcc tcc ccc acc ccg atc 215 Ala Gly Ala Ala Ala Ala Thr Ala Ala Ala Ala Ser Pro Thr Pro Ile                  20 25 30 ccc aca gtc acc gcc ccg tcc ctg ggg gcg ggc gga ggg ggc ggc ggc 263 Pro Thr Val Thr Ala Pro Ser Leu Gly Ala Gly Gly Gly Gly Gly Gly              35 40 45 agc gac ggc agc ggc ggc ggc tgg act aaa cag gtc acc tgc agg tat 311 Ser Asp Gly Ser Gly Gly Gly Trp Thr Lys Gln Val Thr Cys Arg Tyr          50 55 60 ttt atg cat ggg gtt tgt aag gaa gga gac aac tgt cgc tac tcg cat 359 Phe Met His Gly Val Cys Lys Glu Gly Asp Asn Cys Arg Tyr Ser His      65 70 75 gac ctc tct gac agt ccg tat agt gta gtg tgc aag tat ttt cag cga 407 Asp Leu Ser Asp Ser Pro Tyr Ser Val Val Cys Lys Tyr Phe Gln Arg  80 85 90 95 ggg tac tgt att tat gga gac cgc tgc aga tat gaa cat agc aaa cca 455 Gly Tyr Cys Ile Tyr Gly Asp Arg Cys Arg Tyr Glu His Ser Lys Pro                 100 105 110 ttg aaa cag gaa gaa gca act gct aca gag cta act aca aag tca tcc 503 Leu Lys Gln Glu Glu Ala Thr Ala Thr Glu Leu Thr Thr Lys Ser Ser             115 120 125 ctt gct gct tcc tca agt ctc tca tcg ata gtt gga cca ctt gtt gaa 551 Leu Ala Ala Ser Ser Ser Leu Ser Ser Ile Val Gly Pro Leu Val Glu         130 135 140 atg aat aca ggc gaa gct gag tca aga aat tca aac ttt gca act gta 599 Met Asn Thr Gly Glu Ala Glu Ser Arg Asn Ser Asn Phe Ala Thr Val     145 150 155 gga gca ggt tca gag gac tgg gtg aat gct att gag ttt gtt cct ggg 647 Gly Ala Gly Ser Glu Asp Trp Val Asn Ala Ile Glu Phe Val Pro Gly 160 165 170 175 caa ccc tac tgt ggc cgt act gcg cct tcc tgc act gaa gca ccc ctg 695 Gln Pro Tyr Cys Gly Arg Thr Ala Pro Ser Cys Thr Glu Ala Pro Leu                 180 185 190 cag ggc tca gtg acc aag gaa gaa tca gag aaa gag caa acc gcc gtg 743 Gln Gly Ser Val Thr Lys Glu Glu Ser Glu Lys Glu Gln Thr Ala Val             195 200 205 gag aca aag aag cag ctg tgc ccc tat gct gca gtg gga gag tgc cga 791 Glu Thr Lys Lys Gln Leu Cys Pro Tyr Ala Ala Val Gly Glu Cys Arg         210 215 220 tac ggg gag aac tgt gtg tat ctc cac gga gat tct tgt gac atg tgt 839 Tyr Gly Glu Asn Cys Val Tyr Leu His Gly Asp Ser Cys Asp Met Cys     225 230 235 ggg ctg cag gtc ctg cat cca atg gat gct gcc cag aga tcg cag cat 887 Gly Leu Gln Val Leu His Pro Met Asp Ala Ala Gln Arg Ser Gln His 240 245 250 255 atc aaa tcg tgc att gag gcc cat gag aag gac atg gag ctc tca ttt 935 Ile Lys Ser Cys Ile Glu Ala His Glu Lys Asp Met Glu Leu Ser Phe                 260 265 270 gcc gtg cag cgc agc aag gac atg gtg tgt ggg atc tgc atg gag gtg 983 Ala Val Gln Arg Ser Lys Asp Met Val Cys Gly Ile Cys Met Glu Val             275 280 285 gtc tat gag aaa gcc aac ccc agt gag cgc cgc ttc ggg atc ctc tcc 1031 Val Tyr Glu Lys Ala Asn Pro Ser Glu Arg Arg Phe Gly Ile Leu Ser         290 295 300 aac tgc aac cac acc tac tgt ctc aag tgc att cgc aag tgg agg agt 1079 Asn Cys Asn His Thr Tyr Cys Leu Lys Cys Ile Arg Lys Trp Arg Ser     305 310 315 gct aag caa ttt gag agc aag atc ata aag tcc tgc cca gaa tgc cgg 1127 Ala Lys Gln Phe Glu Ser Lys Ile Ile Lys Ser Cys Pro Glu Cys Arg 320 325 330 335 atc aca tct aac ttt gtc att cca agt gag tac tgg gtg gag gag aaa 1175 Ile Thr Ser Asn Phe Val Ile Pro Ser Glu Tyr Trp Val Glu Glu Lys                 340 345 350 gaa gag aag cag aaa ctc att ctg aaa tac aag gag gca atg agc aac 1223 Glu Glu Lys Gln Lys Leu Ile Leu Lys Tyr Lys Glu Ala Met Ser Asn             355 360 365 aag gcg tgc agg tat ttt gat gaa gga cgt ggg agc tgc cca ttt gga 1271 Lys Ala Cys Arg Tyr Phe Asp Glu Gly Arg Gly Ser Cys Pro Phe Gly         370 375 380 ggg aac tgt ttt tac aag cat gcg tac cct gat ggc cgt aga gag gag 1319 Gly Asn Cys Phe Tyr Lys His Ala Tyr Pro Asp Gly Arg Arg Glu Glu     385 390 395 cca cag aga cag aaa gtg gga aca tca agc aga tac cgg gcc caa cga 1367 Pro Gln Arg Gln Lys Val Gly Thr Ser Ser Arg Tyr Arg Ala Gln Arg 400 405 410 415 agg aac cac ttc tgg gaa ctc att gag gaa aga gag aac agc aac ccc 1415 Arg Asn His Phe Trp Glu Leu Ile Glu Glu Arg Glu Asn Ser Asn Pro                 420 425 430 ttt gac aac gat gaa gaa gag gtt gtc acc ttt gag ctg ggc gag atg 1463 Phe Asp Asn Asp Glu Glu Glu Val Val Thr Phe Glu Leu Gly Glu Met             435 440 445 ttg ctt atg ctt ttg gct gca ggt ggg gac gac gaa cta aca gac tct 1511 Leu Leu Met Leu Leu Ala Ala Gly Gly Asp Asp Glu Leu Thr Asp Ser         450 455 460 gaa gat gag tgg gac ttg ttt cat gat gag ctg gaa gat ttt tat gac 1559 Glu Asp Glu Trp Asp Leu Phe His Asp Glu Leu Glu Asp Phe Tyr Asp     465 470 475 ttg gat cta tag caaccttgcg tggcgtgtga actggtctgc tgacctcaga 1611 Leu Asp Leu 480 cagcagctgt cccctgtggt ggtgtggcag tgcctgtgtt ctctcctagg caggcctctc 1671 aactccaggt gctgtcctaa gaatttttac ccagggcctg tcttctcaac ccctcacctt 1731 tccctgagga gtgtgttgtt ttccctgttg aaaaaagtta caaaaataaa tcttaaagtt 1791 agttttttgt aacacgaatt taactgtcag acagttagtg taggtgtgtt gcgtcatctg 1851 ttttcaacca gattgcattt atggactttt cacacactca ttttgaggac cccaggttca 1911 aaagtaaaag cagtggccct gctttggggt ccaagaatag gagtgatggg tgaagggacc 1971 taagctggcc aatagccctc tgccccagac atgggatgtg gatccttgag gtttctggtg 2031 aaatctgcac atctgtgttt ttatatctgt tccctaccct gtaatcccta ccacgtgcac 2091 ttgttctgtg gttttggtct cttgtttaat tgcacacaag taatactact gggtaaccag 2151 aatcaggtgt gaatgtgttg agatttttta ctgttttgca tgataggaaa attgagaaag 2211 aatacgtata aaagatagag aggcataaca tcaatgcaga gttggaagtt ggctcccaag 2271 ggctgacatg gtgtgagtgt gtgggtgtgt gataagcttc tcatccctgc atagatgcag 2331 tattcttagc cttagtagaa aaacctggtt tagtggttta agccttgtgt ggcagataga 2391 tcttaaaggg caaagcagta tattggtagt tgtcaatata gcagtgctag ctctgtctat 2451 ataaatagag aaatggggtt agccatagag gttaaaacta cctggttatc ccatataata 2511 acacaaactg ggtcttggat acacagttgt atttaatgtt ttacgatcta gcctttccag 2571 tacaggcact ttctgagaaa cctttgtcct cacttgaggc attttgttgt cgggtttttg 2631 tgtttgtttt tgtgggtatt tgcctcattc cacccctgag ctttcaggta gacagacgtg 2691 attcaaaact ctgttctaag gtgtttattg tagtggagta atgggtttgc agtgataagt 2751 catacttttc caccgaaagg gagggcttgg gaatccctga gattagctaa agttaagttg 2811 ttggaagaat tccttgattg gaaattgtac ctttgtgtttttgtgtgctctg tttcctgaaa 2871 ataactcggg gatgctcctg gtttgtccat ctactgcttt gattccttgg atcccaccca 2931 ttctttcact ttaagaaaaa acaaataatt gttgcagagg tctctgtatt ttgcagctgc 2991 ccttttgtaa gaagcacttt tcccaaataa aacaatt 3028 <210> 6 <211> 482 <212> PRT <213> Homo sapiens <400> 6 Met Ala Glu Ala Ala Thr Pro Gly Thr Thr Ala Thr Thr Ser Gly Ala   1 5 10 15 Gly Ala Ala Ala Ala Thr Ala Ala Ala Ala Ser Pro Thr Pro Ile Pro              20 25 30 Thr Val Thr Ala Pro Ser Leu Gly Ala Gly Gly Gly Gly Gly Gly Ser          35 40 45 Asp Gly Ser Gly Gly Gly Trp Thr Lys Gln Val Thr Cys Arg Tyr Phe      50 55 60 Met His Gly Val Cys Lys Glu Gly Asp Asn Cys Arg Tyr Ser His Asp  65 70 75 80 Leu Ser Asp Ser Pro Tyr Ser Val Val Cys Lys Tyr Phe Gln Arg Gly                  85 90 95 Tyr Cys Ile Tyr Gly Asp Arg Cys Arg Tyr Glu His Ser Lys Pro Leu             100 105 110 Lys Gln Glu Glu Ala Thr Ala Thr Glu Leu Thr Thr Lys Ser Ser Leu         115 120 125 Ala Ala Ser Ser Ser Leu Ser Ser Ile Val Gly Pro Leu Val Glu Met     130 135 140 Asn Thr Gly Glu Ala Glu Ser Arg Asn Ser Asn Phe Ala Thr Val Gly 145 150 155 160 Ala Gly Ser Glu Asp Trp Val Asn Ala Ile Glu Phe Val Pro Gly Gln                 165 170 175 Pro Tyr Cys Gly Arg Thr Ala Pro Ser Cys Thr Glu Ala Pro Leu Gln             180 185 190 Gly Ser Val Thr Lys Glu Glu Ser Glu Lys Glu Gln Thr Ala Val Glu         195 200 205 Thr Lys Lys Gln Leu Cys Pro Tyr Ala Ala Val Gly Glu Cys Arg Tyr     210 215 220 Gly Glu Asn Cys Val Tyr Leu His Gly Asp Ser Cys Asp Met Cys Gly 225 230 235 240 Leu Gln Val Leu His Pro Met Asp Ala Ala Gln Arg Ser Gln His Ile                 245 250 255 Lys Ser Cys Ile Glu Ala His Glu Lys Asp Met Glu Leu Ser Phe Ala             260 265 270 Val Gln Arg Ser Lys Asp Met Val Cys Gly Ile Cys Met Glu Val Val         275 280 285 Tyr Glu Lys Ala Asn Pro Ser Glu Arg Arg Phe Gly Ile Leu Ser Asn     290 295 300 Cys Asn His Thr Tyr Cys Leu Lys Cys Ile Arg Lys Trp Arg Ser Ala 305 310 315 320 Lys Gln Phe Glu Ser Lys Ile Ile Lys Ser Cys Pro Glu Cys Arg Ile                 325 330 335 Thr Ser Asn Phe Val Ile Pro Ser Glu Tyr Trp Val Glu Glu Lys Glu             340 345 350 Glu Lys Gln Lys Leu Ile Leu Lys Tyr Lys Glu Ala Met Ser Asn Lys         355 360 365 Ala Cys Arg Tyr Phe Asp Glu Gly Arg Gly Ser Cys Pro Phe Gly Gly     370 375 380 Asn Cys Phe Tyr Lys His Ala Tyr Pro Asp Gly Arg Arg Glu Glu Pro 385 390 395 400 Gln Arg Gln Lys Val Gly Thr Ser Ser Arg Tyr Arg Ala Gln Arg Arg                 405 410 415 Asn His Phe Trp Glu Leu Ile Glu Glu Arg Glu Asn Ser Asn Pro Phe             420 425 430 Asp Asn Asp Glu Glu Glu Val Val Thr Phe Glu Leu Gly Glu Met Leu         435 440 445 Leu Met Leu Leu Ala Ala Gly Gly Asp Asp Glu Leu Thr Asp Ser Glu     450 455 460 Asp Glu Trp Asp Leu Phe His Asp Glu Leu Glu Asp Phe Tyr Asp Leu 465 470 475 480 Asp Leu <210> 7 <211> 3844 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (2) .. (2446) <400> 7 c cca gcg ctt gag aag tcg gag gcc aag gcc ggg ccg gtg ccc aag gtg 49   Pro Ala Leu Glu Lys Ser Glu Ala Lys Ala Gly Pro Val Pro Lys Val     1 5 10 15 tca ggc ctg gag cgc agc cgc gag ctc agc gcc gag agc ttc ctg ccc 97 Ser Gly Leu Glu Arg Ser Arg Glu Leu Ser Ala Glu Ser Phe Leu Pro              20 25 30 act gcc agc ccc gcg ccc cat gcc gcg ccc tgc ccg ggg ccc ccg ccc 145 Thr Ala Ser Pro Ala Pro His Ala Ala Pro Cys Pro Gly Pro Pro Pro          35 40 45 ggc tcc cgc gcc aat ccc ttg gtg aag aag gaa ccc ccc gcc ccg cac 193 Gly Ser Arg Ala Asn Pro Leu Val Lys Lys Glu Pro Pro Ala Pro His      50 55 60 cgc cac acc ccg cag ccg cca ccc ccg cag ccc cgc ggc ctg ctc ccg 241 Arg His Thr Pro Gln Pro Pro Pro Pro Gln Pro Arg Gly Leu Leu Pro  65 70 75 80 aca cac gtg cct gca tcc ctg ggc gcc ttc gcg ggc cac agc cag gcg 289 Thr His Val Pro Ala Ser Leu Gly Ala Phe Ala Gly His Ser Gln Ala                  85 90 95 gca gcc aac ggc ctg cac ggc ctc agc agg agc agc agc gcc ccc ctg 337 Ala Ala Asn Gly Leu His Gly Leu Ser Arg Ser Ser Ser Ala Pro Leu             100 105 110 ggc ctg ggg aag cac gtg tcg ctg tcg cca cac ggg ccg ggc ccc cac 385 Gly Leu Gly Lys His Val Ser Leu Ser Pro His Gly Pro Gly Pro His         115 120 125 ctg tct acc tca cac ctg gcg ctc cgg tcc cag gcg cag cac cag ctc 433 Leu Ser Thr Ser His Leu Ala Leu Arg Ser Gln Ala Gln His Gln Leu     130 135 140 cac gcg gcc atg ttt gcc gca ccc ccg aca ctg ccc ccg ccc ccg gcg 481 His Ala Ala Met Phe Ala Ala Pro Pro Thr Leu Pro Pro Pro Pro Ala 145 150 155 160 ctg ccg gcc agc agc ctg gtc ctc cca gga cac ccg gcc gat cac gag 529 Leu Pro Ala Ser Ser Leu Val Leu Pro Gly His Pro Ala Asp His Glu                 165 170 175 ctg ctc agg caa gag ctg aac acg cgg ttt ctg gtg cag agc gcc gag 577 Leu Leu Arg Gln Glu Leu Asn Thr Arg Phe Leu Val Gln Ser Ala Glu             180 185 190 cgg cct ggc gcc tcc ctg ggc ccg ggg gct ctg ctg cgg gcg gag ttc 625 Arg Pro Gly Ala Ser Leu Gly Pro Gly Ala Leu Leu Arg Ala Glu Phe         195 200 205 cat cag cac cag cac aca cac cag cac acg cac caa cac aca cac cag 673 His Gln His Gln His Thr His Gln His Thr His Gln His Thr His Gln     210 215 220 cac caa cac aca ttc gcc ccc ttc ccc gca ggg ctg ccc ccg acg ccg 721 His Gln His Thr Phe Ala Pro Phe Pro Ala Gly Leu Pro Pro Thr Pro 225 230 235 240 ccc gcc gca ccc ccg ccg ttt gac aag tat gcg ccc aag ctg gac agc 769 Pro Ala Ala Pro Pro Pro Phe Asp Lys Tyr Ala Pro Lys Leu Asp Ser                 245 250 255 ccc tac ttc cga cat tcc agc gtg agt ttc ttc ccg tcc ttc cct cct 817 Pro Tyr Phe Arg His Ser Ser Val Ser Phe Phe Pro Ser Phe Pro Pro             260 265 270 gcc atc ccg gga ctg ccc acc ctg ctc cca cac ccc ggc ccc ttc ggg 865 Ala Ile Pro Gly Leu Pro Thr Leu Leu Pro His Pro Gly Pro Phe Gly         275 280 285 tcc ctg cag ggc gct ttt cag cct aag gtg tct gac ccg tac cgg gcg 913 Ser Leu Gln Gly Ala Phe Gln Pro Lys Val Ser Asp Pro Tyr Arg Ala     290 295 300 gtg gtc aag gtg agc acg tgt tgg gaa ggc ccg tgg caa ggg agg act 961 Val Val Lys Val Ser Thr Cys Trp Glu Gly Pro Trp Gln Gly Arg Thr 305 310 315 320 ctg gtg ccc ccg ggg cgg cct cgg ggg gcc cgt gac agc agg agt ctg 1009 Leu Val Pro Pro Gly Arg Pro Arg Gly Ala Arg Asp Ser Arg Ser Leu                 325 330 335 cag aaa aca tgg gtg ggg gtg gca cca gcc cca ctg agc gct tcc atc 1057 Gln Lys Thr Trp Val Gly Val Ala Pro Ala Pro Leu Ser Ala Ser Ile             340 345 350 ctg tcg cag aag ccg ggg agg tgg tgt gcc gtg cac gtg cag atc gcc 1105 Leu Ser Gln Lys Pro Gly Arg Trp Cys Ala Val His Val Gln Ile Ala         355 360 365 tgg cag atc tac cgt cac cag cag aag ata aag gag atg cag ctg gac 1153 Trp Gln Ile Tyr Arg His Gln Gln Lys Ile Lys Glu Met Gln Leu Asp     370 375 380 ccc cac aag ctg gag gtg ggt gca aag ctg gac ctg ttc ggc aga ccc 1201 Pro His Lys Leu Glu Val Gly Ala Lys Leu Asp Leu Phe Gly Arg Pro 385 390 395 400 cct gcc ccg ggc gtg ttt gca ggc ttc cac tac cca cag gac ctg gcc 1249 Pro Ala Pro Gly Val Phe Ala Gly Phe His Tyr Pro Gln Asp Leu Ala                 405 410 415 cgg ccc ctc ttc ccc agc aca ggt gcc gcc cat cct gcc tcc aac cca 1297 Arg Pro Leu Phe Pro Ser Thr Gly Ala Ala His Pro Ala Ser Asn Pro             420 425 430 ttt gga ccc tca gcc cat cct ggc agc ttc ctg ccc act ggc ccc ctg 1345 Phe Gly Pro Ser Ala His Pro Gly Ser Phe Leu Pro Thr Gly Pro Leu         435 440 445 aca gac cct ttc agc aga ccg agc acc ttt ggg ggc ctg ggc agc ctg 1393 Thr Asp Pro Phe Ser Arg Pro Ser Thr Phe Gly Gly Leu Gly Ser Leu     450 455 460 agc agc cac gcc ttt ggg ggc ctg ggc agc cat gca ctg gct ccc ggt 1441 Ser Ser His Ala Phe Gly Gly Leu Gly Ser His Ala Leu Ala Pro Gly 465 470 475 480 ggc agc atc ttt gcc ccc aag gag ggc tcc tcc gtg cac ggc ctg ccc 1489 Gly Ser Ile Phe Ala Pro Lys Glu Gly Ser Ser Val His Gly Leu Pro                 485 490 495 agc ccc cat gag gcc tgg aac cga ctg cac cgg gca ccg ccc tcc ttc 1537 Ser Pro His Glu Ala Trp Asn Arg Leu His Arg Ala Pro Pro Ser Phe             500 505 510 ccg gct ccg ccc ccg tgg ccc aag tcc gtg gac gcg gag cgg gtg tca 1585 Pro Ala Pro Pro Pro Trp Pro Lys Ser Val Asp Ala Glu Arg Val Ser         515 520 525 gcc ctg acc aac cat gac cga gag ccg gac aat ggc aag gag gag cag 1633 Ala Leu Thr Asn His Asp Arg Glu Pro Asp Asn Gly Lys Glu Glu Gln     530 535 540 gaa cgg gac ctc ctg gag aag acg cgc ctg ctg agc cgg gcc tcg ccc 1681 Glu Arg Asp Leu Leu Glu Lys Thr Arg Leu Leu Ser Arg Ala Ser Pro 545 550 555 560 gcc acc ccc gct ggc cac ccc gtc agc ggc ctc ctg ctc cgg gcc cag 1729 Ala Thr Pro Ala Gly His Pro Val Ser Gly Leu Leu Leu Arg Ala Gln                 565 570 575 agc gag ctg ggc cgg tcc ggg gcc ccc gcg gag cgc gag gcc gaa cct 1777 Ser Glu Leu Gly Arg Ser Gly Ala Pro Ala Glu Arg Glu Ala Glu Pro             580 585 590 cgg gtc aag gag agc cgc tcc ccg gcc aag gag gag gtc gcc aag atg 1825 Arg Val Lys Glu Ser Arg Ser Pro Ala Lys Glu Glu Val Ala Lys Met         595 600 605 ccc gcg cgc gca tcc ccg ccc cac agc aag gcg gcc cct gga gac gtg 1873 Pro Ala Arg Ala Ser Pro Pro His Ser Lys Ala Ala Pro Gly Asp Val     610 615 620 aag gtc aag gag gag cgc ggg gag gac gag gcc tcc gag ccc ccg gcg 1921 Lys Val Lys Glu Glu Arg Gly Glu Asp Glu Ala Ser Glu Pro Pro Ala 625 630 635 640 ggc ggc ctg cac ccc gcg ccc ctg cag ctc ggc ctg ggc cgc gag cgc 1969 Gly Gly Leu His Pro Ala Pro Leu Gln Leu Gly Leu Gly Arg Glu Arg                 645 650 655 ctg ggc gcg ccg ggc ttc gcg tgg gag cct ttc cgc ggc ctg gag ctg 2017 Leu Gly Ala Pro Gly Phe Ala Trp Glu Pro Phe Arg Gly Leu Glu Leu             660 665 670 cca cgt cgc gcc ttc ccc gct gcc gcc ccc gcc ccg ggc tcc gcc gcc 2065 Pro Arg Arg Ala Phe Pro Ala Ala Ala Pro Ala Pro Gly Ser Ala Ala         675 680 685 ctc ttg gag ccc ccg gag cgc ccc tac cgc gac cgc gag ccc cac ggc 2113 Leu Leu Glu Pro Pro Glu Arg Pro Tyr Arg Asp Arg Glu Pro His Gly     690 695 700 tac agc ccc gag cgc ctg cgc ggg gag ctg gag cgc gcg cgg gcc ccg 2161 Tyr Ser Pro Glu Arg Leu Arg Gly Glu Leu Glu Arg Ala Arg Ala Pro 705 710 715 720 cac ctg ccg ccc gcc gcc ccc gcc ttg gac ggc gcg ctg ctg ccc tcg 2209 His Leu Pro Pro Ala Ala Pro Ala Leu Asp Gly Ala Leu Leu Pro Ser                 725 730 735 ctg gga gcc ctg cac ttc ccg cgc ctc tcg ccc gcc gcg ctg cac aat 2257 Leu Gly Ala Leu His Phe Pro Arg Leu Ser Pro Ala Ala Leu His Asn             740 745 750 ggg ctc ctg gcg cgg acc ccg ccc gcc gcc gcc gcc ctc ggc gca ccg 2305 Gly Leu Leu Ala Arg Thr Pro Pro Ala Ala Ala Ala Leu Gly Ala Pro         755 760 765 ccc ccc ctg gtg acg gcg gcc ggg ccc ccc acg ccc ccc ggg ccg ccg 2353 Pro Pro Leu Val Thr Ala Ala Gly Pro Pro Thr Pro Pro Gly Pro Pro     770 775 780 cgg agc cgg act act ccg ctg ggg ggc ctc ggg ccg ggc gag gcg cgc 2401 Arg Ser Arg Thr Thr Pro Leu Gly Gly Leu Gly Pro Gly Glu Ala Arg 785 790 795 800 gac tac tcc ccg tcc cga aat ccc ccg gag gtg gag gcg cgg tag 2446 Asp Tyr Ser Pro Ser Arg Asn Pro Pro Glu Val Glu Ala Arg                 805 810 815 ccccggggcc gcagacgcct ctccgagcgg agcgcaccgc tgtccgtctc tccatcagtt 2506 cctagaactc aagcacagct cccgccgatc ctggggcggc gccgcctctc cacccgcagc 2566 ctgcggaggc ggggacttgg gtgtcggctt ttctgagggt gatcttttgt tttccgagtt 2626 tgggattcgg ctgttgggaa aaaaaaatcg cgtttgtacc ttttcccccc acagatgaga 2686 agtgtttgta atggatttgt atttttctta attttatgct ctttagacgt ttaaaagaac 2746 caaaaaagaa acttttgctt cttcgttttc ggttgggatt tgcagtttaa tggcctcaga 2806 tccttctcca gatccccagg gtttctttgt cttatttatg gagaaaaacc ggtcactttg 2866 tccagcgcac tgtgaggccc ccactcaggc cagccctggc ccccccttgg tacttggaac 2926 cgaagttaca gattatatta aaataataat gtacaaaact ttgttttttt gccttattat 2986 gcagaagtgt aatttctttt ttggtttgtt tttttaaaag caaacgaaac gtgtaaatag 3046 tctgttgata taaatatatg acgttactaa attcttaatc tagatagact ttataaaaac 3106 cgtttccaga aacccctctg gttgtttgtc taacatggtc acaaaaaccc aggcgctgct 3166 ggctgtaaac attatcagaa gtttaatggc agcaactttc cttcaactat gcaagcgctt 3226 cccggcggct ctgctggttg ggggaggaag gttccgccag cgacctccca gcccctgggt 3286 ccgtggaggg gttgggtccc cccagcagag cccctgggcc agcagaacag cactcctggg 3346 cggctcctgt gggcttcagg actggccggc tccagccgca agggcgatgc tgtggacgtt 3406 tgtgtggatg gtgcagtgtt cttggaatct gtagaccaga tcggtggagg tatagaagtg 3466 caagagtcta aaggctgatt acacacacac acacacacac acacaaaatc actgctgtgt 3526 gttttcttcc gcctgaggca tcagcgtcac ctcggtgtgg tcgtcgcctc ccaggccctt 3586 ggcctggcct cctctcagtt tgggttttgc cctcacccac atgagccccc ccatgccctg 3646 ccccccttgc ggccttttgt gttccccgat gtctgggctg tgtccctgcc gggattccca 3706 gccttcgggg tcagccgtcg agccacttgc tttgctcagt tctgtgtttc agccacattt 3766 ccacggtgga ccctgtttgt tttaaatatt ctgttcccat gtcaatcagt gacgataaat 3826 acagccttga tttggatg 3844 <210> 8 <211> 814 <212> PRT <213> Homo sapiens <400> 8 Pro Ala Leu Glu Lys Ser Glu Ala Lys Ala Gly Pro Val Pro Lys Val   1 5 10 15 Ser Gly Leu Glu Arg Ser Arg Glu Leu Ser Ala Glu Ser Phe Leu Pro              20 25 30 Thr Ala Ser Pro Ala Pro His Ala Ala Pro Cys Pro Gly Pro Pro Pro          35 40 45 Gly Ser Arg Ala Asn Pro Leu Val Lys Lys Glu Pro Pro Ala Pro His      50 55 60 Arg His Thr Pro Gln Pro Pro Pro Pro Gln Pro Arg Gly Leu Leu Pro  65 70 75 80 Thr His Val Pro Ala Ser Leu Gly Ala Phe Ala Gly His Ser Gln Ala                  85 90 95 Ala Ala Asn Gly Leu His Gly Leu Ser Arg Ser Ser Ser Ala Pro Leu             100 105 110 Gly Leu Gly Lys His Val Ser Leu Ser Pro His Gly Pro Gly Pro His         115 120 125 Leu Ser Thr Ser His Leu Ala Leu Arg Ser Gln Ala Gln His Gln Leu     130 135 140 His Ala Ala Met Phe Ala Ala Pro Pro Thr Leu Pro Pro Pro Pro Ala 145 150 155 160 Leu Pro Ala Ser Ser Leu Val Leu Pro Gly His Pro Ala Asp His Glu                 165 170 175 Leu Leu Arg Gln Glu Leu Asn Thr Arg Phe Leu Val Gln Ser Ala Glu             180 185 190 Arg Pro Gly Ala Ser Leu Gly Pro Gly Ala Leu Leu Arg Ala Glu Phe         195 200 205 His Gln His Gln His Thr His Gln His Thr His Gln His Thr His Gln     210 215 220 His Gln His Thr Phe Ala Pro Phe Pro Ala Gly Leu Pro Pro Thr Pro 225 230 235 240 Pro Ala Ala Pro Pro Pro Phe Asp Lys Tyr Ala Pro Lys Leu Asp Ser                 245 250 255 Pro Tyr Phe Arg His Ser Ser Val Ser Phe Phe Pro Ser Phe Pro Pro             260 265 270 Ala Ile Pro Gly Leu Pro Thr Leu Leu Pro His Pro Gly Pro Phe Gly         275 280 285 Ser Leu Gln Gly Ala Phe Gln Pro Lys Val Ser Asp Pro Tyr Arg Ala     290 295 300 Val Val Lys Val Ser Thr Cys Trp Glu Gly Pro Trp Gln Gly Arg Thr 305 310 315 320 Leu Val Pro Pro Gly Arg Pro Arg Gly Ala Arg Asp Ser Arg Ser Leu                 325 330 335 Gln Lys Thr Trp Val Gly Val Ala Pro Ala Pro Leu Ser Ala Ser Ile             340 345 350 Leu Ser Gln Lys Pro Gly Arg Trp Cys Ala Val His Val Gln Ile Ala         355 360 365 Trp Gln Ile Tyr Arg His Gln Gln Lys Ile Lys Glu Met Gln Leu Asp     370 375 380 Pro His Lys Leu Glu Val Gly Ala Lys Leu Asp Leu Phe Gly Arg Pro 385 390 395 400 Pro Ala Pro Gly Val Phe Ala Gly Phe His Tyr Pro Gln Asp Leu Ala                 405 410 415 Arg Pro Leu Phe Pro Ser Thr Gly Ala Ala His Pro Ala Ser Asn Pro             420 425 430 Phe Gly Pro Ser Ala His Pro Gly Ser Phe Leu Pro Thr Gly Pro Leu         435 440 445 Thr Asp Pro Phe Ser Arg Pro Ser Thr Phe Gly Gly Leu Gly Ser Leu     450 455 460 Ser Ser His Ala Phe Gly Gly Leu Gly Ser His Ala Leu Ala Pro Gly 465 470 475 480 Gly Ser Ile Phe Ala Pro Lys Glu Gly Ser Ser Val His Gly Leu Pro                 485 490 495 Ser Pro His Glu Ala Trp Asn Arg Leu His Arg Ala Pro Pro Ser Phe             500 505 510 Pro Ala Pro Pro Pro Trp Pro Lys Ser Val Asp Ala Glu Arg Val Ser         515 520 525 Ala Leu Thr Asn His Asp Arg Glu Pro Asp Asn Gly Lys Glu Glu Gln     530 535 540 Glu Arg Asp Leu Leu Glu Lys Thr Arg Leu Leu Ser Arg Ala Ser Pro 545 550 555 560 Ala Thr Pro Ala Gly His Pro Val Ser Gly Leu Leu Leu Arg Ala Gln                 565 570 575 Ser Glu Leu Gly Arg Ser Gly Ala Pro Ala Glu Arg Glu Ala Glu Pro             580 585 590 Arg Val Lys Glu Ser Arg Ser Pro Ala Lys Glu Glu Val Ala Lys Met         595 600 605 Pro Ala Arg Ala Ser Pro Pro His Ser Lys Ala Ala Pro Gly Asp Val     610 615 620 Lys Val Lys Glu Glu Arg Gly Glu Asp Glu Ala Ser Glu Pro Pro Ala 625 630 635 640 Gly Gly Leu His Pro Ala Pro Leu Gln Leu Gly Leu Gly Arg Glu Arg                 645 650 655 Leu Gly Ala Pro Gly Phe Ala Trp Glu Pro Phe Arg Gly Leu Glu Leu             660 665 670 Pro Arg Arg Ala Phe Pro Ala Ala Ala Pro Ala Pro Gly Ser Ala Ala         675 680 685 Leu Leu Glu Pro Pro Glu Arg Pro Tyr Arg Asp Arg Glu Pro His Gly     690 695 700 Tyr Ser Pro Glu Arg Leu Arg Gly Glu Leu Glu Arg Ala Arg Ala Pro 705 710 715 720 His Leu Pro Pro Ala Ala Pro Ala Leu Asp Gly Ala Leu Leu Pro Ser                 725 730 735 Leu Gly Ala Leu His Phe Pro Arg Leu Ser Pro Ala Ala Leu His Asn             740 745 750 Gly Leu Leu Ala Arg Thr Pro Pro Ala Ala Ala Ala Leu Gly Ala Pro         755 760 765 Pro Pro Leu Val Thr Ala Ala Gly Pro Pro Thr Pro Pro Gly Pro Pro     770 775 780 Arg Ser Arg Thr Thr Pro Leu Gly Gly Leu Gly Pro Gly Glu Ala Arg 785 790 795 800 Asp Tyr Ser Pro Ser Arg Asn Pro Pro Glu Val Glu Ala Arg                 805 810 <210> 9 <211> 1757 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (77) .. (1450) <400> 9 ggcacgaggc ccaacgaggc tccctggagc ccgacgcaga gcagcgccct ggcctggcca 60 agcaggagcc ggcatc atg gat tcc ttc aaa gta gtg ctg gag ggg cca gca 112                   Met Asp Ser Phe Lys Val Val Leu Glu Gly Pro Ala                     1 5 10 cct tgg ggc ttc cgg ctg caa ggg ggc aag gac ttc aat gtg ccc ctc 160 Pro Trp Gly Phe Arg Leu Gln Gly Gly Lys Asp Phe Asn Val Pro Leu          15 20 25 tcc att tcc cgg ctc act cct ggg ggc aaa gcg gcg cag gcc gga gtg 208 Ser Ile Ser Arg Leu Thr Pro Gly Gly Lys Ala Ala Gln Ala Gly Val      30 35 40 gcc gtg ggt gac tgg gtg ctg agc atc gat ggc gag aat gcg ggt agc 256 Ala Val Gly Asp Trp Val Leu Ser Ile Asp Gly Glu Asn Ala Gly Ser  45 50 55 60 ctc aca cac atc gaa gct cag aac aag atc cgg gcc tgc ggg gag cgc 304 Leu Thr His Ile Glu Ala Gln Asn Lys Ile Arg Ala Cys Gly Glu Arg                  65 70 75 ctc agc ctg ggc ctc agc agg gcc cag ccg gtt cag agc aaa ccg cag 352 Leu Ser Leu Gly Leu Ser Arg Ala Gln Pro Val Gln Ser Lys Pro Gln              80 85 90 aag gcc tcc gcc ccc gcc gcg gac cct ccg cgg tac acc ttt gca ccc 400 Lys Ala Ser Ala Pro Ala Ala Asp Pro Pro Arg Tyr Thr Phe Ala Pro          95 100 105 agc gtc tcc ctc aac aag acg gcc cgg ccc ttt ggg gcg ccc ccg ccc 448 Ser Val Ser Leu Asn Lys Thr Ala Arg Pro Phe Gly Ala Pro Pro Pro     110 115 120 gct gac agc gcc ccg cag cag aat gga cag ccg ctc cga ccg ctg gtc 496 Ala Asp Ser Ala Pro Gln Gln Asn Gly Gln Pro Leu Arg Pro Leu Val 125 130 135 140 cca gat gcc agc aag cag cgg ctg atg gag aac aca gag gac tgg cgg 544 Pro Asp Ala Ser Lys Gln Arg Leu Met Glu Asn Thr Glu Asp Trp Arg                 145 150 155 ccg cgg ccg ggg aca ggc cag tcg cgt tcc ttc cgc atc ctt gcc cac 592 Pro Arg Pro Gly Thr Gly Gln Ser Arg Ser Phe Arg Ile Leu Ala His             160 165 170 ctc aca ggc acc gag ttc atg caa gac ccg gat gag gag cac ctg aag 640 Leu Thr Gly Thr Glu Phe Met Gln Asp Pro Asp Glu Glu His Leu Lys         175 180 185 aaa tca agc cag gtg ccc agg aca gaa gcc cca gcc cca gcc tca tct 688 Lys Ser Ser Gln Val Pro Arg Thr Glu Ala Pro Ala Pro Ala Ser Ser     190 195 200 aca ccc cag gag ccc tgg cct ggc cct acc gcc ccc agc cct acc agc 736 Thr Pro Gln Glu Pro Trp Pro Gly Pro Thr Ala Pro Ser Pro Thr Ser 205 210 215 220 cgc ccg ccc tgg gct gtg gac cct gcg ttt gcc gag cgc tat gcc ccg 784 Arg Pro Pro Trp Ala Val Asp Pro Ala Phe Ala Glu Arg Tyr Ala Pro                 225 230 235 gac aaa acg agc aca gtg ctg acc cgg cac agc cag ccg gcc acg ccc 832 Asp Lys Thr Ser Thr Val Leu Thr Arg His Ser Gln Pro Ala Thr Pro             240 245 250 acg ccg ctg cag agc cgc acc tcc att gtg cag gca gct gcc gga ggg 880 Thr Pro Leu Gln Ser Arg Thr Ser Ile Val Gln Ala Ala Ala Gly Gly         255 260 265 gtg cca gga ggg ggc agc aac aac ggc aag act ccc gtg tgt cac cag 928 Val Pro Gly Gly Gly Ser Asn Asn Gly Lys Thr Pro Val Cys His Gln     270 275 280 tgc cac aag gtc atc cgg ggc cgc tac ctg gtg gcg ctg ggc cac gcg 976 Cys His Lys Val Ile Arg Gly Arg Tyr Leu Val Ala Leu Gly His Ala 285 290 295 300 tac cac ccg gag gag ttt gtg tgt agc cag tgt ggg aag gtc ctg gaa 1024 Tyr His Pro Glu Glu Phe Val Cys Ser Gln Cys Gly Lys Val Leu Glu                 305 310 315 gag ggt ggc ttc ttt gag gag aag ggc gcc atc ttc tgc cca cca tgc 1072 Glu Gly Gly Phe Phe Glu Glu Lys Gly Ala Ile Phe Cys Pro Pro Cys             320 325 330 tat gac gtg cgc tat gca ccc agc tgt gcc aag tgc aag aag aag att 1120 Tyr Asp Val Arg Tyr Ala Pro Ser Cys Ala Lys Cys Lys Lys Lys Ile         335 340 345 aca ggc gag atc atg cac gcc ctg aag atg acc tgg cac gtg cac tgc 1168 Thr Gly Glu Ile Met His Ala Leu Lys Met Thr Trp His Val His Cys     350 355 360 ttt acc tgt gct gcc tgc aag acg ccc atc cgg aac agg gcc ttc tac 1216 Phe Thr Cys Ala Ala Cys Lys Thr Pro Ile Arg Asn Arg Ala Phe Tyr 365 370 375 380 atg gag gag ggc gtg ccc tat tgc gag cga gac tat gag aag atg ttt 1264 Met Glu Glu Gly Val Pro Tyr Cys Glu Arg Asp Tyr Glu Lys Met Phe                 385 390 395 ggc acg aaa tgc cat ggc tgt gac ttc aag atc gac gct ggg gac cgc 1312 Gly Thr Lys Cys His Gly Cys Asp Phe Lys Ile Asp Ala Gly Asp Arg             400 405 410 ttc ctg gag gcc ctg ggc ttc agc tgg cat gac acc tgc ttc gtc tgt 1360 Phe Leu Glu Ala Leu Gly Phe Ser Trp His Asp Thr Cys Phe Val Cys         415 420 425 gcg ata tgt cag atc aac ctg gaa gga aag acc ttc tac tcc aag aag 1408 Ala Ile Cys Gln Ile Asn Leu Glu Gly Lys Thr Phe Tyr Ser Lys Lys     430 435 440 gac agg cct ctc tgc aag agc cat gcc ttc tct cat gtg tga 1450 Asp Arg Pro Leu Cys Lys Ser His Ala Phe Ser His Val 445 450 455 gccccttctg cccacagctg ccgcggtggc ccctagcctg aggggcctgg agtcgtggcc 1510 ctgcatttct gggtagggct ggcaatggtt gccttaaccc tggctcctgg cccgagcctg 1570 gggctccctg ggccctgccc cacccacctt atcctcccac cccactccct ccaccaccac 1630 agcacaccgg tgctggccac accagccccc tttcacctcc agtgccacaa taaacctgta 1690 cccagctgtg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1750 aaaaaaa 1757 <210> 10 <211> 457 <212> PRT <213> Homo sapiens <400> 10 Met Asp Ser Phe Lys Val Val Leu Glu Gly Pro Ala Pro Trp Gly Phe   1 5 10 15 Arg Leu Gln Gly Gly Lys Asp Phe Asn Val Pro Leu Ser Ile Ser Arg              20 25 30 Leu Thr Pro Gly Gly Lys Ala Ala Gln Ala Gly Val Ala Val Gly Asp          35 40 45 Trp Val Leu Ser Ile Asp Gly Glu Asn Ala Gly Ser Leu Thr His Ile      50 55 60 Glu Ala Gln Asn Lys Ile Arg Ala Cys Gly Glu Arg Leu Ser Leu Gly  65 70 75 80 Leu Ser Arg Ala Gln Pro Val Gln Ser Lys Pro Gln Lys Ala Ser Ala                  85 90 95 Pro Ala Ala Asp Pro Pro Arg Tyr Thr Phe Ala Pro Ser Val Ser Leu             100 105 110 Asn Lys Thr Ala Arg Pro Phe Gly Ala Pro Pro Pro Ala Asp Ser Ala         115 120 125 Pro Gln Gln Asn Gly Gln Pro Leu Arg Pro Leu Val Pro Asp Ala Ser     130 135 140 Lys Gln Arg Leu Met Glu Asn Thr Glu Asp Trp Arg Pro Arg Pro Gly 145 150 155 160 Thr Gly Gln Ser Arg Ser Phe Arg Ile Leu Ala His Leu Thr Gly Thr                 165 170 175 Glu Phe Met Gln Asp Pro Asp Glu Glu His Leu Lys Lys Ser Ser Gln             180 185 190 Val Pro Arg Thr Glu Ala Pro Ala Pro Ala Ser Ser Thr Pro Gln Glu         195 200 205 Pro Trp Pro Gly Pro Thr Ala Pro Ser Pro Thr Ser Arg Pro Pro Trp     210 215 220 Ala Val Asp Pro Ala Phe Ala Glu Arg Tyr Ala Pro Asp Lys Thr Ser 225 230 235 240 Thr Val Leu Thr Arg His Ser Gln Pro Ala Thr Pro Thr Pro Leu Gln                 245 250 255 Ser Arg Thr Ser Ile Val Gln Ala Ala Ala Gly Gly Val Pro Gly Gly             260 265 270 Gly Ser Asn Asn Gly Lys Thr Pro Val Cys His Gln Cys His Lys Val         275 280 285 Ile Arg Gly Arg Tyr Leu Val Ala Leu Gly His Ala Tyr His Pro Glu     290 295 300 Glu Phe Val Cys Ser Gln Cys Gly Lys Val Leu Glu Glu Gly Gly Phe 305 310 315 320 Phe Glu Glu Lys Gly Ala Ile Phe Cys Pro Pro Cys Tyr Asp Val Arg                 325 330 335 Tyr Ala Pro Ser Cys Ala Lys Cys Lys Lys Lys Ile Thr Gly Glu Ile             340 345 350 Met His Ala Leu Lys Met Thr Trp His Val His Cys Phe Thr Cys Ala         355 360 365 Ala Cys Lys Thr Pro Ile Arg Asn Arg Ala Phe Tyr Met Glu Glu Gly     370 375 380 Val Pro Tyr Cys Glu Arg Asp Tyr Glu Lys Met Phe Gly Thr Lys Cys 385 390 395 400 His Gly Cys Asp Phe Lys Ile Asp Ala Gly Asp Arg Phe Leu Glu Ala                 405 410 415 Leu Gly Phe Ser Trp His Asp Thr Cys Phe Val Cys Ala Ile Cys Gln             420 425 430 Ile Asn Leu Glu Gly Lys Thr Phe Tyr Ser Lys Lys Asp Arg Pro Leu         435 440 445 Cys Lys Ser His Ala Phe Ser His Val     450 455 <210> 11 <211> 2680 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (1) .. (1599) <400> 11 atg ctc ctg gac gcg ggt ccg cag ttc ccg gcc atc ggg gtg ggc agc 48 Met Leu Leu Asp Ala Gly Pro Gln Phe Pro Ala Ile Gly Val Gly Ser   1 5 10 15 ttc gcg cgc cac cat cac cac tcc gcc gcg gcg gcg gcg gcg gct gcc 96 Phe Ala Arg His His His His Ser Ala Ala Ala Ala Ala Ala Ala Ala              20 25 30 gcc gag atg cag gac cgt gaa ctg agc ctg gcg gcg gcg cag aac ggc 144 Ala Glu Met Gln Asp Arg Glu Leu Ser Leu Ala Ala Ala Gln Asn Gly          35 40 45 ttc gtt gac tcc gcc gcc gcg cac atg gga gcc ttc aag ctc aac ccg 192 Phe Val Asp Ser Ala Ala Ala His Met Gly Ala Phe Lys Leu Asn Pro      50 55 60 ggc gcg cac gag ctg tcc ccg ggc cag agc tcg gcg ttc acg tcg cag 240 Gly Ala His Glu Leu Ser Pro Gly Gln Ser Ser Ala Phe Thr Ser Gln  65 70 75 80 ggc ccc ggc gcc tac ccc ggc tcc gct gcg gct gcc gct gcg gcc gca 288 Gly Pro Gly Ala Tyr Pro Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala                  85 90 95 gcg ctc ggg ccc cac gcc gcg cac gtt ggc tcc tac tct ggg ccg ccc 336 Ala Leu Gly Pro His Ala Ala His Val Gly Ser Tyr Ser Gly Pro Pro             100 105 110 ttc aac tcc acc cgg gac ttc ctg ttc cgc agc cgc ggc ttc ggg gac 384 Phe Asn Ser Thr Arg Asp Phe Leu Phe Arg Ser Arg Gly Phe Gly Asp         115 120 125 tcg gcg ccg ggc ggc ggg cag cac ggg ctg ttc ggg ccg ggc gcg ggc 432 Ser Ala Pro Gly Gly Gly Gln His Gly Leu Phe Gly Pro Gly Ala Gly     130 135 140 ggc ctg cac cac gcg cac tcg gac gcg cag ggc cac ctc ctc ttc ccg 480 Gly Leu His His Ala His Ser Asp Ala Gln Gly His Leu Leu Phe Pro 145 150 155 160 ggc ctg cca gag cag cac ggg ccg cac ggc tcg cag aat gtg ctc aac 528 Gly Leu Pro Glu Gln His Gly Pro His Gly Ser Gln Asn Val Leu Asn                 165 170 175 ggg cag atg cgc ctc ggg ctg ccc ggc gag gtg ttc ggg cgc tcg gag 576 Gly Gln Met Arg Leu Gly Leu Pro Gly Glu Val Phe Gly Arg Ser Glu             180 185 190 caa tac cgc cag gtg gcc agc ccg cgg acc gac ccc tac tcg gcg gcg 624 Gln Tyr Arg Gln Val Ala Ser Pro Arg Thr Asp Pro Tyr Ser Ala Ala         195 200 205 caa ctc cac aac cag tac ggc ccc atg aat atg aac atg ggt atg aac 672 Gln Leu His Asn Gln Tyr Gly Pro Met Asn Met Asn Met Gly Met Asn     210 215 220 atg gca gca gcc gcg gcc cac cac cac cac cac cac cac cac cac ccc 720 Met Ala Ala Ala Ala Ala His His His His His His His His His Pro 225 230 235 240 ggt gcc ttt ttc cgc tat atg cgg cag cag tgc atc aag cag gag cta 768 Gly Ala Phe Phe Arg Tyr Met Arg Gln Gln Cys Ile Lys Gln Glu Leu                 245 250 255 atc tgc aag tgg atc gac ccc gag caa ctg agc aat ccc aag aag agc 816 Ile Cys Lys Trp Ile Asp Pro Glu Gln Leu Ser Asn Pro Lys Lys Ser             260 265 270 tgc aac aaa act ttc agc acc atg cac gag ctg gtg aca cac gtc tcg 864 Cys Asn Lys Thr Phe Ser Thr Met His Glu Leu Val Thr His Val Ser         275 280 285 gtg gag cac gtc ggc ggc ccg gag cag agc aac cac gtc tgc ttc tgg 912 Val Glu His Val Gly Gly Pro Glu Gln Ser Asn His Val Cys Phe Trp     290 295 300 gag gag tgt ccg cgc gag ggc aag ccc ttc aag gcc aaa tac aaa ctg 960 Glu Glu Cys Pro Arg Glu Gly Lys Pro Phe Lys Ala Lys Tyr Lys Leu 305 310 315 320 gtc aac cac atc cgc gtg cac aca ggc gag aaa ccc ttc ccc tgc ccc 1008 Val Asn His Ile Arg Val His Thr Gly Glu Lys Pro Phe Pro Cys Pro                 325 330 335 ttc ccg ggc tgt ggc aaa gtc ttc gcg cgc tcc gag aac ctc aag atc 1056 Phe Pro Gly Cys Gly Lys Val Phe Ala Arg Ser Glu Asn Leu Lys Ile             340 345 350 cac aaa agg acc cac aca ggg gag aag ccg ttc cag tgt gag ttt gag 1104 His Lys Arg Thr His Thr Gly Glu Lys Pro Phe Gln Cys Glu Phe Glu         355 360 365 ggc tgc gac cgg cgc ttc gcc aac agc agc gac agg aag aag cac atg 1152 Gly Cys Asp Arg Arg Phe Ala Asn Ser Ser Asp Arg Lys Lys His Met     370 375 380 cac gtc cac acc tcc gat aag ccc tat ctc tgc aag atg tgc gac aag 1200 His Val His Thr Ser Asp Lys Pro Tyr Leu Cys Lys Met Cys Asp Lys 385 390 395 400 tcc tac acg cac ccc agc tcg ctg cgg aag cac atg aag gtc cat gag 1248 Ser Tyr Thr His Pro Ser Ser Leu Arg Lys His Met Lys Val His Glu                 405 410 415 tcc tcc ccg cag ggc tct gaa tcc tcc ccg gcc gcc agc tcc ggc tat 1296 Ser Ser Pro Gln Gly Ser Glu Ser Ser Pro Ala Ala Ser Ser Gly Tyr             420 425 430 gag tcg tcc acg ccc ccg ggg ctg gtg tcc ccc agc gcc gag ccc cag 1344 Glu Ser Ser Thr Pro Pro Gly Leu Val Ser Pro Ser Ala Glu Pro Gln         435 440 445 agc agc tcc aac ctg tcc cca gcg gcg gcg gca gcg gcg gcg gcg gct 1392 Ser Ser Ser Asn Leu Ser Pro Ala Ala Ala Ala Ala Ala Ala Ala Ala     450 455 460 gcg gcg gcg gcg gcc gcg gtg tcc gcg gtg cac cgg ggc gga ggc tcg 1440 Ala Ala Ala Ala Ala Ala Val Ser Ala Val His Arg Gly Gly Gly Ser 465 470 475 480 ggc agt ggc ggc gcg gga ggc ggc tca ggc ggc ggc agc ggc agt ggc 1488 Gly Ser Gly Gly Ala Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly                 485 490 495 ggg ggc ggc ggc ggg gcg ggc ggc ggg ggc ggc ggc agc tct ggc ggg 1536 Gly Gly Gly Gly Gly Ala Gly Gly Gly Gly Gly Gly Ser Ser Gly Gly             500 505 510 ggc agc ggg aca gcc ggg ggt cac agc ggc ctc tcc tcc aac ttc aat 1584 Gly Ser Gly Thr Ala Gly Gly His Ser Gly Leu Ser Ser Asn Phe Asn         515 520 525 gaa tgg tac gtg tga cgggtcgggg cctctctccc tctccctgtc cccaccccag 1639 Glu Trp Tyr Val     530 cgcagcagcc ctccccgcag ctagcagcga gggcaccttg tgatcatgtt gttaaaatta 1699 tgaatctgat ttttatgatg atgaaaattt taccagcaga aggatttttt aaagtttttt 1759 tttttttttt aataataatc taggcatgaa gagcaaaaat atcccttccg gagtctttga 1819 agctgaaaat ataaaacaaa taaaaaataa aaaaataaaa acccacaaaa atgttgaacc 1879 aaacctccct gctaatctcc atgcccacgt tctttcccac cctgttccca gtcttctgac 1939 aaactgtgta catagcggac tcctcctttc tcctccgagg tggttttaaa ggctttttgg 1999 tgtatagaag tttgtccatt tgtaaaactc cggattgcgt tcctccccgc cttccgcccc 2059 ttcccttccc taaagtgatg ggctttctct tttctctttt tagtttaccc ggtttctttt 2119 taagtaatgt ggaagaaaat ggtttatttt gtattgtggt attgaatatt gtgttccttt 2179 ttatgaggca acctgattgt aaacttcatg taactataga ctggaaaaaa tgagccgtgc 2239 caaagtctcc cttctgtttc ttcagcacat tgacccatag cacacacata cacaccacca 2299 ccaacaacgc ttgtgaatgt atttttctgt tagctgggtt tacatgtgat gttttagtgc 2359 ttttgcaagt tcaatttgtt agttcctgta tgaaagattg tgggggaaaa ataaacgtcg 2419 tgccgttagc tttttccgta ataacaccct tccttctgta aatacccgtt accatattta 2479 tccattngta attaaattat ggtattaact tgctacagag gaaacaatat ttataaagaa 2539 tgtttcttac tataaatatg tacaattgtg ggcataaact gttttagatt ttttatttga 2599 aggttttaag tggtttgatc atttcttgtg atgttttgag agtaatgcat acagaaatat 2659 aataaaatgt gttgaaactg c 2680 <210> 12 <211> 532 <212> PRT <213> Homo sapiens <400> 12 Met Leu Leu Asp Ala Gly Pro Gln Phe Pro Ala Ile Gly Val Gly Ser   1 5 10 15 Phe Ala Arg His His His His Ser Ala Ala Ala Ala Ala Ala Ala Ala              20 25 30 Ala Glu Met Gln Asp Arg Glu Leu Ser Leu Ala Ala Ala Gln Asn Gly          35 40 45 Phe Val Asp Ser Ala Ala Ala His Met Gly Ala Phe Lys Leu Asn Pro      50 55 60 Gly Ala His Glu Leu Ser Pro Gly Gln Ser Ser Ala Phe Thr Ser Gln  65 70 75 80 Gly Pro Gly Ala Tyr Pro Gly Ser Ala Ala Ala Ala Ala Ala Ala Ala                  85 90 95 Ala Leu Gly Pro His Ala Ala His Val Gly Ser Tyr Ser Gly Pro Pro             100 105 110 Phe Asn Ser Thr Arg Asp Phe Leu Phe Arg Ser Arg Gly Phe Gly Asp         115 120 125 Ser Ala Pro Gly Gly Gly Gln His Gly Leu Phe Gly Pro Gly Ala Gly     130 135 140 Gly Leu His His Ala His Ser Asp Ala Gln Gly His Leu Leu Phe Pro 145 150 155 160 Gly Leu Pro Glu Gln His Gly Pro His Gly Ser Gln Asn Val Leu Asn                 165 170 175 Gly Gln Met Arg Leu Gly Leu Pro Gly Glu Val Phe Gly Arg Ser Glu             180 185 190 Gln Tyr Arg Gln Val Ala Ser Pro Arg Thr Asp Pro Tyr Ser Ala Ala         195 200 205 Gln Leu His Asn Gln Tyr Gly Pro Met Asn Met Asn Met Gly Met Asn     210 215 220 Met Ala Ala Ala Ala Ala His His His His His His His His His Pro 225 230 235 240 Gly Ala Phe Phe Arg Tyr Met Arg Gln Gln Cys Ile Lys Gln Glu Leu                 245 250 255 Ile Cys Lys Trp Ile Asp Pro Glu Gln Leu Ser Asn Pro Lys Lys Ser             260 265 270 Cys Asn Lys Thr Phe Ser Thr Met His Glu Leu Val Thr His Val Ser         275 280 285 Val Glu His Val Gly Gly Pro Glu Gln Ser Asn His Val Cys Phe Trp     290 295 300 Glu Glu Cys Pro Arg Glu Gly Lys Pro Phe Lys Ala Lys Tyr Lys Leu 305 310 315 320 Val Asn His Ile Arg Val His Thr Gly Glu Lys Pro Phe Pro Cys Pro                 325 330 335 Phe Pro Gly Cys Gly Lys Val Phe Ala Arg Ser Glu Asn Leu Lys Ile             340 345 350 His Lys Arg Thr His Thr Gly Glu Lys Pro Phe Gln Cys Glu Phe Glu         355 360 365 Gly Cys Asp Arg Arg Phe Ala Asn Ser Ser Asp Arg Lys Lys His Met     370 375 380 His Val His Thr Ser Asp Lys Pro Tyr Leu Cys Lys Met Cys Asp Lys 385 390 395 400 Ser Tyr Thr His Pro Ser Ser Leu Arg Lys His Met Lys Val His Glu                 405 410 415 Ser Ser Pro Gln Gly Ser Glu Ser Ser Pro Ala Ala Ser Ser Gly Tyr             420 425 430 Glu Ser Ser Thr Pro Pro Gly Leu Val Ser Pro Ser Ala Glu Pro Gln         435 440 445 Ser Ser Ser Asn Leu Ser Pro Ala Ala Ala Ala Ala Ala Ala Ala Ala     450 455 460 Ala Ala Ala Ala Ala Ala Val Ser Ala Val His Arg Gly Gly Gly Ser 465 470 475 480 Gly Ser Gly Gly Ala Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly                 485 490 495 Gly Gly Gly Gly Gly Ala Gly Gly Gly Gly Gly Gly Ser Ser Gly Gly             500 505 510 Gly Ser Gly Thr Ala Gly Gly His Ser Gly Leu Ser Ser Asn Phe Asn         515 520 525 Glu Trp Tyr Val     530 <210> 13 <211> 2406 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (674) .. (1645) <400> 13 gcggaggaga acaaacagat catccgcaaa cacgcgcaga ccttcgttgc cctctgtgcc 60 acagatgtga agttcatttc caatccgccc tccatggtgg cagcggggag cgtggtggcc 120 gcagtgcaag gcctgaacct gaggagcccc aacaacttcc tgtcctacta ccgcctcaca 180 cgcttcctct ccagagtgat caagtgtgac ccagactgcc tccgggcctg ccaggagcag 240 atcgaagccc tgctggagtc aagcctgcgc caggcccagc agaacatgga ccccaaggcc 300 gccgaggagg aggaagagga ggaggaggag gtggacctgg cttgcacacc caccgacgtg 360 cgggacgtgg acatctgagg gcgccaggca ggcgggcgcc accgccaccc gcagcgaggg 420 cggagccggc cccaggtgct ccactgacag tccctcctct ccggagcatt ttgataccag 480 aagggaaagc ttcattctcc ttgttgttgg ttgttttttc ctttgctctt tcccccttcc 540 atctctgact taagcaaaag aaaaagatta cccaaaaact gtctttaaaa gagagagaga 600 gaaaggagcc cgagccccga cgagtccccg cgcctcatcc gcccgcgtcc ggtccgcgtt 660 cctccgcccc acc atg gct cgg ggc ccc ggc ctc gcg ccg cca ccg ctg 709                Met Ala Arg Gly Pro Gly Leu Ala Pro Pro Pro Leu                  1 5 10 cgg ctg ccg ctg ctg ctg ctg gtg ctg gcg gcg gtg acc ggc cac acg 757 Arg Leu Pro Leu Leu Leu Leu Val Leu Ala Ala Val Thr Gly His Thr          15 20 25 gcc gcg cag gac aac tgc acg tgt ccc acc aac aag atg acc gtg tgc 805 Ala Ala Gln Asp Asn Cys Thr Cys Pro Thr Asn Lys Met Thr Val Cys      30 35 40 agc ccc gac ggc ccc ggc ggc cgc tgc cag tgc cgc gcg ctg ggc tcg 853 Ser Pro Asp Gly Pro Gly Gly Arg Cys Gln Cys Arg Ala Leu Gly Ser  45 50 55 60 ggc atg gcg gtc gac tgc tcc acg ctg acc tcc aag tgt ctg ctg ctc 901 Gly Met Ala Val Asp Cys Ser Thr Leu Thr Ser Lys Cys Leu Leu Leu                  65 70 75 aag gcg cgc atg agc gcc ccc aag aac gcc cgc acg ctg gtg cgg ccg 949 Lys Ala Arg Met Ser Ala Pro Lys Asn Ala Arg Thr Leu Val Arg Pro              80 85 90 agt gag cac gcg ctc gtg gac aac gat ggc ctc tac gac ccc gac tgc 997 Ser Glu His Ala Leu Val Asp Asn Asp Gly Leu Tyr Asp Pro Asp Cys          95 100 105 gac ccc gag ggc cgc ttc aag gcg cgc cag tgc aac cag acg tcg gtg 1045 Asp Pro Glu Gly Arg Phe Lys Ala Arg Gln Cys Asn Gln Thr Ser Val     110 115 120 tgc tgg tgc gtg aac tcg gtg ggc gtg cgc cgc acg gac aag ggc gac 1093 Cys Trp Cys Val Asn Ser Val Gly Val Arg Arg Thr Asp Lys Gly Asp 125 130 135 140 ctg agc cta cgc tgc gat gag ctg gtg cgc acc cac cac atc ctc att 1141 Leu Ser Leu Arg Cys Asp Glu Leu Val Arg Thr His His Ile Leu Ile                 145 150 155 gac ctg cgc cac cgc ccc acc gcc ggc gcc ttc aac cac tca gac ctg 1189 Asp Leu Arg His Arg Pro Thr Ala Gly Ala Phe Asn His Ser Asp Leu             160 165 170 gac gcc gag ctg agg cgg ctc ttc cgc gag cgc tat cgg ctg cac ccc 1237 Asp Ala Glu Leu Arg Arg Leu Phe Arg Glu Arg Tyr Arg Leu His Pro         175 180 185 aag ttc gtg gcg gcc gtg cac tac gag cag ccc acc atc cag atc gag 1285 Lys Phe Val Ala Ala Val His Tyr Glu Gln Pro Thr Ile Gln Ile Glu     190 195 200 ctg cgg cag aac acg tct cag aag gcc gcc ggt gac gtg gat atc ggc 1333 Leu Arg Gln Asn Thr Ser Gln Lys Ala Ala Gly Asp Val Asp Ile Gly 205 210 215 220 gat gcc gcc tac tac ttc gag agg gac atc aag ggc gag tct cta ttc 1381 Asp Ala Ala Tyr Tyr Phe Glu Arg Asp Ile Lys Gly Glu Ser Leu Phe                 225 230 235 cag ggc cgc ggc ggc ctg gac ttg cgc gtg cgc gga gaa ccc ctg cag 1429 Gln Gly Arg Gly Gly Leu Asp Leu Arg Val Arg Gly Glu Pro Leu Gln             240 245 250 gtg gag cgc acg ctc atc tat tac ctg gac gag att ccc ccg aag ttc 1477 Val Glu Arg Thr Leu Ile Tyr Tyr Leu Asp Glu Ile Pro Pro Lys Phe         255 260 265 tcc atg aag cgc ctc acc gcc ggc ctc atc gcc gtc atc gtg gtg gtc 1525 Ser Met Lys Arg Leu Thr Ala Gly Leu Ile Ala Val Ile Val Val Val     270 275 280 gtg gtg gcc ctc gtc gcc ggc atg gcc gtc ctg gtg atc acc aac cgg 1573 Val Val Ala Leu Val Ala Gly Met Ala Val Leu Val Ile Thr Asn Arg 285 290 295 300 aga aag tcg ggg aag tac aag aag gtg gag atc aag gaa ctg ggg gag 1621 Arg Lys Ser Gly Lys Tyr Lys Lys Val Glu Ile Lys Glu Leu Gly Glu                 305 310 315 ttg aga aag gaa ccg agc ttg tag gtacccggcg gggcagggga tggggtgggg 1675 Leu Arg Lys Glu Pro Ser Leu             320 taccggattt cggtatcgtc ccagacccaa gtgagtcacg cttcctgatt cctcggcgca 1735 aaggagacgt ttatcctttc aaattcctgc cttccccctc ccttttgcgc acacaccagg 1795 tttaatagat cctggcctca gggtctcctt tctttctcac ttctgtcttg aaggaagcat 1855 ttctaaaatg tatccccttt cggtccaaca acaggaaacc tgactggggc agtgaaggaa 1915 gggatggcat agcgttatgt gtaaaaaaca agtatctgta tgacaacccg ggatcgtttg 1975 caagtaactg aatccattgc gacattgtga aggcttaaat gagtttagat gggaaatagc 2035 gttgttatcg ccttgggttt aaattatttg atgagttcca cttgtatcat ggcctacccg 2095 aggagaagag gagtttgtta actgggccta tgtagtagcc tcatttacca tcgtttgtat 2155 tactgaccac atatgcttgt cactgggaaa gaagcctgtt tcagctgcct gaacgcagtt 2215 tggatgtctt tgaggacaga cattgcccgg aaactcagtc tatttattct tcagcttgcc 2275 cttactgcca ctgatattgg taatgttctt ttttgtaaaa tgtttgtaca tatgttgtct 2335 ttgataatgt tgctgtaatt ttttaaaata aaacacgaat ttaataaaat atgggaaagg 2395 cacaaaaaaa a 2406 <210> 14 <211> 323 <212> PRT <213> Homo sapiens <400> 14 Met Ala Arg Gly Pro Gly Leu Ala Pro Pro Pro Leu Arg Leu Pro Leu   1 5 10 15 Leu Leu Leu Val Leu Ala Ala Val Thr Gly His Thr Ala Ala Gln Asp              20 25 30 Asn Cys Thr Cys Pro Thr Asn Lys Met Thr Val Cys Ser Pro Asp Gly          35 40 45 Pro Gly Gly Arg Cys Gln Cys Arg Ala Leu Gly Ser Gly Met Ala Val      50 55 60 Asp Cys Ser Thr Leu Thr Ser Lys Cys Leu Leu Leu Lys Ala Arg Met  65 70 75 80 Ser Ala Pro Lys Asn Ala Arg Thr Leu Val Arg Pro Ser Glu His Ala                  85 90 95 Leu Val Asp Asn Asp Gly Leu Tyr Asp Pro Asp Cys Asp Pro Glu Gly             100 105 110 Arg Phe Lys Ala Arg Gln Cys Asn Gln Thr Ser Val Cys Trp Cys Val         115 120 125 Asn Ser Val Gly Val Arg Arg Thr Asp Lys Gly Asp Leu Ser Leu Arg     130 135 140 Cys Asp Glu Leu Val Arg Thr His His Ile Leu Ile Asp Leu Arg His 145 150 155 160 Arg Pro Thr Ala Gly Ala Phe Asn His Ser Asp Leu Asp Ala Glu Leu                 165 170 175 Arg Arg Leu Phe Arg Glu Arg Tyr Arg Leu His Pro Lys Phe Val Ala             180 185 190 Ala Val His Tyr Glu Gln Pro Thr Ile Gln Ile Glu Leu Arg Gln Asn         195 200 205 Thr Ser Gln Lys Ala Ala Gly Asp Val Asp Ile Gly Asp Ala Ala Tyr     210 215 220 Tyr Phe Glu Arg Asp Ile Lys Gly Glu Ser Leu Phe Gln Gly Arg Gly 225 230 235 240 Gly Leu Asp Leu Arg Val Arg Gly Glu Pro Leu Gln Val Glu Arg Thr                 245 250 255 Leu Ile Tyr Tyr Leu Asp Glu Ile Pro Pro Lys Phe Ser Met Lys Arg             260 265 270 Leu Thr Ala Gly Leu Ile Ala Val Ile Val Val Val Val Val Ala Leu         275 280 285 Val Ala Gly Met Ala Val Leu Val Ile Thr Asn Arg Arg Lys Ser Gly     290 295 300 Lys Tyr Lys Lys Val Glu Ile Lys Glu Leu Gly Glu Leu Arg Lys Glu 305 310 315 320 Pro Ser Leu <210> 15 <211> 10211 <212> DNA <213> Homo sapiens <220> <221> CDS <222> (73) .. (9414) <400> 15 gagaggtcgt tttcccgtcc ccgagagcaa gtttatttac aaatgttgga gtaataaaga 60 aggcagaaca aa atg agc tgg gct ttg gaa gaa tgg aaa gaa ggg ctg cct 111               Met Ser Trp Ala Leu Glu Glu Trp Lys Glu Gly Leu Pro                 1 5 10 aca aga gct ctt cag aaa att caa gag ctt gaa gga cag ctt gac aaa 159 Thr Arg Ala Leu Gln Lys Ile Gln Glu Leu Glu Gly Gln Leu Asp Lys      15 20 25 ctg aag aag gaa aag cag caa agg cag ttt cag ctt gac agt ctc gag 207 Leu Lys Lys Glu Lys Gln Gln Arg Gln Phe Gln Leu Asp Ser Leu Glu  30 35 40 45 gct gcg cct cag aag caa aca cag aag gtt gaa aat gaa aaa acc gag 255 Ala Ala Pro Gln Lys Gln Thr Gln Lys Val Glu Asn Glu Lys Thr Glu                  50 55 60 ggt aca aac ctg aaa agg gag aat caa aga ttg atg gaa ata tgt gaa 303 Gly Thr Asn Leu Lys Arg Glu Asn Gln Arg Leu Met Glu Ile Cys Glu              65 70 75 agt ctg gag aaa act aag cag aag att tct cat gaa ctt caa gtc aag 351 Ser Leu Glu Lys Thr Lys Gln Lys Ile Ser His Glu Leu Gln Val Lys          80 85 90 gag tca caa gtg aat ttc cag gaa gga caa ctg aat tca ggc aaa aaa 399 Glu Ser Gln Val Asn Phe Gln Glu Gly Gln Leu Asn Ser Gly Lys Lys      95 100 105 caa ata gaa aaa ctg gaa cag gaa ctt aaa agg tgt aaa tct gag ctt 447 Gln Ile Glu Lys Leu Glu Gln Glu Leu Lys Arg Cys Lys Ser Glu Leu 110 115 120 125 gaa aga agc caa caa gct gcg cag tct gca gat gtc tct ctg aat cca 495 Glu Arg Ser Gln Gln Ala Ala Gln Ser Ala Asp Val Ser Leu Asn Pro                 130 135 140 tgc aat aca cca caa aaa att ttt aca act cca cta aca cca agt caa 543 Cys Asn Thr Pro Gln Lys Ile Phe Thr Thr Pro Leu Thr Pro Ser Gln             145 150 155 tat tat agt ggt tcc aag tat gaa gat cta aaa gaa aaa tat aat aaa 591 Tyr Tyr Ser Gly Ser Lys Tyr Glu Asp Leu Lys Glu Lys Tyr Asn Lys         160 165 170 gag gtt gaa gaa cga aaa aga tta gag gca gag gtt aaa gcc ttg cag 639 Glu Val Glu Glu Arg Lys Arg Leu Glu Ala Glu Val Lys Ala Leu Gln     175 180 185 gct aaa aaa gca agc cag act ctt cca caa gcc acc atg aat cac cgc 687 Ala Lys Lys Ala Ser Gln Thr Leu Pro Gln Ala Thr Met Asn His Arg 190 195 200 205 gac att gcc cgg cat cag gct tca tca tct gtg ttc tca tgg cag caa 735 Asp Ile Ala Arg His Gln Ala Ser Ser Ser Val Phe Ser Trp Gln Gln                 210 215 220 gag aag acc cca agt cat ctt tca tct aat tct caa aga act cca att 783 Glu Lys Thr Pro Ser His Leu Ser Ser Asn Ser Gln Arg Thr Pro Ile             225 230 235 agg aga gat ttc tct gca tct tac ttt tct ggg gaa caa gag gtg act 831 Arg Arg Asp Phe Ser Ala Ser Tyr Phe Ser Gly Glu Gln Glu Val Thr         240 245 250 cca agt cga tca act ttg caa ata ggg aaa aga gat gct aat agc agt 879 Pro Ser Arg Ser Thr Leu Gln Ile Gly Lys Arg Asp Ala Asn Ser Ser     255 260 265 ttc ttt gac aat tct agc agt cct cat ctt ttg gat caa tta aaa gcg 927 Phe Phe Asp Asn Ser Ser Ser Pro His Leu Leu Asp Gln Leu Lys Ala 270 275 280 285 cag aat caa gag cta aga aac aag att aat gag ttg gaa cta cgc ctg 975 Gln Asn Gln Glu Leu Arg Asn Lys Ile Asn Glu Leu Glu Leu Arg Leu                 290 295 300 caa gga cat gaa aaa gaa atg aaa ggc caa gtg aat aag ttt caa gaa 1023 Gln Gly His Glu Lys Glu Met Lys Gly Gln Val Asn Lys Phe Gln Glu             305 310 315 ctc caa ctc caa ctg gag aaa gca aaa gtg gaa tta att gaa aaa gag 1071 Leu Gln Leu Gln Leu Glu Lys Ala Lys Val Glu Leu Ile Glu Lys Glu         320 325 330 aaa gtt ttg aac aaa tgt agg gat gaa cta gtg aga aca aca gca caa 1119 Lys Val Leu Asn Lys Cys Arg Asp Glu Leu Val Arg Thr Thr Ala Gln     335 340 345 tac gac cag gcg tca acc aag tat act gca ttg gaa caa aaa ctg aaa 1167 Tyr Asp Gln Ala Ser Thr Lys Tyr Thr Ala Leu Glu Gln Lys Leu Lys 350 355 360 365 aaa ttg acg gaa gat ttg agt tgt cag cga caa aat gca gaa agt gcc 1215 Lys Leu Thr Glu Asp Leu Ser Cys Gln Arg Gln Asn Ala Glu Ser Ala                 370 375 380 aga tgt tct ctg gaa cag aaa att aag gaa aaa gaa aag gag ttt caa 1263 Arg Cys Ser Leu Glu Gln Lys Ile Lys Glu Lys Glu Lys Glu Phe Gln             385 390 395 gag gag ctc tcc cgt caa cag cgt tct ttc caa aca ctg gac cag gag 1311 Glu Glu Leu Ser Arg Gln Gln Arg Ser Phe Gln Thr Leu Asp Gln Glu         400 405 410 tgc atc cag atg aag gcc aga ctc acc cag gag tta cag caa gcc aag 1359 Cys Ile Gln Met Lys Ala Arg Leu Thr Gln Glu Leu Gln Gln Ala Lys     415 420 425 aat atg cac aac gtc ctg cag gct gaa ctg gat aaa ctc aca tca gta 1407 Asn Met His Asn Val Leu Gln Ala Glu Leu Asp Lys Leu Thr Ser Val 430 435 440 445 aag caa cag cta gaa aac aat ttg gaa gag ttt aag caa aag ttg tgc 1455 Lys Gln Gln Leu Glu Asn Asn Leu Glu Glu Phe Lys Gln Lys Leu Cys                 450 455 460 aga gct gaa cag gcg ttc cag gcg agt cag atc aag gag aat gag ctg 1503 Arg Ala Glu Gln Ala Phe Gln Ala Ser Gln Ile Lys Glu Asn Glu Leu             465 470 475 agg aga agc atg gag gaa atg aag aag gaa aac aac ctc ctt aag agt 1551 Arg Arg Ser Met Glu Glu Met Lys Lys Glu Asn Asn Leu Leu Lys Ser         480 485 490 cac tct gag caa aag gcc aga gaa gtc tgc cac ctg gag gca gaa ctc 1599 His Ser Glu Gln Lys Ala Arg Glu Val Cys His Leu Glu Ala Glu Leu     495 500 505 aag aac atc aaa cag tgt tta aat cag agc cag aat ttt gca gaa gaa 1647 Lys Asn Ile Lys Gln Cys Leu Asn Gln Ser Gln Asn Phe Ala Glu Glu 510 515 520 525 atg aaa gcg aag aat acc tct cag gaa acc atg tta aga gat ctt caa 1695 Met Lys Ala Lys Asn Thr Ser Gln Glu Thr Met Leu Arg Asp Leu Gln                 530 535 540 gaa aaa ata aat cag caa gaa aac tcc ttg act tta gaa aaa ctg aag 1743 Glu Lys Ile Asn Gln Gln Glu Asn Ser Leu Thr Leu Glu Lys Leu Lys             545 550 555 ctt gct gtg gct gat ctg gaa aag cag cga gat tgt tct caa gac ctt 1791 Leu Ala Val Ala Asp Leu Glu Lys Gln Arg Asp Cys Ser Gln Asp Leu         560 565 570 ttg aag aaa aga gaa cat cac att gaa caa ctt aat gat aag tta agc 1839 Leu Lys Lys Arg Glu His His Ile Glu Gln Leu Asn Asp Lys Leu Ser     575 580 585 aag aca gag aaa gag tcc aaa gcc ttg ctg agt gct tta gag tta aaa 1887 Lys Thr Glu Lys Glu Ser Lys Ala Leu Leu Ser Ala Leu Glu Leu Lys 590 595 600 605 aag aaa gaa tat gaa ttg aaa gaa gag aaa act ctg ttt tct tgt tgg 1935 Lys Lys Glu Tyr Glu Leu Lys Glu Glu Lys Thr Leu Phe Ser Cys Trp                 610 615 620 aaa agt gaa aac gaa aaa ctt tta act cag atg gaa tca gaa aag gaa 1983 Lys Ser Glu Asn Glu Lys Leu Leu Thr Gln Met Glu Ser Glu Lys Glu             625 630 635 aac ttg cag agt aaa att aat cac ttg gaa act tgt ctg aag aca cag 2031 Asn Leu Gln Ser Lys Ile Asn His Leu Glu Thr Cys Leu Lys Thr Gln         640 645 650 caa ata aaa agt cat gaa tac aac gag aga gta aga acg ctg gag atg 2079 Gln Ile Lys Ser His Glu Tyr Asn Glu Arg Val Arg Thr Leu Glu Met     655 660 665 gac aga gaa aac cta agt gtc gag atc aga aac ctt cac aac gtg tta 2127 Asp Arg Glu Asn Leu Ser Val Glu Ile Arg Asn Leu His Asn Val Leu 670 675 680 685 gac agt aag tca gtg gag gta gag acc cag aaa cta gct tat atg gag 2175 Asp Ser Lys Ser Val Glu Val Glu Thr Gln Lys Leu Ala Tyr Met Glu                 690 695 700 cta cag cag aaa gct gag ttc tca gat cag aaa cat cag aag gaa ata 2223 Leu Gln Gln Lys Ala Glu Phe Ser Asp Gln Lys His Gln Lys Glu Ile             705 710 715 gaa aat atg tgt ttg aag act tct cag ctt act ggg caa gtt gaa gat 2271 Glu Asn Met Cys Leu Lys Thr Ser Gln Leu Thr Gly Gln Val Glu Asp         720 725 730 cta gaa cac aag ctt cag tta ctg tca aat gaa ata atg gac aaa gac 2319 Leu Glu His Lys Leu Gln Leu Leu Ser Asn Glu Ile Met Asp Lys Asp     735 740 745 cgg tgt tac caa gac ttg cat gcc gaa tat gag agc ctc agg gat ctg 2367 Arg Cys Tyr Gln Asp Leu His Ala Glu Tyr Glu Ser Leu Arg Asp Leu 750 755 760 765 cta aaa tcc aaa gat gct tct ctg gtg aca aat gaa gat cat cag aga 2415 Leu Lys Ser Lys Asp Ala Ser Leu Val Thr Asn Glu Asp His Gln Arg                 770 775 780 agt ctt ttg gct ttt gat cag cag cct gcc atg cat cat tcc ttt gca 2463 Ser Leu Leu Ala Phe Asp Gln Gln Pro Ala Met His His Ser Phe Ala             785 790 795 aat ata att gga gaa caa gga agc atg cct tca gag agg agt gaa tgt 2511 Asn Ile Ile Gly Glu Gln Gly Ser Met Pro Ser Glu Arg Ser Glu Cys         800 805 810 cgt tta gaa gca gac caa agt ccg aaa aat tct gcc atc cta caa aat 2559 Arg Leu Glu Ala Asp Gln Ser Pro Lys Asn Ser Ala Ile Leu Gln Asn     815 820 825 aga gtt gat tca ctt gaa ttt tca tta gag tct caa aaa cag atg aac 2607 Arg Val Asp Ser Leu Glu Phe Ser Leu Glu Ser Gln Lys Gln Met Asn 830 835 840 845 tca gac ctg caa aag cag tgt gaa gag ttg gtg caa atc aaa gga gaa 2655 Ser Asp Leu Gln Lys Gln Cys Glu Glu Leu Val Gln Ile Lys Gly Glu                 850 855 860 ata gaa gaa aat ctc atg aaa gca gaa cag atg cat caa agt ttt gtg 2703 Ile Glu Glu Asn Leu Met Lys Ala Glu Gln Met His Gln Ser Phe Val             865 870 875 gct gaa aca agt cag cgc att agt aag tta cag gaa gac act tct gct 2751 Ala Glu Thr Ser Gln Arg Ile Ser Lys Leu Gln Glu Asp Thr Ser Ala         880 885 890 cac cag aat gtt gtt gct gaa acc tta agt gcc ctt gag aac aag gaa 2799 His Gln Asn Val Val Ala Glu Thr Leu Ser Ala Leu Glu Asn Lys Glu     895 900 905 aaa gag ctg caa ctt tta aat gat aag gta gaa act gag cag gca gag 2847 Lys Glu Leu Gln Leu Leu Asn Asp Lys Val Glu Thr Glu Gln Ala Glu 910 915 920 925 att caa gaa tta aaa aag agc aac cat cta ctt gaa gac tct cta aag 2895 Ile Gln Glu Leu Lys Lys Ser Asn His Leu Leu Glu Asp Ser Leu Lys                 930 935 940 gag cta caa ctt tta tcc gaa acc cta agc ttg gag aag aaa gaa atg 2943 Glu Leu Gln Leu Leu Ser Glu Thr Leu Ser Leu Glu Lys Lys Glu Met             945 950 955 agt tcc atc att tct cta aat aaa agg gaa att gaa gag ctg acc caa 2991 Ser Ser Ile Ile Ser Leu Asn Lys Arg Glu Ile Glu Glu Leu Thr Gln         960 965 970 gag aat ggg act ctt aag gaa att aat gca tcc tta aat caa gag aag 3039 Glu Asn Gly Thr Leu Lys Glu Ile Asn Ala Ser Leu Asn Gln Glu Lys     975 980 985 atg aac tta atc cag aaa agt gag agt ttt gca aac tat ata gat gaa 3087 Met Asn Leu Ile Gln Lys Ser Glu Ser Phe Ala Asn Tyr Ile Asp Glu 990 995 1000 1005 agg gag aaa agc att tca gag tta tct gat cag tac aag caa gaa aaa 3135 Arg Glu Lys Ser Ile Ser Glu Leu Ser Asp Gln Tyr Lys Gln Glu Lys                1010 1015 1020 ctt att tta cta caa aga tgt gaa gaa acc gga aat gca tat gag gat 3183 Leu Ile Leu Leu Gln Arg Cys Glu Glu Thr Gly Asn Ala Tyr Glu Asp            1025 1030 1035 ctt agt caa aaa tac aaa gca gca cag gaa aag aat tct aaa tta gaa 3231 Leu Ser Gln Lys Tyr Lys Ala Ala Gln Glu Lys Asn Ser Lys Leu Glu        1040 1045 1050 tgc ttg cta aat gaa tgc act agt ctt tgt gaa aat agg aaa aat gag 3279 Cys Leu Leu Asn Glu Cys Thr Ser Leu Cys Glu Asn Arg Lys Asn Glu    1055 1060 1065 ttg gaa cag cta aag gaa gca ttt gca aag gaa cac caa gaa ttc tta 3327 Leu Glu Gln Leu Lys Glu Ala Phe Ala Lys Glu His Gln Glu Phe Leu 1070 1075 1080 1085 aca aaa tta gca ttt gct gaa gaa aga aat cag aat ctg atg cta gag 3375 Thr Lys Leu Ala Phe Ala Glu Glu Arg Asn Gln Asn Leu Met Leu Glu                1090 1095 1100 ttg gag aca gtg cag caa gct ctg aga tct gag atg aca gat aac caa 3423 Leu Glu Thr Val Gln Gln Ala Leu Arg Ser Glu Met Thr Asp Asn Gln            1105 1110 1115 aac aat tct aag agc gag gct ggt ggt tta aag caa gaa atc atg act 3471 Asn Asn Ser Lys Ser Glu Ala Gly Gly Leu Lys Gln Glu Ile Met Thr        1120 1125 1130 tta aag gaa gaa caa aac aaa atg caa aag gaa gtt aat gac tta tta 3519 Leu Lys Glu Glu Gln Asn Lys Met Gln Lys Glu Val Asn Asp Leu Leu    1135 1140 1145 caa gag aat gaa cag ctg atg aag gta atg aag act aaa cat gaa tgt 3567 Gln Glu Asn Glu Gln Leu Met Lys Val Met Lys Thr Lys His Glu Cys 1150 1155 1160 1165 caa aat cta gaa tca gaa cca att agg aac tct gtg aaa gaa aga gag 3615 Gln Asn Leu Glu Ser Glu Pro Ile Arg Asn Ser Val Lys Glu Arg Glu                1170 1175 1180 agt gag aga aat caa tgt aat ttt aaa cct cag atg gat ctt gaa gtt 3663 Ser Glu Arg Asn Gln Cys Asn Phe Lys Pro Gln Met Asp Leu Glu Val            1185 1190 1195 aaa gaa att tct cta gat agt tat aat gcg cag ttg gtg caa tta gaa 3711 Lys Glu Ile Ser Leu Asp Ser Tyr Asn Ala Gln Leu Val Gln Leu Glu        1200 1205 1210 gct atg cta aga aat aag gaa tta aaa ctt cag gaa agt gag aag gag 3759 Ala Met Leu Arg Asn Lys Glu Leu Lys Leu Gln Glu Ser Glu Lys Glu    1215 1220 1225 aag gag tgc ctg cag cat gaa tta cag aca att aga gga gat ctt gaa 3807 Lys Glu Cys Leu Gln His Glu Leu Gln Thr Ile Arg Gly Asp Leu Glu 1230 1235 1240 1245 acc agc aat ttg caa gac atg cag tca caa gaa att agt ggc ctt aaa 3855 Thr Ser Asn Leu Gln Asp Met Gln Ser Gln Glu Ile Ser Gly Leu Lys                1250 1255 1260 gac tgt gaa ata gat gcg gaa gaa aag tat att tca ggg cct cat gag 3903 Asp Cys Glu Ile Asp Ala Glu Glu Lys Tyr Ile Ser Gly Pro His Glu            1265 1270 1275 ttg tca aca agt caa aac gac aat gca cac ctt cag tgc tct ctg caa 3951 Leu Ser Thr Ser Gln Asn Asp Asn Ala His Leu Gln Cys Ser Leu Gln        1280 1285 1290 aca aca atg aac aag ctg aat gag cta gag aaa ata tgt gaa ata ctg 3999 Thr Thr Met Asn Lys Leu Asn Glu Leu Glu Lys Ile Cys Glu Ile Leu    1295 1300 1305 cag gct gaa aag tat gaa ctc gta act gag ctg aat gat tca agg tca 4047 Gln Ala Glu Lys Tyr Glu Leu Val Thr Glu Leu Asn Asp Ser Arg Ser 1310 1315 1320 1325 gaa tgt atc aca gca act agg aaa atg gca gaa gag gta ggg aaa cta 4095 Glu Cys Ile Thr Ala Thr Arg Lys Met Ala Glu Glu Val Gly Lys Leu                1330 1335 1340 cta aat gaa gtt aaa ata tta aat gat gac agt ggt ctt ctc cat ggt 4143 Leu Asn Glu Val Lys Ile Leu Asn Asp Asp Ser Gly Leu Leu His Gly            1345 1350 1355 gag tta gtg gaa gac ata cca gga ggt gaa ttt ggt gaa caa cca aat 4191 Glu Leu Val Glu Asp Ile Pro Gly Gly Glu Phe Gly Glu Gln Pro Asn        1360 1365 1370 gaa cag cac cct gtg tct ttg gct cca ttg gac gag agt aat tcc tac 4239 Glu Gln His Pro Val Ser Leu Ala Pro Leu Asp Glu Ser Asn Ser Tyr    1375 1380 1385 gag cac ttg aca ttg tca gac aaa gaa gtt caa atg cac ttt gcc gaa 4287 Glu His Leu Thr Leu Ser Asp Lys Glu Val Gln Met His Phe Ala Glu 1390 1395 1400 1405 ttg caa gag aaa ttc tta tct tta caa agt gaa cac aaa att tta cat 4335 Leu Gln Glu Lys Phe Leu Ser Leu Gln Ser Glu His Lys Ile Leu His                1410 1415 1420 gat cag cac tgt cag atg agc tct aaa atg tca gag ctg cag acc tat 4383 Asp Gln His Cys Gln Met Ser Ser Lys Met Ser Glu Leu Gln Thr Tyr            1425 1430 1435 gtt gac tca tta aag gcc gaa aat ttg gtc ttg tca acg aat ctg aga 4431 Val Asp Ser Leu Lys Ala Glu Asn Leu Val Leu Ser Thr Asn Leu Arg        1440 1445 1450 aac ttt caa ggt gac ttg gtg aag gag atg cag ctg ggc ttg gag gag 4479 Asn Phe Gln Gly Asp Leu Val Lys Glu Met Gln Leu Gly Leu Glu Glu    1455 1460 1465 ggg ctc gtt cca tcc ctg tca tcc tct tgt gtg cct gac agc tct agt 4527 Gly Leu Val Pro Ser Leu Ser Ser Ser Cys Val Pro Asp Ser Ser Ser 1470 1475 1480 1485 ctt agc agt ttg gga gac tcc tcc ttt tac aga gct ctt tta gaa cag 4575 Leu Ser Ser Leu Gly Asp Ser Ser Phe Tyr Arg Ala Leu Leu Glu Gln                1490 1495 1500 aca gga gat atg tct ctt ttg agt aat tta gaa ggg gct gtt tca gca 4623 Thr Gly Asp Met Ser Leu Leu Ser Asn Leu Glu Gly Ala Val Ser Ala            1505 1510 1515 aac cag tgc agt gta gat gaa gta ttt tgc agc agt ctg cag gag gag 4671 Asn Gln Cys Ser Val Asp Glu Val Phe Cys Ser Ser Leu Gln Glu Glu        1520 1525 1530 aat ctg acc agg aaa gaa acc cct tcg gcc cca gcg aag ggt gtt gaa 4719 Asn Leu Thr Arg Lys Glu Thr Pro Ser Ala Pro Ala Lys Gly Val Glu    1535 1540 1545 gag ctt gag tcc ctc tgt gag gtg tac cgg cag tcc ctc gag aag cta 4767 Glu Leu Glu Ser Leu Cys Glu Val Tyr Arg Gln Ser Leu Glu Lys Leu 1550 1555 1560 1565 gaa gag aaa atg gaa agt caa ggg att atg aaa aat aag gaa att caa 4815 Glu Glu Lys Met Glu Ser Gln Gly Ile Met Lys Asn Lys Glu Ile Gln                1570 1575 1580 gag ctc gag cag tta tta agt tct gaa agg caa gag ctt gac tgc ctt 4863 Glu Leu Glu Gln Leu Leu Ser Ser Glu Arg Gln Glu Leu Asp Cys Leu            1585 1590 1595 agg aag cag tat ttg tca gaa aat gaa cag tgg caa cag aag ctg aca 4911 Arg Lys Gln Tyr Leu Ser Glu Asn Glu Gln Trp Gln Gln Lys Leu Thr        1600 1605 1610 agc gtg act ctg gag atg gag tcc aag ttg gcg gca gaa aag aaa cag 4959 Ser Val Thr Leu Glu Met Glu Ser Lys Leu Ala Ala Glu Lys Lys Gln    1615 1620 1625 acg gaa caa ctg tca ctt gag ctg gaa gta gca cga ctc cag cta caa 5007 Thr Glu Gln Leu Ser Leu Glu Leu Glu Val Ala Arg Leu Gln Leu Gln 1630 1635 1640 1645 ggt ctg gac tta agt tct cgg tct ttg ctt ggc atc gac aca gaa gat 5055 Gly Leu Asp Leu Ser Ser Arg Ser Leu Leu Gly Ile Asp Thr Glu Asp                1650 1655 1660 gct att caa ggc cga aat gag agc tgt gac ata tca aaa gaa cat act 5103 Ala Ile Gln Gly Arg Asn Glu Ser Cys Asp Ile Ser Lys Glu His Thr            1665 1670 1675 tca gaa act aca gaa aga aca cca aag cat gat gtt cat cag att tgt 5151 Ser Glu Thr Thr Glu Arg Thr Pro Lys His Asp Val His Gln Ile Cys        1680 1685 1690 gat aaa gat gct cag cag gac ctc aat cta gac att gag aaa ata act 5199 Asp Lys Asp Ala Gln Gln Asp Leu Asn Leu Asp Ile Glu Lys Ile Thr    1695 1700 1705 gag act ggt gca ttg aaa ccc aca gga gag tgc tct ggg gaa cag tcc 5247 Glu Thr Gly Ala Leu Lys Pro Thr Gly Glu Cys Ser Gly Glu Gln Ser 1710 1715 1720 1725 cca gat acc aat tat gag cct cca ggg gaa gat aaa acc cag ggc tct 5295 Pro Asp Thr Asn Tyr Glu Pro Pro Gly Glu Asp Lys Thr Gln Gly Ser                1730 1735 1740 tca gaa tgc att tct gaa ttg tca ttt tct ggt cct aat gct ttg gta 5343 Ser Glu Cys Ile Ser Glu Leu Ser Phe Ser Gly Pro Asn Ala Leu Val            1745 1750 1755 cct atg gat ttc ctg ggg aat cag gaa gat atc cat aat ctt caa ctg 5391 Pro Met Asp Phe Leu Gly Asn Gln Glu Asp Ile His Asn Leu Gln Leu        1760 1765 1770 cgg gta aaa gag aca tca aat gag aat ttg aga tta ctt cat gtg ata 5439 Arg Val Lys Glu Thr Ser Asn Glu Asn Leu Arg Leu Leu His Val Ile    1775 1780 1785 gag gac cgt gac aga aaa gtt gaa agt ttg cta aat gaa atg aaa gaa 5487 Glu Asp Arg Asp Arg Lys Val Glu Ser Leu Leu Asn Glu Met Lys Glu 1790 1795 1800 1805 tta gac tca aaa ctc cat tta cag gag gta caa cta atg acc aaa att 5535 Leu Asp Ser Lys Leu His Leu Gln Glu Val Gln Leu Met Thr Lys Ile                1810 1815 1820 gaa gca tgc ata gaa ttg gaa aaa ata gtt ggg gaa ctt aag aaa gaa 5583 Glu Ala Cys Ile Glu Leu Glu Lys Ile Val Gly Glu Leu Lys Lys Glu            1825 1830 1835 aac tca gat tta agt gaa aaa ttg gaa tat ttt tct tgt gat cac cag 5631 Asn Ser Asp Leu Ser Glu Lys Leu Glu Tyr Phe Ser Cys Asp His Gln        1840 1845 1850 gag tta ctc cag aga gta gaa act tct gaa ggc ctc aat tct gat tta 5679 Glu Leu Leu Gln Arg Val Glu Thr Ser Glu Gly Leu Asn Ser Asp Leu    1855 1860 1865 gaa atg cat gca gat aaa tca tca cgt gaa gat att gga gat aat gtg 5727 Glu Met His Ala Asp Lys Ser Ser Arg Glu Asp Ile Gly Asp Asn Val 1870 1875 1880 1885 gcc aag gtg aat gac agc tgg aag gag aga ttt ctt gat gtg gaa aat 5775 Ala Lys Val Asn Asp Ser Trp Lys Glu Arg Phe Leu Asp Val Glu Asn                1890 1895 1900 gag ctg agt agg atc aga tcg gag aaa gct agc att gag cat gaa gcc 5823 Glu Leu Ser Arg Ile Arg Ser Glu Lys Ala Ser Ile Glu His Glu Ala            1905 1910 1915 ctc tac ctg gag gct gac tta gag gta gtt caa aca gag aag cta tgt 5871 Leu Tyr Leu Glu Ala Asp Leu Glu Val Val Gln Thr Glu Lys Leu Cys        1920 1925 1930 tta gaa aaa gac aat gaa aat aag cag aag gtt att gtc tgc ctt gaa 5919 Leu Glu Lys Asp Asn Glu Asn Lys Gln Lys Val Ile Val Cys Leu Glu    1935 1940 1945 gaa gaa ctc tca gtg gtc aca agt gag aga aac cag ctt cgt gga gaa 5967 Glu Glu Leu Ser Val Val Thr Ser Glu Arg Asn Gln Leu Arg Gly Glu 1950 1955 1960 1965 tta gat act atg tca aaa aaa acc acg gca ctg gat cag ttg tct gaa 6015 Leu Asp Thr Met Ser Lys Lys Thr Thr Ala Leu Asp Gln Leu Ser Glu                1970 1975 1980 aaa atg aag gag aaa aca caa gag ctt gag tct cat caa agt gag tgt 6063 Lys Met Lys Glu Lys Thr Gln Glu Leu Glu Ser His Gln Ser Glu Cys            1985 1990 1995 ctc cat tgc att cag gtg gca gag gca gag gtg aag gaa aag acg gaa 6111 Leu His Cys Ile Gln Val Ala Glu Ala Glu Val Lys Glu Lys Thr Glu        2000 2005 2010 ctc ctt cag act ttg tcc tct gat gtg agt gag ctg tta aaa gac aaa 6159 Leu Leu Gln Thr Leu Ser Ser Asp Val Ser Glu Leu Leu Lys Asp Lys    2015 2020 2025 act cat ctc cag gaa aag ctg cag agt ttg gaa aag gac tca cag gca 6207 Thr His Leu Gln Glu Lys Leu Gln Ser Leu Glu Lys Asp Ser Gln Ala 2030 2035 2040 2045 ctg tct ttg aca aaa tgt gag ctg gaa aac caa att gca caa ctg aat 6255 Leu Ser Leu Thr Lys Cys Glu Leu Glu Asn Gln Ile Ala Gln Leu Asn                2050 2055 2060 aaa gag aaa gaa ttg ctt gtc aag gaa tct gaa agc ctg cag gcc aga 6303 Lys Glu Lys Glu Leu Leu Val Lys Glu Ser Glu Ser Leu Gln Ala Arg            2065 2070 2075 ctg agt gaa tca gat tat gaa aag ctg aat gtc tcc aag gcc ttg gag 6351 Leu Ser Glu Ser Asp Tyr Glu Lys Leu Asn Val Ser Lys Ala Leu Glu        2080 2085 2090 gcc gca ctg gtg gag aaa ggt gag ttc gca ttg agg ctg agc tca aca 6399 Ala Ala Leu Val Glu Lys Gly Glu Phe Ala Leu Arg Leu Ser Ser Thr    2095 2100 2105 cag gag gaa gtg cat cag ctg aga aga ggc atc gag aaa ctg aga gtt 6447 Gln Glu Glu Val His Gln Leu Arg Arg Gly Ile Glu Lys Leu Arg Val 2110 2115 2120 2125 cgc att gag gcc gat gaa aag aag cag ctg cac atc gca gag aaa ctg 6495 Arg Ile Glu Ala Asp Glu Lys Lys Gln Leu His Ile Ala Glu Lys Leu                2130 2135 2140 aaa gaa cgc gag cgg gag aat gat tca ctt aag gat aaa gtt gag aac 6543 Lys Glu Arg Glu Arg Glu Asn Asp Ser Leu Lys Asp Lys Val Glu Asn            2145 2150 2155 ctt gaa agg gaa ttg cag atg tca gaa gaa aac cag gag cta gtg att 6591 Leu Glu Arg Glu Leu Gln Met Ser Glu Glu Asn Gln Glu Leu Val Ile        2160 2165 2170 ctt gat gcc gag aat tcc aaa gca gaa gta gag act cta aaa aca caa 6639 Leu Asp Ala Glu Asn Ser Lys Ala Glu Val Glu Thr Leu Lys Thr Gln    2175 2180 2185 ata gaa gag atg gcc aga agc ctg aaa gtt ttt gaa tta gac ctt gtc 6687 Ile Glu Glu Met Ala Arg Ser Leu Lys Val Phe Glu Leu Asp Leu Val 2190 2195 2200 2205 acg tta agg tct gaa aaa gaa aat ctg aca aaa caa ata caa gaa aaa 6735 Thr Leu Arg Ser Glu Lys Glu Asn Leu Thr Lys Gln Ile Gln Glu Lys                2210 2215 2220 caa ggt cag ttg tca gaa cta gac aag tta ctc tct tca ttt aaa agt 6783 Gln Gly Gln Leu Ser Glu Leu Asp Lys Leu Leu Ser Ser Phe Lys Ser            2225 2230 2235 ctg tta gaa gaa aag gag caa gca gag ata cag atc aaa gaa gaa tct 6831 Leu Leu Glu Glu Lys Glu Gln Ala Glu Ile Gln Ile Lys Glu Glu Ser        2240 2245 2250 aaa act gca gtg gag atg ctt cag aat cag tta aag gag cta aat gag 6879 Lys Thr Ala Val Glu Met Leu Gln Asn Gln Leu Lys Glu Leu Asn Glu    2255 2260 2265 gca gta gca gcc ttg tgt ggt gac caa gaa att atg aag gcc aca gaa 6927 Ala Val Ala Ala Leu Cys Gly Asp Gln Glu Ile Met Lys Ala Thr Glu 2270 2275 2280 2285 cag agt cta gac cca cca ata gag gaa gag cat cag ctg aga aat agc 6975 Gln Ser Leu Asp Pro Pro Ile Glu Glu Glu His Gln Leu Arg Asn Ser                2290 2295 2300 att gaa aag ctg aga gcc cgc cta gaa gct gat gaa aag aag cag ctc 7023 Ile Glu Lys Leu Arg Ala Arg Leu Glu Ala Asp Glu Lys Lys Gln Leu            2305 2310 2315 tgt gtc tta caa caa ctg aag gaa agt gag cat cat gca gat tta ctt 7071 Cys Val Leu Gln Gln Leu Lys Glu Ser Glu His His Ala Asp Leu Leu        2320 2325 2330 aag ggt aga gtg gag aac ctt gaa aga gag cta gag ata gcc agg aca 7119 Lys Gly Arg Val Glu Asn Leu Glu Arg Glu Leu Glu Ile Ala Arg Thr    2335 2340 2345 aac caa gag cat gca gct ctt gag gca gag aat tcc aaa gga gag gta 7167 Asn Gln Glu His Ala Ala Leu Glu Ala Glu Asn Ser Lys Gly Glu Val 2350 2355 2360 2365 gag acc cta aaa gca aaa ata gaa ggg atg acc caa agt ctg aga ggt 7215 Glu Thr Leu Lys Ala Lys Ile Glu Gly Met Thr Gln Ser Leu Arg Gly                2370 2375 2380 ctg gaa tta gat gtt gtt act ata agg tca gaa aaa gaa aat ctg aca 7263 Leu Glu Leu Asp Val Val Thr Ile Arg Ser Glu Lys Glu Asn Leu Thr            2385 2390 2395 aat gaa tta caa aaa gag caa gag cga ata tct gaa tta gaa ata ata 7311 Asn Glu Leu Gln Lys Glu Gln Glu Arg Ile Ser Glu Leu Glu Ile Ile        2400 2405 2410 aat tca tca ttt gaa aat att ttg caa gaa aaa gag caa gag aaa gta 7359 Asn Ser Ser Phe Glu Asn Ile Leu Gln Glu Lys Glu Gln Glu Lys Val    2415 2420 2425 cag atg aaa gaa aaa tca agc act gcc atg gag atg ctt caa aca caa 7407 Gln Met Lys Glu Lys Ser Ser Thr Ala Met Glu Met Leu Gln Thr Gln 2430 2435 2440 2445 tta aaa gag ctc aat gag aga gtg gca gcc ctg cat aat gac caa gaa 7455 Leu Lys Glu Leu Asn Glu Arg Val Ala Ala Leu His Asn Asp Gln Glu                2450 2455 2460 gcc tgt aag gcc aaa gag cag aat ctt agt agt caa gta gag tgt ctt 7503 Ala Cys Lys Ala Lys Glu Gln Asn Leu Ser Ser Gln Val Glu Cys Leu            2465 2470 2475 gaa ctt gag aag gct cag ttg cta caa ggc ctt gat gag gcc aaa aat 7551 Glu Leu Glu Lys Ala Gln Leu Leu Gln Gly Leu Asp Glu Ala Lys Asn        2480 2485 2490 aat tat att gtt ttg caa tct tca gtg aat ggc ctc att caa gaa gta 7599 Asn Tyr Ile Val Leu Gln Ser Ser Val Asn Gly Leu Ile Gln Glu Val    2495 2500 2505 gaa gat ggc aag cag aaa ctg gag aag aag gat gaa gaa atc agt aga 7647 Glu Asp Gly Lys Gln Lys Leu Glu Lys Lys Asp Glu Glu Ile Ser Arg 2510 2515 2520 2525 ctg aaa aat caa att caa gac caa gag cag ctt gtc tct aaa ctg tcc 7695 Leu Lys Asn Gln Ile Gln Asp Gln Glu Gln Leu Val Ser Lys Leu Ser                2530 2535 2540 cag gtg gaa gga gag cac caa ctt tgg aag gag caa aac tta gaa ctg 7743 Gln Val Glu Gly Glu His Gln Leu Trp Lys Glu Gln Asn Leu Glu Leu            2545 2550 2555 aga aat ctg aca gtg gaa ttg gag cag aag atc caa gtg cta caa tcc 7791 Arg Asn Leu Thr Val Glu Leu Glu Gln Lys Ile Gln Val Leu Gln Ser        2560 2565 2570 aaa aat gcc tct ttg cag gac aca tta gaa gtg ctg cag agt tct tac 7839 Lys Asn Ala Ser Leu Gln Asp Thr Leu Glu Val Leu Gln Ser Ser Tyr    2575 2580 2585 aag aat cta gag aat gag ctt gaa ttg aca aaa atg gac aaa atg tcc 7887 Lys Asn Leu Glu Asn Glu Leu Glu Leu Thr Lys Met Asp Lys Met Ser 2590 2595 2600 2605 ttt gtt gaa aaa gta aac aaa atg act gca aag gaa act gag ctg cag 7935 Phe Val Glu Lys Val Asn Lys Met Thr Ala Lys Glu Thr Glu Leu Gln                2610 2615 2620 agg gaa atg cat gag atg gca cag aaa aca gca gag ctg caa gaa gaa 7983 Arg Glu Met His Glu Met Ala Gln Lys Thr Ala Glu Leu Gln Glu Glu            2625 2630 2635 ctc agt gga gag aaa aat agg cta gct gga gag ttg cag tta ctg ttg 8031 Leu Ser Gly Glu Lys Asn Arg Leu Ala Gly Glu Leu Gln Leu Leu Leu        2640 2645 2650 gaa gaa ata aag agc agc aaa gat caa ttg aag gag ctc aca cta gaa 8079 Glu Glu Ile Lys Ser Ser Lys Asp Gln Leu Lys Glu Leu Thr Leu Glu    2655 2660 2665 aat agt gaa ttg aag aag agc cta gat tgc atg cac aaa gac cag gtg 8127 Asn Ser Glu Leu Lys Lys Ser Leu Asp Cys Met His Lys Asp Gln Val 2670 2675 2680 2685 gaa aag gaa ggg aaa gtg aga gag gaa ata gct gaa tat cag cta cgg 8175 Glu Lys Glu Gly Lys Val Arg Glu Glu Ile Ala Glu Tyr Gln Leu Arg                2690 2695 2700 ctt cat gaa gct gaa aag aaa cac cag gct ttg ctt ttg gac aca aac 8223 Leu His Glu Ala Glu Lys Lys His Gln Ala Leu Leu Leu Asp Thr Asn            2705 2710 2715 aaa cag tat gaa gta gaa atc cag aca tac cga gag aaa ttg act tct 8271 Lys Gln Tyr Glu Val Glu Ile Gln Thr Tyr Arg Glu Lys Leu Thr Ser        2720 2725 2730 aaa gaa gaa tgt ctc agt tca cag aag ctg gag ata gac ctt tta aag 8319 Lys Glu Glu Cys Leu Ser Ser Gln Lys Leu Glu Ile Asp Leu Leu Lys    2735 2740 2745 tct agt aaa gaa gag ctc aat aat tca ttg aaa gct act act cag att 8367 Ser Ser Lys Glu Glu Leu Asn Asn Ser Leu Lys Ala Thr Thr Gln Ile 2750 2755 2760 2765 ttg gaa gaa ttg aag aaa acc aag atg gac aat cta aaa tat gta aat 8415 Leu Glu Glu Leu Lys Lys Thr Lys Met Asp Asn Leu Lys Tyr Val Asn                2770 2775 2780 cag ttg aag aag gaa aat gaa cgt gcc cag ggg aaa atg aag ttg ttg 8463 Gln Leu Lys Lys Glu Asn Glu Arg Ala Gln Gly Lys Met Lys Leu Leu            2785 2790 2795 atc aaa tcc tgt aaa cag ctg gaa gag gaa aag gag ata ctg cag aaa 8511 Ile Lys Ser Cys Lys Gln Leu Glu Glu Glu Lys Glu Ile Leu Gln Lys        2800 2805 2810 gaa ctc tct caa ctt caa gct gca cag gag aag cag aaa aca ggt act 8559 Glu Leu Ser Gln Leu Gln Ala Ala Gln Glu Lys Gln Lys Thr Gly Thr    2815 2820 2825 gtt atg gat acc aag gtc gat gaa tta aca act gag atc aaa gaa ctg 8607 Val Met Asp Thr Lys Val Asp Glu Leu Thr Thr Glu Ile Lys Glu Leu 2830 2835 2840 2845 aaa gaa act ctt gaa gaa aaa acc aag gag gca gat gaa tac ttg gat 8655 Lys Glu Thr Leu Glu Glu Lys Thr Lys Glu Ala Asp Glu Tyr Leu Asp                2850 2855 2860 aag tac tgt tcc ttg ctt ata agc cat gaa aag tta gag aaa gct aaa 8703 Lys Tyr Cys Ser Leu Leu Ile Ser His Glu Lys Leu Glu Lys Ala Lys            2865 2870 2875 gag atg tta gag aca caa gtg gcc cat ctg tgt tca cag caa tct aaa 8751 Glu Met Leu Glu Thr Gln Val Ala His Leu Cys Ser Gln Gln Ser Lys        2880 2885 2890 caa gat tcc cga ggg tct cct ttg cta ggt cca gtt gtt cca gga cca 8799 Gln Asp Ser Arg Gly Ser Pro Leu Leu Gly Pro Val Val Pro Gly Pro    2895 2900 2905 tct cca atc cct tct gtt act gaa aag agg tta tca tct ggc caa aat 8847 Ser Pro Ile Pro Ser Val Thr Glu Lys Arg Leu Ser Ser Gly Gln Asn 2910 2915 2920 2925 aaa gct tca ggc aag agg caa aga tcc agt gga ata tgg gag aat ggt 8895 Lys Ala Ser Gly Lys Arg Gln Arg Ser Ser Gly Ile Trp Glu Asn Gly                2930 2935 2940 gga gga cca aca cct gct acc cca gag agc ttt tct aaa aaa agc aag 8943 Gly Gly Pro Thr Pro Ala Thr Pro Glu Ser Phe Ser Lys Lys Ser Lys            2945 2950 2955 aaa gca gtc atg agt ggt att cac cct gca gaa gac acg gaa ggt act 8991 Lys Ala Val Met Ser Gly Ile His Pro Ala Glu Asp Thr Glu Gly Thr        2960 2965 2970 gag ttt gag cca gag gga ctt cca gaa gtt gta aag aaa ggg ttt gct 9039 Glu Phe Glu Pro Glu Gly Leu Pro Glu Val Val Lys Lys Gly Phe Ala    2975 2980 2985 gac atc ccg aca gga aag act agc cca tat atc ctg cga aga aca acc 9087 Asp Ile Pro Thr Gly Lys Thr Ser Pro Tyr Ile Leu Arg Arg Thr Thr 2990 2995 3000 3005 atg gca act cgg acc agc ccc cgc ctg gct gca cag aag tta gcg cta 9135 Met Ala Thr Arg Thr Ser Pro Arg Leu Ala Ala Gln Lys Leu Ala Leu                3010 3015 3020 tcc cca ctg agt ctc ggc aaa gaa aat ctt gca gag tcc tcc aaa cca 9183 Ser Pro Leu Ser Leu Gly Lys Glu Asn Leu Ala Glu Ser Ser Lys Pro            3025 3030 3035 aca gct ggt ggc agc aga tca caa aag gtc aaa gtt gct cag cgg agc 9231 Thr Ala Gly Gly Ser Arg Ser Gln Lys Val Lys Val Ala Gln Arg Ser        3040 3045 3050 cca gta gat tca ggc acc atc ctc cga gaa ccc acc acg aaa tcc gtc 9279 Pro Val Asp Ser Gly Thr Ile Leu Arg Glu Pro Thr Thr Lys Ser Val    3055 3060 3065 cca gtc aat aat ctt cct gag aga agt ccg act gac agc ccc aga gag 9327 Pro Val Asn Asn Leu Pro Glu Arg Ser Pro Thr Asp Ser Pro Arg Glu 3070 3075 3080 3085 ggc ctg agg gtc aag cga ggc cga ctt gtc ccc agc ccc aaa gct gga 9375 Gly Leu Arg Val Lys Arg Gly Arg Leu Val Pro Ser Pro Lys Ala Gly                3090 3095 3100 ctg gag tcc aag ggc agt gag aac tgt aag gtc cag tga aggcactttg 9424 Leu Glu Ser Lys Gly Ser Glu Asn Cys Lys Val Gln            3105 3110 tgtgtcagta cccctgggag gtgccagtca ttgaatagat aaggctgtgc ctacaggact 9484 tctctttagt cagggcatgc tttattagtg aggagaaaac aattccttag aagtcttaaa 9544 tatattgtac tctttagatc tcccatgtgt aggtattgaa aaagtttgga agcactgatc 9604 acctgttagc attgccattc ctctactgca atgtaaatag tataaagcta tgtatataaa 9664 gctttttggt aatatgttac aattaaaatg acaagcacta tatcacaatc tctgtttgta 9724 tgtgggtttt acactaaaaa aatgcaaaac acattttatt cttctaatta acagctccta 9784 ggaaaatgta gacttttgct ttatgatatt ctatctgtag tatgaggcat ggaatagttt 9844 tgtatcggga atttctcaga gctgagtaaa atgaaggaaa agcatgttat gtgtttttaa 9904 ggaaaatgtg cacacatata catgtaggag tgtttatctt tctcttacaa tctgttttag 9964 acatctttgc ttatgaaacc tgtacatatg tgtgtgtgtggg tatgtgtttattatttccagtga 10024 gggctgcagg cttcctagag gtgtgctata ccatgcgtct gtcgttgtgc ttttttctgt 10084 ttttagacca attttttaca gttctttggt aagcattgtc gtatctggtg atggattaac 10144 atatagcctt tgttttctaa taaaatagtc gccttcgttt tctgtaaaaa aaaaaaaaaa 10204 aaaaaaa 10211 <210> 16 <211> 3113 <212> PRT <213> Homo sapiens <400> 16 Met Ser Trp Ala Leu Glu Glu Trp Lys Glu Gly Leu Pro Thr Arg Ala   1 5 10 15 Leu Gln Lys Ile Gln Glu Leu Glu Gly Gln Leu Asp Lys Leu Lys Lys              20 25 30 Glu Lys Gln Gln Arg Gln Phe Gln Leu Asp Ser Leu Glu Ala Ala Pro          35 40 45 Gln Lys Gln Thr Gln Lys Val Glu Asn Glu Lys Thr Glu Gly Thr Asn      50 55 60 Leu Lys Arg Glu Asn Gln Arg Leu Met Glu Ile Cys Glu Ser Leu Glu  65 70 75 80 Lys Thr Lys Gln Lys Ile Ser His Glu Leu Gln Val Lys Glu Ser Gln                  85 90 95 Val Asn Phe Gln Glu Gly Gln Leu Asn Ser Gly Lys Lys Gln Ile Glu             100 105 110 Lys Leu Glu Gln Glu Leu Lys Arg Cys Lys Ser Glu Leu Glu Arg Ser         115 120 125 Gln Gln Ala Ala Gln Ser Ala Asp Val Ser Leu Asn Pro Cys Asn Thr     130 135 140 Pro Gln Lys Ile Phe Thr Thr Pro Leu Thr Pro Ser Gln Tyr Tyr Ser 145 150 155 160 Gly Ser Lys Tyr Glu Asp Leu Lys Glu Lys Tyr Asn Lys Glu Val Glu                 165 170 175 Glu Arg Lys Arg Leu Glu Ala Glu Val Lys Ala Leu Gln Ala Lys Lys             180 185 190 Ala Ser Gln Thr Leu Pro Gln Ala Thr Met Asn His Arg Asp Ile Ala         195 200 205 Arg His Gln Ala Ser Ser Ser Val Phe Ser Trp Gln Gln Glu Lys Thr     210 215 220 Pro Ser His Leu Ser Ser Asn Ser Gln Arg Thr Pro Ile Arg Arg Asp 225 230 235 240 Phe Ser Ala Ser Tyr Phe Ser Gly Glu Gln Glu Val Thr Pro Ser Arg                 245 250 255 Ser Thr Leu Gln Ile Gly Lys Arg Asp Ala Asn Ser Ser Phe Phe Asp             260 265 270 Asn Ser Ser Ser Pro His Leu Leu Asp Gln Leu Lys Ala Gln Asn Gln         275 280 285 Glu Leu Arg Asn Lys Ile Asn Glu Leu Glu Leu Arg Leu Gln Gly His     290 295 300 Glu Lys Glu Met Lys Gly Gln Val Asn Lys Phe Gln Glu Leu Gln Leu 305 310 315 320 Gln Leu Glu Lys Ala Lys Val Glu Leu Ile Glu Lys Glu Lys Val Leu                 325 330 335 Asn Lys Cys Arg Asp Glu Leu Val Arg Thr Thr Ala Gln Tyr Asp Gln             340 345 350 Ala Ser Thr Lys Tyr Thr Ala Leu Glu Gln Lys Leu Lys Lys Leu Thr         355 360 365 Glu Asp Leu Ser Cys Gln Arg Gln Asn Ala Glu Ser Ala Arg Cys Ser     370 375 380 Leu Glu Gln Lys Ile Lys Glu Lys Glu Lys Glu Phe Gln Glu Glu Leu 385 390 395 400 Ser Arg Gln Gln Arg Ser Phe Gln Thr Leu Asp Gln Glu Cys Ile Gln                 405 410 415 Met Lys Ala Arg Leu Thr Gln Glu Leu Gln Gln Ala Lys Asn Met His             420 425 430 Asn Val Leu Gln Ala Glu Leu Asp Lys Leu Thr Ser Val Lys Gln Gln         435 440 445 Leu Glu Asn Asn Leu Glu Glu Phe Lys Gln Lys Leu Cys Arg Ala Glu     450 455 460 Gln Ala Phe Gln Ala Ser Gln Ile Lys Glu Asn Glu Leu Arg Arg Ser 465 470 475 480 Met Glu Glu Met Lys Lys Glu Asn Asn Leu Leu Lys Ser His Ser Glu                 485 490 495 Gln Lys Ala Arg Glu Val Cys His Leu Glu Ala Glu Leu Lys Asn Ile             500 505 510 Lys Gln Cys Leu Asn Gln Ser Gln Asn Phe Ala Glu Glu Met Lys Ala         515 520 525 Lys Asn Thr Ser Gln Glu Thr Met Leu Arg Asp Leu Gln Glu Lys Ile     530 535 540 Asn Gln Gln Glu Asn Ser Leu Thr Leu Glu Lys Leu Lys Leu Ala Val 545 550 555 560 Ala Asp Leu Glu Lys Gln Arg Asp Cys Ser Gln Asp Leu Leu Lys Lys                 565 570 575 Arg Glu His His Ile Glu Gln Leu Asn Asp Lys Leu Ser Lys Thr Glu             580 585 590 Lys Glu Ser Lys Ala Leu Leu Ser Ala Leu Glu Leu Lys Lys Lys Glu         595 600 605 Tyr Glu Leu Lys Glu Glu Lys Thr Leu Phe Ser Cys Trp Lys Ser Glu     610 615 620 Asn Glu Lys Leu Leu Thr Gln Met Glu Ser Glu Lys Glu Asn Leu Gln 625 630 635 640 Ser Lys Ile Asn His Leu Glu Thr Cys Leu Lys Thr Gln Gln Ile Lys                 645 650 655 Ser His Glu Tyr Asn Glu Arg Val Arg Thr Leu Glu Met Asp Arg Glu             660 665 670 Asn Leu Ser Val Glu Ile Arg Asn Leu His Asn Val Leu Asp Ser Lys         675 680 685 Ser Val Glu Val Glu Thr Gln Lys Leu Ala Tyr Met Glu Leu Gln Gln     690 695 700 Lys Ala Glu Phe Ser Asp Gln Lys His Gln Lys Glu Ile Glu Asn Met 705 710 715 720 Cys Leu Lys Thr Ser Gln Leu Thr Gly Gln Val Glu Asp Leu Glu His                 725 730 735 Lys Leu Gln Leu Leu Ser Asn Glu Ile Met Asp Lys Asp Arg Cys Tyr             740 745 750 Gln Asp Leu His Ala Glu Tyr Glu Ser Leu Arg Asp Leu Leu Lys Ser         755 760 765 Lys Asp Ala Ser Leu Val Thr Asn Glu Asp His Gln Arg Ser Leu Leu     770 775 780 Ala Phe Asp Gln Gln Pro Ala Met His His Ser Phe Ala Asn Ile Ile 785 790 795 800 Gly Glu Gln Gly Ser Met Pro Ser Glu Arg Ser Glu Cys Arg Leu Glu                 805 810 815 Ala Asp Gln Ser Pro Lys Asn Ser Ala Ile Leu Gln Asn Arg Val Asp             820 825 830 Ser Leu Glu Phe Ser Leu Glu Ser Gln Lys Gln Met Asn Ser Asp Leu         835 840 845 Gln Lys Gln Cys Glu Glu Leu Val Gln Ile Lys Gly Glu Ile Glu Glu     850 855 860 Asn Leu Met Lys Ala Glu Gln Met His Gln Ser Phe Val Ala Glu Thr 865 870 875 880 Ser Gln Arg Ile Ser Lys Leu Gln Glu Asp Thr Ser Ala His Gln Asn                 885 890 895 Val Val Ala Glu Thr Leu Ser Ala Leu Glu Asn Lys Glu Lys Glu Leu             900 905 910 Gln Leu Leu Asn Asp Lys Val Glu Thr Glu Gln Ala Glu Ile Gln Glu         915 920 925 Leu Lys Lys Ser Asn His Leu Leu Glu Asp Ser Leu Lys Glu Leu Gln     930 935 940 Leu Leu Ser Glu Thr Leu Ser Leu Glu Lys Lys Glu Met Ser Ser Ile 945 950 955 960 Ile Ser Leu Asn Lys Arg Glu Ile Glu Glu Leu Thr Gln Glu Asn Gly                 965 970 975 Thr Leu Lys Glu Ile Asn Ala Ser Leu Asn Gln Glu Lys Met Asn Leu             980 985 990 Ile Gln Lys Ser Glu Ser Phe Ala Asn Tyr Ile Asp Glu Arg Glu Lys         995 1000 1005 Ser Ile Ser Glu Leu Ser Asp Gln Tyr Lys Gln Glu Lys Leu Ile Leu    1010 1015 1020 Leu Gln Arg Cys Glu Glu Thr Gly Asn Ala Tyr Glu Asp Leu Ser Gln 1025 1030 1035 1040 Lys Tyr Lys Ala Ala Gln Glu Lys Asn Ser Lys Leu Glu Cys Leu Leu                1045 1050 1055 Asn Glu Cys Thr Ser Leu Cys Glu Asn Arg Lys Asn Glu Leu Glu Gln            1060 1065 1070 Leu Lys Glu Ala Phe Ala Lys Glu His Gln Glu Phe Leu Thr Lys Leu        1075 1080 1085 Ala Phe Ala Glu Glu Arg Asn Gln Asn Leu Met Leu Glu Leu Glu Thr    1090 1095 1100 Val Gln Gln Ala Leu Arg Ser Glu Met Thr Asp Asn Gln Asn Asn Ser 1105 1110 1115 1120 Lys Ser Glu Ala Gly Gly Leu Lys Gln Glu Ile Met Thr Leu Lys Glu                1125 1130 1135 Glu Gln Asn Lys Met Gln Lys Glu Val Asn Asp Leu Leu Gln Glu Asn            1140 1145 1150 Glu Gln Leu Met Lys Val Met Lys Thr Lys His Glu Cys Gln Asn Leu        1155 1160 1165 Glu Ser Glu Pro Ile Arg Asn Ser Val Lys Glu Arg Glu Ser Glu Arg    1170 1175 1180 Asn Gln Cys Asn Phe Lys Pro Gln Met Asp Leu Glu Val Lys Glu Ile 1185 1190 1195 1200 Ser Leu Asp Ser Tyr Asn Ala Gln Leu Val Gln Leu Glu Ala Met Leu                1205 1210 1215 Arg Asn Lys Glu Leu Lys Leu Gln Glu Ser Glu Lys Glu Lys Glu Cys            1220 1225 1230 Leu Gln His Glu Leu Gln Thr Ile Arg Gly Asp Leu Glu Thr Ser Asn        1235 1240 1245 Leu Gln Asp Met Gln Ser Gln Glu Ile Ser Gly Leu Lys Asp Cys Glu    1250 1255 1260 Ile Asp Ala Glu Glu Lys Tyr Ile Ser Gly Pro His Glu Leu Ser Thr 1265 1270 1275 1280 Ser Gln Asn Asp Asn Ala His Leu Gln Cys Ser Leu Gln Thr Thr Met                1285 1290 1295 Asn Lys Leu Asn Glu Leu Glu Lys Ile Cys Glu Ile Leu Gln Ala Glu            1300 1305 1310 Lys Tyr Glu Leu Val Thr Glu Leu Asn Asp Ser Arg Ser Glu Cys Ile        1315 1320 1325 Thr Ala Thr Arg Lys Met Ala Glu Glu Val Gly Lys Leu Leu Asn Glu    1330 1335 1340 Val Lys Ile Leu Asn Asp Asp Ser Gly Leu Leu His Gly Glu Leu Val 1345 1350 1355 1360 Glu Asp Ile Pro Gly Gly Glu Phe Gly Glu Gln Pro Asn Glu Gln His                1365 1370 1375 Pro Val Ser Leu Ala Pro Leu Asp Glu Ser Asn Ser Tyr Glu His Leu            1380 1385 1390 Thr Leu Ser Asp Lys Glu Val Gln Met His Phe Ala Glu Leu Gln Glu        1395 1400 1405 Lys Phe Leu Ser Leu Gln Ser Glu His Lys Ile Leu His Asp Gln His    1410 1415 1420 Cys Gln Met Ser Ser Lys Met Ser Glu Leu Gln Thr Tyr Val Asp Ser 1425 1430 1435 1440 Leu Lys Ala Glu Asn Leu Val Leu Ser Thr Asn Leu Arg Asn Phe Gln                1445 1450 1455 Gly Asp Leu Val Lys Glu Met Gln Leu Gly Leu Glu Glu Gly Leu Val            1460 1465 1470 Pro Ser Leu Ser Ser Ser Cys Val Pro Asp Ser Ser Ser Leu Ser Ser        1475 1480 1485 Leu Gly Asp Ser Ser Phe Tyr Arg Ala Leu Leu Glu Gln Thr Gly Asp    1490 1495 1500 Met Ser Leu Leu Ser Asn Leu Glu Gly Ala Val Ser Ala Asn Gln Cys 1505 1510 1515 1520 Ser Val Asp Glu Val Phe Cys Ser Ser Leu Gln Glu Glu Asn Leu Thr                1525 1530 1535 Arg Lys Glu Thr Pro Ser Ala Pro Ala Lys Gly Val Glu Glu Leu Glu            1540 1545 1550 Ser Leu Cys Glu Val Tyr Arg Gln Ser Leu Glu Lys Leu Glu Glu Lys        1555 1560 1565 Met Glu Ser Gln Gly Ile Met Lys Asn Lys Glu Ile Gln Glu Leu Glu    1570 1575 1580 Gln Leu Leu Ser Ser Glu Arg Gln Glu Leu Asp Cys Leu Arg Lys Gln 1585 1590 1595 1600 Tyr Leu Ser Glu Asn Glu Gln Trp Gln Gln Lys Leu Thr Ser Val Thr                1605 1610 1615 Leu Glu Met Glu Ser Lys Leu Ala Ala Glu Lys Lys Gln Thr Glu Gln            1620 1625 1630 Leu Ser Leu Glu Leu Glu Val Ala Arg Leu Gln Leu Gln Gly Leu Asp        1635 1640 1645 Leu Ser Ser Arg Ser Leu Leu Gly Ile Asp Thr Glu Asp Ala Ile Gln    1650 1655 1660 Gly Arg Asn Glu Ser Cys Asp Ile Ser Lys Glu His Thr Ser Glu Thr 1665 1670 1675 1680 Thr Glu Arg Thr Pro Lys His Asp Val His Gln Ile Cys Asp Lys Asp                1685 1690 1695 Ala Gln Gln Asp Leu Asn Leu Asp Ile Glu Lys Ile Thr Glu Thr Gly            1700 1705 1710 Ala Leu Lys Pro Thr Gly Glu Cys Ser Gly Glu Gln Ser Pro Asp Thr        1715 1720 1725 Asn Tyr Glu Pro Pro Gly Glu Asp Lys Thr Gln Gly Ser Ser Glu Cys    1730 1735 1740 Ile Ser Glu Leu Ser Phe Ser Gly Pro Asn Ala Leu Val Pro Met Asp 1745 1750 1755 1760 Phe Leu Gly Asn Gln Glu Asp Ile His Asn Leu Gln Leu Arg Val Lys                1765 1770 1775 Glu Thr Ser Asn Glu Asn Leu Arg Leu Leu His Val Ile Glu Asp Arg            1780 1785 1790 Asp Arg Lys Val Glu Ser Leu Leu Asn Glu Met Lys Glu Leu Asp Ser        1795 1800 1805 Lys Leu His Leu Gln Glu Val Gln Leu Met Thr Lys Ile Glu Ala Cys    1810 1815 1820 Ile Glu Leu Glu Lys Ile Val Gly Glu Leu Lys Lys Glu Asn Ser Asp 1825 1830 1835 1840 Leu Ser Glu Lys Leu Glu Tyr Phe Ser Cys Asp His Gln Glu Leu Leu                1845 1850 1855 Gln Arg Val Glu Thr Ser Glu Gly Leu Asn Ser Asp Leu Glu Met His            1860 1865 1870 Ala Asp Lys Ser Ser Arg Glu Asp Ile Gly Asp Asn Val Ala Lys Val        1875 1880 1885 Asn Asp Ser Trp Lys Glu Arg Phe Leu Asp Val Glu Asn Glu Leu Ser    1890 1895 1900 Arg Ile Arg Ser Glu Lys Ala Ser Ile Glu His Glu Ala Leu Tyr Leu 1905 1910 1915 1920 Glu Ala Asp Leu Glu Val Val Gln Thr Glu Lys Leu Cys Leu Glu Lys                1925 1930 1935 Asp Asn Glu Asn Lys Gln Lys Val Ile Val Cys Leu Glu Glu Glu Leu            1940 1945 1950 Ser Val Val Thr Ser Glu Arg Asn Gln Leu Arg Gly Glu Leu Asp Thr        1955 1960 1965 Met Ser Lys Lys Thr Thr Ala Leu Asp Gln Leu Ser Glu Lys Met Lys    1970 1975 1980 Glu Lys Thr Gln Glu Leu Glu Ser His Gln Ser Glu Cys Leu His Cys 1985 1990 1995 2000 Ile Gln Val Ala Glu Ala Glu Val Lys Glu Lys Thr Glu Leu Leu Gln                2005 2010 2015 Thr Leu Ser Ser Asp Val Ser Glu Leu Leu Lys Asp Lys Thr His Leu            2020 2025 2030 Gln Glu Lys Leu Gln Ser Leu Glu Lys Asp Ser Gln Ala Leu Ser Leu        2035 2040 2045 Thr Lys Cys Glu Leu Glu Asn Gln Ile Ala Gln Leu Asn Lys Glu Lys    2050 2055 2060 Glu Leu Leu Val Lys Glu Ser Glu Ser Leu Gln Ala Arg Leu Ser Glu 2065 2070 2075 2080 Ser Asp Tyr Glu Lys Leu Asn Val Ser Lys Ala Leu Glu Ala Ala Leu                2085 2090 2095 Val Glu Lys Gly Glu Phe Ala Leu Arg Leu Ser Ser Thr Gln Glu Glu            2100 2105 2110 Val His Gln Leu Arg Arg Gly Ile Glu Lys Leu Arg Val Arg Ile Glu        2115 2120 2125 Ala Asp Glu Lys Lys Gln Leu His Ile Ala Glu Lys Leu Lys Glu Arg    2130 2135 2140 Glu Arg Glu Asn Asp Ser Leu Lys Asp Lys Val Glu Asn Leu Glu Arg 2145 2150 2155 2160 Glu Leu Gln Met Ser Glu Glu Asn Gln Glu Leu Val Ile Leu Asp Ala                2165 2170 2175 Glu Asn Ser Lys Ala Glu Val Glu Thr Leu Lys Thr Gln Ile Glu Glu            2180 2185 2190 Met Ala Arg Ser Leu Lys Val Phe Glu Leu Asp Leu Val Thr Leu Arg        2195 2200 2205 Ser Glu Lys Glu Asn Leu Thr Lys Gln Ile Gln Glu Lys Gln Gly Gln    2210 2215 2220 Leu Ser Glu Leu Asp Lys Leu Leu Ser Ser Phe Lys Ser Leu Leu Glu 2225 2230 2235 2240 Glu Lys Glu Gln Ala Glu Ile Gln Ile Lys Glu Glu Ser Lys Thr Ala                2245 2250 2255 Val Glu Met Leu Gln Asn Gln Leu Lys Glu Leu Asn Glu Ala Val Ala            2260 2265 2270 Ala Leu Cys Gly Asp Gln Glu Ile Met Lys Ala Thr Glu Gln Ser Leu        2275 2280 2285 Asp Pro Pro Ile Glu Glu Glu His Gln Leu Arg Asn Ser Ile Glu Lys    2290 2295 2300 Leu Arg Ala Arg Leu Glu Ala Asp Glu Lys Lys Gln Leu Cys Val Leu 2305 2310 2315 2320 Gln Gln Leu Lys Glu Ser Glu His His Ala Asp Leu Leu Lys Gly Arg                2325 2330 2335 Val Glu Asn Leu Glu Arg Glu Leu Glu Ile Ala Arg Thr Asn Gln Glu            2340 2345 2350 His Ala Ala Leu Glu Ala Glu Asn Ser Lys Gly Glu Val Glu Thr Leu        2355 2360 2365 Lys Ala Lys Ile Glu Gly Met Thr Gln Ser Leu Arg Gly Leu Glu Leu    2370 2375 2380 Asp Val Val Thr Ile Arg Ser Glu Lys Glu Asn Leu Thr Asn Glu Leu 2385 2390 2395 2400 Gln Lys Glu Gln Glu Arg Ile Ser Glu Leu Glu Ile Ile Asn Ser Ser                2405 2410 2415 Phe Glu Asn Ile Leu Gln Glu Lys Glu Gln Glu Lys Val Gln Met Lys            2420 2425 2430 Glu Lys Ser Ser Thr Ala Met Glu Met Leu Gln Thr Gln Leu Lys Glu        2435 2440 2445 Leu Asn Glu Arg Val Ala Ala Leu His Asn Asp Gln Glu Ala Cys Lys    2450 2455 2460 Ala Lys Glu Gln Asn Leu Ser Ser Gln Val Glu Cys Leu Glu Leu Glu 2465 2470 2475 2480 Lys Ala Gln Leu Leu Gln Gly Leu Asp Glu Ala Lys Asn Asn Tyr Ile                2485 2490 2495 Val Leu Gln Ser Ser Val Asn Gly Leu Ile Gln Glu Val Glu Asp Gly            2500 2505 2510 Lys Gln Lys Leu Glu Lys Lys Asp Glu Glu Ile Ser Arg Leu Lys Asn        2515 2520 2525 Gln Ile Gln Asp Gln Glu Gln Leu Val Ser Lys Leu Ser Gln Val Glu    2530 2535 2540 Gly Glu His Gln Leu Trp Lys Glu Gln Asn Leu Glu Leu Arg Asn Leu 2545 2550 2555 2560 Thr Val Glu Leu Glu Gln Lys Ile Gln Val Leu Gln Ser Lys Asn Ala                2565 2570 2575 Ser Leu Gln Asp Thr Leu Glu Val Leu Gln Ser Ser Tyr Lys Asn Leu            2580 2585 2590 Glu Asn Glu Leu Glu Leu Thr Lys Met Asp Lys Met Ser Phe Val Glu        2595 2600 2605 Lys Val Asn Lys Met Thr Ala Lys Glu Thr Glu Leu Gln Arg Glu Met    2610 2615 2620 His Glu Met Ala Gln Lys Thr Ala Glu Leu Gln Glu Glu Leu Ser Gly 2625 2630 2635 2640 Glu Lys Asn Arg Leu Ala Gly Glu Leu Gln Leu Leu Leu Glu Glu Ile                2645 2650 2655 Lys Ser Ser Lys Asp Gln Leu Lys Glu Leu Thr Leu Glu Asn Ser Glu            2660 2665 2670 Leu Lys Lys Ser Leu Asp Cys Met His Lys Asp Gln Val Glu Lys Glu        2675 2680 2685 Gly Lys Val Arg Glu Glu Ile Ala Glu Tyr Gln Leu Arg Leu His Glu    2690 2695 2700 Ala Glu Lys Lys His Gln Ala Leu Leu Leu Asp Thr Asn Lys Gln Tyr 2705 2710 2715 2720 Glu Val Glu Ile Gln Thr Tyr Arg Glu Lys Leu Thr Ser Lys Glu Glu                2725 2730 2735 Cys Leu Ser Ser Gln Lys Leu Glu Ile Asp Leu Leu Lys Ser Ser Lys            2740 2745 2750 Glu Glu Leu Asn Asn Ser Leu Lys Ala Thr Thr Gln Ile Leu Glu Glu        2755 2760 2765 Leu Lys Lys Thr Lys Met Asp Asn Leu Lys Tyr Val Asn Gln Leu Lys    2770 2775 2780 Lys Glu Asn Glu Arg Ala Gln Gly Lys Met Lys Leu Leu Ile Lys Ser 2785 2790 2795 2800 Cys Lys Gln Leu Glu Glu Glu Lys Glu Ile Leu Gln Lys Glu Leu Ser                2805 2810 2815 Gln Leu Gln Ala Ala Gln Glu Lys Gln Lys Thr Gly Thr Val Met Asp            2820 2825 2830 Thr Lys Val Asp Glu Leu Thr Thr Glu Ile Lys Glu Leu Lys Glu Thr        2835 2840 2845 Leu Glu Glu Lys Thr Lys Glu Ala Asp Glu Tyr Leu Asp Lys Tyr Cys    2850 2855 2860 Ser Leu Leu Ile Ser His Glu Lys Leu Glu Lys Ala Lys Glu Met Leu 2865 2870 2875 2880 Glu Thr Gln Val Ala His Leu Cys Ser Gln Gln Ser Lys Gln Asp Ser                2885 2890 2895 Arg Gly Ser Pro Leu Leu Gly Pro Val Val Pro Gly Pro Ser Pro Ile            2900 2905 2910 Pro Ser Val Thr Glu Lys Arg Leu Ser Ser Gly Gln Asn Lys Ala Ser        2915 2920 2925 Gly Lys Arg Gln Arg Ser Ser Gly Ile Trp Glu Asn Gly Gly Gly Pro    2930 2935 2940 Thr Pro Ala Thr Pro Glu Ser Phe Ser Lys Lys Ser Lys Lys Ala Val 2945 2950 2955 2960 Met Ser Gly Ile His Pro Ala Glu Asp Thr Glu Gly Thr Glu Phe Glu                2965 2970 2975 Pro Glu Gly Leu Pro Glu Val Val Lys Lys Gly Phe Ala Asp Ile Pro            2980 2985 2990 Thr Gly Lys Thr Ser Pro Tyr Ile Leu Arg Arg Thr Thr Met Ala Thr        2995 3000 3005 Arg Thr Ser Pro Arg Leu Ala Ala Gln Lys Leu Ala Leu Ser Pro Leu    3010 3015 3020 Ser Leu Gly Lys Glu Asn Leu Ala Glu Ser Seru Lys Pro Thr Ala Gly 3025 3030 3035 3040 Gly Ser Arg Ser Gln Lys Val Lys Val Ala Gln Arg Ser Pro Val Asp                3045 3050 3055 Ser Gly Thr Ile Leu Arg Glu Pro Thr Thr Lys Ser Val Pro Val Asn            3060 3065 3070 Asn Leu Pro Glu Arg Ser Pro Thr Asp Ser Pro Arg Glu Gly Leu Arg        3075 3080 3085 Val Lys Arg Gly Arg Leu Val Pro Ser Pro Lys Ala Gly Leu Glu Ser    3090 3095 3100 Lys Gly Ser Glu Asn Cys Lys Val Gln 3105 3110 <210> 17 <211> 4000 <212> DNA <213> Homo sapiens <400> 17 ctcctgcgct caagcagtct gcccccctcg gcctctgaaa gtgttggaat tacaggcgtg 60 agccaccgtg cctggcagaa aatatagttt attctttagg tgtaggcgtg tgtgacttaa 120 cccttacctg acacggcctt aggtcctgat tataatttgg tatcttattg ccataaagag 180 tgcattctgt tagtctatga tctctatttt aacattgatg ctggtcagat gttgtgtctg 240 aactgcaaaa gggagggagt ataaccaggc atgtctgacc ccctgacctg tcatggctgg 300 aaactcagtt tttaaggttt ttctggggtc tccttggcca agagggtcca ttcaattagt 360 tagggggctt aggatttgtt tttagtttac aggggaaata agcctattag gggtagacag 420 atctgcaaag catgagtgtt ggcaggaact taagcaacaa agagatacgg ttaaaatgtc 480 gctttctctt tctccgtaga aagccagagg aatttgtgtt ttctccagag agggtgggac 540 agaggagaga atggtggggc aggagggaga gttagtgatt ttggaggagg ctagagggtg 600 cagggccagt tagaaaacct cagctggggg tgtggaaagg acttctaaaa acttctgagg 660 ggccccctcc ccctcccccg ctccctctcc ccacggtctc cctctctttc cacggtctcc 720 ctctcatgcg gagccgaagc tggactgtac tgctgccatc tcggctcact gcaacctccc 780 tgcctgattc tcctgcctca gcctgccgag tgcctgcgat tgcaggcacg cgtcgccacg 840 cctgactggt tttggtggag acggggtttc gctgtgttgg ccgggccggt ctccagcccc 900 taaccgcgag tgatccgcca gcctcggcct cccgaggtgc cgggattgca gacggagtct 960 cgttcactca gtgctcaatg gtgcccaggc tggagtgcag tggcgtgatc tcggctcact 1020 acaacctaca cctcccagcc gcctgccttg gcctcccaaa gtgccgagat tgcagcctct 1080 gcctggccgc caccccgtat gggaagtgag gagtgtctct gcctggccgc ccatcgtctg 1140 ggatgtgagg agcccctctg cctggctgcc cagtctggaa agtgaggagc gtctccgccc 1200 ggccgccatc ccatctagga agtgaggagc gcctcttccc ggccgccatc acatctagga 1260 agtgaggagc gtctctgccc ggccgcccat cgtctgagat gtggggagcg cctctgcccc 1320 gccgccccat ctgggatatg aggagcgcct ctgcccggca gcgaccccgt ctgggaggtg 1380 aagagcgtct ctgcccggcc gccccgtctg agaagtgagg agaccctctg cctggcaacc 1440 accccgtctg agaagtgagg agcccctccg cccggcagct gccccgtctg agaagtgagg 1500 agcctctccg cccggcagcc accccatctg ggaagtgagg agcgtctccg cccggcagcc 1560 accccgtccg ggagggaggt ggggggtcag ccccccgccc ggccagccgc cccgtccggg 1620 agggaggtag gggggtcagc cccccacccg gccagccgcc ccgtctggga ggtgaggggc 1680 gcctctgccc ggccgcccct actgggaagt gaggagcccc tctgcccggc caccaccccg 1740 tctgggaggt gtgcccaaca gctcattgag aacgggccag gatgacaatg gcgactttgt 1800 ggaatagaaa ggcgggaaag gtggggaaaa gattgagaaa tcggatggtt gccgtgtctg 1860 tgtagaaaga agtagacatg ggagacttct cattttgttc tgcactaaga aaaattcttc 1920 tgccttggga aaaaaaaaaa aaaaaaactt ctgaggggtg agtttaaact gtttgccatg 1980 tatcatatga cctcccccag ggcccagagt accctaatgt ctttgtactc gtcaatgttt 2040 tgtgtgggaa gggtgcgggc agtccttagg gagagctgag tttcctctcc agacttctga 2100 actgtggtac gcaacagcct ggcaaaagca gaaacccaga ggcagagata tttaggagaa 2160 tataaatccc cagatatttg caaatatgtt aagggaggga ctctgacttt caccgtccat 2220 ttttacctca atctcaaagg gcaaggaggt tgacatctaa gttacaaata taatgcacaa 2280 gcatttcaaa aagtagggga aaaaaaagaa aaagaaaaag agaagcagaa agaaggggga 2340 aaaaatcact catccctgcc aggcacggtg gctcacgcct gtaattccag cactttggga 2400 ggctaaggtg ggaggataac ttgagtccag gagttcaaga ccagcctggg caacatggca 2460 aaaccctgtc tctactaaaa ttacaataat tagctgggcg tgtggcgcat gcctgtaatc 2520 ccagctactt gggaggttga ggcaggataa tcgcttgaac ccgggaggcg gaggttgcag 2580 cgggctgaga ttgcgcaact gcactccagc aggggcgaca gagtgaaact gtgtctcaaa 2640 aaaaaaaaaa aaaaaaaaaa tcactcatcc agatagctag gtgtggccta aggagcttgc 2700 ggcctacgga aggtgtggcc gaaggagagg ggaggggtca tctttaatga tgatggaggg 2760 gaggcattgg tcatatacct gagagtcaag ctttgttcat cgtcagatga aagccaactt 2820 cttccaccag attgcctccc agctgctagg tagtttcctg tggtacatct taagcggtag 2880 gttgggataa taggtccctt ccaggtctta aagatgtgga ttaataagaa cagaattttc 2940 tacaacaata aggaggatgt cccctatttt aggtgaataa gcgtattgca taagcacatg 3000 ggaagaaagg ttaagaactc taagaccgta aatttccagt tgtagaagcc tcttgaaggc 3060 ggaaagccct tttttgaaaa ttataggcga tatgatctcc tccagtggac ctagcactgg 3120 gttaagagtc tctccagact tgtcactgca agtcacgtac cttttctagg actaagtttc 3180 ttcactggaa gatgaggagg ttgcactaga tgacctagaa attcccttcc agctttaaat 3240 tccctcttgt gtcacttgct ggacttgttc tactggacct ggcgctcccc tgctcctccc 3300 ttagctgcta cgtccgcatc ccgcaccaga gggcgccaca ggctggcccg gggcagcgtg 3360 cggtgggcgg agaggcagaa ttaggggagt ctccaggagg cgtggtgatt ggccgccgcc 3420 gggcggaagg gggcgtgggg agggaaaggc cgagcagcgc ggtgacgtct cgctggcggg 3480 ggcggggccg ggccgcggag cgtgtgacgc tgcggccgcc gcggacctgg ggattaatgg 3540 gaaaagtttt ggcaggagcg ggagaattct gcggagcctg cgggacggcg gcggtggcgc 3600 cgtaggcagc cgggacaggt cagtccgaga cgagagaagc ggtcaggcaa gtggcggagg 3660 gaagcgccgg gcctgggccg aggcggccag cgggactggg gcgcaaggcc cggcggcggg 3720 gaacggggtg cggggagctg ccggggtccg cggacagcgt cacggcggct tcctgatgct 3780 ccggcccgct ccggtcagcc gtcgtgcgtt gccatgtagg cgccccgctg accctgcgcc 3840 cccccgccct tggaccccca tagctgcttg agtgagtccg aaatacgggc ctccttccac 3900 cctactcttt gccccctctt gggcctggtg gcttcgtctt ctcccacttg tgagaacccc 3960 gtctcaggcc cgggggcctc tcccattccc ctcccctgcc 4000 <210> 18 <211> 1070 <212> DNA <213> Homo sapiens <400> 18 tagtgatttg ctgcatggag agatattgtc caatgaaccc tcacccagca gagggtgatg 60 attcaggagg agtcagaaat aaagaaagga aggagtgtgc agccctcgcc atggaaagcc 120 acacagccgt tcacatctgg gtagcagtga ggggtgggca atgttctcgc gaattctaga 180 ttctggagga ggggtgcgct ggttctgcag ggaccaggag tccctctttg tgtccttgga 240 tctgctggca actcctggga accagctgcc aggcttcctg acttgctgcc cagccctgca 300 tggacgggaa ctagagttct gctgggcgct gggatgggat acaatggagg tgcctagggg 360 cttgttgggg gctgggccag ctccgtgggc atctgtgcct cctctgtgag caggctaagc 420 tatagtaagg gcttatctcc tttgttttaa cagttggggc tttggcttcc atagcaatga 480 tttgcaaata gggtaattta ttggcttctc tcctcctgcc ttgataaatc tcatatctta 540 catcctttgg agcctcattt gaaatcaaac acttaaaaaa aaaaaaaaag gagcactcat 600 gcctttgtta tcttttggac acttctcaaa agaagatccc tggaccccat aggatgcagg 660 caacacagag atgtgaggtg agagcgggta gacattagaa cttgacacac agtgatgcta 720 caggcatgac tttatttatt tatttattta tttatttatt tatttagaga cagagtctca 780 gtctcaccca ggctggagtg cggtggcgcg atctcggctc actgcaacct ccaactcctg 840 gtttcaagtg attctcatgc ctcagcctcc cgagtagctg ggattacagg catgtgccac 900 cacgcctggc taatttttgt atttttagta gagacagagt ttccccaggt tggccaggct 960 ggtcttgaac tcctaacttc aggtgatcca ccctccttgg tctcccaaag tgctgggatt 1020 acaggtatga gccaccgtgc ccagcctagt gtgactttaa aagtggcttt 1070

[Brief description of drawings]

FIG. 1 shows the results of Western blot analysis showing the reactivity of the antigen peptide (SEQ ID NO: 2) expressed by the polynucleotide having the nucleotide sequence shown in SEQ ID NO: 1 with the antibody in patient serum.

FIG. 2 shows the results of Western blot analysis showing the reactivity of the antigen peptide (SEQ ID NO: 4) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 3 with the antibody in the serum of patients.

FIG. 3 shows the results of Western blot analysis showing the reactivity between the antigenic peptide (SEQ ID NO: 6) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 5 and the antibody in the patient serum.

FIG. 4 shows the results of Western blot analysis showing the reactivity between the antigen peptide (SEQ ID NO: 8) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 7 and the antibody in the patient serum.

FIG. 5 shows the results of Western blot analysis showing the reactivity between the antigen peptide (SEQ ID NO: 10) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 9 and the antibody in patient serum.

FIG. 6 shows the results of Western blot analysis showing the reactivity between the antigen peptide (SEQ ID NO: 12) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 11 and the antibody in the patient serum.

FIG. 7 shows the results of Western blot analysis showing the reactivity of the antigen peptide (SEQ ID NO: 14) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 13 with the antibody in the patient serum.

FIG. 8 shows the results of Western blot analysis showing the reactivity between the antigen peptide (SEQ ID NO: 16) expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 15 and the antibody in patient serum.

FIG. 9 shows the results of Western blot analysis showing the reactivity between the antigen peptide expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 17 and the antibody in the patient serum.

FIG. 10 shows the results of Western blot analysis showing the reactivity between the antigen peptide expressed by the polynucleotide having the nucleotide sequence of SEQ ID NO: 19 and the antibody in the patient serum.

─────────────────────────────────────────────────── ─── Continued Front Page (51) Int.Cl. ⁷ Identification Code FI Theme Coat (Reference) C12N 1/21 G01N 33/574 A 5/10 C12N 15/00 ZNAA G01N 33/574 5/00 A (72 ) Inventor Masaki Takiguchi 1-14-17-107 Maehara East, Funabashi City, Chiba F-Term (reference) 4B024 AA12 BA36 CA04 CA12 DA06 EA03 HA11 4B065 AA26X AA93Y AB01 CA24 CA46 4H045 AA10 AA11 AA20 AA30 BA10 CA41 DA75 DA86 EA51 FA74

Claims (15)

[Claims] 1. SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 1
A human esophageal cancer antigen peptide which is expressed by a polynucleotide consisting of the nucleotide sequences of 7 and 19. 2. SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 1
A polynucleotide comprising each of the nucleotide sequences of 7 and 19 or a partially continuous sequence of each. 3. A recombinant expression vector carrying the polynucleotide of claim 2, respectively. 4. A transformed cell with the recombinant expression vector according to claim 3. 5. An antibody that binds to the antigenic peptide of claim 1. 6. A labeled antibody which binds to the antigenic peptide of claim 1. 7. A subject's serum is tested for the presence of an antibody that binds to the antigenic peptide of claim 1, and a subject whose serum has at least one antibody is tested as an esophageal cancer patient or esophageal cancer. A method for diagnosing human esophageal cancer, which is characterized by determining that a person is at high risk. 8. The diagnostic method according to claim 7, wherein the binding of the antibody of the subject's serum to the antigen peptide is tested on a plate on which one or more of the antigen peptides of claim 1 are immobilized. 9. A subject's biological sample is tested for the presence of an antigen peptide that binds to the antibody of claim 5 or the labeled antibody of claim 6, and the antigen peptide in the sample is 1
A method for diagnosing human esophageal cancer, characterized in that a subject having more than one type is determined to be an esophageal cancer patient or a high-risk esophageal cancer patient. 10. The diagnostic method according to claim 9, wherein the binding between the antibody and the antigen peptide is tested on a plate on which one or more of the antibodies according to claim 5 are immobilized. 11. At least the following elements: (1) one or more of the antigenic peptides of claim 1; and (2)
An esophageal cancer diagnostic kit comprising a labeled antibody that specifically binds to an antibody in serum. 12. At least the following elements: (1) A plate on which one or more of the antigenic peptides of claim 1 are immobilized; and (2) a labeled antibody that specifically binds to serum antibodies. Esophageal cancer diagnostic kit. 13. An esophageal cancer diagnostic kit comprising at least one kind of the labeled antibody according to claim 6. 14. At least the following elements: (1) one or more of the antibodies of claim 5; and (2) said
An esophageal cancer diagnostic kit comprising the labeled antibody of claim 6 which binds to the same antigenic peptide as the antibody of (1). 15. At least the following elements: (1) a plate on which one or more kinds of the antibodies of claim 5 are immobilized; and (2) the same antigenic peptide as the antibody immobilized on the plate of (1), bound to the same antigen peptide. An esophageal cancer diagnostic kit comprising the labeled antibody according to claim 6.