Patent application title: POLYPEPTIDE MARKER FOR DIAGNOSIS OF ARTERIOSCLEROSIS, METHOD FOR DETECTION OF ARTERIOSCLEROSIS BY USING THE MAKER OR THE LIKE, AND KIT FOR DIAGNOSIS OF ARTERIOSCLEROSIS
Inventors:
Rika Nakamura (Saitama-Shi, JP)
Hideyuki Kuroda (Ora-Gun, JP)
Go Tomiyoshi (Kawaguchi-Shi, JP)
Takaki Hiwasa (Chiba-Shi, JP)
Masaki Takiguchi (Funabashi-Shi, JP)
Naokatsu Saeki (Chiba-Shi, JP)
Toshio Machida (Chiba-Shi, JP)
Assignees:
NATIONAL UNIVERSITY CORPORATION CHIBA UNIVERSITY
FUJIKURA KASEI CO., LTD.
IPC8 Class: AC40B3004FI
USPC Class:
506 9
Class name: Combinatorial chemistry technology: method, library, apparatus method of screening a library by measuring the ability to specifically bind a target molecule (e.g., antibody-antigen binding, receptor-ligand binding, etc.)
Publication date: 2011-11-24
Patent application number: 20110287955
Abstract:
Disclosed are: a polypeptide marker for diagnosing arteriosclerosis; a
gene marker for diagnosing arteriosclerosis; an antibody; a probe for
detecting an arteriosclerosis marker gene; a DNA microarray or a DNA chip
for detecting an arteriosclerosis marker gene; a method for detecting
arteriosclerosis; and a kit for diagnosing arteriosclerosis; with which
an arteriosclerotic lesion can be detected with much improved accuracy.
Specifically disclosed are: a polypeptide marker for diagnosing
arteriosclerosis, which comprises a polypeptide having an amino acid
sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15,
17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 of the Sequence Listing, or a
partial amino acid sequence thereof; a gene which encodes the amino acid
sequence; a probe for detecting the gene; a DNA microarray or a DNA chip
comprising the probe; an antibody bindable to the polypeptide as an
antigen; a kit comprising any one of the above-mentioned items; and a
method for detecting arteriosclerosis by using any one of the
above-mentioned items.Claims:
1. A polypeptide marker for diagnosing arteriosclerosis, which comprises
a polypeptide having an amino acid sequence set forth in any one of SEQ
ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33,
and 35 of the Sequence Listing, or a partial amino acid sequence thereof.
2. A gene marker for diagnosing arteriosclerosis, which comprises a gene represented by a nucleotide sequence that encodes the amino acid sequence according to claim 1, or a partial amino acid sequence thereof.
3. A gene marker for diagnosing arteriosclerosis, which comprises a gene having a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing, or a partial nucleotide sequence thereof.
4. An antibody specifically bindable to the polypeptide according to claim 1 as an antigen.
5. A probe for detecting an arteriosclerosis marker gene, which comprises all or a part of DNA that is hybridizable with the gene according to either one of claim 2 and claim 3 under a stringent condition.
6. The probe for detecting an arteriosclerosis marker gene according to claim 5, which comprises all or a part of antisense DNA for the gene according to claim 3.
7. A DNA microarray or a DNA chip for detecting an arteriosclerosis marker gene, wherein the probe for detecting an arteriosclerosis marker gene according to claim 5 and/or the probe for detecting an arteriosclerosis marker gene according to claim 6 is/are immobilized on a base plate.
8. A method for detecting arteriosclerosis, wherein the antibody according to claim 4 is used to detect the expression of an arteriosclerosis marker polypeptide that is specifically bindable to the antibody, in a specimen sample.
9. A method for detecting arteriosclerosis, wherein the polypeptide marker for diagnosing arteriosclerosis according to claim 1 is used to detect the expression of an arteriosclerosis marker antibody that is specifically bindable to the polypeptide marker for diagnosing arteriosclerosis, in specimen blood.
10. A method for detecting arteriosclerosis, wherein the probe for detecting an arteriosclerosis marker gene according to either one of claim 5 and claim 6 is used to detect the expression of an arteriosclerosis marker gene that is hybridizable with the probe for detecting an arteriosclerosis marker gene, in a specimen cell.
11. A method for detecting arteriosclerosis, wherein a primer is constructed based on a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing, and PCR is conducted with use of the primer to detect the expression of an arteriosclerosis marker gene.
12. A kit for diagnosing arteriosclerosis, including at least one item selected from the group consisting of the probe for detecting an arteriosclerosis marker gene according to either one of claim 5 and claim 6, the DNA microarray or the DNA chip for detecting an arteriosclerosis marker gene according to claim 7, and the antibody according to claim 4.
13. A kit for diagnosing arteriosclerosis, including a polypeptide marker for diagnosing arteriosclerosis which comprises a polypeptide having an amino acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 of the Sequence Listing, or a partial amino acid sequence thereof.
Description:
TECHNICAL FIELD
[0001] The present invention relates to polypeptide markers for diagnosing arteriosclerosis, gene markers for diagnosing arteriosclerosis, antibodies, probes for detecting an arteriosclerosis marker gene, a DNA microarray or a DNA chip for detecting the arteriosclerosis marker genes, a method for detecting arteriosclerosis, and a kit for diagnosing arteriosclerosis.
[0002] Priority is claimed on Japanese Patent Application No. 2008-209210, filed Aug. 15, 2008, the content of which is incorporated herein by reference.
BACKGROUND ART
[0003] Arteriosclerosis is a disease frequently found in aorta, coronary arteries, cerebral arteries, and carotid arteries, being a main cause of myocardial infarction and cerebral infarction. At present, the presence of atherosclerosis is said to be crucial for the ground of the onset of ischemic organ diseases such as ischemic heart disease and cerebrovascular disorder, which are top leading causes of death. Arteriosclerotic lesions are pathomorphologically characterized by: fatty streaks which are subendothelial accumulations of cholesterol ester-storing cells (foam cells); and as an advanced stage thereof, invasions of smooth muscle cells, macrophages, T cells, and the like; as well as fibrous plaques showing cellular necrosis and fat accumulation. The site with fat accumulation is structurally fragile, where plaques are ruptured, triggered by a hemodynamic force, and thereby a thrombus is rapidly formed by reactions of tissue factors and blood coagulation factors. It has been elucidated that the occurrence of thrombotic blockage by the rupture of plaques in a coronary artery is closely associated with the onset of so-called acute coronary syndromes such as acute myocardial infarction, unstable angina pectoris, and cardiac sudden death (Non-Patent Document 1)
[0004] Arteriosclerosis is gradually developed without subjective symptoms, and all of the sudden, myocardial infarction, cerebral infarction, or angina pectoris occurs. Thus, early stage detection is required. So far, ultrasonography, angiography, imaging tests with MRI (magnetic resonance imaging devices) or such a device, electrocardiography, electroencephalography, and the like have been widely carried out for the diagnosis of arteriosclerotic lesions. However, methods by means of biochemical examination have been demanded so that diagnosis of an arteriosclerotic lesion can achieve an early detection.
[0005] In the diagnosis of an arteriosclerotic lesion by means of biochemical examination, there has been known measurements of arteriosclerosis-induced lipoproteins which are associated with lipid accumulation in the vascular wall such as LDL (low density lipoprotein), lipoprotein (Lp-α), remnant lipoprotein, and oxidized LDL in serum or plasma. In particular, measurement of arteriosclerosis-associated substances in blood are attracting attention in recent years. It is reported that measurement of an inflammatory substance: CRP (C-reactive protein), and measurement of the chlamydia antibody titer are useful.
[0006] As for the diagnosis method of an arteriosclerotic lesion by means of such measurement of an arteriosclerosis-induced lipoprotein, the following methods are known. For example, regarding the LDL measurement, the followings have been proposed: measurement of neutrophil, monocyte/macrophage or like inflammatory cell-originated components such as lactoferrin, myeloperoxidase, granulocytic elastase in serum or plasma, forming a complex with the oxidized LDL existing in the serum or the plasma, by an immunological means (Patent Document 1); use of an immunoassay method with a fused polypeptide comprising the extracellular region of an oxidized LDL receptor and a part of the heavy chain constant region of an immunoglobulin (Patent Document 2); use of an anti-human aldehyde-modified al antitrypsin monoclonal antibody capable of specifically recognizing oxidized LDL-al antitrypsin complex (Patent Documents 3 and 4); measurement of the degree of oxidative denaturation of LDL in plasma by an oxidizing agent comprising an azo compound such as V-70 (Patent Document 5); and the like.
[0007] Furthermore, regarding the diagnosis of an arteriosclerotic lesion by means of lipoprotein measurement, the followings have been disclosed: measurement of remnant lipoprotein (RLP) in denatured blood (Patent Document 6); diagnosis of rheumatoid or arteriosclerotic lesions through detection of the expression of the human cartilage GP39-L polypeptide gene (Patent Document 7); diagnosis of arteriosclerotic lesions through measurement of apoB100 lipoprotein in blood (Patent Document 8); measurement of human phospholipid transfer protein (PLTP) with use of a monoclonal antibody against PLTP (Patent Document 9); use of an apo lipoprotein A-I antibody as a marker for diagnosing arteriosclerosis (Patent Document 10); and the like.
[0008] In addition, regarding other means related to the diagnosis of an arteriosclerotic lesion, the followings have been proposed: diagnosis of hyperlipemia or arteriosclerotic lesions with use of an antibody against a sodium dependent bile acid transporter protein (Patent Document 11); diagnosis through measurement of the coagulation factor VII-activating protease (FSAP) as a risk factor for atherosclerosis (Patent Document 12); examination of arteriosclerosis through detection of an endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN) or the gene expression thereof (Patent Document 13); use of an anti-human hepatic triglyceride lipase antibody (Patent Document 14); diagnosis of arteriosclerotic lesions by using the serotonin concentration in a plasma sample as a marker (Patent Documents 15 and 16); and the like.
[0009] Furthermore, regarding yet other means related to the diagnosis of an arteriosclerotic lesion, the followings have been proposed: diagnosis of chronic renal failure or atherosclerosis by using, as the analyte, an sMAD3 polypeptide which is an iso-form of MAD required for the signal transduction of DPP which is a TGF-family member of cytokine/growth factor (Patent Document 17); measurement of a complex of Lp-α and α2-macroglobulin/interleukin 6 in blood as the analyte by an immunological means using an antibody thereof (Patent Document 18); use of a monoclonal antibody against a paraoxonase (Patent Document 19); detection of arteriosclerosis through measurement of a saturated ultra long-chain fatty acid (Patent Document 20); diagnosis of atherosclerosis by using an RC-9 protein and an antibody thereof (Patent Document 21); and the like.
[0010] In this way, many methods have been proposed regarding the biochemical examination related to the diagnosis of an arteriosclerotic lesion. However, most of the detection markers of them are risk markers. For more radical and specific diagnosis of an arteriosclerotic lesion, an advanced development of markers capable of specifically detecting such a lesion has been demanded.
[0011] Therefore, Patent Document 22 has proposed, as a marker for specifically detecting an arteriosclerotic lesion, a polypeptide marker for diagnosing arteriosclerosis, a gene marker for diagnosing arteriosclerosis, an antibody specifically bindable to the polypeptide marker for diagnosing arteriosclerosis, a probe for detecting the gene marker for diagnosing arteriosclerosis, and a method for detecting an arteriosclerotic lesion. [0012] Patent Document 1: Japanese Unexamined Patent Application, First Publication No. 2002-48790 [0013] Patent Document 2: Japanese Unexamined Patent Application, First Publication No. 2002-17353 [0014] Patent Document 3: Japanese Unexamined Patent Application, First Publication No. 2000-184885 [0015] Patent Document 4: Japanese Unexamined Patent Application, First Publication No. H10-142226 [0016] Patent Document 5: Japanese Unexamined Patent Application, First Publication No. H9-203736 [0017] Patent Document 6: Japanese Unexamined Patent Application, First Publication No. 2002-181820 [0018] Patent Document 7: Japanese Unexamined Patent Application, First Publication No. 2002-142781 [0019] Patent Document 8: Japanese Unexamined Patent Application, First Publication No. 2002-55106 [0020] Patent Document 9: Japanese Unexamined Patent Application, First Publication No. H11-346782 [0021] Patent Document 10: Japanese Unexamined Patent Application, First Publication No. H8-160042 [0022] Patent Document 11: Japanese Unexamined Patent Application, First Publication No. 2003-310281 [0023] Patent Document 12: Japanese Unexamined Patent Application, First Publication No. 2003-304873 [0024] Patent Document 13: Japanese Unexamined Patent Application, First Publication No. 2003-189872 [0025] Patent Document 14: Japanese Unexamined Patent Application, First Publication No. 2002-308900 [0026] Patent Document 15: Japanese Unexamined Patent Application, First Publication No. 2002-277461 [0027] Patent Document 16: Japanese Unexamined Patent Application, First Publication No. 2002-131313 [0028] Patent Document 17: Japanese Unexamined Patent Application, First Publication No. 2002-238589 [0029] Patent Document 18: Japanese Unexamined Patent Application, First Publication No. 2001-249128 [0030] Patent Document 19: Japanese Unexamined Patent Application, First Publication No. 2000-333674 [0031] Patent Document 20: Japanese Unexamined Patent Application, First Publication No. 2000-206113 [0032] Patent Document 21: Published Japanese translation No. 2000-503764 of PCT International Publication [0033] Patent Document 22: Japanese Unexamined Patent Application, First Publication No. 2005-168498 [0034] Non-Patent Document 1: N. Eng. J. Med., 326, 242-250, 1992. [0035] Non-Patent Document 2: Journal of Biological Chemistry, 272, 556, 1997.
[0036] According to the technique of Patent Document 22, an arteriosclerotic lesion can be detected with easy manipulation, and an early detection of arteriosclerosis can be expected. However, it does not satisfy an adequate level. There has been a demand for more accurate detection of an arteriosclerotic lesion with use of a greater number of polypeptide markers for diagnosing arteriosclerosis, gene markers for diagnosing arteriosclerosis, and the like.
[0037] Therefore, it is an object of the present invention to provide polypeptide markers for diagnosing arteriosclerosis, gene markers for diagnosing arteriosclerosis, antibodies, probes for detecting an arteriosclerosis marker gene, a DNA microarray or a DNA chip for detecting an arteriosclerosis marker gene, a method for detecting arteriosclerosis, and a kit for diagnosing arteriosclerosis, with which an arteriosclerotic lesion can be detected with much improved accuracy.
DISCLOSURE OF INVENTION
[0038] The inventors of the present invention have searched for proteins which are expressed in serum of a diseased patient with an arteriosclerotic lesion so as to find out more markers for diagnosing arteriosclerosis which can specifically detect an arteriosclerotic lesion. As a result, they found out novel polypeptide markers for diagnosing arteriosclerosis which can specifically detect an arteriosclerotic lesion, which has led to the completion of the present invention.
[0039] In the specific search method, the screening was conducted in the following manner by using serum of diseased patients with arteriosclerotic lesions who had been hospitalized in a hospital or cooperative institutes with the consent of patients or their families. The obtained cDNA clone was inserted in a plasmid pBluescript II to determine the nucleotide sequence. Thereafter, it was recombined in a pGEX plasmid and transfected in E. coli. The protein was abundantly expressed with IPTG (isopropyl β-D-thiogalactoside) to thereby prepare the protein extract. Next, the protein extract was solid-phased in a 96-well plate. The antibody level in the serum was measured by the ELISA method. Using these measured values, a significance test was conducted between the arteriosclerosis patient group and the normal group. As a result, significant differences were found between the patient group and the normal group with thirteen clones serving as the marker of the present invention. Furthermore, the reaction between the protein extract and a large number of patient serums was examined by the western blotting method. As a result, five clones serving as the marker of the present invention newly exhibited a positive reaction with the serums of diseased patients with arteriosclerotic lesion, by which these five clones were found to be useful as specific markers for the presence of an arteriosclerotic lesion, or for an unstable plaque. Then, it became possible by utilizing the antigenicity of these clones or probes for these genes, to develop a method for detecting arteriosclerosis, and moreover to produce a diagnosis kit for use in such a detection method.
[0040] That is, the present invention includes polypeptide markers for diagnosing arteriosclerosis, gene markers for diagnosing arteriosclerosis, antibodies, probes for detecting an arteriosclerosis marker gene, a DNA microarray or a DNA chip for detecting an arteriosclerosis marker gene, a method for detecting arteriosclerosis, and a kit for diagnosing arteriosclerosis, which are described below.
[0041] [1] A polypeptide marker for diagnosing arteriosclerosis, which comprises a polypeptide having an amino acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 of the Sequence Listing, or a partial amino acid sequence thereof.
[0042] [2] A gene marker for diagnosing arteriosclerosis, which comprises a gene represented by a nucleotide sequence that encodes the amino acid sequence of the polypeptide marker for diagnosing arteriosclerosis according to [1], or a partial amino acid sequence thereof
[0043] [3] A gene marker for diagnosing arteriosclerosis, which comprises a gene having a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing, or a partial nucleotide sequence thereof.
[0044] [4] An antibody specifically bindable to the polypeptide according to [1] as an antigen.
[0045] [5] A probe for detecting an arteriosclerosis marker gene, which comprises all or a part of DNA that is hybridizable with the gene according to [2] or [3] under a stringent condition.
[0046] [6] The probe for detecting an arteriosclerosis marker gene according to [5], which comprises all or a part of antisense DNA for the gene according to [3].
[0047] [7] A DNA microarray or a DNA chip for detecting an arteriosclerosis marker gene, wherein the probe for detecting an arteriosclerosis marker gene according to [5] and/or the probe for detecting an arteriosclerosis marker gene according to [6] is/are immobilized on a base plate.
[0048] [8] A method for detecting arteriosclerosis, wherein the antibody according to [4] is used to detect the expression of an arteriosclerosis marker polypeptide that is specifically bindable to the antibody, in a specimen sample.
[0049] [9] A method for detecting arteriosclerosis, wherein the polypeptide marker for diagnosing arteriosclerosis according to [1] is used to detect the expression of an antibody that is specifically bindable to the polypeptide marker for diagnosing arteriosclerosis, in specimen blood.
[0050] [10] A method for detecting arteriosclerosis, wherein the probe for detecting an arteriosclerosis marker gene according to [5] or [6] is used to detect the expression of a gene that is hybridizable with the probe for detecting an arteriosclerosis marker gene, in a specimen cell.
[0051] [11] A method for detecting arteriosclerosis, wherein a primer is constructed based on a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing, and PCR is conducted with use of the primer to detect the expression of an arteriosclerosis marker gene.
[0052] [12] A kit for diagnosing arteriosclerosis, including at least one item selected from the group consisting of the probe for detecting an arteriosclerosis marker gene according to [5] or [6], the DNA microarray or the DNA chip for detecting an arteriosclerosis marker gene according to [7], and the antibody according to [4].
[0053] [13] A kit for diagnosing arteriosclerosis, including a polypeptide marker for diagnosing arteriosclerosis which comprises a polypeptide having an amino acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, and 35 of the Sequence Listing, or a partial amino acid sequence thereof.
[0054] An arteriosclerotic lesion can be detected with much higher accuracy by using the polypeptide marker for diagnosing arteriosclerosis, the gene marker for diagnosing arteriosclerosis, the antibody, the probe for detecting an arteriosclerosis marker gene, the DNA microarray or the DNA chip for detecting an arteriosclerosis marker gene, the method for detecting arteriosclerosis, and the kit for diagnosing arteriosclerosis of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0055] FIG. 1 shows the results of the expression of arteriosclerosis marker genes by the western blotting method in the Examples.
DESCRIPTION OF EMBODIMENTS
[0056] The polypeptide marker for diagnosing arteriosclerosis and the gene marker for diagnosing arteriosclerosis of the present invention can be used for the detection of arteriosclerosis as they are specifically expressed in arteriosclerotic lesions. Polypeptides serving as the polypeptide marker for diagnosing arteriosclerosis of the present invention are polypeptides having an amino acid sequence set forth in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, and 29 of the Sequence Listing, or a partial amino acid sequence thereof.
[0057] Here, the term "partial amino acid sequence" refers to a sequence being a part of the amino acid sequence set forth in any one of SEQ ID NOs of the Sequence Listing mentioned above, consisting of four or more, preferably five or more, more preferably six or more, and yet more preferably seven or more amino acids.
[0058] The information on the amino acid sequences of the above-mentioned polypeptides of the present invention are available from the NCBI GeneBank database as of Jul. 31, 2008, with the accession numbers: XM--001129783 (SEQ ID NO: 1), NM--006088 (SEQ ID NO: 3), NM--014878 (SEQ ID NO: 5), NM--207514 (SEQ ID NO: 7), NM--001128847 (SEQ ID NO: 9), NM--001017408 (SEQ ID NO: 11), NM--015089 (SEQ ID NO: 13), NM--133337 (SEQ ID NO: 15), NM--022406 (SEQ ID NO: 17), NM--001402 (SEQ ID NO: 19), NM--005349 (SEQ ID NO: 21), NM--005406 (SEQ ID NO: 23), NM--016436 (SEQ ID NO: 25), NM--032408 (SEQ ID NO: 27), and NM--014377 (SEQ ID NO: 29).
[0059] In addition, the gene marker for diagnosing arteriosclerosis of the present invention comprises a gene represented by a nucleotide sequence which encodes the above-mentioned polypeptide having the amino acid sequence or a partial amino acid sequence thereof. The gene marker for diagnosing arteriosclerosis may be a gene having a nucleotide sequence capable of expressing the above-mentioned polypeptide.
[0060] The gene serving as the gene marker for diagnosing arteriosclerosis of the present invention can be exemplified by genes of the following clones, as well as being genes having a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing, or a partial nucleotide sequence thereof. The information on these genes (nucleotide sequence information) are respectively available from the NCBI GeneBank database, with the following accession numbers.
[0061] That is, the gene serving as the gene marker for diagnosing arteriosclerosis can be exemplified by [Clone Name: S19A3; SEQ ID NO: 2 of the Sequence Listing; Accession No. XM--001129783; Gene Name: (PREDICTED) similar to LIM and senescent domain 1 (LOC729260); Gene Description: similar to the LIMS1 gene. LIMS1 is an adaptor protein which contains five LIM domains, or double zinc fingers. LIMS1 may possibly play a role in integrin-mediated cell adhesion or spreading.], [Clone Name: TS27A2; SEQ ID NO: 4 of the Sequence Listing; Accession No. NM--006088; Gene Name: tubulin, beta 2C (TUBB2C); Gene Description: a component protein of microtubules], [Clone Name: S21B1; SEQ ID NO: 6 of the Sequence Listing; Accession No. NM--014878; Gene Name: KIAA0020 (KIAA0020); Gene Description; reportedly a minor histocompatibility antigen], [Clone Name: S25E1; SEQ ID NO: 8 of the Sequence Listing; Accession No. NM--207514; Gene Name: differentially expressed in FDCP 8 homolog (mouse) (DEF8); Gene Description: unknown function], [Clone Name: TS12D2; SEQ ID NO: 10 of the Sequence Listing; Accession No. NM--001128847; Gene Name: SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4); Gene Description: unknown], [Clone Name: 536C3; SEQ ID NO: 12 of the Sequence Listing; Accession No. NM--001017408; Gene Name: golgi associated PDZ and coiled-coil motif containing (GOPC); Gene Description: bindable to Rhotekin, an effector of a low molecular weight GTP-binding protein Rho. Moreover, reportedly, the binding between Rhotekin and GOPC is regulated in a Rho dependent manner.], [Clone Name: N48B1; SEQ ID NO: 14 of the Sequence Listing; Accession No. NM--015089; Gene Name: p53-associated parkin-like cytoplasmic protein (PARC); Gene Description: associated with transition from metaphase to anaphase during cell division, and also associated with ubiquitin-dependent protein degradation], [Clone Name: S28D1; SEQ ID NO: 16 of the Sequence Listing; Accession No. NM--133337; Gene Name: fer-1-like 3, myoferlin (C. elegans) (FER1L3); Gene Description: a type II membrane protein similar to a skeletal muscle protein, dysferlin, this gene having a C2 domain is suggested to be possibly associated with regeneration and repair of cytoplasmic membrane and nuclear membrane], [Clone Name: TS27H1; SEQ ID NO: 18 of the Sequence Listing; Accession No. NM--022406; Gene Name: X-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4); Gene Description: a protein encoded by this gene acts to complete the repair of a DNA double strand through nonhomologous end-joining and V(D)J recombination, together with DNA ligase IV and DNA-dependent protein kinase. The nonhomologous end-joining pathway is necessary for the normal development and suppression on tumors.], [Clone Name: PA105; SEQ ID NO: 20 of the Sequence Listing; Accession No. NM--031229; Gene Name: RanBP-type and C3HC4-type zinc finger containing 1 (RBCK1); Gene Description: unknown function. Its amino acid sequence is similar to that of mouse UIP28/UbcM4 interacting protein], [Clone Name: S16D2; SEQ ID NO: 22 of the Sequence Listing; Accession No. NM--005349; Gene Name: recombination signal binding protein for immunoglobulin kappa J region (RBPJ); Gene Description: unknown], [Clone Name: S27D3; SEQ ID NO: 24 of the Sequence Listing; Accession No. NM--005406; Gene Name: Rho-associated, coiled-coil containing protein kinase 1 (ROCK1); Gene Description: serine/threonine kinase activated by a low molecular weight GTP-binding protein Rho, and associated not only with cell contraction but also with morphological regulation, migration, regulation of gene expression, and like physiological functions.], [Clone Name: S36E1; SEQ ID NO: 26 of the Sequence Listing; Accession No. NM--016436; Gene Name: PHD finger protein 20 (PHF20); Gene Description: associated with DNA-dependent transcriptional regulation.], [Clone Name: S39D6; SEQ ID NO: 28 of the Sequence Listing; Accession No. NM--032408; Gene Name: bromodomain adjacent to zinc finger domain, 1B (BAZ1B); Gene Description: a member of the bromodomain protein family involved in chromatin-dependent regulation of transcription.], [Clone Name: TS27B2; SEQ ID NO: 30 of the Sequence Listing; Accession No. NM--014377; Gene Name: zuotin related factor 1 (ZRF1); Gene Description: a member of the M-phase phosphoprotein family, acting as a molecular chaperone.], [Clone Name: PA202; SEQ ID NO: 32 of the Sequence Listing; Accession No. NM--003692; Gene Name: transmembrane protein with EGF-like and two follistatin-like domains 1 (TMEFF1); Gene Description: reportedly inhibits nodal signaling through binding to the nodal coreceptor Cripto in Xenopus], [Clone Name: PA213; SEQ ID NO: 34 of the Sequence Listing; Accession No. NM--006807; Gene Name: chromobox homolog 1 (HP1 beta homolog Drosophila) (CBX1); Gene Description: localized at heterochromatin sites, where it mediates gene silencing.], [Clone Name: PA234; SEQ ID NO: 36 of the Sequence Listing; Accession No. BCO30642; Gene Name: PARK2 co-regulated (PACRG); Gene Description: Parkinson's disease-associated gene, and reportedly regulated by the ubiquitin-proteasome system.].
[0062] In addition, the term "partial nucleotide sequence" refers to a sequence being a part of the nucleotide sequence set forth in any one of SEQ ID NOs of the Sequence Listing mentioned above, consisting of twelve or more, preferably fifteen or more, more preferably eighteen or more, and yet more preferably twenty or more nucleotides (hereunder, the same definition will be applied).
[0063] The above-mentioned genes serving as the gene marker for diagnosing arteriosclerosis are summarized in Table 1.
TABLE-US-00001 TABLE 1 Clone SEQ Name ID NO. Accession No. Gene Name 1 S19A3 2 XM_001129783 (PREDICTED) similar to LIM and senescent domain 1 (LOC729260) 2 TS27A2 4 NM_006088 tubulin, beta 2C (TUBB2C) 3 S21B1 6 NM_014878 KIAA0020 (KIAA0020) 4 S25E1 8 NM_207514 differentially expressed in FDCP 8 homolog (mouse) (DEF8) 5 TS12D2 10 NM_001128847 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) 6 S36C3 12 NM_001017408 golgi associated PDZ and coiled- coil motif containing (GOPC) 7 N48B1 14 NM_015089 p53-associated parkin-like cytoplasmic protein (PARC) 8 S28D1 16 NM_133337 fer-1-like 3, myoferlin (C. elegans) (FER1L3) 9 TS27H1 18 NM_022406 X-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) 10 PA105 20 NM_031229 Ran-BP-type and C3HC4- type zinc finger containing 1 (RBCK1) 11 S16D2 22 NM_005349 recombination signal binding protein for immunoglobulin kappa J region (RBPJ) 12 S27D3 24 NM_005406 Rho-associated, coiled-coil containing protein kinase 1 (ROCK1) 13 S36E1 26 NM_016436 PHD finger protein 20 (PHF20) 14 S39D6 28 NM_032408 bromodomain adjacent to zinc finger domain, 1B (BAZ1B) 15 TS27B2 30 NM_014377 zuotin related factor 1 (ZRF1) 16 PA202 32 NM_003692 transmembrane protein with EGF-like and two follistatin- like domains 1 (TMEFF1) 17 PA213 34 NM_006807 chromobox homolog 1 (HP1 beta homolog Drosphila) (CBX1) 18 PA234 36 BC030642 PARK2 co-regulated (PACRG)
[0064] The antibody of the present invention is an antibody specifically bindable to, as an antigen, a polypeptide serving as the above-mentioned polypeptide marker for diagnosing arteriosclerosis. The antibody may be either monoclonal or polyclonal. These antibodies can be produced by a usual method using the above-mentioned polypeptide as an antigen.
[0065] The antibody of the present invention may be labeled with a labeling substance. As for the labeling substance, it is possible to use an enzyme, a radioisotope, a fluorescent dye, biotin, digoxigenin, or the like. The enzyme is not specifically limited as long as it fulfills the requirements such as a large turnover number (number of revolution), stability in the antibody-binding state, and capability of rendering the substrate a specific color. For example, peroxidases for use in usual EIA (enzyme immunoassay), 3-galactosidase, alkaline phosphatase, glucose oxidase, acetylcholine esterase, glucose-6-phosphate dehydrogenase, malate dehydrogenase, or the like can be used. In addition, it is also possible to use an enzyme inhibitory substance, a coenzyme, or the like. These enzymes can be bound to the antibody by a known method using a maleimide compound or such a crosslinking agent.
[0066] As for the substrate, it is possible to use a known substance according to the type of the enzyme to be used. For example, 3,3',5,5'-tetramethylbenzidine can be used as a substrate when peroxidase is used as an enzyme, while paranitrophenol can be used as a substrate when alkaline phosphatase is used as an enzyme.
[0067] As for the radioisotope, it is possible to use 125I, 3H, or such a substance for use in usual RIA (radioimmunoassay).
[0068] As for the fluorescent dye, it is possible to use fluorescein isothiocianate (FITC), tetramethylrhodamine isothiocyanate (TRITC), or such a substance for use in usual fluorescence antibody technique.
[0069] In addition, these labeled antibodies may be tagged with a metal such as manganese or iron. By administering such a metal-tagged antibody into the body and assaying the metal by MRI or such a means, the presence of an antigen peptide bound to this antibody (a polypeptide marker for diagnosing arteriosclerosis) can be detected.
[0070] In addition, the probe for detecting an arteriosclerosis marker gene of the present invention is a probe which comprises all or a part of DNA that is hybridizable with the gene serving as the gene marker for diagnosing arteriosclerosis mentioned above under a stringent condition. Here, the term "stringent condition" of the present invention can be exemplified by: hybridization in a buffer solution containing 50% formamide, 5×SSC, 5×Denhardt' s solution, 0.1M sodium dihydrogenphosphate (pH6.5), 0.5% SDS, and 100 μg/ml denatured salmon sperm DNA, at 42° C., followed by a washing treatment in a buffer solution containing 1×SSC (0.15M NaCl and 0.015M sodium citrate) and 0.1% SDS (sodium dodecyl sulfate) at 42° C. (Condition 1); or, hybridization in a buffer solution containing 5×SSC, SxDenhardt's solution, 0.1M sodium dihydrogenphosphate (pH6.5), 0.5% SDS, and 100 μg/ml denatured salmon sperm DNA, at 65° C., followed by a washing treatment in a buffer solution containing 0.1×SSC and 0.1% SDS at 65° C. (Condition 2). The latter (Condition 2) is more preferred. As for the factors to influence the stringency of hybridization, there are various kinds of factors other than the temperature condition mentioned above. It is possible for those skilled in the art to combine various kinds of such factors to achieve equivalent stringency to the stringency of hybridization exemplified above.
[0071] Moreover, the probe for detecting an arteriosclerosis marker gene of the present invention can be exemplified by a probe which comprises all or a part of antisense DNA for the gene having a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing. That is, it is a probe which comprises DNA having a nucleotide sequence complementary to the nucleotide sequence set forth in any one of SEQ ID NOs mentioned above, or a partial nucleotide sequence thereof.
[0072] These probes for detecting an arteriosclerosis marker gene may be appropriately labeled with a fluorescent label or the like.
[0073] Moreover, the DNA microarray or the DNA chip for detecting an arteriosclerosis marker gene of the present invention is used for the detection of the expression of the gene serving as the gene marker for diagnosing arteriosclerosis mentioned above, and for the diagnosis of an arteriosclerotic lesion through the detection, wherein the above-mentioned probe for detecting an arteriosclerosis marker gene is immobilized on a base plate. Regarding the above-mentioned probe for detecting an arteriosclerosis marker gene to be immobilized, it is either possible to use a single kind or a plurality of kinds thereof.
[0074] The DNA microarray or the DNA chip can be produced by a usual method. The DNA microarray can be obtained by, for example, spotting a solution containing respective probe(s) for detecting an arteriosclerosis marker gene that has been prepared in advance on a base plate and drying this plate. In addition, the DNA chip can be obtained by, for example, synthesizing DNA having a desired nucleotide sequence on a base plate by photolithography.
[0075] Hereunder is a description of the method for detecting arteriosclerosis of the present invention.
[0076] The method for detecting arteriosclerosis of the present invention is a method in which the above-mentioned polypeptide marker for diagnosing arteriosclerosis is used to detect the expression of an antibody (arteriosclerosis marker antibody) that is specifically bindable to the polypeptide marker for diagnosing arteriosclerosis, in a specimen blood (hereunder, referred to as the "detection method (1)"). In the specimen blood collected from a diseased patient with an arteriosclerotic lesion, the above-mentioned arteriosclerosis marker antibody is induced by the expression of the polypeptide serving as the polypeptide marker for diagnosing arteriosclerosis. So, it is possible to detect arteriosclerosis through detection of the arteriosclerosis marker antibody with use of the polypeptide marker for diagnosing arteriosclerosis.
[0077] The detection method (1) can be specifically exemplified by a method in which: the solid-phased polypeptide marker for diagnosing arteriosclerosis is contacted with a serum collected from a test subject so that the marker can bind to antibodies in the serum; unbound proteins are removed; next a labeled antibody (secondary antibody) that is specifically bindable to the antibodies in the serum is added to allow a reaction therebetween; and the signal from the labeled antibody is detected. As to the labeling substance for the abovementioned labeled antibody, it is possible to use an enzyme, a radioisotope, a fluorescent dye, biotin, digoxigenin, or the like, which has been enumerated as a substance to label the antibody of the present invention.
[0078] When an enzyme is used as a labeling substance, the amount of the antibody can be calculated by: adding a substrate which is decomposed to take a color by an enzymatic action; optically measuring the amount of the decomposed substrate to thereby obtain the enzymatic activity; converting this value into the amount of the antibody bound; and making a comparison between the converted value and a reference value. Alternatively, the amount of the antibody can also be obtained with high sensitivity by: adding a substrate which emits light by an enzymatic action; and measuring with a weak luminescence analyzer (luminometer).
[0079] When a radioisotope is used as a labeling substance, the amount of the antibody can be calculated by measuring the level of radiation emitted from the radioisotope with a scintillation counter or such a device. When a fluorescent dye is used as a labeling substance, the amount of the antibody can be calculated by measuring the quantity of fluorescence with a measurement device equipped with a fluorescence spectrometer or such a device.
[0080] In the detection method (1), the western blotting method can be applied. Moreover, it is also possible to isolate a conjugate of the polypeptide marker for diagnosing arteriosclerosis, the antibody of the specimen blood, and the labeled antibody, by a known isolation method (a chromatography method, a salting-out method, an alcohol precipitation method, an enzyme method, an in-phase method, or the like), followed by the detection of the signal from the labeled antibody.
[0081] Moreover, in the diagnosis of arteriosclerosis by using the detection method (1), it is also possible to examine whether or not the arteriosclerosis marker antibody (antibodies) is (are) present in the specimen blood collected from a test subject so as to determine that the test subject showing the presence of one or more types of arteriosclerosis marker antibodies is a diseased patient with an arteriosclerotic lesion, or a person with a high risk of an arteriosclerotic lesion.
[0082] In addition, the method for detecting arteriosclerosis of the present invention is a method in which the above-mentioned probe for detecting an arteriosclerosis marker gene is used to detect the expression of a gene (arteriosclerosis marker gene) that is hybridizable with the probe for detecting an arteriosclerosis marker gene, in a specimen cell (hereunder, referred to as the "detection method (2)"). In the specimen cell collected from a diseased patient with an arteriosclerotic lesion, the arteriosclerosis marker gene is expressed. So, it is possible to detect arteriosclerosis through detection of the expression of the arteriosclerosis marker gene with use of the probe for detecting an arteriosclerosis marker gene.
[0083] The detection method (2) can be specifically exemplified by a method in which: a probe for detecting an arteriosclerosis marker gene, which has a nucleotide sequence as mentioned above in a suitable length for hybridization is prepared; a fluorescence label or such a label is appropriately added thereto; this labeled probe is contacted with a sample collected from a specimen cell to perform a hybridization reaction; and the expression of the gene serving as the gene marker for diagnosing arteriosclerosis is detected.
[0084] In the detection method (2), it is possible to employ a known detection method except for using the probe for detecting an arteriosclerosis marker gene of the present invention. For example, a northern blotting method can be employed. Moreover, in the detection method (2), any one of the above-mentioned probes for detecting an arteriosclerosis marker gene can be used. It is either possible to use a single kind of probe for detecting an arteriosclerosis marker gene or a plurality of kinds of probes for detecting an arteriosclerosis marker gene.
[0085] In addition, the detection method (2) may also use a DNA microarray or a DNA chip in which the probe(s) for detecting an arteriosclerosis marker gene is/are immobilized on a base plate.
[0086] Furthermore, in the detection method (2), it is also possible to employ quantitative or semi-quantitative PCR (Polymerase Chain Reaction) in order to amplify the arteriosclerosis marker gene in the sample collected from the specimen cell. The PCR may be either RT-PCR (reverse transcription PCR) or real-time RT-PCR. For carrying out the PCR, a primer set including a sense primer and an antisense primer for amplifying the arteriosclerosis marker gene is used. These primers can be appropriately constructed based on a nucleotide sequence set forth in any one of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, and 36 of the Sequence Listing.
[0087] On the completion of the amplification of the arteriosclerosis marker gene by such quantitative or semi-quantitative PCR in this way, the expression of the arteriosclerosis marker gene can be detected by using this sample. By so doing, the detection sensitivity can be improved.
[0088] Moreover, in the diagnosis of arteriosclerosis by using the detection method (2), it is possible to detect the arteriosclerosis marker gene in a test subject and compare the result with a result of a healthy subject detected by the same method to thereby determine that the test subject showing a large detection level is a diseased patient with an arteriosclerotic lesion, or a person with a high risk of an arteriosclerotic lesion.
[0089] In addition, the method for detecting arteriosclerosis of the present invention is a method in which the antibody bindable to, as an antigen, a polypeptide serving as the polypeptide marker for diagnosing arteriosclerosis of present invention, is used to detect the expression of a polypeptide (arteriosclerosis marker polypeptide) that is specifically bindable to the antibody, in a specimen sample (hereunder, referred to as the "detection method (3)"). In the specimen sample collected from a diseased patient with an arteriosclerotic lesion, the arteriosclerosis marker polypeptide is expressed. So, it is possible to detect arteriosclerosis through detection of the arteriosclerosis marker polypeptide with use of the antibody of the present invention.
[0090] The detection method (3) can be executed by a known immunoassay method except for using the antibody of the present invention. The immunoassay method can be exemplified by the western blotting method, the ELISA (Enzyme-Linked Immunosorbent Assay) method, a radioimmunoassay method, or a fluorescence antibody technique.
[0091] The antibody for use in the detection method (3) may be either monoclonal or polyclonal.
[0092] When the fluorescence antibody technique is applied to the detection method (3), either a direct fluorescence antibody test or an indirect fluorescence antibody test may be used. The direct fluorescence antibody test is a method in which an antibody for use in the detection is labeled with fluorescence, and then the antibody is contacted to a sample cell as being the test sample to bind them to each other so that a cell expressing the arteriosclerosis marker polypeptide can be labeled. In addition, the indirect fluorescence antibody test is a method in which a non-labeled antibody of the present invention is contacted to a sample cell to bind them to each other, and then the antibody is further bound to a labeled secondary antibody (anti-immunoglobulin antibody) so that a cell expressing the arteriosclerosis marker polypeptide can be labeled.
[0093] Moreover, when detecting arteriosclerosis through detection of the expression of the arteriosclerosis marker polypeptide, it is also possible, rather than using the antibody of the present invention as mentioned above, to use TOF-MASS to directly detect the arteriosclerosis marker polypeptide, or to use a chip in which a protein that is interactive with the arteriosclerosis marker polypeptide is immobilized on a base plate.
[0094] Moreover, in the diagnosis of arteriosclerosis by using the detection method (3), it is possible to examine whether or not the arteriosclerosis marker polypeptide(s) is (are) present in the specimen sample collected from a test subject so as to determine that the test subject showing the presence of one or more types of arteriosclerosis marker polypeptides is a diseased patient with an arteriosclerotic lesion, or a person with a high risk of an arteriosclerotic lesion.
[0095] The probe for detecting an arteriosclerosis marker gene for use in the detection of an arteriosclerotic lesion of the present invention, the DNA microarray or the DNA chip for detecting an arteriosclerosis marker gene in which the probe for detecting an arteriosclerosis marker gene is immobilized, and the antibody for detecting the arteriosclerosis marker polypeptide of the present invention can be prepared as a product of a kit for diagnosing arteriosclerosis which comprises at least one of these items and with which arteriosclerosis can be detected and diagnosed as mentioned above.
[0096] In addition, the polypeptide marker for diagnosing arteriosclerosis of the present invention can also be prepared as a product of a kit for diagnosing arteriosclerosis with which arteriosclerosis can be detected and diagnosed as mentioned above.
[0097] When the polypeptide marker for diagnosing arteriosclerosis, the gene marker for diagnosing arteriosclerosis, the antibody, and the probe for detecting an arteriosclerosis marker gene of the present invention described above are jointly used with those of the Patent Document 22, arteriosclerosis can be detected with much higher accuracy.
EXAMPLES
[0098] Hereunder is a detailed description of the present invention with reference to Examples. However, the present invention is not to be limited by the following description.
Production Example
Preparation of Samples
[0099] (1) The subjects were patients with carotid artery stenoses who had visited our hospital or cooperative institutes. The reference (control) healthy subjects were selected from outpatients so that both groups had matched gender and age (±5 years). When they were visiting as outpatients or hospitalized in the neurosurgery department; 1) their families were explained that this study was to be conducted for research purposes and that cooperation with the study was not compulsory, and informed consents were obtained from them; 2) questions about the family history, the past history, the life style such as drinking and smoking habits, and the work style were asked; 3) blood was collected and separated into serum and corpuscle components and cryopreserved; and furthermore, 4) the clinical seriousness, the therapeutic process, the findings of the blood examination and the like were recorded on the basis of the medical record of the doctor. The patient blood as the analyte was separated into serum and cryopreserved at -80° C. until the study was started. The antibodies and the medical records were used after encryption and anonymization. (2) Regarding the target of screening with serum, commercial λZAP II phage vectors (STRATAGENE) recombined with a human microvascular endothelium-derived cDNA library were used.
(Expression Cloning Method)
[0100] (3) The screening by the expression cloning method was conducted with reference to the method of St John, T et. al. (Science, 231, 845-850, 1986).
[0101] 1) The above-mentioned phage vector of (2) was infected into E. coli (XL1-Blue) and cultured on a NZY agar medium (15 cm dish).
[0102] 2) After confirming the emergence of plaques, an IPTG-treated nitrocellulose membrane was placed on the medium, and the phage-derived protein was expressed and transferred to the nitrocellulose membrane.
[0103] 3) The patient serum which had been diluted 2000-fold with 1% BSA/PBS and the nitrocellulose membrane were incubated overnight to cause a reaction between the expression proteins and the antibodies in the serum (serum IgG).
[0104] 4) After washing, the alkaline phosphatase-labeled goat anti-human IgG antibody as a secondary antibody was reacted with the nitrocellulose membrane.
[0105] 5) Serum IgG-recognizing clones were identified by using NBT (nitroblue terazolium) and BCIP (5-bromo-4-chloro-3-indolyl-phosphate) as a coloring reagent.
[0106] 6) The positive clones were subjected to secondary and tertiary screening (in φ10 cm dish) and false positive clones were removed.
[0107] 7) The selected phage was converted to pBlueScript with the ExAssist helper phage system (Stratagene, La Jolla, Calif.).
[0108] 8) The plasmid was purified with use of the Plasmid Miniprep kit (Sigma).
[0109] 9) The nucleotide sequences of the obtained clones were determined by a sequencer, and were subjected to a homology search using published databases. By so doing, the genes were identified and these clones were used as candidate antigen proteins.
(Elisa Method)
(4) ELISA Method as Secondary Screening
[0110] 1) The pBluescript including the insert of the candidate antigen protein was recombined into a protein expression and purification vector pGEX-4T (Amersham Bioscience). From the obtained nucleotide sequence information, restriction enzymes suitable for the recombination from pBluescript to pGEX-4T were selected, and treatments were done with restriction enzymes such as BamH I, Sal I, Not I, EcoR I, Xho I, and Sma I.
[0111] 2) After agarose gel electophoresis, the band of interest was cut out by using the purification kit GeneElute Minus EtBr Spin Columns (SIGMA), and the restriction enzyme digested insert and the pGEX-4T were recovered.
[0112] 3) The insert and the pGEX-4T were ligated with the Ligation-Convenience Kit (Nippongene) to thereby produce a plasmid containing the insert.
[0113] 4) When there was no restriction enzyme suitable for some clones, the inserts thereof were produced by PCR. Primers having a restriction enzyme recognition site were produced in advance, and RNA extracted from aneurysmal tissue was used as a template to conduct reverse transcription PCR. Thereby, cDNA was produced. Another PCR was conducted to obtain the total length of the insert. Thereafter, the same treatment was carried out using the restriction enzymes and the ligation kit.
[0114] 5) The obtained recombinant pGEX-4T was used to transform E. coli competent cell BL21 (Nippongene) modified for eukaryotic protein expression.
[0115] 6) This product was cultured in an ampicillin-containing LB medium, and the expression of the insert DNA-derived protein was induced with IPTG.
[0116] 7) E. coli was recovered through centrifugal separation and ruptured by sonication to separate into a soluble fraction and an insoluble fraction.
[0117] 8) If the target protein was in the insoluble fraction, this was solubilized by using urea.
[0118] 9) The antigen protein was purified with the glutathione-Sepharose (Amersham Pharmacia).
[0119] 10) The antigen protein was injected in a 96-well ELISA plate at a concentration of 10 μg/ml, stored at 4° C. overnight, and solid-phased.
[0120] 11) After washing with PBS and blocking with a PBS solution containing 10% fetal bovine serum, patient serum and control serum (serum of healthy subject) were diluted 2000-fold and reacted with the solid-phased protein.
[0121] 12) After washing with PBS, HRP-labeled goat anti-human IgG antibody was added.
[0122] 13) A color was developed by adding a substrate, and the absorption at OD 490 nm was measured using a plate reader.
(Western Blotting Method)
(5) Secondary Screening by Western Blotting Method
[0123] 1) E. coli (SOLR, JM109, BL21) transformed with the pBluescript or the pGEX-4T including the insert of the candidate antigen protein obtained from the above, was cultured with 2 ml of LB ampicillin (50 μg/ml) overnight.
[0124] 2) This was transferred to 20 ml of LB ampicillin and cultured for one hour, and was then added with IPTG to give a final concentration of 1 mM. The resultant sample with IPTG and a control sample (without the addition of IPTG) were cultured for another 3 hours.
[0125] 3) The culture liquid was centrifuged, and E. coli was recovered therefrom. This was dissolved with a SDS sample buffer for use as a sample of the western method.
[0126] 4) This sample was electophoresed on a 10% polyacrylamide gel, and the protein was transferred to a nitrocellulose membrane using a blotting apparatus.
[0127] 5) This was blocked with 1% skim milk and then was added with a 2000-fold diluted patient serum as a primary antibody, followed by overnight incubation.
[0128] 6) After washing with PBST (20 mM Tris-HCl (pH 7.6), 50 mM NaCl, 0.1% Tween-20), 30.000-fold diluted HRP-labeled goat anti-human IgG antibody was added and allowed to react for 20 minutes.
[0129] 7) After washing with PBST, a luminescent reagent Immobilon Western (MILLIPORE) was used to effect light emission.
[0130] 8) The membrane was exposed to a film and developed.
[0131] 9) The band which became detectable depending on the IPTG treatment was assumed to be of an antigen protein.
Verification of the Gene Marker for Diagnosing Arteriosclerosis by Sequencing
[0132] The nucleotide sequences of the genes (gene markers for diagnosing arteriosclerosis) of the detected clones were determined by sequencing. The thus determined nucleotide sequences were cross-checked with nucleotide sequences in published gene databases. As a result, the genes of the obtained clones had consistent nucleotide sequences with those of the genes that encode the polypeptides for diagnosing arteriosclerosis mentioned above.
Example 1
Measurement of the Antibody Titer by ELISA Method
[0133] Using the experimental protocol of the Production Example mentioned above, the antibody levels of the thirteen out of the eighteen types of the detected arteriosclerosis diagnostic marker candidates were measured by ELISA, and the presence of the serum antibodies was confirmed. The results of the measurement are shown in Table 2.
TABLE-US-00002 TABLE 2 Healthy Patient (P) subject (N) standard p value Standard Clone name Average deviation (two-sided) Average deviation S19A3 0.386 0.00912 0.0000 0.272 0.0624 TS27A2 0.306 0.1246 0.0011 0.229 0.0909 S21B1 0.206 0.1271 0.0078 0.146 0.0779 S25E1 0.346 0.3338 0.0145 0.210 0.1515 TS12D2 0.318 0.1959 0.0227 0.242 0.1019 S36C3 0.050 0.0407 0.0281 0.035 0.0207 N48B1 0.211 0.1109 0.0472 0.165 0.1065 S28D1 0.493 0.2525 0.0642 0.400 0.2251 TS27H1 0.093 0.0827 0.0645 0.067 0.0393 PA105 0.256 0.1414 0.0000 0.1417 0.0891 PA202 0.289 0.1546 0.0097 0.2157 0.1054 PA213 0.440 0.2052 0.0002 0.2955 0.1368 PA234 0.150 0.1001 0.0131 0.1046 0.0705
Example 2
Verification of the Expression of Arteriosclerosis Marker Genes by Western Blotting Method
[0134] The five types of clones of the candidate gene markers identified by the expression cloning method, that is, those unused in Example 1, were verified for the expression of the arteriosclerosis marker gene in arteriosclerosis patients by the western blotting method. The detection results thereof are shown in FIG. 1 (positive signal in western blots is indicated by the arrow in the figure). FIG. 1(a) shows the results of Clone Name: S16D2 (SEQ ID NO: 22 of the Sequence Listing), FIG. 1(b) shows the results of Clone Name: S27D3 (SEQ ID NO: 24 of the Sequence Listing), FIG. 1(c) shows the results of Clone Name: S36E1 (SEQ ID NO: 26 of the Sequence Listing), FIG. 1(d) shows the results of Clone Name: S39D6 (SEQ ID NO: 28 of the Sequence Listing), and FIG. 1(e) shows the results of Clone Name: TS27B2 (SEQ ID NO: 30 of the Sequence Listing).
[0135] As shown in Table 2, with the thirteen types of candidate gene markers for diagnosing arteriosclerosis obtained from the screening of this Example, the measurement by the ELISA method showed a difference between the antibody titer of patients and the antibody titer of healthy subject serums. Furthermore, with eleven types of candidate gene markers, a significant difference was found.
[0136] In addition, as shown in FIG. 1, with five types of candidate gene markers obtained from the screening of this Example, positive signals for the specific reaction were confirmed by the western blotting method.
INDUSTRIAL APPLICABILITY
[0137] According to the polypeptide markers for diagnosing arteriosclerosis, the gene markers for diagnosing arteriosclerosis, the antibodies, the probes for detecting the arteriosclerosis marker genes, the DNA microarray or the DNA chip for detecting the arteriosclerosis marker genes, the method for detecting arteriosclerosis, and the kit for diagnosing arteriosclerosis of the present invention, arteriosclerosis can be readily detected with high accuracy. These can be favorably used for the early stage diagnosis of arteriosclerosis.
Sequence CWU
1
361568PRTHomo sapiens 1Met Glu Ser Phe Leu Leu Asp Asp Ile Ser Ser Val Ile
Gln Asn Lys1 5 10 15Gly
Ile Glu Arg Ile Ile Ser Pro Met Ile Val Gln Leu Cys His Leu 20
25 30Leu Ile Ser Met Glu Arg Lys Glu
Val Glu Asn Glu Val Phe Ala Ser 35 40
45Leu Glu Lys Met Ala Glu Glu Leu Ala Lys Ala Cys Glu Asp Phe Val
50 55 60Gln Val Val Lys Ser Ser Gly Asn
Thr Glu Ala Val Ser Val Ser Pro65 70 75
80Val Ile Val Asn Ala Ala Leu Val Phe Gln Lys Ala Val
Val Val Trp 85 90 95Val
Phe Lys Ser Glu Lys His Gly Ile Val Asp Glu Val Leu Trp Gln
100 105 110Ile Cys Lys Ala Arg Val Asp
Ile Ser Phe Ser Trp Arg Leu Thr Arg 115 120
125Leu Thr Cys Val Gly Thr Val Gly Val Thr Leu Ala Gly Lys Gln
Gly 130 135 140Gly Leu Asp Ile Val Ser
Pro Gly Ser Val Ser Cys His Ser His Pro145 150
155 160Cys Ala Gln Ser Ser Gln Ala Pro Thr Met Ala
Phe Ser Gly Arg Ala 165 170
175Arg Pro Cys Ile Ile Pro Glu Asn Glu Glu Ile Pro Arg Ala Ala Leu
180 185 190Asn Thr Val His Glu Ala
Asn Gly Thr Glu Asp Glu Arg Ala Val Ser 195 200
205Lys Leu Gln Arg Arg His Ser Asp Val Lys Val Tyr Lys Glu
Phe Cys 210 215 220Asp Phe Tyr Ala Lys
Phe Asn Met Ala Asn Ala Leu Ala Ser Ala Thr225 230
235 240Cys Glu Arg Cys Lys Gly Gly Phe Ala Pro
Ala Glu Thr Ile Val Asn 245 250
255Ser Asn Gly Glu Leu Tyr His Glu Gln Cys Phe Val Cys Ala Gln Cys
260 265 270Phe Gln Gln Phe Pro
Glu Gly Leu Phe Tyr Glu Phe Glu Gly Arg Lys 275
280 285Tyr Cys Glu His Asp Phe Gln Met Leu Phe Ala Pro
Cys Cys His Gln 290 295 300Cys Gly Glu
Phe Ile Ile Gly Arg Val Ile Lys Ala Met Asn Asn Ser305
310 315 320Trp His Pro Glu Cys Phe Arg
Cys Asp Leu Cys Gln Glu Val Leu Ala 325
330 335Asp Ile Gly Phe Val Lys Asn Ala Gly Arg His Leu
Cys Arg Pro Cys 340 345 350His
Asn Arg Glu Lys Ala Arg Gly Leu Gly Lys Tyr Ile Cys Gln Lys 355
360 365Cys His Ala Ile Ile Asp Glu Gln Pro
Leu Ile Phe Lys Asn Asp Pro 370 375
380Tyr His Pro Asp His Phe Asn Cys Ala Asn Cys Gly Lys Asp Leu Thr385
390 395 400Ala Asp Ala Gln
Glu Leu Lys Gly Glu Leu Tyr Cys Leu Pro Cys His 405
410 415Asp Lys Met Gly Val Pro Ile Cys Gly Ala
Cys Arg Arg Pro Ile Glu 420 425
430Gly Arg Val Val Asn Ala Met Gly Lys Gln Trp His Val Glu His Phe
435 440 445Val Cys Ala Lys Cys Glu Lys
Pro Phe Leu Gly His Arg His Tyr Glu 450 455
460Arg Lys Gly Leu Ala Tyr Cys Glu Thr His Tyr Asn Gln Leu Phe
Gly465 470 475 480Asp Val
Cys Phe His Cys Asn Arg Val Ile Glu Gly Asp Val Val Ser
485 490 495Ala Leu Asn Lys Ala Trp Cys
Val Asn Cys Phe Ala Cys Ser Thr Cys 500 505
510Asn Thr Lys Leu Thr Leu Lys Asp Lys Phe Val Glu Ile Asp
Leu Lys 515 520 525Pro Val Cys Lys
His Cys Tyr Glu Lys Met Pro Glu Glu Phe Lys Arg 530
535 540Arg Leu Ala Lys Arg Glu Arg Glu Ala Lys Asp Lys
Asp Lys Gln Lys545 550 555
560Lys Lys Lys Pro Val Cys Leu Leu 56521707DNAHomo
sapiens 2atggagtctt tcctcttgga tgacatcagc tctgtgatac agaacaaagg
cattgagaga 60atcatctcac caatgatcgt tcagctttgc catctgctca tctcaatgga
gaggaaagaa 120gtggagaatg aagtatttgc ctcgttggag aagatggctg aggaattggc
gaaagcttgt 180gaagacttcg tgcaagttgt caaaagttca ggcaacacgg aagctgtgtc
tgtttctcct 240gtcattgtaa atgcagccct ggtctttcaa aaagctgtgg ttgtgtgggt
ctttaagagt 300gaaaagcacg gcattgttga tgaagtcttg tggcaaatat gcaaggcacg
tgtggatatt 360tctttctctt ggaggcttac aaggctgacg tgcgtgggaa cagtgggagt
gaccctggct 420gggaagcagg gaggcctgga tattgtttct cctggctctg tgtcctgcca
ttctcatccc 480tgtgctcaga gctctcaagc acccacgatg gccttctcag gccgagcgcg
cccctgcatt 540atcccagaga acgaagaaat cccccgagca gcccttaaca ctgtccacga
ggccaatggg 600accgaggacg agagggctgt ttccaaactg cagcgcaggc acagtgacgt
gaaagtctac 660aaggagttct gtgactttta tgcgaaattc aacatggcca acgccctggc
cagcgccact 720tgcgagcgct gcaagggcgg ctttgcgccc gctgagacga tcgtgaacag
taatggggag 780ctgtaccatg agcagtgttt cgtgtgcgct cagtgcttcc agcagttccc
agaaggactc 840ttctatgagt ttgaaggaag aaagtactgt gaacatgact ttcagatgct
ctttgcccct 900tgctgtcatc agtgtggtga attcatcatt ggccgagtta tcaaagccat
gaataacagc 960tggcatccgg agtgcttccg ctgtgacctc tgccaggaag ttctggcaga
tatcgggttt 1020gtcaagaatg ctgggagaca cctgtgtcgc ccctgtcata atcgtgagaa
agccagaggc 1080cttgggaaat acatctgcca gaaatgccat gctatcatcg atgagcagcc
tctgatattc 1140aagaacgacc cctaccatcc agaccatttc aactgcgcca actgcgggaa
ggatctgact 1200gccgatgcac aggagctgaa aggggagcta tactgcctgc catgccatga
taaaatgggg 1260gtccccatct gtggcgcttg ccgacggccc atcgaagggc gtgtggtgaa
cgccatgggc 1320aagcagtggc atgtggagca ttttgtttgt gccaagtgtg agaaaccctt
tcttggacat 1380cgccattatg agaggaaagg cctggcgtat tgtgaaactc actataacca
gctatttggt 1440gatgtttgct tccactgcaa tcgtgttata gaaggtgatg tggtctctgc
tcttaataag 1500gcctggtgcg tgaactgctt tgcctgttct acctgcaaca ctaaattaac
actcaaggat 1560aagtttgttg aaattgacct aaagccagtc tgcaaacact gttatgagaa
aatgccagaa 1620gaatttaaga ggcgacttgc caaacgggag agagaagcaa aggataagga
caagcagaaa 1680aagaaaaagc cagtctgttt attgtaa
17073445PRTHomo sapiens 3Met Arg Glu Ile Val His Leu Gln Ala
Gly Gln Cys Gly Asn Gln Ile1 5 10
15Gly Ala Lys Phe Trp Glu Val Ile Ser Asp Glu His Gly Ile Asp
Pro 20 25 30Thr Gly Thr Tyr
His Gly Asp Ser Asp Leu Gln Leu Glu Arg Ile Asn 35
40 45Val Tyr Tyr Asn Glu Ala Thr Gly Gly Lys Tyr Val
Pro Arg Ala Val 50 55 60Leu Val Asp
Leu Glu Pro Gly Thr Met Asp Ser Val Arg Ser Gly Pro65 70
75 80Phe Gly Gln Ile Phe Arg Pro Asp
Asn Phe Val Phe Gly Gln Ser Gly 85 90
95Ala Gly Asn Asn Trp Ala Lys Gly His Tyr Thr Glu Gly Ala
Glu Leu 100 105 110Val Asp Ser
Val Leu Asp Val Val Arg Lys Glu Ala Glu Ser Cys Asp 115
120 125Cys Leu Gln Gly Phe Gln Leu Thr His Ser Leu
Gly Gly Gly Thr Gly 130 135 140Ser Gly
Met Gly Thr Leu Leu Ile Ser Lys Ile Arg Glu Glu Tyr Pro145
150 155 160Asp Arg Ile Met Asn Thr Phe
Ser Val Val Pro Ser Pro Lys Val Ser 165
170 175Asp Thr Val Val Glu Pro Tyr Asn Ala Thr Leu Ser
Val His Gln Leu 180 185 190Val
Glu Asn Thr Asp Glu Thr Tyr Cys Ile Asp Asn Glu Ala Leu Tyr 195
200 205Asp Ile Cys Phe Arg Thr Leu Lys Leu
Thr Thr Pro Thr Tyr Gly Asp 210 215
220Leu Asn His Leu Val Ser Ala Thr Met Ser Gly Val Thr Thr Cys Leu225
230 235 240Arg Phe Pro Gly
Gln Leu Asn Ala Asp Leu Arg Lys Leu Ala Val Asn 245
250 255Met Val Pro Phe Pro Arg Leu His Phe Phe
Met Pro Gly Phe Ala Pro 260 265
270Leu Thr Ser Arg Gly Ser Gln Gln Tyr Arg Ala Leu Thr Val Pro Glu
275 280 285Leu Thr Gln Gln Met Phe Asp
Ala Lys Asn Met Met Ala Ala Cys Asp 290 295
300Pro Arg His Gly Arg Tyr Leu Thr Val Ala Ala Val Phe Arg Gly
Arg305 310 315 320Met Ser
Met Lys Glu Val Asp Glu Gln Met Leu Asn Val Gln Asn Lys
325 330 335Asn Ser Ser Tyr Phe Val Glu
Trp Ile Pro Asn Asn Val Lys Thr Ala 340 345
350Val Cys Asp Ile Pro Pro Arg Gly Leu Lys Met Ser Ala Thr
Phe Ile 355 360 365Gly Asn Ser Thr
Ala Ile Gln Glu Leu Phe Lys Arg Ile Ser Glu Gln 370
375 380Phe Thr Ala Met Phe Arg Arg Lys Ala Phe Leu His
Trp Tyr Thr Gly385 390 395
400Glu Gly Met Asp Glu Met Glu Phe Thr Glu Ala Glu Ser Asn Met Asn
405 410 415Asp Leu Val Ser Glu
Tyr Gln Gln Tyr Gln Asp Ala Thr Ala Glu Glu 420
425 430Glu Gly Glu Phe Glu Glu Glu Ala Glu Glu Glu Val
Ala 435 440 44541338DNAHomo
sapiens 4atgagggaaa tcgtgcactt gcaggccggg cagtgcggca accaaatcgg
cgccaagttt 60tgggaggtga tcagcgatga gcacggcatc gaccccacgg gcacctacca
cggggacagc 120gacctgcagc tggaacgcat caacgtgtac tacaatgagg ccaccggcgg
caagtacgtg 180ccccgcgccg tgctcgtgga tctggagccc ggcaccatgg actccgtgcg
ctcggggccc 240ttcgggcaga tcttccggcc ggacaacttc gttttcggtc agagtggtgc
tgggaacaac 300tgggccaagg ggcactacac agaaggcgcg gagctggtgg actcggtgct
ggatgttgtg 360agaaaggagg ctgagagctg tgactgcctg cagggtttcc agctgaccca
ctccctgggt 420ggggggactg ggtctgggat gggtaccctc ctcatcagca agatccggga
ggagtaccca 480gacaggatca tgaacacgtt tagtgtggtg ccttcgccca aagtgtcaga
cacagtggtg 540gagccctaca acgccaccct ctcagtccac cagctcgtag aaaacacaga
cgagacctac 600tgcattgata acgaagctct ctacgacatt tgcttcagaa ccctaaagct
gaccacgccc 660acctatggtg acctgaacca cctggtgtct gctaccatga gtggggtcac
cacctgcctg 720cgcttcccag gccagctcaa tgctgacctg cggaagctgg ctgtgaacat
ggtcccgttt 780ccccggctgc acttcttcat gcccggcttt gccccactga ccagccgggg
cagccagcag 840taccgggcgc tgaccgtgcc cgagctcacc cagcagatgt ttgatgccaa
gaacatgatg 900gctgcctgcg acccccgcca tggccgctac ctgacggttg ccgccgtgtt
caggggccgc 960atgtccatga aggaggtgga tgagcaaatg cttaatgtcc aaaacaaaaa
cagcagctat 1020tttgttgagt ggatccccaa caatgtgaaa acggctgtct gtgacatccc
acctcggggg 1080ctaaaaatgt ccgccacctt cattggcaac agcacggcca tccaggagct
gttcaagcgc 1140atctccgagc agttcacggc catgttccgg cgcaaggcct tcctgcactg
gtacacgggc 1200gagggcatgg acgagatgga gttcaccgag gccgagagca acatgaatga
cctggtgtcc 1260gagtaccagc agtaccagga tgccacagcc gaggaggagg gcgagttcga
ggaggaggct 1320gaggaggagg tggcctag
13385648PRTHomo sapiens 5Met Glu Val Lys Gly Lys Lys Gln Phe
Thr Gly Lys Ser Thr Lys Thr1 5 10
15Ala Gln Glu Lys Asn Arg Phe His Lys Asn Ser Asp Ser Gly Ser
Ser 20 25 30Lys Thr Phe Pro
Thr Arg Lys Val Ala Lys Glu Gly Gly Pro Lys Val 35
40 45Thr Ser Arg Asn Phe Glu Lys Ser Ile Thr Lys Leu
Gly Lys Lys Gly 50 55 60Val Lys Gln
Phe Lys Asn Lys Gln Gln Gly Asp Lys Ser Pro Lys Asn65 70
75 80Lys Phe Gln Pro Ala Asn Lys Phe
Asn Lys Lys Arg Lys Phe Gln Pro 85 90
95Asp Gly Arg Ser Asp Glu Ser Ala Ala Lys Lys Pro Lys Trp
Asp Asp 100 105 110Phe Lys Lys
Lys Lys Lys Glu Leu Lys Gln Ser Arg Gln Leu Ser Asp 115
120 125Lys Thr Asn Tyr Asp Ile Val Val Arg Ala Lys
Gln Met Trp Glu Ile 130 135 140Leu Arg
Arg Lys Asp Cys Asp Lys Glu Lys Arg Val Lys Leu Met Ser145
150 155 160Asp Leu Gln Lys Leu Ile Gln
Gly Lys Ile Lys Thr Ile Ala Phe Ala 165
170 175His Asp Ser Thr Arg Val Ile Gln Cys Tyr Ile Gln
Tyr Gly Asn Glu 180 185 190Glu
Gln Arg Lys Gln Ala Phe Glu Glu Leu Arg Asp Asp Leu Val Glu 195
200 205Leu Ser Lys Ala Lys Tyr Ser Arg Asn
Ile Val Lys Lys Phe Leu Met 210 215
220Tyr Gly Ser Lys Pro Gln Ile Ala Glu Ile Ile Arg Ser Phe Lys Gly225
230 235 240His Val Arg Lys
Met Leu Arg His Ala Glu Ala Ser Ala Ile Val Glu 245
250 255Tyr Ala Tyr Asn Asp Lys Ala Ile Leu Glu
Gln Arg Asn Met Leu Thr 260 265
270Glu Glu Leu Tyr Gly Asn Thr Phe Gln Leu Tyr Lys Ser Ala Asp His
275 280 285Arg Thr Leu Asp Lys Val Leu
Glu Val Gln Pro Glu Lys Leu Glu Leu 290 295
300Ile Met Asp Glu Met Lys Gln Ile Leu Thr Pro Met Ala Gln Lys
Glu305 310 315 320Ala Val
Ile Lys His Ser Leu Val His Lys Val Phe Leu Asp Phe Phe
325 330 335Thr Tyr Ala Pro Pro Lys Leu
Arg Ser Glu Met Ile Glu Ala Ile Arg 340 345
350Glu Ala Val Val Tyr Leu Ala His Thr His Asp Gly Ala Arg
Val Ala 355 360 365Met His Cys Leu
Trp His Gly Thr Pro Lys Asp Arg Lys Val Ile Val 370
375 380Lys Thr Met Lys Thr Tyr Val Glu Lys Val Ala Asn
Gly Gln Tyr Ser385 390 395
400His Leu Val Leu Leu Ala Ala Phe Asp Cys Ile Asp Asp Thr Lys Leu
405 410 415Val Lys Gln Ile Ile
Ile Ser Glu Ile Ile Ser Ser Leu Pro Ser Ile 420
425 430Val Asn Asp Lys Tyr Gly Arg Lys Val Leu Leu Tyr
Leu Leu Ser Pro 435 440 445Arg Asp
Pro Ala His Thr Val Arg Glu Ile Ile Glu Val Leu Gln Lys 450
455 460Gly Asp Gly Asn Ala His Ser Lys Lys Asp Thr
Glu Val Arg Arg Arg465 470 475
480Glu Leu Leu Glu Ser Ile Ser Pro Ala Leu Leu Ser Tyr Leu Gln Glu
485 490 495His Ala Gln Glu
Val Val Leu Asp Lys Ser Ala Cys Val Leu Val Ser 500
505 510Asp Ile Leu Gly Ser Ala Thr Gly Asp Val Gln
Pro Thr Met Asn Ala 515 520 525Ile
Ala Ser Leu Ala Ala Thr Gly Leu His Pro Gly Gly Lys Asp Gly 530
535 540Glu Leu His Ile Ala Glu His Pro Ala Gly
His Leu Val Leu Lys Trp545 550 555
560Leu Ile Glu Gln Asp Lys Lys Met Lys Glu Asn Gly Arg Glu Gly
Cys 565 570 575Phe Ala Lys
Thr Leu Val Glu His Val Gly Met Lys Asn Leu Lys Ser 580
585 590Trp Ala Ser Val Asn Arg Gly Ala Ile Ile
Leu Ser Ser Leu Leu Gln 595 600
605Ser Cys Asp Leu Glu Val Ala Asn Lys Val Lys Ala Ala Leu Lys Ser 610
615 620Leu Ile Pro Thr Leu Glu Lys Thr
Lys Ser Thr Ser Lys Gly Ile Glu625 630
635 640Ile Leu Leu Glu Lys Leu Ser Thr
64561947DNAHomo sapiens 6atggaagtta aagggaaaaa gcaattcaca ggaaagagta
caaagacagc acaagaaaaa 60aacagatttc ataaaaatag tgattctggt tcttcaaaga
catttccaac aaggaaagtt 120gctaaagaag gtggacctaa agtcacatct aggaactttg
agaaaagtat cacaaaactt 180gggaaaaagg gtgtaaagca gttcaagaat aagcagcaag
gggacaaatc accaaagaac 240aaattccagc cggcaaataa attcaacaag aagagaaaat
tccagccaga tggtagaagc 300gatgaatcag cagccaagaa gcccaaatgg gatgacttca
aaaagaagaa gaaagaactg 360aagcaaagca gacaactcag tgataaaacc aactatgaca
ttgttgttcg ggcaaagcag 420atgtgggaga ttttaagaag aaaagactgt gacaaagaaa
aaagagtaaa gttaatgagt 480gatttgcaga agttgattca agggaaaatt aaaactattg
catttgcaca cgattcaact 540cgtgtgatcc agtgttacat tcagtatggt aatgaagaac
agagaaaaca ggcttttgaa 600gaattgcgag atgatttggt tgagttaagt aaagccaaat
attcgagaaa tattgttaag 660aaatttctca tgtatggaag taaaccacag attgcagaga
taatcagaag ttttaaaggc 720cacgtgagga agatgctgcg gcatgcggaa gcatcagcca
tcgtggagta cgcatacaat 780gacaaagcca ttttggagca gaggaacatg ctgacggaag
agctctatgg gaacacattt 840cagctttaca agtcagcaga tcaccgaact ctggacaaag
tgttagaggt acagccagaa 900aaattagaac ttattatgga tgaaatgaaa cagattctaa
ctccaatggc ccaaaaggaa 960gctgtgatta agcactcatt ggtgcataaa gtattcttgg
acttttttac ctatgcaccc 1020cccaaactca gatcagaaat gattgaagcc atccgcgaag
cggtggtcta cctggcacac 1080acacacgatg gcgccagagt ggccatgcac tgcctgtggc
atggcacgcc caaggacagg 1140aaagtgattg tgaaaacaat gaagacttat gttgaaaagg
tggctaatgg ccaatactcc 1200catttggttt tactggcggc atttgattgt attgatgata
ctaagcttgt gaagcagata 1260atcatatcag aaattatcag ttcattgcct agcatagtaa
atgacaaata tggaaggaag 1320gtcctattgt acttactaag ccccagagat cctgcacata
cagtacgaga aatcattgaa 1380gttctgcaaa aaggagatgg aaatgcacac agtaagaaag
atacagaggt ccgcagacgg 1440gagctcctag aatccatttc tccagctttg ttaagctacc
tgcaagaaca cgcccaagaa 1500gtggtgctag ataagtctgc gtgtgtgttg gtgtctgaca
ttctgggatc tgccactgga 1560gacgttcagc ctaccatgaa tgccatcgcc agcttggcag
caacaggact gcatcctggt 1620ggcaaggacg gagagcttca cattgcagaa catcctgcag
gacatctagt tctgaagtgg 1680ttaatagagc aagataaaaa gatgaaagaa aatgggagag
aaggttgttt tgcaaaaaca 1740cttgtagagc atgttggtat gaagaacctg aagtcctggg
ctagtgtaaa tcgaggtgcc 1800attattcttt ctagcctcct ccagagttgt gacctggaag
ttgcaaacaa agtcaaagct 1860gcactgaaaa gcttgattcc tacattggaa aaaaccaaaa
gcaccagcaa aggaatagaa 1920attctacttg aaaaactgag cacatag
19477512PRTHomo sapiens 7Met Ala Ile Leu Ser Leu
Arg Ala Pro Gly Pro Trp Gln Ala Met Gln1 5
10 15Val Trp Ala Asp Arg Thr Leu Leu Thr Pro His Thr
Gly Val Thr Ser 20 25 30Gln
Val Leu Gly Val Ala Ala Ala Val Met Thr Pro Leu Pro Gly Gly 35
40 45His Ala Ala Gly Arg Thr Arg Glu Ala
Arg Trp Asp Ala Met Glu Tyr 50 55
60Asp Glu Lys Leu Ala Arg Phe Arg Gln Ala His Leu Asn Pro Phe Asn65
70 75 80Lys Gln Ser Gly Pro
Arg Gln His Glu Gln Gly Pro Gly Glu Glu Val 85
90 95Pro Asp Val Thr Pro Glu Glu Ala Leu Pro Glu
Leu Pro Pro Gly Glu 100 105
110Pro Glu Phe Arg Cys Pro Glu Arg Val Met Asp Leu Gly Leu Ser Glu
115 120 125Asp His Phe Ser Arg Pro Val
Gly Leu Phe Leu Ala Ser Asp Val Gln 130 135
140Gln Leu Arg Gln Ala Ile Glu Glu Cys Lys Gln Val Ile Leu Glu
Leu145 150 155 160Pro Glu
Gln Ser Glu Lys Gln Lys Asp Ala Val Val Arg Leu Ile His
165 170 175Leu Arg Leu Lys Leu Gln Glu
Leu Lys Asp Pro Asn Glu Asp Glu Pro 180 185
190Asn Ile Arg Val Leu Leu Glu His Arg Phe Tyr Lys Glu Lys
Ser Lys 195 200 205Ser Val Lys Gln
Thr Cys Asp Lys Cys Asn Thr Ile Ile Trp Gly Leu 210
215 220Ile Gln Thr Trp Tyr Thr Cys Thr Gly Cys Tyr Tyr
Arg Cys His Ser225 230 235
240Lys Cys Leu Asn Leu Ile Ser Lys Pro Cys Val Ser Ser Lys Val Ser
245 250 255His Gln Ala Glu Tyr
Glu Leu Asn Ile Cys Pro Glu Thr Gly Leu Asp 260
265 270Ser Gln Asp Tyr Arg Cys Ala Glu Cys Arg Ala Pro
Ile Ser Leu Arg 275 280 285Gly Val
Pro Ser Glu Ala Arg Gln Cys Asp Tyr Thr Gly Gln Tyr Tyr 290
295 300Cys Ser His Cys His Trp Asn Asp Leu Ala Val
Ile Pro Ala Arg Val305 310 315
320Val His Asn Trp Asp Phe Glu Pro Arg Lys Val Ser Arg Cys Ser Met
325 330 335Arg Tyr Leu Ala
Leu Met Val Ser Arg Pro Val Leu Arg Leu Arg Glu 340
345 350Ile Asn Pro Leu Leu Phe Ser Tyr Val Glu Glu
Leu Val Glu Ile Arg 355 360 365Lys
Leu Arg Gln Asp Ile Leu Leu Met Lys Pro Tyr Phe Ile Thr Cys 370
375 380Arg Glu Ala Met Glu Ala Arg Leu Leu Leu
Gln Leu Gln Asp Arg Gln385 390 395
400His Phe Val Glu Asn Asp Glu Met Tyr Ser Val Gln Asp Leu Leu
Asp 405 410 415Val His Ala
Gly Arg Leu Gly Cys Ser Leu Thr Glu Ile His Thr Leu 420
425 430Phe Ala Lys His Ile Lys Leu Asp Cys Glu
Arg Cys Gln Ala Lys Gly 435 440
445Phe Val Cys Glu Leu Cys Arg Glu Gly Asp Val Leu Phe Pro Phe Asp 450
455 460Ser His Thr Ser Val Cys Ala Asp
Cys Ser Ala Val Phe His Arg Asp465 470
475 480Cys Tyr Tyr Asp Asn Ser Thr Thr Cys Pro Lys Cys
Ala Arg Leu Ser 485 490
495Leu Arg Lys Gln Ser Leu Phe Gln Glu Pro Gly Pro Asp Val Glu Ala
500 505 51081539DNAHomo sapiens
8gaatggccat cctgtccctg cgagcccctg ggccctggca ggcgatgcag gtatgggcag
60acaggacgct gttgactccg cacaccggcg tgacttctca ggttctcggg gtggcagctg
120cagtgatgac accgcttcct ggtggtcacg ccgcgggcag gacgcgggag gccaggtggg
180atgctatgga atatgatgag aagctggccc gtttccggca ggcccacctc aaccccttca
240acaagcagtc tgggccgaga cagcatgagc agggccctgg ggaggaggtc ccggacgtca
300ctcctgaaga ggccctgcct gagctgcccc ctggggagcc ggaattccgc tgccctgaac
360gcgtgatgga tctcggcctg tctgaggacc acttctcccg ccctgtgggt ctgttcctgg
420cctctgacgt ccagcagctg cggcaggcga tcgaggagtg caagcaggtg attctggagc
480tgcccgagca gtcggagaag cagaaggatg ccgtggtgcg actcatccac ctccggctga
540agctccagga gctgaaggac cccaatgagg atgagccaaa catccgagtg ctccttgagc
600accgctttta caaggagaag agcaagagcg tcaagcagac ctgtgacaag tgtaacacca
660tcatctgggg gctcattcag acctggtaca cctgcacagg gtgttattac cgctgtcaca
720gtaagtgctt gaacctcatc tccaagccct gtgtgagctc caaagtcagc caccaagctg
780aatacgaact gaacatctgc cctgagacag ggctggacag ccaggattac cgctgtgccg
840agtgccgggc gcccatctct ctgcggggtg tgcccagtga ggccaggcag tgcgactaca
900ccggccagta ctactgcagc cactgccact ggaacgacct ggctgtgatc cctgcacgcg
960ttgtacacaa ctgggacttt gagcctcgaa aggtttctcg ctgcagcatg cgctacctgg
1020cgctgatggt gtctcggccc gtactcaggc tccgggagat caaccctctg ctgttcagct
1080acgtggagga gctggtggag attcgcaagc tgcgccagga catcctgctc atgaagccgt
1140acttcatcac ctgcagggag gccatggagg ctcgtctgct gctgcagctc caggatcggc
1200agcattttgt ggagaacgac gagatgtact ctgtccagga cctcctggac gtgcatgccg
1260gccgcctggg ctgctcgctc accgagatcc acacgctctt cgccaagcac atcaagctgg
1320actgcgagcg gtgccaggcc aagggcttcg tgtgtgagct ctgcagagag ggcgacgtgc
1380tgttcccgtt cgacagccac acgtctgtgt gcgccgactg ctccgcggtc ttccacaggg
1440actgctacta cgacaactcc accacttgtc ccaagtgtgc ccggctcagc ctgaggaagc
1500agtcgctctt ccaggagcca ggtcccgatg tggaggcct
153991614PRTHomo sapiens 9Met Ser Thr Pro Asp Pro Pro Leu Gly Gly Thr Pro
Arg Pro Gly Pro1 5 10
15Ser Pro Gly Pro Gly Pro Ser Pro Gly Ala Met Leu Gly Pro Ser Pro
20 25 30Gly Pro Ser Pro Gly Ser Ala
His Ser Met Met Gly Pro Ser Pro Gly 35 40
45Pro Pro Ser Ala Gly His Pro Ile Pro Thr Gln Gly Pro Gly Gly
Tyr 50 55 60Pro Gln Asp Asn Met His
Gln Met His Lys Pro Met Glu Ser Met His65 70
75 80Glu Lys Gly Met Ser Asp Asp Pro Arg Tyr Asn
Gln Met Lys Gly Met 85 90
95Gly Met Arg Ser Gly Gly His Ala Gly Met Gly Pro Pro Pro Ser Pro
100 105 110Met Asp Gln His Ser Gln Gly
Tyr Pro Ser Pro Leu Gly Gly Ser Glu 115 120
125His Ala Ser Ser Pro Val Pro Ala Ser Gly Pro Ser Ser Gly Pro
Gln 130 135 140Met Ser Ser Gly Pro Gly
Gly Ala Pro Leu Asp Gly Ala Asp Pro Gln145 150
155 160Ala Leu Gly Gln Gln Asn Arg Gly Pro Thr Pro
Phe Asn Gln Asn Gln 165 170
175Leu His Gln Leu Arg Ala Gln Ile Met Ala Tyr Lys Met Leu Ala Arg
180 185 190Gly Gln Pro Leu Pro Asp
His Leu Gln Met Ala Val Gln Gly Lys Arg 195 200
205Pro Met Pro Gly Met Gln Gln Gln Met Pro Thr Leu Pro Pro
Pro Ser 210 215 220Val Ser Ala Thr Gly
Pro Gly Pro Gly Pro Gly Pro Gly Pro Gly Pro225 230
235 240Gly Pro Gly Pro Ala Pro Pro Asn Tyr Ser
Arg Pro His Gly Met Gly 245 250
255Gly Pro Asn Met Pro Pro Pro Gly Pro Ser Gly Val Pro Pro Gly Met
260 265 270Pro Gly Gln Pro Pro
Gly Gly Pro Pro Lys Pro Trp Pro Glu Gly Pro 275
280 285Met Ala Asn Ala Ala Ala Pro Thr Ser Thr Pro Gln
Lys Leu Ile Pro 290 295 300Pro Gln Pro
Thr Gly Arg Pro Ser Pro Ala Pro Pro Ala Val Pro Pro305
310 315 320Ala Ala Ser Pro Val Met Pro
Pro Gln Thr Gln Ser Pro Gly Gln Pro 325
330 335Ala Gln Pro Ala Pro Met Val Pro Leu His Gln Lys
Gln Ser Arg Ile 340 345 350Thr
Pro Ile Gln Lys Pro Arg Gly Leu Asp Pro Val Glu Ile Leu Gln 355
360 365Glu Arg Glu Tyr Arg Leu Gln Ala Arg
Ile Ala His Arg Ile Gln Glu 370 375
380Leu Glu Asn Leu Pro Gly Ser Leu Ala Gly Asp Leu Arg Thr Lys Ala385
390 395 400Thr Ile Glu Leu
Lys Ala Leu Arg Leu Leu Asn Phe Gln Arg Gln Leu 405
410 415Arg Gln Glu Val Val Val Cys Met Arg Arg
Asp Thr Ala Leu Glu Thr 420 425
430Ala Leu Asn Ala Lys Ala Tyr Lys Arg Ser Lys Arg Gln Ser Leu Arg
435 440 445Glu Ala Arg Ile Thr Glu Lys
Leu Glu Lys Gln Gln Lys Ile Glu Gln 450 455
460Glu Arg Lys Arg Arg Gln Lys His Gln Glu Tyr Leu Asn Ser Ile
Leu465 470 475 480Gln His
Ala Lys Asp Phe Lys Glu Tyr His Arg Ser Val Thr Gly Lys
485 490 495Ile Gln Lys Leu Thr Lys Ala
Val Ala Thr Tyr His Ala Asn Thr Glu 500 505
510Arg Glu Gln Lys Lys Glu Asn Glu Arg Ile Glu Lys Glu Arg
Met Arg 515 520 525Arg Leu Met Ala
Glu Asp Glu Glu Gly Tyr Arg Lys Leu Ile Asp Gln 530
535 540Lys Lys Asp Lys Arg Leu Ala Tyr Leu Leu Gln Gln
Thr Asp Glu Tyr545 550 555
560Val Ala Asn Leu Thr Glu Leu Val Arg Gln His Lys Ala Ala Gln Val
565 570 575Ala Lys Glu Lys Lys
Lys Lys Lys Lys Lys Lys Lys Ala Glu Asn Ala 580
585 590Glu Gly Gln Thr Pro Ala Ile Gly Pro Asp Gly Glu
Pro Leu Asp Glu 595 600 605Thr Ser
Gln Met Ser Asp Leu Pro Val Lys Val Ile His Val Glu Ser 610
615 620Gly Lys Ile Leu Thr Gly Thr Asp Ala Pro Lys
Ala Gly Gln Leu Glu625 630 635
640Ala Trp Leu Glu Met Asn Pro Gly Tyr Glu Val Ala Pro Arg Ser Asp
645 650 655Ser Glu Glu Ser
Gly Ser Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu 660
665 670Gln Pro Gln Ala Ala Gln Pro Pro Thr Leu Pro
Val Glu Glu Lys Lys 675 680 685Lys
Ile Pro Asp Pro Asp Ser Asp Asp Val Ser Glu Val Asp Ala Arg 690
695 700His Ile Ile Glu Asn Ala Lys Gln Asp Val
Asp Asp Glu Tyr Gly Val705 710 715
720Ser Gln Ala Leu Ala Arg Gly Leu Gln Ser Tyr Tyr Ala Val Ala
His 725 730 735Ala Val Thr
Glu Arg Val Asp Lys Gln Ser Ala Leu Met Val Asn Gly 740
745 750Val Leu Lys Gln Tyr Gln Ile Lys Gly Leu
Glu Trp Leu Val Ser Leu 755 760
765Tyr Asn Asn Asn Leu Asn Gly Ile Leu Ala Asp Glu Met Gly Leu Gly 770
775 780Lys Thr Ile Gln Thr Ile Ala Leu
Ile Thr Tyr Leu Met Glu His Lys785 790
795 800Arg Ile Asn Gly Pro Phe Leu Ile Ile Val Pro Leu
Ser Thr Leu Ser 805 810
815Asn Trp Ala Tyr Glu Phe Asp Lys Trp Ala Pro Ser Val Val Lys Val
820 825 830Ser Tyr Lys Gly Ser Pro
Ala Ala Arg Arg Ala Phe Val Pro Gln Leu 835 840
845Arg Ser Gly Lys Phe Asn Val Leu Leu Thr Thr Tyr Glu Tyr
Ile Ile 850 855 860Lys Asp Lys His Ile
Leu Ala Lys Ile Arg Trp Lys Tyr Met Ile Val865 870
875 880Asp Glu Gly His Arg Met Lys Asn His His
Cys Lys Leu Thr Gln Val 885 890
895Leu Asn Thr His Tyr Val Ala Pro Arg Arg Leu Leu Leu Thr Gly Thr
900 905 910Pro Leu Gln Asn Lys
Leu Pro Glu Leu Trp Ala Leu Leu Asn Phe Leu 915
920 925Leu Pro Thr Ile Phe Lys Ser Cys Ser Thr Phe Glu
Gln Trp Phe Asn 930 935 940Ala Pro Phe
Ala Met Thr Gly Glu Lys Val Asp Leu Asn Glu Glu Glu945
950 955 960Thr Ile Leu Ile Ile Arg Arg
Leu His Lys Val Leu Arg Pro Phe Leu 965
970 975Leu Arg Arg Leu Lys Lys Glu Val Glu Ala Gln Leu
Pro Glu Lys Val 980 985 990Glu
Tyr Val Ile Lys Cys Asp Met Ser Ala Leu Gln Arg Val Leu Tyr 995
1000 1005Arg His Met Gln Ala Lys Gly Val Leu
Leu Thr Asp Gly Ser Glu Lys 1010 1015
1020Asp Lys Lys Gly Lys Gly Gly Thr Lys Thr Leu Met Asn Thr Ile Met1025
1030 1035 1040Gln Leu Arg Lys
Ile Cys Asn His Pro Tyr Met Phe Gln His Ile Glu 1045
1050 1055Glu Ser Phe Ser Glu His Leu Gly Phe Thr
Gly Gly Ile Val Gln Gly 1060 1065
1070Leu Asp Leu Tyr Arg Ala Ser Gly Lys Phe Glu Leu Leu Asp Arg Ile
1075 1080 1085Leu Pro Lys Leu Arg Ala Thr
Asn His Lys Val Leu Leu Phe Cys Gln 1090 1095
1100Met Thr Ser Leu Met Thr Ile Met Glu Asp Tyr Phe Ala Tyr Arg
Gly1105 1110 1115 1120Phe
Lys Tyr Leu Arg Leu Asp Gly Thr Thr Lys Ala Glu Asp Arg Gly
1125 1130 1135Met Leu Leu Lys Thr Phe Asn
Glu Pro Gly Ser Glu Tyr Phe Ile Phe 1140 1145
1150Leu Leu Ser Thr Arg Ala Gly Gly Leu Gly Leu Asn Leu Gln
Ser Ala 1155 1160 1165Asp Thr Val
Ile Ile Phe Asp Ser Asp Trp Asn Pro His Gln Asp Leu 1170
1175 1180Gln Ala Gln Asp Arg Ala His Arg Ile Gly Gln Gln
Asn Glu Val Arg1185 1190 1195
1200Val Leu Arg Leu Cys Thr Val Asn Ser Val Glu Glu Lys Ile Leu Ala
1205 1210 1215Ala Ala Lys Tyr Lys
Leu Asn Val Asp Gln Lys Val Ile Gln Ala Gly 1220
1225 1230Met Phe Asp Gln Lys Ser Ser Ser His Glu Arg Arg
Ala Phe Leu Gln 1235 1240 1245Ala
Ile Leu Glu His Glu Glu Gln Asp Glu Glu Glu Asp Glu Val Pro 1250
1255 1260Asp Asp Glu Thr Val Asn Gln Met Ile Ala
Arg His Glu Glu Glu Phe1265 1270 1275
1280Asp Leu Phe Met Arg Met Asp Leu Asp Arg Arg Arg Glu Glu Ala
Arg 1285 1290 1295Asn Pro
Lys Arg Lys Pro Arg Leu Met Glu Glu Asp Glu Leu Pro Ser 1300
1305 1310Trp Ile Ile Lys Asp Asp Ala Glu Val
Glu Arg Leu Thr Cys Glu Glu 1315 1320
1325Glu Glu Glu Lys Met Phe Gly Arg Gly Ser Arg His Arg Lys Glu Val
1330 1335 1340Asp Tyr Ser Asp Ser Leu Thr
Glu Lys Gln Trp Leu Lys Ala Ile Glu1345 1350
1355 1360Glu Gly Thr Leu Glu Glu Ile Glu Glu Glu Val Arg
Gln Lys Lys Ser 1365 1370
1375Ser Arg Lys Arg Lys Arg Asp Ser Asp Ala Gly Ser Ser Thr Pro Thr
1380 1385 1390Thr Ser Thr Arg Ser Arg
Asp Lys Asp Asp Glu Ser Lys Lys Gln Lys 1395 1400
1405Lys Arg Gly Arg Pro Pro Ala Glu Lys Leu Ser Pro Asn Pro
Pro Asn 1410 1415 1420Leu Thr Lys Lys
Met Lys Lys Ile Val Asp Ala Val Ile Lys Tyr Lys1425 1430
1435 1440Asp Ser Ser Ser Gly Arg Gln Leu Ser
Glu Val Phe Ile Gln Leu Pro 1445 1450
1455Ser Arg Lys Glu Leu Pro Glu Tyr Tyr Glu Leu Ile Arg Lys Pro
Val 1460 1465 1470Asp Phe Lys
Lys Ile Lys Glu Arg Ile Arg Asn His Lys Tyr Arg Ser 1475
1480 1485Leu Asn Asp Leu Glu Lys Asp Val Met Leu Leu
Cys Gln Asn Ala Gln 1490 1495 1500Thr
Phe Asn Leu Glu Gly Ser Leu Ile Tyr Glu Asp Ser Ile Val Leu1505
1510 1515 1520Gln Ser Val Phe Thr Ser
Val Arg Gln Lys Ile Glu Lys Glu Asp Asp 1525
1530 1535Ser Glu Gly Glu Glu Ser Glu Glu Glu Glu Glu Gly
Glu Glu Glu Gly 1540 1545
1550Ser Glu Ser Glu Ser Arg Ser Val Lys Val Lys Ile Lys Leu Gly Arg
1555 1560 1565Lys Glu Lys Ala Gln Asp Arg
Leu Lys Gly Gly Arg Arg Arg Pro Ser 1570 1575
1580Arg Gly Ser Arg Ala Lys Pro Val Val Ser Asp Asp Asp Ser Glu
Glu1585 1590 1595 1600Glu
Gln Glu Glu Asp Arg Ser Gly Ser Gly Ser Glu Glu Asp 1605
1610104845DNAHomo sapiens 10atgtccactc cagacccacc cctgggcgga
actcctcggc caggtccttc cccgggccct 60ggcccttccc ctggagccat gctgggccct
agcccgggtc cctcgccggg ctccgcccac 120agcatgatgg ggcccagccc agggccgccc
tcagcaggac accccatccc cacccagggg 180cctggagggt accctcagga caacatgcac
cagatgcaca agcccatgga gtccatgcat 240gagaagggca tgtcggacga cccgcgctac
aaccagatga aaggaatggg gatgcggtca 300gggggccatg ctgggatggg gcccccgccc
agccccatgg accagcactc ccaaggttac 360ccctcgcccc tgggtggctc tgagcatgcc
tctagtccag ttccagccag tggcccgtct 420tcggggcccc agatgtcttc cgggccagga
ggtgccccgc tggatggtgc tgacccccag 480gccttggggc agcagaaccg gggcccaacc
ccatttaacc agaaccagct gcaccagctc 540agagctcaga tcatggccta caagatgctg
gccagggggc agcccctccc cgaccacctg 600cagatggcgg tgcagggcaa gcggccgatg
cccgggatgc agcagcagat gccaacgcta 660cctccaccct cggtgtccgc aacaggaccc
ggccctggcc ctggccctgg ccccggcccg 720ggtcccggcc cggcacctcc aaattacagc
aggcctcatg gtatgggagg gcccaacatg 780cctcccccag gaccctcggg cgtgcccccc
gggatgccag gccagcctcc tggagggcct 840cccaagccct ggcctgaagg acccatggcg
aatgctgctg cccccacgag cacccctcag 900aagctgattc ccccgcagcc aacgggccgc
ccttcccccg cgccccctgc cgtcccaccc 960gccgcctcgc ccgtgatgcc accgcagacc
cagtcccccg ggcagccggc ccagcccgcg 1020cccatggtgc cactgcacca gaagcagagc
cgcatcaccc ccatccagaa gccgcggggc 1080ctcgaccctg tggagatcct gcaggagcgc
gagtacaggc tgcaggctcg catcgcacac 1140cgaattcagg aacttgaaaa ccttcccggg
tccctggccg gggatttgcg aaccaaagcg 1200accattgagc tcaaggccct caggctgctg
aacttccaga ggcagctgcg ccaggaggtg 1260gtggtgtgca tgcggaggga cacagcgctg
gagacagccc tcaatgctaa ggcctacaag 1320cgcagcaagc gccagtccct gcgcgaggcc
cgcatcactg agaagctgga gaagcagcag 1380aagatcgagc aggagcgcaa gcgccggcag
aagcaccagg aatacctcaa tagcattctc 1440cagcatgcca aggatttcaa ggaatatcac
agatccgtca caggcaaaat ccagaagctg 1500accaaggcag tggccacgta ccatgccaac
acggagcggg agcagaagaa agagaacgag 1560cggatcgaga aggagcgcat gcggaggctc
atggctgaag atgaggaggg gtaccgcaag 1620ctcatcgacc agaagaagga caagcgcctg
gcctacctct tgcagcagac agacgagtac 1680gtggctaacc tcacggagct ggtgcggcag
cacaaggctg cccaggtcgc caaggagaaa 1740aagaagaaaa agaaaaagaa gaaggcagaa
aatgcagaag gacagacgcc tgccattggg 1800ccggatggcg agcctctgga cgagaccagc
cagatgagcg acctcccggt gaaggtgatc 1860cacgtggaga gtgggaagat cctcacaggc
acagatgccc ccaaagccgg gcagctggag 1920gcctggctcg agatgaaccc ggggtatgaa
gtagctccga ggtctgatag tgaagaaagt 1980ggctcagaag aagaggaaga ggaggaggag
gaagagcagc cgcaggcagc acagcctccc 2040accctgcccg tggaggagaa gaagaagatt
ccagatccag acagcgatga cgtctctgag 2100gtggacgcgc ggcacatcat tgagaatgcc
aagcaagatg tcgatgatga atatggcgtg 2160tcccaggccc ttgcacgtgg cctgcagtcc
tactatgccg tggcccatgc tgtcactgag 2220agagtggaca agcagtcagc gcttatggtc
aatggtgtcc tcaaacagta ccagatcaaa 2280ggtttggagt ggctggtgtc cctgtacaac
aacaacctga acggcatcct ggccgacgag 2340atgggcctgg ggaagaccat ccagaccatc
gcgctcatca cgtacctcat ggagcacaaa 2400cgcatcaatg ggcccttcct catcatcgtg
cctctctcaa cgctgtccaa ctgggcgtac 2460gagtttgaca agtgggcccc ctccgtggtg
aaggtgtctt acaagggatc cccagcagca 2520agacgggcct ttgtccccca gctccggagt
gggaagttca acgtcttgct gacgacgtac 2580gagtacatca tcaaagacaa gcacatcctc
gccaagatcc gttggaagta catgattgtg 2640gacgaaggtc accgcatgaa gaaccaccac
tgcaagctga cgcaggtgct caacacgcac 2700tatgtggcac cccgccgcct gctgctgacg
ggcacaccgc tgcagaacaa gcttcccgag 2760ctctgggcgc tgctcaactt cctgctgccc
accatcttca agagctgcag caccttcgag 2820cagtggttta acgcaccctt tgccatgacc
ggggaaaagg tggacctgaa tgaggaggaa 2880accattctca tcatccggcg tctccacaaa
gtgctgcggc ccttcttgct ccgacgactc 2940aagaaggaag tcgaggccca gttgcccgaa
aaggtggagt acgtcatcaa gtgcgacatg 3000tctgcgctgc agcgagtgct ctaccgccac
atgcaggcca agggcgtgct gctgactgat 3060ggctccgaga aggacaagaa gggcaaaggc
ggcaccaaga ccctgatgaa caccatcatg 3120cagctgcgga agatctgcaa ccacccctac
atgttccagc acatcgagga gtccttttcc 3180gagcacttgg ggttcactgg cggcattgtc
caagggctgg acctgtaccg agcctcgggt 3240aaatttgagc ttcttgatag aattcttccc
aaactccgag caaccaacca caaagtgctg 3300ctgttctgcc aaatgacctc cctcatgacc
atcatggaag attactttgc gtatcgcggc 3360tttaaatacc tcaggcttga tggaaccacg
aaggcggagg accggggcat gctgctgaaa 3420accttcaacg agcccggctc tgagtacttc
atcttcctgc tcagcacccg ggctgggggg 3480ctcggcctga acctccagtc ggcagacact
gtgatcattt ttgacagcga ctggaatcct 3540caccaggacc tgcaagcgca ggaccgagcc
caccgcatcg ggcagcagaa cgaggtgcgt 3600gtgctccgcc tctgcaccgt caacagcgtg
gaggagaaga tcctagctgc agccaagtac 3660aagctcaacg tggaccagaa ggtgatccag
gccggcatgt tcgaccagaa gtcctccagc 3720catgagcggc gcgccttcct gcaggccatc
ctggagcacg aggagcagga tgaggaggaa 3780gacgaggtgc ccgacgacga gaccgtcaac
cagatgatcg cccggcacga ggaggagttt 3840gatctgttca tgcgcatgga cctggaccgc
aggcgcgagg aggcccgcaa ccccaagcgg 3900aagccgcgcc tcatggagga ggacgagctc
ccctcgtgga tcatcaagga cgacgcggag 3960gtggagcggc tgacctgtga ggaggaggag
gagaagatgt tcggccgtgg ctcccgccac 4020cgcaaggagg tggactacag cgactcactg
acggagaagc agtggctcaa ggccatcgag 4080gagggcacgc tggaggagat cgaagaggag
gtccggcaga agaaatcatc acggaagcgc 4140aagcgagaca gcgacgccgg ctcctccacc
ccgaccacca gcacccgcag ccgcgacaag 4200gacgacgaga gcaagaagca gaagaagcgc
gggcggccgc ctgccgagaa actctcccct 4260aacccaccca acctcaccaa gaagatgaag
aagattgtgg atgccgtgat caagtacaag 4320gacagcagca gtggacgtca gctcagcgag
gtcttcatcc agctgccctc gcgaaaggag 4380ctgcccgagt actacgagct catccgcaag
cccgtggact tcaagaagat aaaggagcgc 4440attcgcaacc acaagtaccg cagcctcaac
gacctagaga aggacgtcat gctcctgtgc 4500cagaacgcac agaccttcaa cctggagggc
tccctgatct atgaagactc catcgtcttg 4560cagtcggtct tcaccagcgt gcggcagaaa
atcgagaagg aggatgacag tgaaggcgag 4620gagagtgagg aggaggaaga gggcgaggag
gaaggctccg aatccgaatc tcggtccgtc 4680aaagtgaaga tcaagcttgg ccggaaggag
aaggcacagg accggctgaa gggcggccgg 4740cggcggccga gccgagggtc ccgagccaag
ccggtcgtga gtgacgatga cagtgaggag 4800gaacaagagg aggaccgctc aggaagtggc
agcgaagaag actga 484511454PRTHomo sapiens 11Met Ser Ala
Gly Gly Pro Cys Pro Ala Ala Ala Gly Gly Gly Pro Gly1 5
10 15Gly Ala Ser Cys Ser Val Gly Ala Pro
Gly Gly Val Ser Met Phe Arg 20 25
30Trp Leu Glu Val Leu Glu Lys Glu Phe Asp Lys Ala Phe Val Asp Val
35 40 45Asp Leu Leu Leu Gly Glu Ile
Asp Pro Asp Gln Ala Asp Ile Thr Tyr 50 55
60Glu Gly Arg Gln Lys Met Thr Ser Leu Ser Ser Cys Phe Ala Gln Leu65
70 75 80Cys His Lys Ala
Gln Ser Val Ser Gln Ile Asn His Lys Leu Glu Ala 85
90 95Gln Leu Val Asp Leu Lys Ser Glu Leu Thr
Glu Thr Gln Ala Glu Lys 100 105
110Val Val Leu Glu Lys Glu Val His Asp Gln Leu Leu Gln Leu His Ser
115 120 125Ile Gln Leu Gln Leu His Ala
Lys Thr Gly Gln Ser Ala Asp Ser Gly 130 135
140Thr Ile Lys Ala Lys Leu Glu Arg Glu Leu Glu Ala Asn Lys Lys
Glu145 150 155 160Lys Met
Lys Glu Ala Gln Leu Glu Ala Glu Val Lys Leu Leu Arg Lys
165 170 175Glu Asn Glu Ala Leu Arg Arg
His Ile Ala Val Leu Gln Ala Glu Val 180 185
190Tyr Gly Ala Arg Leu Ala Ala Lys Tyr Leu Asp Lys Glu Leu
Ala Gly 195 200 205Arg Val Gln Gln
Ile Gln Leu Leu Gly Arg Asp Met Lys Gly Pro Ala 210
215 220His Asp Lys Leu Trp Asn Gln Leu Glu Ala Glu Ile
His Leu His Arg225 230 235
240His Lys Thr Val Ile Arg Ala Cys Arg Gly Arg Asn Asp Leu Lys Arg
245 250 255Pro Met Gln Ala Pro
Pro Gly His Asp Gln Asp Ser Leu Lys Lys Ser 260
265 270Gln Gly Val Gly Pro Ile Arg Lys Val Leu Leu Leu
Lys Glu Asp His 275 280 285Glu Gly
Leu Gly Ile Ser Ile Thr Gly Gly Lys Glu His Gly Val Pro 290
295 300Ile Leu Ile Ser Glu Ile His Pro Gly Gln Pro
Ala Asp Arg Cys Gly305 310 315
320Gly Leu His Val Gly Asp Ala Ile Leu Ala Val Asn Gly Val Asn Leu
325 330 335Arg Asp Thr Lys
His Lys Glu Ala Val Thr Ile Leu Ser Gln Gln Arg 340
345 350Gly Glu Ile Glu Phe Glu Val Val Tyr Val Ala
Pro Glu Val Asp Ser 355 360 365Asp
Asp Glu Asn Val Glu Tyr Glu Asp Glu Ser Gly His Arg Tyr Arg 370
375 380Leu Tyr Leu Asp Glu Leu Glu Gly Gly Gly
Asn Pro Gly Ala Ser Cys385 390 395
400Lys Asp Thr Ser Gly Glu Ile Lys Val Leu Gln Gly Phe Asn Lys
Lys 405 410 415Ala Val Thr
Asp Thr His Glu Asn Gly Asp Leu Gly Thr Ala Ser Glu 420
425 430Thr Pro Leu Asp Asp Gly Ala Ser Lys Leu
Asp Asp Leu His Thr Leu 435 440
445Tyr His Lys Lys Ser Tyr 450121365DNAHomo sapiens 12ccatgtcggc
gggcggtcca tgcccagcag cagccggagg gggcccaggg ggcgcctcct 60gctccgtggg
ggcccctggc ggggtatcca tgttccggtg gctggaggtg ctggagaagg 120agttcgacaa
agcttttgtg gatgtggatc tgctcctggg agagatcgat ccagaccaag 180cggacatcac
ttatgagggg cgacagaaga tgaccagcct gagctcctgc tttgcacagc 240tttgccacaa
agcccagtct gtgtctcaaa tcaaccacaa gctggaggca cagttggtgg 300atctgaaatc
tgaactgaca gaaacccaag cagagaaagt tgttttggag aaagaagtac 360atgatcagct
tttacagctg cactctattc agctgcagct tcatgctaaa actggtcaaa 420gtgctgactc
tggtaccatt aaggcaaaat tggaaagaga gcttgaggca aacaaaaaag 480aaaaaatgaa
agaagcacaa cttgaagctg aagtgaaatt gttgagaaaa gagaatgaag 540cccttcgtag
acatatagct gttctccagg ctgaagtata tggggcgaga ctagctgcca 600agtacttgga
taaggaactg gcaggaaggg tccaacagat acaattgcta ggacgagata 660tgaagggacc
tgctcatgat aagctttgga accaattaga agctgaaata catttgcatc 720gtcacaaaac
tgtgatccga gcctgcagag gacgtaatga cttgaaacga ccaatgcaag 780caccaccagg
ccatgatcaa gattccctaa agaaaagcca aggtgttggt ccaattagaa 840aagttctcct
ccttaaggaa gatcatgaag gccttggcat ttcaattaca ggtgggaaag 900aacatggtgt
tccaatcctc atctctgaga tccatccggg gcaacctgct gatagatgcg 960gagggctgca
cgttggggat gctattttgg cagtcaacgg agttaaccta agggacacaa 1020agcataaaga
agctgtaact attctttctc agcagagagg agagattgaa tttgaagtag 1080tttatgtggc
tcctgaagtg gattctgatg atgaaaacgt agagtatgaa gatgagagtg 1140gacatcgtta
ccgtttgtac cttgatgagt tagaaggagg tggtaaccct ggtgctagtt 1200gcaaagacac
aagtggggaa atcaaagtat tacaaggatt taataagaag gcagtaactg 1260acacacatga
aaatggagac ctgggcactg caagtgaaac tccgctagat gacggtgctt 1320caaaattaga
tgatctgcac actctgtatc ataaaaaatc ttatt
1365132517PRTHomo sapiens 13Met Val Gly Glu Arg His Ala Gly Asp Leu Met
Val Pro Leu Gly Pro1 5 10
15Arg Leu Gln Ala Tyr Pro Glu Glu Leu Ile Arg Gln Arg Pro Gly His
20 25 30Asp Gly His Pro Glu Tyr Leu
Ile Arg Trp Ser Val Leu Lys Cys Gly 35 40
45Glu Val Gly Lys Val Gly Val Glu Glu Gly Lys Ala Glu His Ile
Leu 50 55 60Met Trp Leu Ser Ala Pro
Glu Val Tyr Ala Asn Cys Pro Gly Leu Leu65 70
75 80Gly Glu Arg Ala Leu Ser Lys Gly Leu Gln His
Glu Pro Ala Gly Val 85 90
95Ser Gly Ser Phe Pro Arg Asp Pro Gly Gly Leu Asp Glu Val Ala Met
100 105 110Gly Glu Met Glu Ala Asp
Val Gln Ala Leu Val Arg Arg Ala Ala Arg 115 120
125Gln Leu Ala Glu Ser Gly Thr Pro Ser Leu Thr Ala Ala Val
Leu His 130 135 140Thr Ile His Val Leu
Ser Ala Tyr Ala Ser Ile Gly Pro Leu Thr Gly145 150
155 160Val Phe Arg Glu Thr Gly Ala Leu Asp Leu
Leu Met His Met Leu Cys 165 170
175Asn Pro Glu Pro Gln Ile Arg Arg Ser Ala Gly Lys Met Leu Gln Ala
180 185 190Leu Ala Ala His Asp
Ala Gly Ser Arg Ala His Val Leu Leu Ser Leu 195
200 205Ser Gln Gln Asp Gly Ile Glu Gln His Met Asp Phe
Asp Ser Arg Tyr 210 215 220Thr Leu Leu
Glu Leu Phe Ala Glu Thr Thr Ser Ser Glu Glu His Cys225
230 235 240Met Ala Phe Glu Gly Ile His
Leu Pro Gln Ile Pro Gly Lys Leu Leu 245
250 255Phe Ser Leu Val Lys Arg Tyr Leu Cys Val Thr Ser
Leu Leu Asp Gln 260 265 270Leu
Asn Ser Ser Pro Glu Leu Gly Ala Gly Asp Gln Ser Ser Pro Cys 275
280 285Ala Thr Arg Glu Lys Ser Arg Gly Gln
Arg Glu Leu Glu Phe Ser Met 290 295
300Ala Val Gly Asn Leu Ile Ser Glu Leu Val Arg Ser Met Gly Trp Ala305
310 315 320Arg Asn Leu Ser
Glu Gln Gly Met Ser Pro Pro Arg Pro Thr Arg Ser 325
330 335Ile Phe Gln Pro Tyr Ile Ser Gly Pro Ser
Leu Leu Leu Pro Thr Ile 340 345
350Val Thr Thr Pro Arg Arg Gln Gly Trp Val Phe Arg Gln Arg Ser Glu
355 360 365Phe Ser Ser Arg Ser Gly Tyr
Gly Glu Tyr Val Gln Gln Thr Leu Gln 370 375
380Pro Gly Met Arg Val Arg Met Leu Asp Asp Tyr Glu Glu Ile Ser
Ala385 390 395 400Gly Asp
Glu Gly Glu Phe Arg Gln Ser Asn Asn Gly Ile Pro Pro Val
405 410 415Gln Val Phe Trp Gln Ser Thr
Gly Arg Thr Tyr Trp Val His Trp His 420 425
430Met Leu Glu Ile Leu Gly Pro Glu Glu Ala Thr Glu Asp Lys
Ala Ser 435 440 445Ala Ala Val Glu
Lys Gly Ala Gly Ala Thr Val Leu Gly Thr Ala Phe 450
455 460Pro Ser Trp Asp Trp Asn Pro Met Asp Gly Leu Tyr
Pro Leu Pro Tyr465 470 475
480Leu Gln Pro Glu Pro Gln Lys Asn Glu Arg Val Gly Tyr Leu Thr Gln
485 490 495Ala Glu Trp Trp Glu
Leu Leu Phe Phe Ile Lys Lys Leu Asp Leu Cys 500
505 510Glu Gln Gln Pro Ile Phe Gln Asn Leu Trp Lys Asn
Leu Asp Glu Thr 515 520 525Leu Gly
Glu Lys Ala Leu Gly Glu Ile Ser Val Ser Val Glu Met Ala 530
535 540Glu Ser Leu Leu Gln Val Leu Ser Ser Arg Phe
Glu Gly Ser Thr Leu545 550 555
560Asn Asp Leu Leu Asn Ser Gln Ile Tyr Thr Lys Tyr Gly Leu Leu Ser
565 570 575Asn Glu Pro Ser
Ser Ser Ser Thr Ser Arg Asn His Ser Cys Thr Pro 580
585 590Asp Pro Glu Glu Glu Ser Lys Ser Glu Ala Ser
Phe Ser Glu Glu Glu 595 600 605Thr
Glu Ser Leu Lys Ala Lys Ala Glu Ala Pro Lys Thr Glu Ala Glu 610
615 620Pro Thr Lys Thr Arg Thr Glu Thr Pro Met
Ala Gln Ser Asp Ser Gln625 630 635
640Leu Phe Asn Gln Leu Leu Val Thr Glu Gly Met Thr Leu Pro Thr
Glu 645 650 655Met Lys Glu
Ala Ala Ser Glu Met Ala Arg Ala Leu Arg Gly Pro Gly 660
665 670Pro Arg Ser Ser Leu Asp Gln His Val Ala
Ala Val Val Ala Thr Val 675 680
685Gln Ile Ser Ser Leu Asp Thr Asn Leu Gln Leu Ser Gly Leu Ser Ala 690
695 700Leu Ser Gln Ala Val Glu Glu Val
Thr Glu Arg Asp His Pro Leu Val705 710
715 720Arg Pro Asp Arg Ser Leu Arg Glu Lys Leu Val Lys
Met Leu Val Glu 725 730
735Leu Leu Thr Asn Gln Val Gly Glu Lys Met Val Val Val Gln Ala Leu
740 745 750Arg Leu Leu Tyr Leu Leu
Met Thr Lys His Glu Trp Arg Pro Leu Phe 755 760
765Ala Arg Glu Gly Gly Ile Tyr Ala Val Leu Val Cys Met Gln
Glu Tyr 770 775 780Lys Thr Ser Val Leu
Val Gln Gln Ala Gly Leu Ala Ala Leu Lys Met785 790
795 800Leu Ala Val Ala Ser Ser Ser Glu Ile Pro
Thr Phe Val Thr Gly Arg 805 810
815Asp Ser Ile His Ser Leu Phe Asp Ala Gln Met Thr Arg Glu Ile Phe
820 825 830Ala Ser Ile Asp Ser
Ala Thr Arg Pro Gly Ser Glu Ser Leu Leu Leu 835
840 845Thr Val Pro Ala Ala Val Ile Leu Met Leu Asn Thr
Glu Gly Cys Ser 850 855 860Ser Ala Ala
Arg Asn Gly Leu Leu Leu Leu Asn Leu Leu Leu Cys Asn865
870 875 880His His Thr Leu Gly Asp Gln
Ile Ile Thr Gln Glu Leu Arg Asp Thr 885
890 895Leu Phe Arg His Ser Gly Ile Ala Pro Arg Thr Glu
Pro Met Pro Thr 900 905 910Thr
Arg Thr Ile Leu Met Met Leu Leu Asn Arg Tyr Ser Glu Pro Pro 915
920 925Gly Ser Pro Glu Arg Ala Ala Leu Glu
Thr Pro Ile Ile Gln Gly Gln 930 935
940Asp Gly Ser Pro Glu Leu Leu Ile Arg Ser Leu Val Gly Gly Pro Ser945
950 955 960Ala Glu Leu Leu
Leu Asp Leu Glu Arg Val Leu Cys Arg Glu Gly Ser 965
970 975Pro Gly Gly Ala Val Arg Pro Leu Leu Lys
Arg Leu Gln Gln Glu Thr 980 985
990Gln Pro Phe Leu Leu Leu Leu Arg Thr Leu Asp Ala Pro Gly Pro Asn
995 1000 1005Lys Thr Leu Leu Leu Ser Val
Leu Arg Val Ile Thr Arg Leu Leu Asp 1010 1015
1020Phe Pro Glu Ala Met Val Leu Pro Trp His Glu Val Leu Glu Pro
Cys1025 1030 1035 1040Leu
Asn Cys Leu Ser Gly Pro Ser Ser Asp Ser Glu Ile Val Gln Glu
1045 1050 1055Leu Thr Cys Phe Leu His Arg
Leu Ala Ser Met His Lys Asp Tyr Ala 1060 1065
1070Val Val Leu Cys Cys Leu Gly Ala Lys Glu Ile Leu Ser Lys
Val Leu 1075 1080 1085Asp Lys His
Ser Ala Gln Leu Leu Leu Gly Cys Glu Leu Arg Asp Leu 1090
1095 1100Val Thr Glu Cys Glu Lys Tyr Ala Gln Leu Tyr Ser
Asn Leu Thr Ser1105 1110 1115
1120Ser Ile Leu Ala Gly Cys Ile Gln Met Val Leu Gly Gln Ile Glu Asp
1125 1130 1135His Arg Arg Thr His
Gln Pro Ile Asn Ile Pro Phe Phe Asp Val Phe 1140
1145 1150Leu Arg His Leu Cys Gln Gly Ser Ser Val Glu Val
Lys Glu Asp Lys 1155 1160 1165Cys
Trp Glu Lys Val Glu Val Ser Ser Asn Pro His Arg Ala Ser Lys 1170
1175 1180Leu Thr Asp His Asn Pro Lys Thr Tyr Trp
Glu Ser Asn Gly Ser Thr1185 1190 1195
1200Gly Ser His Tyr Ile Thr Leu His Met His Arg Gly Val Leu Val
Arg 1205 1210 1215Gln Leu
Thr Leu Leu Val Ala Ser Glu Asp Ser Ser Tyr Met Pro Ala 1220
1225 1230Arg Val Val Val Phe Gly Gly Asp Ser
Thr Ser Cys Ile Gly Thr Glu 1235 1240
1245Leu Asn Thr Val Asn Val Met Pro Ser Ala Ser Arg Val Ile Leu Leu
1250 1255 1260Glu Asn Leu Asn Arg Phe Trp
Pro Ile Ile Gln Ile Arg Ile Lys Arg1265 1270
1275 1280Cys Gln Gln Gly Gly Ile Asp Thr Arg Val Arg Gly
Val Glu Val Leu 1285 1290
1295Gly Pro Lys Pro Thr Phe Trp Pro Leu Phe Arg Glu Gln Leu Cys Arg
1300 1305 1310Arg Thr Cys Leu Phe Tyr
Thr Ile Arg Ala Gln Ala Trp Ser Arg Asp 1315 1320
1325Ile Ala Glu Asp His Arg Arg Leu Leu Gln Leu Cys Pro Arg
Leu Asn 1330 1335 1340Arg Val Leu Arg
His Glu Gln Asn Phe Ala Asp Arg Phe Leu Pro Asp1345 1350
1355 1360Asp Glu Ala Ala Gln Ala Leu Gly Lys
Thr Cys Trp Glu Ala Leu Val 1365 1370
1375Ser Pro Leu Val Gln Asn Ile Thr Ser Pro Asp Ala Glu Gly Val
Ser 1380 1385 1390Ala Leu Gly
Trp Leu Leu Asp Gln Tyr Leu Glu Gln Arg Glu Thr Ser 1395
1400 1405Arg Asn Pro Leu Ser Arg Ala Ala Ser Phe Ala
Ser Arg Val Arg Arg 1410 1415 1420Leu
Cys His Leu Leu Val His Val Glu Pro Pro Pro Gly Pro Ser Pro1425
1430 1435 1440Glu Pro Ser Thr Arg Pro
Phe Ser Lys Asn Ser Lys Gly Arg Asp Arg 1445
1450 1455Ser Pro Ala Pro Ser Pro Val Leu Pro Ser Ser Ser
Leu Arg Asn Ile 1460 1465
1470Thr Gln Cys Trp Leu Ser Val Val Gln Glu Gln Val Ser Arg Phe Leu
1475 1480 1485Ala Ala Ala Trp Arg Ala Pro
Asp Phe Val Pro Arg Tyr Cys Lys Leu 1490 1495
1500Tyr Glu His Leu Gln Arg Ala Gly Ser Glu Leu Phe Gly Pro Arg
Ala1505 1510 1515 1520Ala
Phe Met Leu Ala Leu Arg Ser Gly Phe Ser Gly Ala Leu Leu Gln
1525 1530 1535Gln Ser Phe Leu Thr Ala Ala
His Met Ser Glu Gln Phe Ala Arg Tyr 1540 1545
1550Ile Asp Gln Gln Ile Gln Gly Gly Leu Ile Gly Gly Ala Pro
Gly Val 1555 1560 1565Glu Met Leu
Gly Gln Leu Gln Arg His Leu Glu Pro Ile Met Val Leu 1570
1575 1580Ser Gly Leu Glu Leu Ala Thr Thr Phe Glu His Phe
Tyr Gln His Tyr1585 1590 1595
1600Met Ala Asp Arg Leu Leu Ser Phe Gly Ser Ser Trp Leu Glu Gly Ala
1605 1610 1615Val Leu Glu Gln Ile
Gly Leu Cys Phe Pro Asn Arg Leu Pro Gln Leu 1620
1625 1630Met Leu Gln Ser Leu Ser Thr Ser Glu Glu Leu Gln
Arg Gln Phe His 1635 1640 1645Leu
Phe Gln Leu Gln Arg Leu Asp Lys Leu Phe Leu Glu Gln Glu Asp 1650
1655 1660Glu Glu Glu Lys Arg Leu Glu Glu Glu Glu
Glu Glu Glu Glu Glu Glu1665 1670 1675
1680Glu Ala Glu Lys Glu Leu Phe Ile Glu Asp Pro Ser Pro Ala Ile
Ser 1685 1690 1695Ile Leu
Val Leu Ser Pro Arg Cys Trp Pro Val Ser Pro Leu Cys Tyr 1700
1705 1710Leu Tyr His Pro Arg Lys Cys Leu Pro
Thr Glu Phe Cys Asp Ala Leu 1715 1720
1725Asp Arg Phe Ser Ser Phe Tyr Ser Gln Ser Gln Asn His Pro Val Leu
1730 1735 1740Asp Met Gly Pro His Arg Arg
Leu Gln Trp Thr Trp Leu Gly Arg Ala1745 1750
1755 1760Glu Leu Gln Phe Gly Lys Gln Ile Leu His Val Ser
Thr Val Gln Met 1765 1770
1775Trp Leu Leu Leu Lys Phe Asn Gln Thr Glu Glu Val Ser Val Glu Thr
1780 1785 1790Leu Leu Lys Asp Ser Asp
Leu Ser Pro Glu Leu Leu Leu Gln Ala Leu 1795 1800
1805Val Pro Leu Thr Ser Gly Asn Gly Pro Leu Thr Leu His Glu
Gly Gln 1810 1815 1820Asp Phe Pro His
Gly Gly Val Leu Arg Leu His Glu Pro Gly Pro Gln1825 1830
1835 1840Arg Ser Gly Glu Ala Leu Trp Leu Ile
Pro Pro Gln Ala Tyr Leu Asn 1845 1850
1855Val Glu Lys Asp Glu Gly Arg Thr Leu Glu Gln Lys Arg Asn Leu
Leu 1860 1865 1870Ser Cys Leu
Leu Val Arg Ile Leu Lys Ala His Gly Glu Lys Gly Leu 1875
1880 1885His Ile Asp Gln Leu Val Cys Leu Val Leu Glu
Ala Trp Gln Lys Gly 1890 1895 1900Pro
Asn Pro Pro Gly Thr Leu Gly His Thr Val Ala Gly Gly Val Ala1905
1910 1915 1920Cys Thr Ser Thr Asp Val
Leu Ser Cys Ile Leu His Leu Leu Gly Gln 1925
1930 1935Gly Tyr Val Lys Arg Arg Asp Asp Arg Pro Gln Ile
Leu Met Tyr Ala 1940 1945
1950Ala Pro Glu Pro Met Gly Pro Cys Arg Gly Gln Ala Asp Val Pro Phe
1955 1960 1965Cys Gly Ser Gln Ser Glu Thr
Ser Lys Pro Ser Pro Glu Ala Val Ala 1970 1975
1980Thr Leu Ala Ser Leu Gln Leu Pro Ala Gly Arg Thr Met Ser Pro
Gln1985 1990 1995 2000Glu
Val Glu Gly Leu Met Lys Gln Thr Val Arg Gln Val Gln Glu Thr
2005 2010 2015Leu Asn Leu Glu Pro Asp Val
Ala Gln His Leu Leu Ala His Ser His 2020 2025
2030Trp Gly Ala Glu Gln Leu Leu Gln Ser Tyr Ser Glu Asp Pro
Glu Pro 2035 2040 2045Leu Leu Leu
Ala Ala Gly Leu Cys Val His Gln Ala Gln Ala Val Pro 2050
2055 2060Val Arg Pro Asp His Cys Pro Val Cys Val Ser Pro
Leu Gly Cys Asp2065 2070 2075
2080Asp Asp Leu Pro Ser Leu Cys Cys Met His Tyr Cys Cys Lys Ser Cys
2085 2090 2095Trp Asn Glu Tyr Leu
Thr Thr Arg Ile Glu Gln Asn Leu Val Leu Asn 2100
2105 2110Cys Thr Cys Pro Ile Ala Asp Cys Pro Ala Gln Pro
Thr Gly Ala Phe 2115 2120 2125Ile
Arg Ala Ile Val Ser Ser Pro Glu Val Ile Ser Lys Tyr Glu Lys 2130
2135 2140Ala Leu Leu Arg Gly Tyr Val Glu Ser Cys
Ser Asn Leu Thr Trp Cys2145 2150 2155
2160Thr Asn Pro Gln Gly Cys Asp Arg Ile Leu Cys Arg Gln Gly Leu
Gly 2165 2170 2175Cys Gly
Thr Thr Cys Ser Lys Cys Gly Trp Ala Ser Cys Phe Asn Cys 2180
2185 2190Ser Phe Pro Glu Ala His Tyr Pro Ala
Ser Cys Gly His Met Ser Gln 2195 2200
2205Trp Val Asp Asp Gly Gly Tyr Tyr Asp Gly Met Ser Val Glu Ala Gln
2210 2215 2220Ser Lys His Leu Ala Lys Leu
Ile Ser Lys Arg Cys Pro Ser Cys Gln2225 2230
2235 2240Ala Pro Ile Glu Lys Asn Glu Gly Cys Leu His Met
Thr Cys Ala Lys 2245 2250
2255Cys Asn His Gly Phe Cys Trp Arg Cys Leu Lys Ser Trp Lys Pro Asn
2260 2265 2270His Lys Asp Tyr Tyr Asn
Cys Ser Ala Met Val Ser Lys Ala Ala Arg 2275 2280
2285Gln Glu Lys Arg Phe Gln Asp Tyr Asn Glu Arg Cys Thr Phe
His His 2290 2295 2300Gln Ala Arg Glu
Phe Ala Val Asn Leu Arg Asn Arg Val Ser Ala Ile2305 2310
2315 2320His Glu Val Pro Pro Pro Arg Ser Phe
Thr Phe Leu Asn Asp Ala Cys 2325 2330
2335Gln Gly Leu Glu Gln Ala Arg Lys Val Leu Ala Tyr Ala Cys Val
Tyr 2340 2345 2350Ser Phe Tyr
Ser Gln Asp Ala Glu Tyr Met Asp Val Val Glu Gln Gln 2355
2360 2365Thr Glu Asn Leu Glu Leu His Thr Asn Ala Leu
Gln Ile Leu Leu Glu 2370 2375 2380Glu
Thr Leu Leu Arg Cys Arg Asp Leu Ala Ser Ser Leu Arg Leu Leu2385
2390 2395 2400Arg Ala Asp Cys Leu Ser
Thr Gly Met Glu Leu Leu Arg Arg Ile Gln 2405
2410 2415Glu Arg Leu Leu Ala Ile Leu Gln His Ser Ala Gln
Asp Phe Arg Val 2420 2425
2430Gly Leu Gln Ser Pro Ser Val Glu Ala Trp Glu Ala Lys Gly Pro Asn
2435 2440 2445Met Pro Gly Ser Gln Pro Gln
Ala Ser Ser Gly Pro Glu Ala Glu Glu 2450 2455
2460Glu Glu Glu Asp Asp Glu Asp Asp Val Pro Glu Trp Gln Gln Asp
Glu2465 2470 2475 2480Phe
Asp Glu Glu Leu Asp Asn Asp Ser Phe Ser Tyr Asp Glu Ser Glu
2485 2490 2495Asn Leu Asp Gln Glu Thr Phe
Phe Phe Gly Asp Glu Glu Glu Asp Glu 2500 2505
2510Asp Glu Ala Tyr Asp 2515147554DNAHomo sapiens
14atggtggggg aacggcatgc tggggacctc atggtgccct tagggcctcg gctgcaggca
60tatcctgaag aactcattcg acagaggcct gggcatgacg ggcatcctga atacctgatc
120cgatggagtg tcctgaagtg tggggaagtg ggcaaagtgg gtgtggaaga aggcaaagca
180gagcacatcc tcatgtggct gtcggctcct gaggtctacg ccaactgccc tgggctgtta
240ggtgagcggg cactatctaa gggacttcag cacgaaccag ctggggtttc aggaagcttt
300cctcgagatc caggaggcct ggatgaagtg gcaatgggag agatggaggc tgatgttcag
360gcgctggtac gcagggcggc caggcagctg gcagaaagtg ggaccccaag cctcacggcc
420gctgtgcttc acaccatcca cgtgctcagt gcctacgcca gcatcgggcc cctcactggt
480gtcttcaggg agacaggagc cctggacctg ctcatgcaca tgttatgcaa tcctgagcct
540cagatccgcc ggagtgcagg caaaatgctg caggctctgg cagcccacga tgctgggagt
600cgggctcacg tccttctatc actgagccag caagatggca tcgagcagca catggatttt
660gacagtcgct atacattgct ggagctgttt gcagaaacca catcctctga agaacactgc
720atggcctttg agggcattca tctgcctcag atcccaggaa agctgctttt ctccttggtg
780aagcgctacc tttgtgtcac gtccctcctg gatcagctga atagcagtcc agagctggga
840gctggagacc aaagctcccc atgtgccaca agagagaaaa gccggggaca gcgggaactg
900gagttcagca tggctgtggg caacctcatc tctgagcttg tgcggagcat gggctgggcc
960cggaacctca gcgaacaggg catgtcacct ccccggccaa cccggtccat ctttcagccc
1020tacatttcag gccccagcct tttactcccc accattgtca ccacccccag aagacaaggg
1080tgggtcttcc gccagcgctc tgaattctcc agccgtagtg gctatggaga atatgtgcag
1140cagacactcc agccagggat gcgagtgcgg atgctggatg attatgagga gatcagtgct
1200ggggacgagg gcgagttccg gcagagcaac aacggcattc cccctgtgca ggttttctgg
1260cagtcgacag gccgcactta ctgggtgcac tggcacatgc tggagatcct gggccctgag
1320gaagccactg aggataaggc ttcagcagct gtggagaagg gggcaggggc tactgtgttg
1380ggcacagcat ttccctcctg ggactggaat cctatggatg ggctgtaccc tttgccgtac
1440ctccagcccg aacctcagaa gaatgagaga gtgggatatc tgacccaggc tgaatggtgg
1500gagctgcttt tctttatcaa aaagttggac ttgtgtgagc agcagccaat tttccagaat
1560ctttggaaga acctggatga gaccctgggt gaaaaggccc taggtgagat ctctgtgtcc
1620gtggaaatgg ccgagagtct gctgcaggtt ctcagtagtc gatttgaggg cagcactctc
1680aatgacctgc tcaactccca gatctacacc aagtatgggc tgctgtctaa tgaaccaagc
1740agctcgtcta cttcacgaaa tcactcctgt accccagatc cagaagagga gtccaagtcg
1800gaggccagct tctcagagga agagactgag tccctcaaag caaaggccga ggcccctaag
1860acagaggccg agcccaccaa gacaaggacc gagaccccca tggcacagag tgattctcag
1920ctgtttaacc agcttctggt gactgagggg atgaccctgc ccactgagat gaaggaggca
1980gccagtgaaa tggccagagc cttgcggggt cccggtcctc gcagctccct ggatcagcat
2040gtggcagcgg tcgtggccac tgtgcagata tccagcttgg acacaaacct gcagctttca
2100gggctctctg ccctctctca ggctgtggag gaggtcactg agcgggacca ccctctggtc
2160cgtcctgaca gatcgctgag agagaagcta gtgaagatgc tggtggagct gctgaccaac
2220caggtgggag agaagatggt ggtcgtgcag gccctgcgcc tcctttacctg ctcatgacc
2280aagcacgagt ggcggccgct ctttgccagg gagggtggca tctatgctgt gctggtctgc
2340atgcaagaat ataagacttc tgtcttggtg cagcaggctg ggctggcggc actgaagatg
2400ctggccgtcg ccagctcctc ggagatcccc acttttgtta ctggccgaga ttctatccac
2460tctttgtttg atgctcagat gaccagagag atcttcgcca gcatcgactc agccacacgc
2520ccgggctctg agagcctgct cctcactgtc cctgcagccg tgatcctgat gctgaatact
2580gaggggtgct cttctgcagc gagaaatggc ttactcctgc tcaacctact tttgtgcaac
2640caccacactc tgggagacca gattataacc caagagctga gagacacgtt gtttaggcac
2700tcagggatag caccaagaac agaacctatg cctaccacac gcaccatcct catgatgctt
2760ctcaatcgct actcagagcc gccgggcagc cctgagcgtg cagcactaga gacccccatc
2820atccagggtc aggatgggtc ccctgagcta ctgattcgat ccctggttgg gggcccatct
2880gcagaactac tcctggactt ggagcgtgtg ctgtgccgtg agggcagccc cggaggtgcc
2940gtgaggcccc tcctcaagcg cctccagcag gagacccagc ctttcctcct gttgctgcgg
3000actctggatg ctccggggcc caacaagact ctgctgctgt ctgtgctgag ggtcataacc
3060cgactgctgg atttccctga ggcaatggtc ctcccctggc acgaggtctt ggagccctgc
3120ctcaactgcc tgagtggccc tagcagtgac tccgagattg ttcaggagct gacctgcttc
3180ctacatcgcc tggcctcgat gcataaggac tatgctgtgg tgctctgctg cctgggagca
3240aaagagatcc tctccaaagt cctggacaag cactcagctc agctgctgct gggctgtgag
3300cttcgggacc tggtgacaga gtgtgagaag tacgcacagc tctatagcaa cctcacctcc
3360agcatcctgg ccggctgcat tcagatggtg ctgggccaga tcgaagacca cagacgaacc
3420caccaaccca tcaatatccc cttctttgat gtgttcctca ggcatctctg ccagggctcc
3480agtgtggaag tgaaggagga caagtgctgg gagaaggtgg aggtgtcctc caacccgcac
3540cgagccagca agctgacgga ccacaacccc aagacctact gggagtccaa cggcagcacc
3600ggctcccact acatcaccct gcacatgcac cgtggtgttc ttgttaggca gctcactttg
3660ctggtggcca gtgaggactc aagctacatg ccagccaggg tggtggtgtt tgggggtgac
3720agcaccagct gcatcggcac tgagctcaac acggtgaatg tgatgccctc tgccagccgg
3780gtgatcctct tggagaacct gaaccgcttc tggcccatca tccagatccg cataaagcgc
3840tgccagcagg gcggcattga cacccgggtt cggggtgtgg aggtcctggg ccctaagccc
3900acattctggc cactgttccg ggagcagctg tgtcgccgaa catgtctctt ctacacaatt
3960cgggcacaag cctggagccg ggacatagca gaggaccacc ggcgcctcct ccagctctgt
4020cccagactga acagggtttt gcgccacgag cagaattttg ctgaccgctt cctccctgat
4080gatgaggccg cccaggcact gggcaagacc tgctgggagg ccctggtcag ccccctggtg
4140cagaacatca cctctcccga tgcggaaggc gtgagtgccc tgggatggct gctggatcag
4200tacttagaac agagagagac ctctcggaac cccttgagtc gagcagcgtc ctttgcttct
4260cgagttcgtc gcctttgcca cttgctggtg catgtggaac ctcctcctgg gccttctcct
4320gagccatcca ctcggccctt cagcaagaac agcaagggtc gggaccggag cccggcgcct
4380tcgccagtgc ttccaagcag cagcctgagg aacataaccc agtgctggct gagcgtggtg
4440caggagcagg tcagcagatt cctggctgca gcttggaggg ccccagactt tgtgcctcgt
4500tactgtaaac tctatgagca cttgcagaga gcaggctccg agctgtttgg gcctcgggca
4560gccttcatgc tggctctgcg cagtggcttc tctggcgcct tgctgcagca gtccttcctc
4620actgctgctc acatgagtga gcagtttgcc aggtacattg accaacagat ccagggtggc
4680ctgattggtg gagcccctgg agtggaaatg ctggggcagc ttcagcggca cctggaaccc
4740attatggtcc tttctggtct ggaactggcc acaacttttg agcacttcta tcagcattat
4800atggcggacc gtctcctgag ctttggttcg agctggctgg agggggctgt gctagagcag
4860attggcctct gttttcccaa ccgcctccca cagctgatgc tgcagagcct gagcacctct
4920gaggagctgc agcgccagtt ccacctcttc cagctccagc ggctcgacaa gttgttcttg
4980gagcaggaag atgaggagga aaagagacta gaggaagagg aggaggaaga ggaggaagag
5040gaagctgaga aagaattatt tatcgaagat ccaagtccag ccatttctat actggtcctg
5100tcaccacgct gctggcccgt ctccccactc tgctacctgt accatcccag aaagtgcctt
5160cccacagaat tctgtgatgc ccttgaccgt ttctccagtt tctacagcca gagtcagaac
5220catccagtcc tggacatggg accacatcgg cgactgcagt ggacgtggct gggccgggct
5280gagctgcagt ttgggaagca gatactgcat gtgtccaccg tgcagatgtg gctgctgctg
5340aaattcaatc agacagagga ggtgtcagta gagaccttgc tgaaggattc tgacctctcc
5400ccagagctgc tgctccaggc actcgtgccc ctcacctcag ggaatggccc tttgaccctg
5460catgagggcc aggactttcc acacgggggt gtgctgcggc ttcatgagcc tgggccccag
5520cgcagtgggg aggccctgtg gctgatacct ccccaggcat acctgaacgt agagaaggat
5580gaaggccgaa ccctggaaca gaagaggaat ctcttgagct gtcttcttgt tcgtattctc
5640aaagcccatg gggaaaaggg cctccacatt gatcagctgg tttgtctggt gctggaggcc
5700tggcagaagg gtccaaatcc tcctggaacc ctgggccaca ctgttgctgg gggtgtggcc
5760tgtaccagta cagatgtcct ctcttgcatc ctgcacctct taggccaggg ctacgtgaaa
5820cggcgtgatg accggcccca gatcctgatg tatgccgctc cagagcccat ggggccctgc
5880cggggtcagg cagatgtccc tttctgtggc agccagagcg aaacctccaa gcccagccca
5940gaagctgtgg ctaccctggc atctctacag ctgcctgcag gccgcaccat gagcccccag
6000gaagtagaag ggttgatgaa gcagacggtg cgtcaggtgc aggagacgct gaacttagag
6060ccagatgtcg ctcagcacct tttggctcat tcccactggg gcgctgaaca gctgctgcag
6120agctacagtg aggaccctga gccactgctg ctggcagctg ggctgtgcgt acaccaggct
6180caggctgtac ccgtacggcc tgaccactgc cccgtctgtg tgagccccct ggggtgtgac
6240gacgacctgc cctctctctg ctgcatgcac tattgctgta agtcttgctg gaatgagtac
6300ctgacaactc ggatcgagca gaaccttgtt ttgaattgca cctgccccat tgccgactgc
6360cccgcccagc ccaccggagc cttcattcgt gccatcgtct cctcgccaga ggtcatctcc
6420aagtatgaga aggcgctcct gcgtggctat gtggagagct gctccaacct gacctggtgc
6480accaaccccc agggctgcga ccgcatcctg tgccgccagg gcctgggctg tgggaccacc
6540tgctccaagt gtggctgggc ctcttgcttc aactgtagct tccctgaggc acactaccct
6600gctagctgtg gccatatgtc tcagtgggtc gacgacggtg gctactatga cggcatgagc
6660gtggaggcgc agagcaagca cctggccaag ctcatctcca agcgctgtcc cagctgtcag
6720gctcccatcg agaagaacga ggggtgcctg cacatgacct gtgccaaatg taaccatgga
6780ttctgctggc gctgcctcaa gtcctggaag ccaaatcaca aagactatta caactgctct
6840gccatggtaa gcaaggcagc tcgccaggag aagcggtttc aggactataa tgagaggtgc
6900actttccatc accaggcgcg ggagtttgct gtgaacttgc ggaaccgggt gtctgccatc
6960catgaagtgc ccccgcccag atccttcacc ttcctcaatg atgcctgcca gggactggag
7020caggctcgga aggtgctggc ctacgcctgc gtgtacagct tctacagcca ggacgcagag
7080tacatggatg tggtggagca gcagacagag aacctggagc tgcacaccaa tgccctgcag
7140atcctcctgg aggaaaccct gctgcggtgc agagacctgg cctcctccct gcgcctcctg
7200cgggccgact gcctcagcac gggcatggag ctgctccggc ggatccagga gaggctgctt
7260gccatcctgc agcattctgc ccaggatttc cgggttggtc ttcagagtcc atcagtagag
7320gcctgggagg caaaaggacc caacatgcct ggcagtcagc cccaggcctc ctcagggcca
7380gaggcagaag aggaggagga agacgatgag gatgatgtgc ccgagtggca gcaggatgag
7440tttgatgagg agctggacaa tgacagcttc tcctacgatg agtctgagaa cctggaccaa
7500gagactttct tctttggtga tgaggaagag gatgaagatg aggcctatga ctga
7554152048PRTHomo sapiens 15Met Leu Arg Val Ile Val Glu Ser Ala Ser Asn
Ile Pro Lys Thr Lys1 5 10
15Phe Gly Lys Pro Asp Pro Ile Val Ser Val Ile Phe Lys Asp Glu Lys
20 25 30Lys Lys Thr Lys Lys Val Asp
Asn Glu Leu Asn Pro Val Trp Asn Glu 35 40
45Ile Leu Glu Phe Asp Leu Arg Gly Ile Pro Leu Asp Phe Ser Ser
Ser 50 55 60Leu Gly Ile Ile Val Lys
Asp Phe Glu Thr Ile Gly Gln Asn Lys Leu65 70
75 80Ile Gly Thr Ala Thr Val Ala Leu Lys Asp Leu
Thr Gly Asp Gln Ser 85 90
95Arg Ser Leu Pro Tyr Lys Leu Ile Ser Leu Leu Asn Glu Lys Gly Gln
100 105 110Asp Thr Gly Ala Thr Ile
Asp Leu Val Ile Gly Tyr Asp Pro Pro Ser 115 120
125Ala Pro His Pro Asn Asp Leu Ser Gly Pro Ser Val Pro Gly
Met Gly 130 135 140Gly Asp Gly Glu Glu
Asp Glu Gly Asp Glu Asp Arg Leu Asp Asn Ala145 150
155 160Val Arg Gly Pro Gly Pro Lys Gly Pro Val
Gly Thr Val Ser Glu Ala 165 170
175Gln Leu Ala Arg Arg Leu Thr Lys Val Lys Asn Ser Arg Arg Met Leu
180 185 190Ser Asn Lys Pro Gln
Asp Phe Gln Ile Arg Val Arg Val Ile Glu Gly 195
200 205Arg Gln Leu Ser Gly Asn Asn Ile Arg Pro Val Val
Lys Val His Val 210 215 220Cys Gly Gln
Thr His Arg Thr Arg Ile Lys Arg Gly Asn Asn Pro Phe225
230 235 240Phe Asp Glu Leu Phe Phe Tyr
Asn Val Asn Met Thr Pro Ser Glu Leu 245
250 255Met Asp Glu Ile Ile Ser Ile Arg Val Tyr Asn Ser
His Ser Leu Arg 260 265 270Ala
Asp Cys Leu Met Gly Glu Phe Lys Ile Asp Val Gly Phe Val Tyr 275
280 285Asp Glu Pro Gly His Ala Val Met Arg
Lys Trp Leu Leu Leu Asn Asp 290 295
300Pro Glu Asp Thr Ser Ser Gly Ser Lys Gly Tyr Met Lys Val Ser Met305
310 315 320Phe Val Leu Gly
Thr Gly Asp Glu Pro Pro Pro Glu Arg Arg Asp Arg 325
330 335Asp Asn Asp Ser Asp Asp Val Glu Ser Asn
Leu Leu Leu Pro Ala Gly 340 345
350Ile Ala Leu Arg Trp Val Thr Phe Leu Leu Lys Ile Tyr Arg Ala Glu
355 360 365Asp Ile Pro Gln Met Asp Asp
Ala Phe Ser Gln Thr Val Lys Glu Ile 370 375
380Phe Gly Gly Asn Ala Asp Lys Lys Asn Leu Val Asp Pro Phe Val
Glu385 390 395 400Val Ser
Phe Ala Gly Lys Lys Val Cys Thr Asn Ile Ile Glu Lys Asn
405 410 415Ala Asn Pro Glu Trp Asn Gln
Val Val Asn Leu Gln Ile Lys Phe Pro 420 425
430Ser Val Cys Glu Lys Ile Lys Leu Thr Ile Tyr Asp Trp Asp
Arg Leu 435 440 445Thr Lys Asn Asp
Val Val Gly Thr Thr Tyr Leu His Leu Ser Lys Ile 450
455 460Ala Ala Ser Gly Gly Glu Val Glu Val Asn Thr Gly
Glu Thr Glu Val465 470 475
480Gly Phe Val Pro Thr Phe Gly Pro Cys Tyr Leu Asn Leu Tyr Gly Ser
485 490 495Pro Arg Glu Tyr Thr
Gly Phe Pro Asp Pro Tyr Asp Glu Leu Asn Thr 500
505 510Gly Lys Gly Glu Gly Val Ala Tyr Arg Gly Arg Ile
Leu Val Glu Leu 515 520 525Ala Thr
Phe Leu Glu Lys Thr Pro Pro Asp Lys Lys Leu Glu Pro Ile 530
535 540Ser Asn Asp Asp Leu Leu Val Val Glu Lys Tyr
Gln Arg Arg Arg Lys545 550 555
560Tyr Ser Leu Ser Ala Val Phe His Ser Ala Thr Met Leu Gln Asp Val
565 570 575Gly Glu Ala Ile
Gln Phe Glu Val Ser Ile Gly Asn Tyr Gly Asn Lys 580
585 590Phe Asp Thr Thr Cys Lys Pro Leu Ala Ser Thr
Thr Gln Tyr Ser Arg 595 600 605Ala
Val Phe Asp Gly Asn Tyr Tyr Tyr Tyr Leu Pro Trp Ala His Thr 610
615 620Lys Pro Val Val Thr Leu Thr Ser Tyr Trp
Glu Asp Ile Ser His Arg625 630 635
640Leu Asp Ala Val Asn Thr Leu Leu Ala Met Ala Glu Arg Leu Gln
Thr 645 650 655Asn Ile Glu
Ala Leu Lys Ser Gly Ile Gln Gly Lys Ile Pro Ala Asn 660
665 670Gln Leu Ala Glu Leu Trp Leu Lys Leu Ile
Asp Glu Val Ile Glu Asp 675 680
685Thr Arg Tyr Thr Leu Pro Leu Thr Glu Gly Lys Ala Asn Val Thr Val 690
695 700Leu Asp Thr Gln Ile Arg Lys Leu
Arg Ser Arg Ser Leu Ser Gln Ile705 710
715 720His Glu Ala Ala Val Arg Met Arg Ser Glu Ala Thr
Asp Val Lys Ser 725 730
735Thr Leu Ala Glu Ile Glu Asp Trp Leu Asp Lys Leu Met Gln Leu Thr
740 745 750Glu Glu Pro Gln Asn Ser
Met Pro Asp Ile Ile Ile Trp Met Ile Arg 755 760
765Gly Glu Lys Arg Leu Ala Tyr Ala Arg Ile Pro Ala His Gln
Val Leu 770 775 780Tyr Ser Thr Ser Gly
Glu Asn Ala Ser Gly Lys Tyr Cys Gly Lys Thr785 790
795 800Gln Thr Ile Phe Leu Lys Tyr Pro Gln Glu
Lys Asn Asn Gly Pro Lys 805 810
815Val Pro Val Glu Leu Arg Val Asn Ile Trp Leu Gly Leu Ser Ala Val
820 825 830Glu Lys Lys Phe Asn
Ser Phe Ala Glu Gly Thr Phe Thr Val Phe Ala 835
840 845Glu Met Tyr Glu Asn Gln Ala Leu Met Phe Gly Lys
Trp Gly Thr Ser 850 855 860Gly Leu Val
Gly Arg His Lys Phe Ser Asp Val Thr Gly Lys Ile Lys865
870 875 880Leu Lys Arg Glu Phe Phe Leu
Pro Pro Lys Gly Trp Glu Trp Glu Gly 885
890 895Glu Trp Ile Val Asp Pro Glu Arg Ser Leu Leu Thr
Glu Ala Asp Ala 900 905 910Gly
His Thr Glu Phe Thr Asp Glu Val Tyr Gln Asn Glu Ser Arg Tyr 915
920 925Pro Gly Gly Asp Trp Lys Pro Ala Glu
Asp Thr Tyr Thr Asp Ala Asn 930 935
940Gly Asp Lys Ala Ala Ser Pro Ser Glu Leu Thr Cys Pro Pro Gly Trp945
950 955 960Glu Trp Glu Asp
Asp Ala Trp Ser Tyr Asp Ile Asn Arg Ala Val Asp 965
970 975Glu Lys Gly Trp Glu Tyr Gly Ile Thr Ile
Pro Pro Asp His Lys Pro 980 985
990Lys Ser Trp Val Ala Ala Glu Lys Met Tyr His Thr His Arg Arg Arg
995 1000 1005Arg Leu Val Arg Lys Arg Lys
Lys Asp Leu Thr Gln Thr Ala Ser Ser 1010 1015
1020Thr Ala Arg Ala Met Glu Glu Leu Gln Asp Gln Glu Gly Trp Glu
Tyr1025 1030 1035 1040Ala
Ser Leu Ile Gly Trp Lys Phe His Trp Lys Gln Arg Ser Ser Asp
1045 1050 1055Thr Phe Arg Arg Arg Arg Trp
Arg Arg Lys Met Ala Pro Ser Glu Thr 1060 1065
1070His Gly Ala Ala Ala Ile Phe Lys Leu Glu Gly Ala Leu Gly
Ala Asp 1075 1080 1085Thr Thr Glu
Asp Gly Asp Glu Lys Ser Leu Glu Lys Gln Lys His Ser 1090
1095 1100Ala Thr Thr Val Phe Gly Ala Asn Thr Pro Ile Val
Ser Cys Asn Phe1105 1110 1115
1120Asp Arg Val Tyr Ile Tyr His Leu Arg Cys Tyr Val Tyr Gln Ala Arg
1125 1130 1135Asn Leu Leu Ala Leu
Asp Lys Asp Ser Phe Ser Asp Pro Tyr Ala His 1140
1145 1150Ile Cys Phe Leu His Arg Ser Lys Thr Thr Glu Ile
Ile His Ser Thr 1155 1160 1165Leu
Asn Pro Thr Trp Asp Gln Thr Ile Ile Phe Asp Glu Val Glu Ile 1170
1175 1180Tyr Gly Glu Pro Gln Thr Val Leu Gln Asn
Pro Pro Lys Val Ile Met1185 1190 1195
1200Glu Leu Phe Asp Asn Asp Gln Val Gly Lys Asp Glu Phe Leu Gly
Arg 1205 1210 1215Ser Ile
Phe Ser Pro Val Val Lys Leu Asn Ser Glu Met Asp Ile Thr 1220
1225 1230Pro Lys Leu Leu Trp His Pro Val Met
Asn Gly Asp Lys Ala Cys Gly 1235 1240
1245Asp Val Leu Val Thr Ala Glu Leu Ile Leu Arg Gly Lys Asp Gly Ser
1250 1255 1260Asn Leu Pro Ile Leu Pro Pro
Gln Arg Ala Pro Asn Leu Tyr Met Val1265 1270
1275 1280Pro Gln Gly Ile Arg Pro Val Val Gln Leu Thr Ala
Ile Glu Ile Leu 1285 1290
1295Ala Trp Gly Leu Arg Asn Met Lys Asn Phe Gln Met Ala Ser Ile Thr
1300 1305 1310Ser Pro Ser Leu Val Val
Glu Cys Gly Gly Glu Arg Val Glu Ser Val 1315 1320
1325Val Ile Lys Asn Leu Lys Lys Thr Pro Asn Phe Pro Ser Ser
Val Leu 1330 1335 1340Phe Met Lys Val
Phe Leu Pro Lys Glu Glu Leu Tyr Met Pro Pro Leu1345 1350
1355 1360Val Ile Lys Val Ile Asp His Arg Gln
Phe Gly Arg Lys Pro Val Val 1365 1370
1375Gly Gln Cys Thr Ile Glu Arg Leu Asp Arg Phe Arg Cys Asp Pro
Tyr 1380 1385 1390Ala Gly Lys
Glu Asp Ile Val Pro Gln Leu Lys Ala Ser Leu Leu Ser 1395
1400 1405Ala Pro Pro Cys Arg Asp Ile Val Ile Glu Met
Glu Asp Thr Lys Pro 1410 1415 1420Leu
Leu Ala Ser Lys Leu Thr Glu Lys Glu Glu Glu Ile Val Asp Trp1425
1430 1435 1440Trp Ser Lys Phe Tyr Ala
Ser Ser Gly Glu His Glu Lys Cys Gly Gln 1445
1450 1455Tyr Ile Gln Lys Gly Tyr Ser Lys Leu Lys Ile Tyr
Asn Cys Glu Leu 1460 1465
1470Glu Asn Val Ala Glu Phe Glu Gly Leu Thr Asp Phe Ser Asp Thr Phe
1475 1480 1485Lys Leu Tyr Arg Gly Lys Ser
Asp Glu Asn Glu Asp Pro Ser Val Val 1490 1495
1500Gly Glu Phe Lys Gly Ser Phe Arg Ile Tyr Pro Leu Pro Asp Asp
Pro1505 1510 1515 1520Ser
Val Pro Ala Pro Pro Arg Gln Phe Arg Glu Leu Pro Asp Ser Val
1525 1530 1535Pro Gln Glu Cys Thr Val Arg
Ile Tyr Ile Val Arg Gly Leu Glu Leu 1540 1545
1550Gln Pro Gln Asp Asn Asn Gly Leu Cys Asp Pro Tyr Ile Lys
Ile Thr 1555 1560 1565Leu Gly Lys
Lys Val Ile Glu Asp Arg Asp His Tyr Ile Pro Asn Thr 1570
1575 1580Leu Asn Pro Val Phe Gly Arg Met Tyr Glu Leu Ser
Cys Tyr Leu Pro1585 1590 1595
1600Gln Glu Lys Asp Leu Lys Ile Ser Val Tyr Asp Tyr Asp Thr Phe Thr
1605 1610 1615Arg Asp Glu Lys Val
Gly Glu Thr Ile Ile Asp Leu Glu Asn Arg Phe 1620
1625 1630Leu Ser Arg Phe Gly Ser His Cys Gly Ile Pro Glu
Glu Tyr Cys Val 1635 1640 1645Ser
Gly Val Asn Thr Trp Arg Asp Gln Leu Arg Pro Thr Gln Leu Leu 1650
1655 1660Gln Asn Val Ala Arg Phe Lys Gly Phe Pro
Gln Pro Ile Leu Ser Glu1665 1670 1675
1680Asp Gly Ser Arg Ile Arg Tyr Gly Gly Arg Asp Tyr Ser Leu Asp
Glu 1685 1690 1695Phe Glu
Ala Asn Lys Ile Leu His Gln His Leu Gly Ala Pro Glu Glu 1700
1705 1710Arg Leu Ala Leu His Ile Leu Arg Thr
Gln Gly Leu Val Pro Glu His 1715 1720
1725Val Glu Thr Arg Thr Leu His Ser Thr Phe Gln Pro Asn Ile Ser Gln
1730 1735 1740Gly Lys Leu Gln Met Trp Val
Asp Val Phe Pro Lys Ser Leu Gly Pro1745 1750
1755 1760Pro Gly Pro Pro Phe Asn Ile Thr Pro Arg Lys Ala
Lys Lys Tyr Tyr 1765 1770
1775Leu Arg Val Ile Ile Trp Asn Thr Lys Asp Val Ile Leu Asp Glu Lys
1780 1785 1790Ser Ile Thr Gly Glu Glu
Met Ser Asp Ile Tyr Val Lys Gly Trp Ile 1795 1800
1805Pro Gly Asn Glu Glu Asn Lys Gln Lys Thr Asp Val His Tyr
Arg Ser 1810 1815 1820Leu Asp Gly Glu
Gly Asn Phe Asn Trp Arg Phe Val Phe Pro Phe Asp1825 1830
1835 1840Tyr Leu Pro Ala Glu Gln Leu Cys Ile
Val Ala Lys Lys Glu His Phe 1845 1850
1855Trp Ser Ile Asp Gln Thr Glu Phe Arg Ile Pro Pro Arg Leu Ile
Ile 1860 1865 1870Gln Ile Trp
Asp Asn Asp Lys Phe Ser Leu Asp Asp Tyr Leu Gly Phe 1875
1880 1885Leu Glu Leu Asp Leu Arg His Thr Ile Ile Pro
Ala Lys Ser Pro Glu 1890 1895 1900Lys
Cys Arg Leu Asp Met Ile Pro Asp Leu Lys Ala Met Asn Pro Leu1905
1910 1915 1920Lys Ala Lys Thr Ala Ser
Leu Phe Glu Gln Lys Ser Met Lys Gly Trp 1925
1930 1935Trp Pro Cys Tyr Ala Glu Lys Asp Gly Ala Arg Val
Met Ala Gly Lys 1940 1945
1950Val Glu Met Thr Leu Glu Ile Leu Asn Glu Lys Glu Ala Asp Glu Arg
1955 1960 1965Pro Ala Gly Lys Gly Arg Asp
Glu Pro Asn Met Asn Pro Lys Leu Asp 1970 1975
1980Leu Pro Asn Arg Pro Glu Thr Ser Phe Leu Trp Phe Thr Asn Pro
Cys1985 1990 1995 2000Lys
Thr Met Lys Phe Ile Val Trp Arg Arg Phe Lys Trp Val Ile Ile
2005 2010 2015Gly Leu Leu Phe Leu Leu Ile
Leu Leu Leu Phe Val Ala Val Leu Leu 2020 2025
2030Tyr Ser Leu Pro Asn Tyr Leu Ser Met Lys Ile Val Lys Pro
Asn Val 2035 2040 2045166147DNAHomo
sapiens 16catgctgcga gtgattgtgg aatctgccag caatatccct aaaacgaaat
ttggcaagcc 60ggatcctatt gtttctgtca tttttaagga tgagaaaaag aaaacaaaga
aagttgataa 120tgaattgaac cctgtctgga atgagatttt ggagtttgac ttgaggggta
taccactgga 180cttttcatct tcccttggga ttattgtgaa agattttgag acaattggac
aaaataaatt 240aattggcacg gcgactgtag ccctgaagga cctgactggt gaccagagca
gatccctgcc 300gtacaagctg atctccctgc taaatgaaaa agggcaagat actggggcca
ccattgactt 360ggtgatcggc tatgatccgc cttctgctcc acatccaaat gacctgagcg
ggcccagcgt 420gccaggcatg ggaggagatg gggaagaaga tgaaggtgat gaagacaggt
tggacaatgc 480agtcaggggc cctgggccca aggggccagt tgggacggtg tcggaagctc
agcttgctcg 540gaggctcacc aaagtaaaga acagccggcg gatgctgtca aataagccac
aggacttcca 600gatccgcgtc cgagtgattg agggccgaca gttaagtggt aacaacataa
ggcctgtggt 660caaagttcac gtctgtggcc agacacaccg aacaagaatc aagagaggaa
acaacccttt 720ttttgatgag ttgtttttct acaatgtcaa catgacccct tctgaattga
tggatgagat 780catcagcatc cgggtttata attctcactc tctgcgggca gattgtctga
tgggggaatt 840taagattgat gttggatttg tttatgatga acctggccat gctgtcatga
gaaagtggct 900tcttctcaat gacccggaag ataccagttc aggttctaaa ggttatatga
aagtcagcat 960gtttgtcctg ggaaccggag atgagcctcc tcctgagaga cgagatcgtg
ataatgacag 1020tgatgatgtg gagagtaatt tgttactccc tgctggcatt gccctccggt
gggtgacctt 1080cttgctgaaa atctaccgag ctgaggacat cccccagatg gatgatgcct
tctcacagac 1140agtaaaggaa atatttggag gcaatgcaga taagaaaaat ctcgtggatc
cttttgtaga 1200agtttccttt gctggaaaaa aggtttgtac aaacataatt gagaaaaatg
caaacccaga 1260gtggaatcag gtcgtcaatc ttcagatcaa gtttccttca gtgtgtgaaa
aaataaaact 1320aacaatatat gactgggacc gtcttactaa aaatgatgta gttggaacaa
catatctaca 1380cctctctaaa attgctgcct ctggtgggga agtggaagta aacacaggag
aaacagaggt 1440aggctttgtt ccaacgtttg gaccttgtta cctgaatctt tatggaagcc
ccagggagta 1500cacgggattc ccagacccct atgatgagct gaatactgga aagggggaag
gagttgccta 1560cagaggcagg atcttggttg aattagccac ttttcttgag aagacaccac
cagataaaaa 1620gcttgagccc atttcaaatg atgacctgct ggttgttgag aaataccagc
gaaggcggaa 1680gtacagcctg tctgccgtgt ttcattcagc caccatgttg caagatgttg
gtgaggccat 1740tcagtttgaa gtcagcattg ggaactatgg caacaagttt gacaccacct
gtaagccttt 1800ggcatcaaca actcagtaca gccgtgctgt atttgatggc aactactatt
attacttgcc 1860ttgggcccac accaagccag ttgttaccct gacttcatac tgggaggata
ttagtcatcg 1920cctggatgcg gtgaacactc tcctagctat ggcagaacgg ctgcaaacaa
atatagaagc 1980tctaaaatca gggatacaag gtaaaattcc tgcaaaccag ctggctgaat
tgtggctgaa 2040gctgatagat gaagttatag aagacacgag atacacgttg cctctcacag
aaggaaaagc 2100caacgtcaca gttctcgata ctcagatccg aaagctgcgg tccaggtctc
tctcccaaat 2160acatgaggcg gctgtgagga tgaggtcgga agccacagat gtgaagtcca
cactggcaga 2220aattgaggac tggcttgata aattaatgca gctgactgaa gagccacaga
acagcatgcc 2280tgacatcatc atctggatga tccggggaga gaagagactg gcctatgcac
gaattcccgc 2340acatcaggtc ttgtactcca ccagtggtga gaatgcatct ggaaaatact
gtgggaaaac 2400ccaaaccatc tttctgaagt atccacagga gaaaaacaac gggccaaagg
tgcctgtgga 2460gttgcgagtg aacatctggc taggcttaag tgctgtggag aagaagttta
acagcttcgc 2520agaaggaact ttcaccgtct ttgctgaaat gtatgaaaat caagctctca
tgtttggaaa 2580atggggtact tctggattag taggacgtca taagttttct gatgtcacag
gaaaaataaa 2640actcaagagg gaattttttc tgcctccaaa aggctgggaa tgggaaggag
agtggatagt 2700tgatcctgaa agaagcttgc tgactgaggc agatgcaggt cacacggagt
tcactgatga 2760agtctatcag aacgagagcc gctaccccgg gggcgactgg aagccggccg
aggacaccta 2820cacggatgcg aacggcgata aagcagcatc acccagcgag ttgacttgtc
ctccaggttg 2880ggaatgggaa gatgatgcat ggtcttatga cataaatcga gcggtggatg
agaaaggctg 2940ggaatatgga atcaccattc ctcctgatca taagcccaaa tcctgggttg
cagcagagaa 3000aatgtaccac actcatagac ggcgaaggct ggtccgaaaa cgcaagaaag
atttaacaca 3060gactgcttca agcaccgcaa gggccatgga ggaattgcaa gaccaagagg
gctgggaata 3120tgcttctcta attggctgga aatttcactg gaaacaacgt agttcagata
ccttccgccg 3180cagacgctgg aggagaaaaa tggctccttc agaaacacat ggtgcagctg
ccatctttaa 3240acttgaaggt gcccttgggg cagacactac cgaagatggg gatgagaaga
gcctggagaa 3300acagaagcac agtgccacca ctgtgttcgg agcaaacacc cccattgttt
cctgcaattt 3360tgacagagtc tacatctacc atctgcgctg ctatgtctat caagccagaa
acctcttggc 3420tttagataag gatagctttt cagatccata tgctcatatc tgtttcctcc
atcggagcaa 3480aaccactgag atcatccatt caaccctgaa tcccacgtgg gaccaaacaa
ttatattcga 3540tgaagttgaa atctatgggg aaccccaaac agttctacag aatccaccca
aagttatcat 3600ggaacttttt gacaatgacc aagtgggcaa agatgaattt ttaggacgaa
gcattttctc 3660tcctgtggtg aaactgaact cagaaatgga catcacaccc aaacttctct
ggcacccagt 3720aatgaatgga gacaaagcct gcggggatgt tcttgtaact gcagagctga
ttctgagggg 3780caaggatggc tccaaccttc ccattcttcc ccctcaaagg gcgccaaatc
tatacatggt 3840cccccagggg atcaggcctg tggtccagct cactgccatt gagattctag
cttggggctt 3900aagaaatatg aaaaacttcc agatggcttc tatcacatcc cccagtcttg
ttgtggagtg 3960tggaggagaa agggtggaat cggtggtgat caaaaacctt aagaagacac
ccaactttcc 4020aagttctgtt ctcttcatga aagtgttctt gcccaaggag gaattgtaca
tgcccccact 4080ggtgatcaag gtcatcgacc acaggcagtt tgggcggaag cctgtcgtcg
gccagtgcac 4140catcgagcgc ctggaccgct ttcgctgtga cccttatgca gggaaagagg
acatcgtccc 4200acagctcaaa gcctcccttc tgtctgcccc accatgccgg gacatcgtta
tcgaaatgga 4260agacaccaaa ccattactgg cttctaagct gacagaaaag gaggaagaaa
tcgtggactg 4320gtggagtaaa ttttatgctt cctcagggga acatgaaaaa tgcggacagt
atattcagaa 4380aggctattcc aagctcaaga tatataattg tgaactagaa aatgtagcag
aatttgaggg 4440cctgacagac ttctcagata cgttcaagtt gtaccgaggc aagtcggatg
aaaatgaaga 4500tccttctgtg gttggagagt ttaagggctc ctttcggatc taccctctgc
cggatgaccc 4560cagcgtgcca gcccctccca gacagtttcg ggaattacct gacagcgtcc
cacaggaatg 4620cacggttagg atttacattg ttcgaggctt agagctccag ccccaggaca
acaatggcct 4680gtgtgaccct tacataaaaa taacactggg caaaaaagtc attgaagacc
gagatcacta 4740cattcccaac actctcaacc cagtctttgg caggatgtac gaactgagct
gctacttacc 4800tcaagaaaaa gacctgaaaa tttctgtcta tgattatgac acctttaccc
gggatgaaaa 4860agtaggagaa acaattattg atctggaaaa ccgattcctt tcccgctttg
ggtcccactg 4920cggcatacca gaggagtact gtgtttctgg agtcaatacc tggcgagatc
aactgagacc 4980aacacagctg cttcaaaatg tcgccagatt caaaggcttc ccacaaccca
tcctttccga 5040agatgggagt agaatcagat atggaggacg agactacagc ttggatgaat
ttgaagccaa 5100caaaatcctg caccagcacc tcggggcccc tgaagagcgg cttgctcttc
acatcctcag 5160gactcagggg ctggtccctg agcacgtgga aacaaggact ttgcacagca
ccttccagcc 5220caacatttcc cagggaaaac ttcagatgtg ggtggatgtt ttccccaaga
gtttggggcc 5280accaggccct cctttcaaca tcacaccccg gaaagccaag aaatactacc
tgcgtgtgat 5340catctggaac accaaggacg ttatcttgga cgagaaaagc atcacaggag
aggaaatgag 5400tgacatctac gtcaaaggct ggattcctgg caatgaagaa aacaaacaga
aaacagatgt 5460ccattacaga tctttggatg gtgaagggaa ttttaactgg cgatttgttt
tcccgtttga 5520ctaccttcca gccgaacaac tctgtatcgt tgcgaaaaaa gagcatttct
ggagtattga 5580ccaaacggaa tttcgaatcc cacccaggct gatcattcag atatgggaca
atgacaagtt 5640ttctctggat gactacttgg gtttcctaga acttgacttg cgtcacacga
tcattcctgc 5700aaaatcacca gagaaatgca ggttggacat gattccggac ctcaaagcca
tgaaccccct 5760taaagccaag acagcctccc tctttgagca gaagtccatg aaaggatggt
ggccatgcta 5820cgcagagaaa gatggcgccc gcgtaatggc tgggaaagtg gagatgacat
tggaaatcct 5880caacgagaag gaggccgacg agaggccagc cgggaagggg cgggacgaac
ccaacatgaa 5940ccccaagctg gacttaccaa atcgaccaga aacctccttc ctctggttca
ccaacccatg 6000caagaccatg aagttcatcg tgtggcgccg ctttaagtgg gtcatcatcg
gcttgctgtt 6060cctgcttatc ctgctgctct tcgtggccgt gctcctctac tctttgccga
actatttgtc 6120aatgaagatt gtaaagccaa atgtgta
614717336PRTHomo sapiens 17Met Glu Arg Lys Ile Ser Arg Ile His
Leu Val Ser Glu Pro Ser Ile1 5 10
15Thr His Phe Leu Gln Val Ser Trp Glu Lys Thr Leu Glu Ser Gly
Phe 20 25 30Val Ile Thr Leu
Thr Asp Gly His Ser Ala Trp Thr Gly Thr Val Ser 35
40 45Glu Ser Glu Ile Ser Gln Glu Ala Asp Asp Met Ala
Met Glu Lys Gly 50 55 60Lys Tyr Val
Gly Glu Leu Arg Lys Ala Leu Leu Ser Gly Ala Gly Pro65 70
75 80Ala Asp Val Tyr Thr Phe Asn Phe
Ser Lys Glu Ser Cys Tyr Phe Phe 85 90
95Phe Glu Lys Asn Leu Lys Asp Val Ser Phe Arg Leu Gly Ser
Phe Asn 100 105 110Leu Glu Lys
Val Glu Asn Pro Ala Glu Val Ile Arg Glu Leu Ile Cys 115
120 125Tyr Cys Leu Asp Thr Ile Ala Glu Asn Gln Ala
Lys Asn Glu His Leu 130 135 140Gln Lys
Glu Asn Glu Arg Leu Leu Arg Asp Trp Asn Asp Val Gln Gly145
150 155 160Arg Phe Glu Lys Cys Val Ser
Ala Lys Glu Ala Leu Glu Thr Asp Leu 165
170 175Tyr Lys Arg Phe Ile Leu Val Leu Asn Glu Lys Lys
Thr Lys Ile Arg 180 185 190Ser
Leu His Asn Lys Leu Leu Asn Ala Ala Gln Glu Arg Glu Lys Asp 195
200 205Ile Lys Gln Glu Gly Glu Thr Ala Ile
Cys Ser Glu Met Thr Ala Asp 210 215
220Arg Asp Pro Val Tyr Asp Glu Ser Thr Asp Glu Glu Ser Glu Asn Gln225
230 235 240Thr Asp Leu Ser
Gly Leu Ala Ser Ala Ala Val Ser Lys Asp Asp Ser 245
250 255Ile Ile Ser Ser Leu Asp Val Thr Asp Ile
Ala Pro Ser Arg Lys Arg 260 265
270Arg Gln Arg Met Gln Arg Asn Leu Gly Thr Glu Pro Lys Met Ala Pro
275 280 285Gln Glu Asn Gln Leu Gln Glu
Lys Glu Asn Ser Arg Pro Asp Ser Ser 290 295
300Leu Pro Glu Thr Ser Lys Lys Glu His Ile Ser Ala Glu Asn Met
Ser305 310 315 320Leu Glu
Thr Leu Arg Asn Ser Ser Pro Glu Asp Leu Phe Asp Glu Ile
325 330 335181011DNAHomo sapiens
18aatggagaga aaaataagca gaatccacct tgtttctgaa cccagtataa ctcattttct
60acaagtatct tgggagaaaa cactggaatc tggttttgtt attacactta ctgatggtca
120ttcagcatgg actgggacag tttctgaatc agagatttcc caagaagctg atgacatggc
180aatggaaaaa gggaaatatg ttggtgaact gagaaaagca ttgttgtcag gagcaggacc
240agctgatgta tacacgttta atttttctaa agagtcttgt tatttcttct ttgagaaaaa
300cctgaaagat gtctcattca gacttggttc cttcaaccta gagaaagttg aaaacccagc
360tgaagtcatt agagaactta tttgttattg cttggacacc attgcagaaa atcaagccaa
420aaatgagcac ctgcagaaag aaaatgaaag gcttctgaga gattggaatg atgttcaagg
480acgatttgaa aaatgtgtga gtgctaagga agctttggag actgatcttt ataagcggtt
540tattctggtg ttgaatgaga agaaaacaaa aatcagaagt ttgcataata aattattaaa
600tgcagctcaa gaacgagaaa aggacatcaa acaagaaggg gaaactgcaa tctgttctga
660aatgactgct gaccgagatc cagtctatga tgagagtact gatgaggaaa gtgaaaacca
720aactgatctc tctgggttgg cttcagctgc tgtaagtaaa gatgattcca ttatttcaag
780tcttgatgtc actgatattg caccaagtag aaaaaggaga cagcgaatgc aaagaaatct
840tgggacagaa cctaaaatgg ctcctcagga gaatcagctt caagaaaagg aaaattctag
900gcctgattct tcactacctg agacgtcgaa aaaggagcac atctcagctg aaaacatgtc
960tttagaaact ctgagaaaca gcagcccaga agacctcttt gatgagattt a
101119510PRTHomo sapiens 19Met Asp Glu Lys Thr Lys Lys Ala Glu Glu Met
Ala Leu Ser Leu Thr1 5 10
15Arg Ala Val Ala Gly Gly Asp Glu Gln Val Ala Met Lys Cys Ala Ile
20 25 30Trp Leu Ala Glu Gln Arg Val
Pro Leu Ser Val Gln Leu Lys Pro Glu 35 40
45Val Ser Pro Thr Gln Asp Ile Arg Leu Trp Val Ser Val Glu Asp
Ala 50 55 60Gln Met His Thr Val Thr
Ile Trp Leu Thr Val Arg Pro Asp Met Thr65 70
75 80Val Ala Ser Leu Lys Asp Met Val Phe Leu Asp
Tyr Gly Phe Pro Pro 85 90
95Val Leu Gln Gln Trp Val Ile Gly Gln Arg Leu Ala Arg Asp Gln Glu
100 105 110Thr Leu His Ser His Gly
Val Arg Gln Asn Gly Asp Ser Ala Tyr Leu 115 120
125Tyr Leu Leu Ser Ala Arg Asn Thr Ser Leu Asn Pro Gln Glu
Leu Gln 130 135 140Arg Glu Arg Gln Leu
Arg Met Leu Glu Asp Leu Gly Phe Lys Asp Leu145 150
155 160Thr Leu Gln Pro Arg Gly Pro Leu Glu Pro
Gly Pro Pro Lys Pro Gly 165 170
175Val Pro Gln Glu Pro Gly Arg Gly Gln Pro Asp Ala Val Pro Glu Pro
180 185 190Pro Pro Val Gly Trp
Gln Cys Pro Gly Cys Thr Phe Ile Asn Lys Pro 195
200 205Thr Arg Pro Gly Cys Glu Met Cys Cys Arg Ala Arg
Pro Glu Ala Tyr 210 215 220Gln Val Pro
Ala Ser Tyr Gln Pro Asp Glu Glu Glu Arg Ala Arg Leu225
230 235 240Ala Gly Glu Glu Glu Ala Leu
Arg Gln Tyr Gln Gln Arg Lys Gln Gln 245
250 255Gln Gln Glu Gly Asn Tyr Leu Gln His Val Gln Leu
Asp Gln Arg Ser 260 265 270Leu
Val Leu Asn Thr Glu Pro Ala Glu Cys Pro Val Cys Tyr Ser Val 275
280 285Leu Ala Pro Gly Glu Ala Val Val Leu
Arg Glu Cys Leu His Thr Phe 290 295
300Cys Arg Glu Cys Leu Gln Gly Thr Ile Arg Asn Ser Gln Glu Ala Glu305
310 315 320Val Ser Cys Pro
Phe Ile Asp Asn Thr Tyr Ser Cys Ser Gly Lys Leu 325
330 335Leu Glu Arg Glu Ile Lys Ala Leu Leu Thr
Pro Glu Asp Tyr Gln Arg 340 345
350Phe Leu Asp Leu Gly Ile Ser Ile Ala Glu Asn Arg Ser Ala Phe Ser
355 360 365Tyr His Cys Lys Thr Pro Asp
Cys Lys Gly Trp Cys Phe Phe Glu Asp 370 375
380Asp Val Asn Glu Phe Thr Cys Pro Val Cys Phe His Val Asn Cys
Leu385 390 395 400Leu Cys
Lys Ala Ile His Glu Gln Met Asn Cys Lys Glu Tyr Gln Glu
405 410 415Asp Leu Ala Leu Arg Ala Gln
Asn Asp Val Ala Ala Arg Gln Thr Thr 420 425
430Glu Met Leu Lys Val Met Leu Gln Gln Gly Glu Ala Met Arg
Cys Pro 435 440 445Gln Cys Gln Ile
Val Val Gln Lys Lys Asp Gly Cys Asp Trp Ile Arg 450
455 460Cys Thr Val Cys His Thr Glu Ile Cys Trp Val Thr
Lys Gly Pro Arg465 470 475
480Trp Gly Pro Gly Gly Pro Gly Asp Thr Ser Gly Gly Cys Arg Cys Arg
485 490 495Val Asn Gly Ile Pro
Cys His Pro Ser Cys Gln Asn Cys His 500 505
510201533DNAHomo sapiens 20atggacgaga agaccaagaa agcagaggaa
atggccctga gcctcacccg agcagtggcg 60ggcggggatg aacaggtggc aatgaagtgt
gccatctggc tggcagagca acgggtgccc 120ctgagtgtgc aactgaagcc tgaggtctcc
ccaacgcagg acatcaggct gtgggtgagc 180gtggaggatg ctcagatgca caccgtcacc
atctggctca cagtgcgccc tgatatgaca 240gtggcgtctc tcaaggacat ggtttttctg
gactatggct tcccaccagt cttgcagcag 300tgggtgattg ggcagcggct ggcacgagac
caggagaccc tgcactccca tggggtgcgg 360cagaatgggg acagtgccta cctctatctg
ctgtcagccc gcaacacctc cctcaaccct 420caggagctgc agcgggagcg gcagctgcgg
atgctggaag atctgggctt caaggacctc 480acgctgcagc cgcggggccc tctggagcca
ggccccccaa agcccggggt cccccaggaa 540cccggacggg ggcagccaga tgcagtgcct
gagcccccac cggtgggctg gcagtgcccc 600gggtgcacct tcatcaacaa gcccacgcgg
cctggctgtg agatgtgctg ccgggcgcgc 660cccgaggcct accaggtccc cgcctcatac
cagcccgacg aggaggagcg agcgcgcctg 720gcgggcgagg aggaggcgct gcgtcagtac
cagcagcgga agcagcagca gcaggagggg 780aactacctgc agcacgtcca gctggaccag
aggagcctgg tgctgaacac ggagcccgcc 840gagtgccccg tgtgctactc ggtgctggcg
cccggcgagg ccgtggtgct gcgtgagtgt 900ctgcacacct tctgcaggga gtgcctgcag
ggcaccatcc gcaacagcca ggaggcggag 960gtctcctgcc ccttcattga caacacctac
tcgtgctcgg gcaagctgct ggagagggag 1020atcaaggcgc tcctgacccc tgaggattac
cagcgatttc tagacctggg catctccatt 1080gctgaaaacc gcagtgcctt cagctaccat
tgcaagaccc cagattgcaa gggatggtgc 1140ttctttgagg atgatgtcaa tgagttcacc
tgccctgtgt gtttccacgt caactgcctg 1200ctctgcaagg ccatccatga gcagatgaac
tgcaaggagt atcaggagga cctggccctg 1260cgggctcaga acgatgtggc tgcccggcag
acgacagaga tgctgaaggt gatgctgcag 1320cagggcgagg ccatgcgctg cccccagtgc
cagatcgtgg tacagaagaa ggacggctgc 1380gactggatcc gctgcaccgt ctgccacacc
gagatctgct gggtcaccaa gggcccacgc 1440tggggccctg ggggcccagg agacaccagc
gggggctgcc gctgcagggt aaatgggatt 1500ccttgccacc caagctgtca gaactgccac
tga 153321500PRTHomo sapiens 21Met Asp His
Thr Glu Gly Ser Pro Ala Glu Glu Pro Pro Ala His Ala1 5
10 15Pro Ser Pro Gly Lys Phe Gly Glu Arg
Pro Pro Pro Lys Arg Leu Thr 20 25
30Arg Glu Ala Met Arg Asn Tyr Leu Lys Glu Arg Gly Asp Gln Thr Val
35 40 45Leu Ile Leu His Ala Lys Val
Ala Gln Lys Ser Tyr Gly Asn Glu Lys 50 55
60Arg Phe Phe Cys Pro Pro Pro Cys Val Tyr Leu Met Gly Ser Gly Trp65
70 75 80Lys Lys Lys Lys
Glu Gln Met Glu Arg Asp Gly Cys Ser Glu Gln Glu 85
90 95Ser Gln Pro Cys Ala Phe Ile Gly Ile Gly
Asn Ser Asp Gln Glu Met 100 105
110Gln Gln Leu Asn Leu Glu Gly Lys Asn Tyr Cys Thr Ala Lys Thr Leu
115 120 125Tyr Ile Ser Asp Ser Asp Lys
Arg Lys His Phe Met Leu Ser Val Lys 130 135
140Met Phe Tyr Gly Asn Ser Asp Asp Ile Gly Val Phe Leu Ser Lys
Arg145 150 155 160Ile Lys
Val Ile Ser Lys Pro Ser Lys Lys Lys Gln Ser Leu Lys Asn
165 170 175Ala Asp Leu Cys Ile Ala Ser
Gly Thr Lys Val Ala Leu Phe Asn Arg 180 185
190Leu Arg Ser Gln Thr Val Ser Thr Arg Tyr Leu His Val Glu
Gly Gly 195 200 205Asn Phe His Ala
Ser Ser Gln Gln Trp Gly Ala Phe Phe Ile His Leu 210
215 220Leu Asp Asp Asp Glu Ser Glu Gly Glu Glu Phe Thr
Val Arg Asp Gly225 230 235
240Tyr Ile His Tyr Gly Gln Thr Val Lys Leu Val Cys Ser Val Thr Gly
245 250 255Met Ala Leu Pro Arg
Leu Ile Ile Arg Lys Val Asp Lys Gln Thr Ala 260
265 270Leu Leu Asp Ala Asp Asp Pro Val Ser Gln Leu His
Lys Cys Ala Phe 275 280 285Tyr Leu
Lys Asp Thr Glu Arg Met Tyr Leu Cys Leu Ser Gln Glu Arg 290
295 300Ile Ile Gln Phe Gln Ala Thr Pro Cys Pro Lys
Glu Pro Asn Lys Glu305 310 315
320Met Ile Asn Asp Gly Ala Ser Trp Thr Ile Ile Ser Thr Asp Lys Ala
325 330 335Glu Tyr Thr Phe
Tyr Glu Gly Met Gly Pro Val Leu Ala Pro Val Thr 340
345 350Pro Val Pro Val Val Glu Ser Leu Gln Leu Asn
Gly Gly Gly Asp Val 355 360 365Ala
Met Leu Glu Leu Thr Gly Gln Asn Phe Thr Pro Asn Leu Arg Val 370
375 380Trp Phe Gly Asp Val Glu Ala Glu Thr Met
Tyr Arg Cys Gly Glu Ser385 390 395
400Met Leu Cys Val Val Pro Asp Ile Ser Ala Phe Arg Glu Gly Trp
Arg 405 410 415Trp Val Arg
Gln Pro Val Gln Val Pro Val Thr Leu Val Arg Asn Asp 420
425 430Gly Ile Ile Tyr Ser Thr Ser Leu Thr Phe
Thr Tyr Thr Pro Glu Pro 435 440
445Gly Pro Arg Pro His Cys Ser Ala Ala Gly Ala Ile Leu Arg Ala Asn 450
455 460Ser Ser Gln Val Pro Pro Asn Glu
Ser Asn Thr Asn Ser Glu Gly Ser465 470
475 480Tyr Thr Asn Ala Ser Thr Asn Ser Thr Ser Val Thr
Ser Ser Thr Ala 485 490
495Thr Val Val Ser 500221503DNAHomo sapiens 22ccatggacca
cacggagggc tcgcccgcgg aggagccgcc tgcgcatgct ccatcgcctg 60ggaaatttgg
tgagcggcct ccacctaaac gacttactag ggaagctatg cgaaattatt 120taaaagagcg
aggggatcaa acagtactta ttcttcatgc aaaagttgca cagaagtcat 180atggaaatga
aaaaaggttt ttttgcccac ctccttgtgt atatcttatg ggcagtggat 240ggaagaaaaa
aaaagaacaa atggaacgcg atggttgttc tgaacaagag tctcaaccgt 300gtgcatttat
tgggatagga aatagtgacc aagaaatgca gcagctaaac ttggaaggaa 360agaactattg
cacagccaaa acattgtata tatctgactc agacaagcga aagcacttca 420tgttgtctgt
aaagatgttc tatggcaaca gtgatgacat tggtgtgttc ctcagcaagc 480ggataaaagt
catctccaaa ccttccaaaa agaagcagtc attgaaaaat gctgacttat 540gcattgcctc
aggaacaaag gtggctctgt ttaatcgact acgatcccag acagttagta 600ccagatactt
gcatgtagaa ggaggtaatt ttcatgccag ttcacagcag tggggagcct 660tttttattca
tctcttggat gatgatgaat cagaaggaga agaattcaca gtccgagatg 720gctacatcca
ttatggacaa acagtcaaac ttgtgtgctc agttactggc atggcactcc 780caagattgat
aattaggaaa gttgataagc agaccgcatt attggatgca gatgatcctg 840tgtcacaact
ccataaatgt gcattttacc ttaaggatac agaaagaatg tatttgtgcc 900tttctcaaga
aagaataatt caatttcagg ccactccatg tccaaaagaa ccaaataaag 960agatgataaa
tgatggcgct tcctggacaa tcattagcac agataaggca gagtatacat 1020tttatgaggg
aatgggccct gtccttgccc cagtcactcc tgtgcctgtg gtagagagcc 1080ttcagttgaa
tggcggtggg gacgtagcaa tgcttgaact tacaggacag aatttcactc 1140caaatttacg
agtgtggttt ggggatgtag aagctgaaac tatgtacagg tgtggagaga 1200gtatgctctg
tgtcgtccca gacatttctg cattccgaga aggttggaga tgggtccggc 1260aaccagtcca
ggttccagta actttggtcc gaaatgatgg aatcatttat tccaccagcc 1320ttacctttac
ctacacacca gaaccagggc cgcggccaca ttgcagtgca gcaggagcaa 1380tccttcgagc
caattcaagc caggtgcccc ctaacgaatc aaacacaaac agcgagggaa 1440gttacacaaa
cgccagcaca aattcaacca gtgtcacatc atctacagcc acagtggtat 1500cct
1503231354PRTHomo
sapiens 23Met Ser Thr Gly Asp Ser Phe Glu Thr Arg Phe Glu Lys Met Asp
Asn1 5 10 15Leu Leu Arg
Asp Pro Lys Ser Glu Val Asn Ser Asp Cys Leu Leu Asp 20
25 30Gly Leu Asp Ala Leu Val Tyr Asp Leu Asp
Phe Pro Ala Leu Arg Lys 35 40
45Asn Lys Asn Ile Asp Asn Phe Leu Ser Arg Tyr Lys Asp Thr Ile Asn 50
55 60Lys Ile Arg Asp Leu Arg Met Lys Ala
Glu Asp Tyr Glu Val Val Lys65 70 75
80Val Ile Gly Arg Gly Ala Phe Gly Glu Val Gln Leu Val Arg
His Lys 85 90 95Ser Thr
Arg Lys Val Tyr Ala Met Lys Leu Leu Ser Lys Phe Glu Met 100
105 110Ile Lys Arg Ser Asp Ser Ala Phe Phe
Trp Glu Glu Arg Asp Ile Met 115 120
125Ala Phe Ala Asn Ser Pro Trp Val Val Gln Leu Phe Tyr Ala Phe Gln
130 135 140Asp Asp Arg Tyr Leu Tyr Met
Val Met Glu Tyr Met Pro Gly Gly Asp145 150
155 160Leu Val Asn Leu Met Ser Asn Tyr Asp Val Pro Glu
Lys Trp Ala Arg 165 170
175Phe Tyr Thr Ala Glu Val Val Leu Ala Leu Asp Ala Ile His Ser Met
180 185 190Gly Phe Ile His Arg Asp
Val Lys Pro Asp Asn Met Leu Leu Asp Lys 195 200
205Ser Gly His Leu Lys Leu Ala Asp Phe Gly Thr Cys Met Lys
Met Asn 210 215 220Lys Glu Gly Met Val
Arg Cys Asp Thr Ala Val Gly Thr Pro Asp Tyr225 230
235 240Ile Ser Pro Glu Val Leu Lys Ser Gln Gly
Gly Asp Gly Tyr Tyr Gly 245 250
255Arg Glu Cys Asp Trp Trp Ser Val Gly Val Phe Leu Tyr Glu Met Leu
260 265 270Val Gly Asp Thr Pro
Phe Tyr Ala Asp Ser Leu Val Gly Thr Tyr Ser 275
280 285Lys Ile Met Asn His Lys Asn Ser Leu Thr Phe Pro
Asp Asp Asn Asp 290 295 300Ile Ser Lys
Glu Ala Lys Asn Leu Ile Cys Ala Phe Leu Thr Asp Arg305
310 315 320Glu Val Arg Leu Gly Arg Asn
Gly Val Glu Glu Ile Lys Arg His Leu 325
330 335Phe Phe Lys Asn Asp Gln Trp Ala Trp Glu Thr Leu
Arg Asp Thr Val 340 345 350Ala
Pro Val Val Pro Asp Leu Ser Ser Asp Ile Asp Thr Ser Asn Phe 355
360 365Asp Asp Leu Glu Glu Asp Lys Gly Glu
Glu Glu Thr Phe Pro Ile Pro 370 375
380Lys Ala Phe Val Gly Asn Gln Leu Pro Phe Val Gly Phe Thr Tyr Tyr385
390 395 400Ser Asn Arg Arg
Tyr Leu Ser Ser Ala Asn Pro Asn Asp Asn Arg Thr 405
410 415Ser Ser Asn Ala Asp Lys Ser Leu Gln Glu
Ser Leu Gln Lys Thr Ile 420 425
430Tyr Lys Leu Glu Glu Gln Leu His Asn Glu Met Gln Leu Lys Asp Glu
435 440 445Met Glu Gln Lys Cys Arg Thr
Ser Asn Ile Lys Leu Asp Lys Ile Met 450 455
460Lys Glu Leu Asp Glu Glu Gly Asn Gln Arg Arg Asn Leu Glu Ser
Thr465 470 475 480Val Ser
Gln Ile Glu Lys Glu Lys Met Leu Leu Gln His Arg Ile Asn
485 490 495Glu Tyr Gln Arg Lys Ala Glu
Gln Glu Asn Glu Lys Arg Arg Asn Val 500 505
510Glu Asn Glu Val Ser Thr Leu Lys Asp Gln Leu Glu Asp Leu
Lys Lys 515 520 525Val Ser Gln Asn
Ser Gln Leu Ala Asn Glu Lys Leu Ser Gln Leu Gln 530
535 540Lys Gln Leu Glu Glu Ala Asn Asp Leu Leu Arg Thr
Glu Ser Asp Thr545 550 555
560Ala Val Arg Leu Arg Lys Ser His Thr Glu Met Ser Lys Ser Ile Ser
565 570 575Gln Leu Glu Ser Leu
Asn Arg Glu Leu Gln Glu Arg Asn Arg Ile Leu 580
585 590Glu Asn Ser Lys Ser Gln Thr Asp Lys Asp Tyr Tyr
Gln Leu Gln Ala 595 600 605Ile Leu
Glu Ala Glu Arg Arg Asp Arg Gly His Asp Ser Glu Met Ile 610
615 620Gly Asp Leu Gln Ala Arg Ile Thr Ser Leu Gln
Glu Glu Val Lys His625 630 635
640Leu Lys His Asn Leu Glu Lys Val Glu Gly Glu Arg Lys Glu Ala Gln
645 650 655Asp Met Leu Asn
His Ser Glu Lys Glu Lys Asn Asn Leu Glu Ile Asp 660
665 670Leu Asn Tyr Lys Leu Lys Ser Leu Gln Gln Arg
Leu Glu Gln Glu Val 675 680 685Asn
Glu His Lys Val Thr Lys Ala Arg Leu Thr Asp Lys His Gln Ser 690
695 700Ile Glu Glu Ala Lys Ser Val Ala Met Cys
Glu Met Glu Lys Lys Leu705 710 715
720Lys Glu Glu Arg Glu Ala Arg Glu Lys Ala Glu Asn Arg Val Val
Gln 725 730 735Ile Glu Lys
Gln Cys Ser Met Leu Asp Val Asp Leu Lys Gln Ser Gln 740
745 750Gln Lys Leu Glu His Leu Thr Gly Asn Lys
Glu Arg Met Glu Asp Glu 755 760
765Val Lys Asn Leu Thr Leu Gln Leu Glu Gln Glu Ser Asn Lys Arg Leu 770
775 780Leu Leu Gln Asn Glu Leu Lys Thr
Gln Ala Phe Glu Ala Asp Asn Leu785 790
795 800Lys Gly Leu Glu Lys Gln Met Lys Gln Glu Ile Asn
Thr Leu Leu Glu 805 810
815Ala Lys Arg Leu Leu Glu Phe Glu Leu Ala Gln Leu Thr Lys Gln Tyr
820 825 830Arg Gly Asn Glu Gly Gln
Met Arg Glu Leu Gln Asp Gln Leu Glu Ala 835 840
845Glu Gln Tyr Phe Ser Thr Leu Tyr Lys Thr Gln Val Lys Glu
Leu Lys 850 855 860Glu Glu Ile Glu Glu
Lys Asn Arg Glu Asn Leu Lys Lys Ile Gln Glu865 870
875 880Leu Gln Asn Glu Lys Glu Thr Leu Ala Thr
Gln Leu Asp Leu Ala Glu 885 890
895Thr Lys Ala Glu Ser Glu Gln Leu Ala Arg Gly Leu Leu Glu Glu Gln
900 905 910Tyr Phe Glu Leu Thr
Gln Glu Ser Lys Lys Ala Ala Ser Arg Asn Arg 915
920 925Gln Glu Ile Thr Asp Lys Asp His Thr Val Ser Arg
Leu Glu Glu Ala 930 935 940Asn Ser Met
Leu Thr Lys Asp Ile Glu Ile Leu Arg Arg Glu Asn Glu945
950 955 960Glu Leu Thr Glu Lys Met Lys
Lys Ala Glu Glu Glu Tyr Lys Leu Glu 965
970 975Lys Glu Glu Glu Ile Ser Asn Leu Lys Ala Ala Phe
Glu Lys Asn Ile 980 985 990Asn
Thr Glu Arg Thr Leu Lys Thr Gln Ala Val Asn Lys Leu Ala Glu 995
1000 1005Ile Met Asn Arg Lys Asp Phe Lys Ile
Asp Arg Lys Lys Ala Asn Thr 1010 1015
1020Gln Asp Leu Arg Lys Lys Glu Lys Glu Asn Arg Lys Leu Gln Leu Glu1025
1030 1035 1040Leu Asn Gln Glu
Arg Glu Lys Phe Asn Gln Met Val Val Lys His Gln 1045
1050 1055Lys Glu Leu Asn Asp Met Gln Ala Gln Leu
Val Glu Glu Cys Ala His 1060 1065
1070Arg Asn Glu Leu Gln Met Gln Leu Ala Ser Lys Glu Ser Asp Ile Glu
1075 1080 1085Gln Leu Arg Ala Lys Leu Leu
Asp Leu Ser Asp Ser Thr Ser Val Ala 1090 1095
1100Ser Phe Pro Ser Ala Asp Glu Thr Asp Gly Asn Leu Pro Glu Ser
Arg1105 1110 1115 1120Ile
Glu Gly Trp Leu Ser Val Pro Asn Arg Gly Asn Ile Lys Arg Tyr
1125 1130 1135Gly Trp Lys Lys Gln Tyr Val
Val Val Ser Ser Lys Lys Ile Leu Phe 1140 1145
1150Tyr Asn Asp Glu Gln Asp Lys Glu Gln Ser Asn Pro Ser Met
Val Leu 1155 1160 1165Asp Ile Asp
Lys Leu Phe His Val Arg Pro Val Thr Gln Gly Asp Val 1170
1175 1180Tyr Arg Ala Glu Thr Glu Glu Ile Pro Lys Ile Phe
Gln Ile Leu Tyr1185 1190 1195
1200Ala Asn Glu Gly Glu Cys Arg Lys Asp Val Glu Met Glu Pro Val Gln
1205 1210 1215Gln Ala Glu Lys Thr
Asn Phe Gln Asn His Lys Gly His Glu Phe Ile 1220
1225 1230Pro Thr Leu Tyr His Phe Pro Ala Asn Cys Asp Ala
Cys Ala Lys Pro 1235 1240 1245Leu
Trp His Val Phe Lys Pro Pro Pro Ala Leu Glu Cys Arg Arg Cys 1250
1255 1260His Val Lys Cys His Arg Asp His Leu Asp
Lys Lys Glu Asp Leu Ile1265 1270 1275
1280Cys Pro Cys Lys Val Ser Tyr Asp Val Thr Ser Ala Arg Asp Met
Leu 1285 1290 1295Leu Leu
Ala Cys Ser Gln Asp Glu Gln Lys Lys Trp Val Thr His Leu 1300
1305 1310Val Lys Lys Ile Pro Lys Asn Pro Pro
Ser Gly Phe Val Arg Ala Ser 1315 1320
1325Pro Arg Thr Leu Ser Thr Arg Ser Thr Ala Asn Gln Ser Phe Arg Lys
1330 1335 1340Val Val Lys Asn Thr Ser Gly
Lys Thr Ser1345 1350244065DNAHomo sapiens 24acatgtcgac
tggggacagt tttgagactc gatttgaaaa aatggacaac ctgctgcggg 60atcccaaatc
ggaagtgaat tcggattgtt tgctggatgg attggatgct ttggtatatg 120atttggattt
tcctgcctta agaaaaaaca aaaatattga caacttttta agcagatata 180aagacacaat
aaataaaatc agagatttac gaatgaaagc tgaagattat gaagtagtga 240aggtgattgg
tagaggtgca tttggagaag ttcaattggt aaggcataaa tccaccagga 300aggtatatgc
tatgaagctt ctcagcaaat ttgaaatgat aaagagatct gattctgctt 360ttttctggga
agaaagggac atcatggctt ttgccaacag tccttgggtt gttcagcttt 420tttatgcatt
ccaagatgat cgttatctct acatggtgat ggaatacatg cctggtggag 480atcttgtaaa
cttaatgagc aactatgatg tgcctgaaaa atgggcacga ttctatactg 540cagaagtagt
tcttgcattg gatgcaatcc attccatggg ttttattcac agagatgtga 600agcctgataa
catgctgctg gataaatctg gacatttgaa gttagcagat tttggtactt 660gtatgaagat
gaataaggaa ggcatggtac gatgtgatac agcggttgga acacctgatt 720atatttcccc
tgaagtatta aaatcccaag gtggtgatgg ttattatgga agagaatgtg 780actggtggtc
ggttggggta tttttatacg aaatgcttgt aggtgataca cctttttatg 840cagattcttt
ggttggaact tacagtaaaa ttatgaacca taaaaattca cttacctttc 900ctgatgataa
tgacatatca aaagaagcaa aaaaccttat ttgtgccttc cttactgaca 960gggaagtgag
gttagggcga aatggtgtag aagaaatcaa acgacatctc ttcttcaaaa 1020atgaccagtg
ggcttgggaa acgctccgag acactgtagc accagttgta cccgatttaa 1080gtagtgacat
tgatactagt aattttgatg acttggaaga agataaagga gaggaagaaa 1140cattccctat
tcctaaagct ttcgttggca atcaactacc ttttgtagga tttacatatt 1200atagcaatcg
tagatactta tcttcagcaa atcctaatga taacagaact agctccaatg 1260cagataaaag
cttgcaggaa agtttgcaaa aaacaatcta taagctggaa gaacagctgc 1320ataatgaaat
gcagttaaaa gatgaaatgg agcagaagtg cagaacctca aacataaaac 1380tagacaagat
aatgaaagaa ttggatgaag agggaaatca aagaagaaat ctagaatcta 1440cagtgtctca
gattgagaag gagaaaatgt tgctacagca tagaattaat gagtaccaaa 1500gaaaagctga
acaggaaaat gagaagagaa gaaatgtaga aaatgaagtt tctacattaa 1560aggatcagtt
ggaagactta aagaaagtca gtcagaattc acagcttgct aatgagaagc 1620tgtcccagtt
acaaaagcag ctagaagaag ccaatgactt acttaggaca gaatcggaca 1680cagctgtaag
attgaggaag agtcacacag agatgagcaa gtcaattagt cagttagagt 1740ccctgaacag
agagttgcaa gagagaaatc gaattttaga gaattctaag tcacaaacag 1800acaaagatta
ttaccagctg caagctatat tagaagctga acgaagagac agaggtcatg 1860attctgagat
gattggagac cttcaagctc gaattacatc tttacaagag gaggtgaagc 1920atctcaaaca
taatctcgaa aaagtggaag gagaaagaaa agaggctcaa gacatgctta 1980atcactcaga
aaaggaaaag aataatttag agatagattt aaactacaaa cttaaatcat 2040tacaacaacg
gttagaacaa gaggtaaatg aacacaaagt aaccaaagct cgtttaactg 2100acaaacatca
atctattgaa gaggcaaagt ctgtggcaat gtgtgagatg gaaaaaaagc 2160tgaaagaaga
aagagaagct cgagagaagg ctgaaaatcg ggttgttcag attgagaaac 2220agtgttccat
gctagacgtt gatctgaagc aatctcagca gaaactagaa catttgactg 2280gaaataaaga
aaggatggag gatgaagtta agaatctaac cctgcaactg gagcaggaat 2340caaataagcg
gctgttgtta caaaatgaat tgaagactca agcatttgag gcagacaatt 2400taaaaggttt
agaaaagcag atgaaacagg aaataaatac tttattggaa gcaaagagat 2460tattagaatt
tgagttagct cagcttacga aacagtatag aggaaatgaa ggacagatgc 2520gggagctaca
agatcagctt gaagctgagc aatatttctc gacactttat aaaacccagg 2580taaaggaact
taaagaagaa attgaagaaa aaaacagaga aaatttaaag aaaatacagg 2640aactacaaaa
tgaaaaagaa actcttgcta ctcagttgga tctagcagaa acaaaagctg 2700agtctgagca
gttggcgcga ggccttctgg aagaacagta ttttgaattg acgcaagaaa 2760gcaagaaagc
tgcttcaaga aatagacaag agattacaga taaagatcac actgttagtc 2820ggcttgaaga
agcaaacagc atgctaacca aagatattga aatattaaga agagagaatg 2880aagagctaac
agagaaaatg aagaaggcag aggaagaata taaactggag aaggaggagg 2940agatcagtaa
tcttaaggct gcctttgaaa agaatatcaa cactgaacga acccttaaaa 3000cacaggctgt
taacaaattg gcagaaataa tgaatcgaaa agattttaaa attgatagaa 3060agaaagctaa
tacacaagat ttgagaaaga aagaaaagga aaatcgaaag ctgcaactgg 3120aactcaacca
agaaagagag aaattcaacc agatggtagt gaaacatcag aaggaactga 3180atgacatgca
agcgcaattg gtagaagaat gtgcacatag gaatgagctt cagatgcagt 3240tggccagcaa
agagagtgat attgagcaat tgcgtgctaa acttttggac ctctcggatt 3300ctacaagtgt
tgctagtttt cctagtgctg atgaaactga tggtaacctc ccagagtcaa 3360gaattgaagg
ttggctttca gtaccaaata gaggaaatat caaacgatat ggctggaaga 3420aacagtatgt
tgtggtaagc agcaaaaaaa ttttgttcta taatgacgaa caagataagg 3480agcaatccaa
tccatctatg gtattggaca tagataaact gtttcacgtt agacctgtaa 3540cccaaggaga
tgtgtataga gctgaaactg aagaaattcc taaaatattc cagatactat 3600atgcaaatga
aggtgaatgt agaaaagatg tagagatgga accagtacaa caagctgaaa 3660aaactaattt
ccaaaatcac aaaggccatg agtttattcc tacactctac cactttcctg 3720ccaattgtga
tgcctgtgcc aaacctctct ggcatgtttt taagccaccc cctgccctag 3780agtgtcgaag
atgccatgtt aagtgccaca gagatcactt agataagaaa gaggacttaa 3840tttgtccatg
taaagtaagt tatgatgtaa catcagcaag agatatgctg ctgttagcat 3900gttctcagga
tgaacaaaaa aaatgggtaa ctcatttagt aaagaaaatc cctaagaatc 3960caccatctgg
ttttgttcgt gcttcccctc gaacgctttc tacaagatcc actgcaaatc 4020agtctttccg
gaaagtggtc aaaaatacat ctggaaaaac tagtt
4065251012PRTHomo sapiens 25Met Thr Lys His Pro Pro Asn Arg Arg Gly Ile
Ser Phe Glu Val Gly1 5 10
15Ala Gln Leu Glu Ala Arg Asp Arg Leu Lys Asn Trp Tyr Pro Ala His
20 25 30Ile Glu Asp Ile Asp Tyr Glu
Glu Gly Lys Val Leu Ile His Phe Lys 35 40
45Arg Trp Asn His Arg Tyr Asp Glu Trp Phe Cys Trp Asp Ser Pro
Tyr 50 55 60Leu Arg Pro Leu Glu Lys
Ile Gln Leu Arg Lys Glu Gly Leu His Glu65 70
75 80Glu Asp Gly Ser Ser Glu Phe Gln Ile Asn Glu
Gln Val Leu Ala Cys 85 90
95Trp Ser Asp Cys Arg Phe Tyr Pro Ala Lys Val Thr Ala Val Asn Lys
100 105 110Asp Gly Thr Tyr Thr Val
Lys Phe Tyr Asp Gly Val Val Gln Thr Val 115 120
125Lys His Ile His Val Lys Ala Phe Ser Lys Asp Gln Asn Ile
Val Gly 130 135 140Asn Ala Arg Pro Lys
Glu Thr Asp His Lys Ser Leu Ser Ser Ser Pro145 150
155 160Asp Lys Arg Glu Lys Phe Lys Glu Gln Arg
Lys Ala Thr Val Asn Val 165 170
175Lys Lys Asp Lys Glu Asp Lys Pro Leu Lys Thr Glu Lys Arg Pro Lys
180 185 190Gln Pro Asp Lys Glu
Gly Lys Leu Ile Cys Ser Glu Lys Gly Lys Val 195
200 205Ser Glu Lys Ser Leu Pro Lys Asn Glu Lys Glu Asp
Lys Glu Asn Ile 210 215 220Ser Glu Asn
Asp Arg Glu Tyr Ser Gly Asp Ala Gln Val Asp Lys Lys225
230 235 240Pro Glu Asn Asp Ile Val Lys
Ser Pro Gln Glu Asn Leu Arg Glu Pro 245
250 255Lys Arg Lys Arg Gly Arg Pro Pro Ser Ile Ala Pro
Thr Ala Val Asp 260 265 270Ser
Asn Ser Gln Thr Leu Gln Pro Ile Thr Leu Glu Leu Arg Arg Arg 275
280 285Lys Ile Ser Lys Gly Cys Glu Val Pro
Leu Lys Arg Pro Arg Leu Asp 290 295
300Lys Asn Ser Ser Gln Glu Lys Ser Lys Asn Tyr Ser Glu Asn Thr Asp305
310 315 320Lys Asp Leu Ser
Arg Arg Arg Ser Ser Arg Leu Ser Thr Asn Gly Thr 325
330 335His Glu Ile Leu Asp Pro Asp Leu Val Val
Ser Asp Leu Val Asp Thr 340 345
350Asp Pro Leu Gln Asp Thr Leu Ser Ser Thr Lys Glu Ser Glu Glu Gly
355 360 365Gln Leu Lys Ser Ala Leu Glu
Ala Gly Gln Val Ser Ser Ala Leu Thr 370 375
380Cys His Ser Phe Gly Asp Gly Ser Gly Ala Ala Gly Leu Glu Leu
Asn385 390 395 400Cys Pro
Ser Met Gly Glu Asn Thr Met Lys Thr Glu Pro Thr Ser Pro
405 410 415Leu Val Glu Leu Gln Glu Ile
Ser Thr Val Glu Val Thr Asn Thr Phe 420 425
430Lys Lys Thr Asp Asp Phe Gly Ser Ser Asn Ala Pro Ala Val
Asp Leu 435 440 445Asp His Lys Phe
Arg Cys Lys Val Val Asp Cys Leu Lys Phe Phe Arg 450
455 460Lys Ala Lys Leu Leu His Tyr His Met Lys Tyr Phe
His Gly Met Glu465 470 475
480Lys Ser Leu Glu Pro Glu Glu Ser Pro Gly Lys Arg His Val Gln Thr
485 490 495Arg Gly Pro Ser Ala
Ser Asp Lys Pro Ser Gln Glu Thr Leu Thr Arg 500
505 510Lys Arg Val Ser Ala Ser Ser Pro Thr Thr Lys Asp
Lys Glu Lys Asn 515 520 525Lys Glu
Lys Lys Phe Lys Glu Phe Val Arg Val Lys Pro Lys Lys Lys 530
535 540Lys Lys Lys Lys Lys Lys Thr Lys Pro Glu Cys
Pro Cys Ser Glu Glu545 550 555
560Ile Ser Asp Thr Ser Gln Glu Pro Ser Pro Pro Lys Ala Phe Ala Val
565 570 575Thr Arg Cys Gly
Ser Ser His Lys Pro Gly Val His Met Ser Pro Gln 580
585 590Leu His Gly Pro Glu Ser Gly His His Lys Gly
Lys Val Lys Ala Leu 595 600 605Glu
Glu Asp Asn Leu Ser Glu Ser Ser Ser Glu Ser Phe Leu Trp Ser 610
615 620Asp Asp Glu Tyr Gly Gln Asp Val Asp Val
Thr Thr Asn Pro Asp Glu625 630 635
640Glu Leu Asp Gly Asp Asp Arg Tyr Asp Phe Glu Val Val Arg Cys
Ile 645 650 655Cys Glu Val
Gln Glu Glu Asn Asp Phe Met Ile Gln Cys Glu Glu Cys 660
665 670Gln Cys Trp Gln His Gly Val Cys Met Gly
Leu Leu Glu Glu Asn Val 675 680
685Pro Glu Lys Tyr Thr Cys Tyr Val Cys Gln Asp Pro Pro Gly Gln Arg 690
695 700Pro Gly Phe Lys Tyr Trp Tyr Asp
Lys Glu Trp Leu Ser Arg Gly His705 710
715 720Met His Gly Leu Ala Phe Leu Glu Glu Asn Tyr Ser
His Gln Asn Ala 725 730
735Lys Lys Ile Val Ala Thr His Gln Leu Leu Gly Asp Val Gln Arg Val
740 745 750Ile Glu Val Leu His Gly
Leu Gln Leu Lys Met Ser Ile Leu Gln Ser 755 760
765Arg Glu His Pro Asp Leu Pro Leu Trp Cys Gln Pro Trp Lys
Gln His 770 775 780Ser Gly Glu Gly Arg
Ser His Phe Arg Asn Ile Pro Val Thr Asp Thr785 790
795 800Arg Ser Lys Glu Glu Ala Pro Ser Tyr Arg
Thr Leu Asn Gly Ala Val 805 810
815Glu Lys Pro Arg Pro Leu Ala Leu Pro Leu Pro Arg Ser Val Glu Glu
820 825 830Ser Tyr Ile Thr Ser
Glu His Cys Tyr Gln Lys Pro Arg Ala Tyr Tyr 835
840 845Pro Ala Val Glu Gln Lys Leu Val Val Glu Thr Arg
Gly Ser Ala Leu 850 855 860Asp Asp Ala
Val Asn Pro Leu His Glu Asn Gly Asp Asp Ser Leu Ser865
870 875 880Pro Arg Leu Gly Trp Pro Leu
Asp Gln Asp Arg Ser Lys Gly Asp Ser 885
890 895Asp Pro Lys Pro Gly Ser Pro Lys Val Lys Glu Tyr
Val Ser Lys Lys 900 905 910Ala
Leu Pro Glu Glu Ala Pro Ala Arg Lys Leu Leu Asp Arg Gly Gly 915
920 925Glu Gly Leu Leu Ser Ser Gln His Gln
Trp Gln Phe Asn Leu Leu Thr 930 935
940His Val Glu Ser Leu Gln Asp Glu Val Thr His Arg Met Asp Ser Ile945
950 955 960Glu Lys Glu Leu
Asp Val Leu Glu Ser Trp Leu Asp Tyr Thr Gly Glu 965
970 975Leu Glu Pro Pro Glu Pro Leu Ala Arg Leu
Pro Gln Leu Lys His Cys 980 985
990Ile Lys Gln Leu Leu Met Asp Leu Gly Lys Val Gln Gln Ile Ala Leu
995 1000 1005Cys Cys Ser Thr
1010263039DNAHomo sapiens 26atgacaaagc atccacctaa cagacgagga atcagctttg
aagtgggagc ccagttggaa 60gcccgggacc gtttaaaaaa ctggtatcca gctcacatag
aagacattga ctacgaggaa 120ggaaaagtac tcatccattt caagcgttgg aaccatcgtt
atgatgagtg gttctgctgg 180gacagtcctt atttacgccc tttagagaaa atacagctga
ggaaagaggg cttgcatgaa 240gaggatggat cttctgaatt tcaaataaat gagcaggtcc
ttgcttgctg gtctgattgt 300cgtttttacc cggccaaagt cactgctgtt aacaaggatg
gtacttacac tgtgaaattt 360tatgatggag tagttcagac tgtcaaacat attcatgtca
aagctttttc caaagatcag 420aatattgtgg gtaatgctag gcctaaagaa acagatcaca
aaagtctttc atcatctcct 480gataaacgag agaagtttaa agaacagaga aaagcaacag
tgaatgtgaa gaaagacaaa 540gaagataaac ccttaaagac agaaaagcga cccaagcagc
ctgataaaga aggaaagtta 600atctgttctg aaaaggggaa agtgtcagag aaaagtcttc
ccaagaacga gaaggaagac 660aaggaaaaca tttccgaaaa tgacagagag tattctggag
atgcccaagt ggataagaaa 720cctgaaaatg acattgtgaa gagtccacaa gaaaacttga
gggaacccaa aagaaaacga 780ggcagacccc cttccatagc tcctactgct gtggattcaa
actctcaaac tttgcaacca 840ataacattgg aactgagaag aaggaaaata tcaaaaggat
gtgaagtccc attaaaacgt 900cctcggcttg acaaaaattc atcccaggaa aagtcaaaaa
actactcgga aaacactgac 960aaagacttat cgaggagacg ttcctccagg ctgtccacta
atgggaccca tgagatccta 1020gatcctgact tggttgtatc agatttggtt gatacggatc
ctttgcaaga cacgttgtct 1080agtaccaagg aatctgaaga aggtcagttg aagtctgctt
tggaagctgg ccaggtctca 1140tctgcactga cttgccactc ctttggggat ggatccgggg
ctgcaggctt ggagttgaac 1200tgcccatcaa tgggagaaaa cacgatgaaa acagaaccga
cttctcccct tgtggaatta 1260caagagattt cgactgtgga agtaacaaat acttttaaga
aaacagatga ttttgggtca 1320tctaatgcac cagctgtcga cctagaccat aagtttagat
gcaaagttgt ggactgttta 1380aaatttttcc gcaaagccaa actgttgcac tatcacatga
agtatttcca tggaatggag 1440aagtcactgg agccagaaga gagcccggga aagaggcatg
tccaaaccag gggcccttca 1500gcttcagaca agcccagcca ggagaccctg accaggaagc
gggtctctgc cagttcccca 1560actacaaaag acaaggaaaa gaataaagag aagaaattca
aggagtttgt gagagtgaag 1620ccaaagaaga aaaagaaaaa gaaaaagaaa accaaacctg
aatgcccctg cagtgaggag 1680atcagtgaca cctcccagga accttctcca cccaaggcat
ttgctgttac caggtgtggg 1740tcctcacaca agccaggggt ccatatgagc ccgcagcttc
atggcccaga atctggacac 1800cacaaaggga aagtgaaagc attggaggag gataatttga
gtgagtcctc ttctgagagc 1860tttctctgga gtgatgatga gtatggccaa gatgtggatg
tgaccaccaa cccagatgag 1920gaacttgatg gggatgaccg ctatgacttc gaggtggtcc
gctgcatctg tgaggtccag 1980gaggaaaatg acttcatgat tcagtgtgaa gagtgccagt
gctggcagca tggggtctgc 2040atgggattac tggaagaaaa tgtgcccgag aaatacacct
gttatgtttg ccaagaccct 2100ccaggtcaga ggcctggctt caagtactgg tatgacaagg
agtggctgag caggggacat 2160atgcatggcc tggcatttct agaagagaac tactcccatc
agaatgccaa gaagatcgtg 2220gccacccacc agcttcttgg tgatgtgcag agagtgattg
aggttctgca tggcctgcag 2280ctcaagatga gcatcttgca aagccgggag catcctgatc
tgccgctgtg gtgccagcct 2340tggaaacagc actcagggga ggggagatct catttcagaa
acatccctgt cactgacacc 2400aggagcaagg aggaagctcc aagctataga actttgaacg
gggcagtgga gaagcccagg 2460cccctggccc tgcccctgcc gcgttctgtg gaggaatcct
atatcaccag tgagcattgc 2520taccagaagc cccgcgccta ttaccctgcc gtggagcaga
agctggtggt ggagacgagg 2580ggctctgccc tcgacgatgc ggtcaacccc ctccatgaga
acggcgatga ttccctttcc 2640ccgcgcctgg gctggcctct agaccaagac aggagcaagg
gggacagtga ccccaaaccc 2700ggctccccaa aggtgaagga atatgtctcc aaaaaggccc
taccagaaga agcccctgct 2760cggaagctgc tggacagagg tggagagggg ctgctgagct
cccagcacca gtggcagttt 2820aacctgctga cccatgtgga atctcttcag gatgaagtta
cgcacaggat ggactccatt 2880gagaaggagt tggatgtgtt ggagagctgg ctggactaca
ctggggaact ggagccccct 2940gagccgctgg ccaggcttcc gcagctcaag cattgtatca
agcagctgct gatggacctg 3000ggcaaggtgc agcagatcgc cctctgctgc tcaacatga
3039271483PRTHomo sapiens 27Met Ala Pro Leu Leu Gly
Arg Lys Pro Phe Pro Leu Val Lys Pro Leu1 5
10 15Pro Gly Glu Glu Pro Leu Phe Thr Ile Pro His Thr
Gln Glu Ala Phe 20 25 30Arg
Thr Arg Glu Glu Tyr Glu Ala Arg Leu Glu Arg Tyr Ser Glu Arg 35
40 45Ile Trp Thr Cys Lys Ser Thr Gly Ser
Ser Gln Leu Thr His Lys Glu 50 55
60Ala Trp Glu Glu Glu Gln Glu Val Ala Glu Leu Leu Lys Glu Glu Phe65
70 75 80Pro Ala Trp Tyr Glu
Lys Leu Val Leu Glu Met Val His His Asn Thr 85
90 95Ala Ser Leu Glu Lys Leu Val Asp Thr Ala Trp
Leu Glu Ile Met Thr 100 105
110Lys Tyr Ala Val Gly Glu Glu Cys Asp Phe Glu Val Gly Lys Glu Lys
115 120 125Met Leu Lys Val Lys Ile Val
Lys Ile His Pro Leu Glu Lys Val Asp 130 135
140Glu Glu Ala Thr Glu Lys Lys Ser Asp Gly Ala Cys Asp Ser Pro
Ser145 150 155 160Ser Asp
Lys Glu Asn Ser Ser Gln Ile Ala Gln Asp His Gln Lys Lys
165 170 175Glu Thr Val Val Lys Glu Asp
Glu Gly Arg Arg Glu Ser Ile Asn Asp 180 185
190Arg Ala Arg Arg Ser Pro Arg Lys Leu Pro Thr Ser Leu Lys
Lys Gly 195 200 205Glu Arg Lys Trp
Ala Pro Pro Lys Phe Leu Pro His Lys Tyr Asp Val 210
215 220Lys Leu Gln Asn Glu Asp Lys Ile Ile Ser Asn Val
Pro Ala Asp Ser225 230 235
240Leu Ile Arg Thr Glu Arg Pro Pro Asn Lys Glu Ile Val Arg Tyr Phe
245 250 255Ile Arg His Asn Ala
Leu Arg Ala Gly Thr Gly Glu Asn Ala Pro Trp 260
265 270Val Val Glu Asp Glu Leu Val Lys Lys Tyr Ser Leu
Pro Ser Lys Phe 275 280 285Ser Asp
Phe Leu Leu Asp Pro Tyr Lys Tyr Met Thr Leu Asn Pro Ser 290
295 300Thr Lys Arg Lys Asn Thr Gly Ser Pro Asp Arg
Lys Pro Ser Lys Lys305 310 315
320Ser Lys Thr Asp Asn Ser Ser Leu Ser Ser Pro Leu Asn Pro Lys Leu
325 330 335Trp Cys His Val
His Leu Lys Lys Ser Leu Ser Gly Ser Pro Leu Lys 340
345 350Val Lys Asn Ser Lys Asn Ser Lys Ser Pro Glu
Glu His Leu Glu Glu 355 360 365Met
Met Lys Met Met Ser Pro Asn Lys Leu His Thr Asn Phe His Ile 370
375 380Pro Lys Lys Gly Pro Pro Ala Lys Lys Pro
Gly Lys His Ser Asp Lys385 390 395
400Pro Leu Lys Ala Lys Gly Arg Ser Lys Gly Ile Leu Asn Gly Gln
Lys 405 410 415Ser Thr Gly
Asn Ser Lys Ser Pro Lys Lys Gly Leu Lys Thr Pro Lys 420
425 430Thr Lys Met Lys Gln Met Thr Leu Leu Asp
Met Ala Lys Gly Thr Gln 435 440
445Lys Met Thr Arg Ala Pro Arg Asn Ser Gly Gly Thr Pro Arg Thr Ser 450
455 460Ser Lys Pro His Lys His Leu Pro
Pro Ala Ala Leu His Leu Ile Ala465 470
475 480Tyr Tyr Lys Glu Asn Lys Asp Arg Glu Asp Lys Arg
Ser Ala Leu Ser 485 490
495Cys Val Ile Ser Lys Thr Ala Arg Leu Leu Ser Ser Glu Asp Arg Ala
500 505 510Arg Leu Pro Glu Glu Leu
Arg Ser Leu Val Gln Lys Arg Tyr Glu Leu 515 520
525Leu Glu His Lys Lys Arg Trp Ala Ser Met Ser Glu Glu Gln
Arg Lys 530 535 540Glu Tyr Leu Lys Lys
Lys Arg Glu Glu Leu Lys Lys Lys Leu Lys Glu545 550
555 560Lys Ala Lys Glu Arg Arg Glu Lys Glu Met
Leu Glu Arg Leu Glu Lys 565 570
575Gln Lys Arg Tyr Glu Asp Gln Glu Leu Thr Gly Lys Asn Leu Pro Ala
580 585 590Phe Arg Leu Val Asp
Thr Pro Glu Gly Leu Pro Asn Thr Leu Phe Gly 595
600 605Asp Val Ala Met Val Val Glu Phe Leu Ser Cys Tyr
Ser Gly Leu Leu 610 615 620Leu Pro Asp
Ala Gln Tyr Pro Ile Thr Ala Val Ser Leu Met Glu Ala625
630 635 640Leu Ser Ala Asp Lys Gly Gly
Phe Leu Tyr Leu Asn Arg Val Leu Val 645
650 655Ile Leu Leu Gln Thr Leu Leu Gln Asp Glu Ile Ala
Glu Asp Tyr Gly 660 665 670Glu
Leu Gly Met Lys Leu Ser Glu Ile Pro Leu Thr Leu His Ser Val 675
680 685Ser Glu Leu Val Arg Leu Cys Leu Arg
Arg Ser Asp Val Gln Glu Glu 690 695
700Ser Glu Gly Ser Asp Thr Asp Asp Asn Lys Asp Ser Ala Ala Phe Glu705
710 715 720Asp Asn Glu Val
Gln Asp Glu Phe Leu Glu Lys Leu Glu Thr Ser Glu 725
730 735Phe Phe Glu Leu Thr Ser Glu Glu Lys Leu
Gln Ile Leu Thr Ala Leu 740 745
750Cys His Arg Ile Leu Met Thr Tyr Ser Val Gln Asp His Met Glu Thr
755 760 765Arg Gln Gln Met Ser Ala Glu
Leu Trp Lys Glu Arg Leu Ala Val Leu 770 775
780Lys Glu Glu Asn Asp Lys Lys Arg Ala Glu Lys Gln Lys Arg Lys
Glu785 790 795 800Met Glu
Ala Lys Asn Lys Glu Asn Gly Lys Val Glu Asn Gly Leu Gly
805 810 815Lys Thr Asp Arg Lys Lys Glu
Ile Val Lys Phe Glu Pro Gln Val Asp 820 825
830Thr Glu Ala Glu Asp Met Ile Ser Ala Val Lys Ser Arg Arg
Leu Leu 835 840 845Ala Ile Gln Ala
Lys Lys Glu Arg Glu Ile Gln Glu Arg Glu Met Lys 850
855 860Val Lys Leu Glu Arg Gln Ala Glu Glu Glu Arg Ile
Arg Lys His Lys865 870 875
880Ala Ala Ala Glu Lys Ala Phe Gln Glu Gly Ile Ala Lys Ala Lys Leu
885 890 895Val Met Arg Arg Thr
Pro Ile Gly Thr Asp Arg Asn His Asn Arg Tyr 900
905 910Trp Leu Phe Ser Asp Glu Val Pro Gly Leu Phe Ile
Glu Lys Gly Trp 915 920 925Val His
Asp Ser Ile Asp Tyr Arg Phe Asn His His Cys Lys Asp His 930
935 940Thr Val Ser Gly Asp Glu Asp Tyr Cys Pro Arg
Ser Lys Lys Ala Asn945 950 955
960Leu Gly Lys Asn Ala Ser Met Asn Thr Gln His Gly Thr Ala Thr Glu
965 970 975Val Ala Val Glu
Thr Thr Thr Pro Lys Gln Gly Gln Asn Leu Trp Phe 980
985 990Leu Cys Asp Ser Gln Lys Glu Leu Asp Glu Leu
Leu Asn Cys Leu His 995 1000
1005Pro Gln Gly Ile Arg Glu Ser Gln Leu Lys Glu Arg Leu Glu Lys Arg
1010 1015 1020Tyr Gln Asp Ile Ile His Ser
Ile His Leu Ala Arg Lys Pro Asn Leu1025 1030
1035 1040Gly Leu Lys Ser Cys Asp Gly Asn Gln Glu Leu Leu
Asn Phe Leu Arg 1045 1050
1055Ser Asp Leu Ile Glu Val Ala Thr Arg Leu Gln Lys Gly Gly Leu Gly
1060 1065 1070Tyr Val Glu Glu Thr Ser
Glu Phe Glu Ala Arg Val Ile Ser Leu Glu 1075 1080
1085Lys Leu Lys Asp Phe Gly Glu Cys Val Ile Ala Leu Gln Ala
Ser Val 1090 1095 1100Ile Lys Lys Phe
Leu Gln Gly Phe Met Ala Pro Lys Gln Lys Arg Arg1105 1110
1115 1120Lys Leu Gln Ser Glu Asp Ser Ala Lys
Thr Glu Glu Val Asp Glu Glu 1125 1130
1135Lys Lys Met Val Glu Glu Ala Lys Val Ala Ser Ala Leu Glu Lys
Trp 1140 1145 1150Lys Thr Ala
Ile Arg Glu Ala Gln Thr Phe Ser Arg Met His Val Leu 1155
1160 1165Leu Gly Met Leu Asp Ala Cys Ile Lys Trp Asp
Met Ser Ala Glu Asn 1170 1175 1180Ala
Arg Cys Lys Val Cys Arg Lys Lys Gly Glu Asp Asp Lys Leu Ile1185
1190 1195 1200Leu Cys Asp Glu Cys Asn
Lys Ala Phe His Leu Phe Cys Leu Arg Pro 1205
1210 1215Ala Leu Tyr Glu Val Pro Asp Gly Glu Trp Gln Cys
Pro Ala Cys Gln 1220 1225
1230Pro Ala Thr Ala Arg Arg Asn Ser Arg Gly Arg Asn Tyr Thr Glu Glu
1235 1240 1245Ser Ala Ser Glu Asp Ser Glu
Asp Asp Glu Ser Asp Glu Glu Glu Glu 1250 1255
1260Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Tyr Glu Val Ala Gly
Leu1265 1270 1275 1280Arg
Leu Arg Pro Arg Lys Thr Ile Arg Gly Lys His Ser Val Ile Pro
1285 1290 1295Pro Ala Ala Arg Ser Gly Arg
Arg Pro Gly Lys Lys Pro His Ser Thr 1300 1305
1310Arg Arg Ser Gln Pro Lys Ala Pro Pro Val Asp Asp Ala Glu
Val Asp 1315 1320 1325Glu Leu Val
Leu Gln Thr Lys Arg Ser Ser Arg Arg Gln Ser Leu Glu 1330
1335 1340Leu Gln Lys Cys Glu Glu Ile Leu His Lys Ile Val
Lys Tyr Arg Phe1345 1350 1355
1360Ser Trp Pro Phe Arg Glu Pro Val Thr Arg Asp Glu Ala Glu Asp Tyr
1365 1370 1375Tyr Asp Val Ile Thr
His Pro Met Asp Phe Gln Thr Val Gln Asn Lys 1380
1385 1390Cys Ser Cys Gly Ser Tyr Arg Ser Val Gln Glu Phe
Leu Thr Asp Met 1395 1400 1405Lys
Gln Val Phe Thr Asn Ala Glu Val Tyr Asn Cys Arg Gly Ser His 1410
1415 1420Val Leu Ser Cys Met Val Lys Thr Glu Gln
Cys Leu Val Ala Leu Leu1425 1430 1435
1440His Lys His Leu Pro Gly His Pro Tyr Val Arg Arg Lys Arg Lys
Lys 1445 1450 1455Phe Pro
Asp Arg Leu Ala Glu Asp Glu Gly Asp Ser Glu Pro Glu Ala 1460
1465 1470Val Gly Gln Ser Arg Gly Arg Arg Gln
Lys Lys 1475 1480284452DNAHomo sapiens 28atggcgccgc
tcctgggccg caagcccttc ccgctggtga agccgttgcc cggagaggag 60ccgctcttca
ccatcccgca cactcaggag gccttccgca cccgggaaga gtatgaagcc 120cgcttggaaa
ggtacagtga gcgcatttgg acgtgcaaga gtactggaag cagtcagcta 180acacacaagg
aagcctggga ggaagaacag gaagttgctg agcttttgaa ggaggagttt 240cctgcctggt
atgagaagct tgttctggaa atggttcacc ataacacagc ctccttagag 300aagttagtag
atactgcttg gttggagatc atgaccaaat atgctgtggg agaagagtgt 360gacttcgagg
ttgggaagga gaaaatgctc aaggtgaaga ttgtgaagat tcatcctttg 420gagaaagtgg
atgaagaggc cactgagaag aaatctgatg gtgcctgtga ttctccatca 480agtgacaaag
agaactccag tcagattgct caggaccatc agaagaagga gacagttgtg 540aaagaggatg
aaggaaggag agagagtatt aatgacagag cacgtagatc gccacgaaaa 600cttcctactt
cattaaaaaa aggagaaagg aaatgggctc ctccaaaatt tctgcctcac 660aaatatgatg
tgaaactaca aaatgaagat aagatcatca gtaacgtgcc agcagacagc 720ttgattcgta
cagagcgccc accaaataag gagatagttc gatactttat acggcataat 780gcattacgag
ctggtactgg tgaaaatgca ccttgggtcg tagaagatga attggtgaag 840aaatactctc
tgcccagcaa gttcagtgac tttttacttg atccatacaa gtatatgact 900ctcaaccctt
ctactaagag gaagaatact ggatccccag acaggaagcc ctcaaagaaa 960tccaagacag
acaactcttc tcttagttca ccactaaatc ctaagttatg gtgtcacgta 1020cacttgaaga
agtcattgag tggctcgcca ctcaaagtga agaactcaaa gaattccaaa 1080tctcctgaag
aacatctaga agaaatgatg aagatgatgt cgcccaataa gctgcacact 1140aactttcaca
ttcctaaaaa aggcccacct gccaagaaac cagggaagca cagtgacaag 1200cctttgaagg
caaagggcag aagcaaaggc atcctgaatg gacagaaatc cacagggaat 1260tccaaatctc
ccaaaaaagg actgaagact cctaaaacca aaatgaagca gatgactttg 1320ttggatatgg
ccaaaggcac gcagaagatg acacgagccc cacggaattc tgggggtaca 1380cctaggacct
ctagtaaacc tcataaacat ctgcctcctg cagccctaca cctcattgca 1440tactacaaag
aaaacaaaga cagggaggac aagaggagcg ccctgtcctg tgttatctcc 1500aaaacagctc
gtcttctctc tagtgaagat agagctcgtc tcccagaaga attgcgaagt 1560cttgttcaaa
aacgctatga acttctagag cacaaaaaga ggtgggcttc tatgtctgaa 1620gaacaacgga
aagaatattt gaaaaagaaa cgggaggagc tgaaaaagaa gttgaaggaa 1680aaagccaaag
aacgaagaga gaaagaaatg cttgagagat tagaaaaaca gaagcggtat 1740gaggaccaag
agttaactgg caaaaacctt ccagcattca gattggtgga tacccctgaa 1800gggctgccca
acacgctgtt tggggatgtg gccatggtgg tggaattctt gagctgttat 1860tctgggctac
ttttaccaga tgctcagtat cctattactg ctgtgtccct tatggaagcc 1920ttgagtgcag
ataagggtgg ctttttatac cttaacaggg tgttggtcat cctcttacag 1980accctcctac
aagatgagat agcagaagac tatggtgaat tgggaatgaa gctgtcggaa 2040atccccttga
ctctgcattc tgtttcagag ctggtgcggc tctgcttgcg cagatctgat 2100gttcaggagg
aaagcgaggg ctcagacaca gatgacaata aagattcagc tgcatttgag 2160gataatgagg
tacaagatga gttcctagaa aagctggaga cctctgaatt ttttgagctg 2220acgtcagagg
agaagctaca gatcttgaca gcactgtgcc accggatcct catgacatac 2280tcagtgcaag
accacatgga gaccagacag cagatgtctg cagagttgtg gaaggaacgg 2340cttgctgtgt
tgaaggaaga aaatgataag aagagagcag agaaacagaa acggaaagaa 2400atggaagcca
aaaataaaga aaatggaaaa gttgagaatg ggttaggcaa aactgatagg 2460aaaaaagaaa
ttgtgaagtt tgagccccaa gtagatacag aagctgaaga catgattagt 2520gctgtgaaga
gcagaaggtt gcttgccatt caagctaaga aggaacggga aatccaggaa 2580agagaaatga
aagtgaaact ggaacgccaa gctgaagaag aacgaatacg gaagcacaaa 2640gcagctgctg
agaaagcttt ccaggaaggg attgccaagg ccaaactagt catgcgcagg 2700actcctattg
gcacagatcg aaaccataat agatactggc tcttctcaga tgaagttcca 2760ggattattca
ttgaaaaagg ctgggtacat gacagcattg actaccgatt caaccatcac 2820tgcaaagacc
acacagtctc tggtgatgag gattactgtc ctcgcagtaa gaaagcaaac 2880ttaggtaaaa
atgcaagcat gaacacacaa catggaacag caacagaagt tgctgtagag 2940acaaccacac
ccaaacaagg acagaaccta tggtttttat gtgatagtca aaaggagctg 3000gatgagttgc
taaactgtct tcaccctcag ggaataagag aaagtcaact taaagagaga 3060ctagagaaga
ggtaccagga cattattcac tctattcatc tagcacggaa gccaaatttg 3120ggtctaaaat
cttgtgatgg caaccaggag cttttaaact tccttcgtag tgatctcatt 3180gaagttgcaa
caaggttaca aaaaggagga cttggatatg tggaagaaac atcagaattt 3240gaagcccggg
tcatttcatt agagaaattg aaggattttg gtgagtgtgt gattgccctt 3300caggccagtg
tcataaagaa atttctccaa ggcttcatgg ctcccaagca aaagagaaga 3360aaactccaaa
gtgaagattc agcaaaaact gaggaagtgg atgaagagaa gaaaatggta 3420gaggaagcaa
aggttgcatc tgcactggag aaatggaaga cagcaatccg ggaagctcag 3480actttctcca
ggatgcacgt gctgcttggg atgcttgatg cctgtatcaa gtgggatatg 3540tccgcagaaa
atgctaggtg caaagtttgt cgaaagaaag gtgaggatga caaattgatc 3600ttgtgtgatg
agtgtaataa agccttccac ctgttttgtc tgaggccggc cctctatgaa 3660gtaccagatg
gtgagtggca gtgcccagct tgccagcccg ctactgccag gcgcaactcc 3720cgtggcagga
actatactga agagtctgct tctgaggaca gtgaagatga tgagagtgat 3780gaagaggagg
aggaggaaga agaggaggag gaggaagaag attatgaggt ggctggtttg 3840cgattgagac
ctcgaaagac catccggggc aagcacagcg tcatcccccc tgcagcaagg 3900tcaggccggc
gcccgggtaa gaagccacac tctaccagga ggtctcagcc caaggcacca 3960cctgtggatg
atgctgaggt ggatgagctg gtgcttcaga ccaagcggag ctcccggagg 4020caaagcctgg
agctgcagaa gtgtgaagag atcctccaca agatcgtgaa gtaccgcttc 4080agctggccct
tcagggagcc tgtgaccaga gatgaggccg aggactacta tgatgtgatc 4140acgcacccca
tggactttca gacagtgcag aacaaatgtt cctgtgggag ctaccgctct 4200gtgcaggagt
ttcttactga catgaagcaa gtgtttacca atgctgaggt ttacaactgc 4260cgtggcagcc
atgtgctaag ctgcatggtg aagacagaac agtgtctagt ggctctgttg 4320cataaacacc
ttcctggcca cccatatgtc cgcaggaagc gcaagaagtt tcctgatagg 4380cttgctgaag
atgaagggga cagtgagcca gaggccgttg gacagtccag gggacgaaga 4440cagaagaagt
ag 445229621PRTHomo
sapiens 29Met Leu Leu Leu Pro Ser Ala Ala Asp Gly Arg Gly Thr Ala Ile
Thr1 5 10 15His Ala Leu
Thr Ser Ala Ser Thr Leu Cys Gln Val Glu Pro Val Gly 20
25 30Arg Trp Phe Glu Ala Phe Val Lys Arg Arg
Asn Arg Asn Ala Ser Ala 35 40
45Ser Phe Gln Glu Leu Glu Asp Lys Lys Glu Leu Ser Glu Glu Ser Glu 50
55 60Asp Glu Glu Leu Gln Leu Glu Glu Phe
Pro Met Leu Lys Thr Leu Asp65 70 75
80Pro Lys Asp Trp Lys Asn Gln Asp His Tyr Ala Val Leu Gly
Leu Gly 85 90 95His Val
Arg Tyr Lys Ala Thr Gln Arg Gln Ile Lys Ala Ala His Lys 100
105 110Ala Met Val Leu Lys His His Pro Asp
Lys Arg Lys Ala Ala Gly Glu 115 120
125Pro Ile Lys Glu Gly Asp Asn Asp Tyr Phe Thr Cys Ile Thr Lys Ala
130 135 140Tyr Glu Met Leu Ser Asp Pro
Val Lys Arg Arg Ala Phe Asn Ser Val145 150
155 160Asp Pro Thr Phe Asp Asn Ser Val Pro Ser Lys Ser
Glu Ala Lys Asp 165 170
175Asn Phe Phe Glu Val Phe Thr Pro Val Phe Glu Arg Asn Ser Arg Trp
180 185 190Ser Asn Lys Lys Asn Val
Pro Lys Leu Gly Asp Met Asn Ser Ser Phe 195 200
205Glu Asp Val Asp Ile Phe Tyr Ser Phe Trp Tyr Asn Phe Asp
Ser Trp 210 215 220Arg Glu Phe Ser Tyr
Leu Asp Glu Glu Glu Lys Glu Lys Ala Glu Cys225 230
235 240Arg Asp Glu Arg Arg Trp Ile Glu Lys Gln
Asn Arg Ala Thr Arg Ala 245 250
255Gln Arg Lys Lys Glu Glu Met Asn Arg Ile Arg Thr Leu Val Asp Asn
260 265 270Ala Tyr Ser Cys Asp
Pro Arg Ile Lys Lys Phe Lys Glu Glu Glu Lys 275
280 285Ala Lys Lys Glu Ala Glu Lys Lys Ala Lys Ala Glu
Ala Lys Arg Lys 290 295 300Glu Gln Glu
Ala Lys Glu Lys Gln Arg Gln Ala Glu Leu Glu Ala Ala305
310 315 320Arg Leu Ala Lys Glu Lys Glu
Glu Glu Glu Val Arg Gln Gln Ala Leu 325
330 335Leu Ala Lys Lys Glu Lys Asp Ile Gln Lys Lys Ala
Ile Lys Lys Glu 340 345 350Arg
Gln Lys Leu Arg Asn Ser Cys Lys Thr Trp Asn His Phe Ser Asp 355
360 365Asn Glu Ala Glu Arg Val Lys Met Met
Glu Glu Val Glu Lys Leu Cys 370 375
380Asp Arg Leu Glu Leu Ala Ser Leu Gln Cys Leu Asn Glu Thr Leu Thr385
390 395 400Ser Cys Thr Lys
Glu Val Gly Lys Ala Ala Leu Glu Lys Gln Ile Glu 405
410 415Glu Ile Asn Glu Gln Ile Arg Lys Glu Lys
Glu Glu Ala Glu Ala Arg 420 425
430Met Arg Gln Ala Ser Lys Asn Thr Glu Lys Ser Thr Gly Gly Gly Gly
435 440 445Asn Gly Ser Lys Asn Trp Ser
Glu Asp Asp Leu Gln Leu Leu Ile Lys 450 455
460Ala Val Asn Leu Phe Pro Ala Gly Thr Asn Ser Arg Trp Glu Val
Ile465 470 475 480Ala Asn
Tyr Met Asn Ile His Ser Ser Ser Gly Val Lys Arg Thr Ala
485 490 495Lys Asp Val Ile Gly Lys Ala
Lys Ser Leu Gln Lys Leu Asp Pro His 500 505
510Gln Lys Asp Asp Ile Asn Lys Lys Ala Phe Asp Lys Phe Lys
Lys Glu 515 520 525His Gly Val Val
Pro Gln Ala Asp Asn Ala Thr Pro Ser Glu Arg Phe 530
535 540Glu Gly Pro Tyr Thr Asp Phe Thr Pro Trp Thr Thr
Glu Glu Gln Lys545 550 555
560Leu Leu Glu Gln Ala Leu Lys Thr Tyr Pro Val Asn Thr Pro Glu Arg
565 570 575Trp Glu Lys Ile Ala
Glu Ala Val Pro Gly Arg Thr Lys Lys Asp Cys 580
585 590Met Lys Arg Tyr Lys Glu Leu Val Glu Met Val Lys
Ala Lys Lys Ala 595 600 605Ala Gln
Glu Gln Val Leu Asn Ala Ser Arg Ala Lys Lys 610 615
620301866DNAHomo sapiens 30tcatgctgct tctgccaagc gccgcggacg
gccggggcac cgccatcacc cacgctctga 60cctctgcctc tacactctgt caagttgaac
ctgtgggaag atggtttgaa gcttttgtta 120agaggagaaa cagaaatgct tctgcctctt
ttcaggaact ggaggataag aaagagttat 180ccgaggaatc agaagatgaa gaattgcagt
tggaagagtt tcccatgctg aaaacacttg 240atcccaaaga ctggaagaac caagatcatt
atgcagttct tggacttggc catgtgagat 300acaaggctac acagagacag atcaaagcag
ctcataaagc aatggtttta aaacatcacc 360cagacaaacg gaaagcagct ggtgaaccaa
taaaagaagg agataatgac tacttcactt 420gcataactaa agcttatgaa atgttatctg
atccagtgaa aagacgagca tttaacagtg 480tagatcctac ttttgataac tcagttcctt
ctaaaagtga agcaaaggat aatttcttcg 540aagtgtttac cccagtgttt gaaaggaatt
ccagatggtc aaataaaaaa aatgttccta 600aacttggtga tatgaattca tcatttgaag
atgtagatat attttattct ttctggtata 660attttgattc ttggagagaa ttttcttatt
tagatgaaga agaaaaagaa aaagcagaat 720gtcgtgatga gaggagatgg attgaaaagc
agaacagagc aacaagagca caaagaaaaa 780aagaagaaat gaacagaata agaacattag
ttgacaatgc atacagctgt gatccaagga 840taaaaaagtt caaggaagaa gaaaaagcca
agaaagaagc agaaaagaaa gcaaaagcag 900aagctaaacg gaaggagcaa gaagctaaag
aaaaacaaag acaagctgaa ttagaagctg 960ctcggttagc taaggagaaa gaagaggagg
aagtcagaca gcaagcattg ctggcaaaga 1020aggaaaaaga tatccagaaa aaagccatta
agaaggaaag gcaaaaactt cgaaactcat 1080gcaagacctg gaatcatttt tctgataatg
aggcagagcg ggttaaaatg atggaagaag 1140tggaaaaact ttgtgatcgg cttgaactgg
caagcttaca gtgcttgaat gaaacactca 1200catcatgcac aaaagaagta ggaaaggctg
ctttggaaaa acagatagaa gaaataaatg 1260agcaaatcag aaaagagaaa gaggaagctg
aggctcgtat gcgacaagca tctaagaaca 1320cagagaaatc aactggtgga ggtggaaatg
gaagtaaaaa ttggtcagaa gatgatctac 1380aattactaat taaagctgtg aatctgttcc
ctgctggaac aaattcaaga tgggaagtta 1440ttgctaatta catgaacata cattcttcct
ctggagtcaa aagaactgcc aaagatgtta 1500ttggcaaagc aaagagtctc caaaaacttg
accctcatca aaaagatgac ataaataaaa 1560aggcatttga taagttcaaa aaagaacatg
gagtggtacc tcaagcagac aacgcaacgc 1620cttcagaacg atttgaaggt ccatatacag
acttcacccc ttggacaaca gaagaacaga 1680agcttttgga acaagctttg aaaacatacc
cagtaaatac acctgaaaga tgggaaaaaa 1740tagcagaagc ggtgcctggc aggacaaaga
aggactgcat gaaacgatac aaggaacttg 1800tcgagatggt aaaagcaaag aaagctgctc
aagaacaagt gctgaatgca agtagagcca 1860agaaat
186631380PRTHomo sapiens 31Met Gly Ala
Ala Ala Ala Glu Ala Pro Leu Arg Leu Pro Ala Ala Pro1 5
10 15Pro Leu Ala Phe Cys Cys Tyr Thr Ser
Val Leu Leu Leu Phe Ala Phe 20 25
30Ser Leu Pro Gly Ser Arg Ala Ser Asn Gln Pro Pro Gly Gly Gly Gly
35 40 45Gly Ser Gly Gly Asp Cys Pro
Gly Gly Lys Gly Lys Ser Ile Asn Cys 50 55
60Ser Glu Leu Asn Val Arg Glu Ser Asp Val Arg Val Cys Asp Glu Ser65
70 75 80Ser Cys Lys Tyr
Gly Gly Val Cys Lys Glu Asp Gly Asp Gly Leu Lys 85
90 95Cys Ala Cys Gln Phe Gln Cys His Thr Asn
Tyr Ile Pro Val Cys Gly 100 105
110Ser Asn Gly Asp Thr Tyr Gln Asn Glu Cys Phe Leu Arg Arg Ala Ala
115 120 125Cys Lys His Gln Lys Glu Ile
Thr Val Ile Ala Arg Gly Pro Cys Tyr 130 135
140Ser Asp Asn Gly Ser Gly Ser Gly Glu Gly Glu Glu Glu Gly Ser
Gly145 150 155 160Ala Glu
Val His Arg Lys His Ser Lys Cys Gly Pro Cys Lys Tyr Lys
165 170 175Ala Glu Cys Asp Glu Asp Ala
Glu Asn Val Gly Cys Val Cys Asn Ile 180 185
190Asp Cys Ser Gly Tyr Ser Phe Asn Pro Val Cys Ala Ser Asp
Gly Ser 195 200 205Ser Tyr Asn Asn
Pro Cys Phe Val Arg Glu Ala Ser Cys Ile Lys Gln 210
215 220Glu Gln Ile Asp Ile Arg His Leu Gly His Cys Thr
Asp Thr Asp Asp225 230 235
240Thr Ser Leu Leu Gly Lys Lys Asp Asp Gly Leu Gln Tyr Arg Pro Asp
245 250 255Val Lys Asp Ala Ser
Asp Gln Arg Glu Asp Val Tyr Ile Gly Asn His 260
265 270Met Pro Cys Pro Glu Asn Leu Asn Gly Tyr Cys Ile
His Gly Lys Cys 275 280 285Glu Phe
Ile Tyr Ser Thr Gln Lys Ala Ser Cys Arg Cys Glu Ser Gly 290
295 300Tyr Thr Gly Gln His Cys Glu Lys Thr Asp Phe
Ser Ile Leu Tyr Val305 310 315
320Val Pro Ser Arg Gln Lys Leu Thr His Val Leu Ile Ala Ala Ile Ile
325 330 335Gly Ala Val Gln
Ile Ala Ile Ile Val Ala Ile Val Met Cys Ile Thr 340
345 350Arg Lys Cys Pro Lys Asn Asn Arg Gly Arg Arg
Gln Lys Gln Asn Leu 355 360 365Gly
His Phe Thr Ser Asp Thr Ser Ser Arg Met Val 370 375
380321143DNAHomo sapiens 32atgggcgccg cagccgctga ggcgccgctc
cggctgcctg ccgcgcctcc gctcgccttc 60tgctgctaca cgtcggtgct tctgctcttc
gccttctctc tgcccgggag ccgcgcgtcc 120aaccagcccc cgggtggtgg cggcggcagc
ggcggggact gtcccggcgg caaaggcaag 180agcatcaact gctcagaatt aaatgtgagg
gagtctgacg taagagtttg tgatgagtca 240tcatgtaaat atggaggagt ctgtaaagaa
gatggagatg gtttgaaatg tgcatgccaa 300tttcagtgcc atacaaatta tattcctgtc
tgtggatcaa atggggacac ttatcaaaat 360gaatgctttc tcagaagggc tgcttgtaag
caccagaaag agataacagt aatagcaaga 420ggaccatgct actctgataa tggatctgga
tctggagaag gagaagagga agggtcaggg 480gcagaagttc acagaaaaca ctccaagtgt
ggaccctgca aatataaagc tgagtgtgat 540gaagatgcag aaaatgttgg gtgtgtatgt
aatatagatt gcagtggata cagttttaat 600cctgtgtgtg cttctgatgg gagttcctat
aacaatccct gttttgttcg agaagcatct 660tgtataaagc aagaacaaat tgatataagg
catcttggtc attgcacaga tacagatgac 720actagtttgt tgggaaagaa agatgatgga
ctacaatatc gaccagatgt gaaagatgct 780agtgatcaaa gagaagatgt ttatattgga
aaccacatgc cttgccctga aaacctcaat 840ggttactgca tccatggaaa atgtgaattc
atctattcta ctcagaaggc ttcttgtaga 900tgtgaatctg gctacactgg acagcactgt
gaaaagacag actttagtat tctctatgta 960gtgccaagta ggcaaaagct cactcatgtt
cttattgcag caattattgg agctgtacag 1020attgccatca tagtagcaat tgtaatgtgc
ataacaagaa aatgccccaa aaacaataga 1080ggacgtcgac agaagcaaaa cctaggtcat
tttacttcag atacgtcatc cagaatggtt 1140taa
114333185PRTHomo sapiens 33Met Gly Lys
Lys Gln Asn Lys Lys Lys Val Glu Glu Val Leu Glu Glu1 5
10 15Glu Glu Glu Glu Tyr Val Val Glu Lys
Val Leu Asp Arg Arg Val Val 20 25
30Lys Gly Lys Val Glu Tyr Leu Leu Lys Trp Lys Gly Phe Ser Asp Glu
35 40 45Asp Asn Thr Trp Glu Pro Glu
Glu Asn Leu Asp Cys Pro Asp Leu Ile 50 55
60Ala Glu Phe Leu Gln Ser Gln Lys Thr Ala His Glu Thr Asp Lys Ser65
70 75 80Glu Gly Gly Lys
Arg Lys Ala Asp Ser Asp Ser Glu Asp Lys Gly Glu 85
90 95Glu Ser Lys Pro Lys Lys Lys Lys Glu Glu
Ser Glu Lys Pro Arg Gly 100 105
110Phe Ala Arg Gly Leu Glu Pro Glu Arg Ile Ile Gly Ala Thr Asp Ser
115 120 125Ser Gly Glu Leu Met Phe Leu
Met Lys Trp Lys Asn Ser Asp Glu Ala 130 135
140Asp Leu Val Pro Ala Lys Glu Ala Asn Val Lys Cys Pro Gln Val
Val145 150 155 160Ile Ser
Phe Tyr Glu Glu Arg Leu Thr Trp His Ser Tyr Pro Ser Glu
165 170 175Asp Asp Asp Lys Lys Asp Asp
Lys Asn 180 18534558DNAHomo sapiens
34atggggaaaa aacaaaacaa gaagaaagtg gaggaggtgc tagaagagga ggaagaggaa
60tatgtggtgg aaaaagttct cgaccgtcga gtggtaaagg gcaaagtgga gtacctccta
120aagtggaagg gattctcaga tgaggacaac acatgggagc cagaagagaa cctggattgc
180cccgacctca ttgctgagtt tctgcagtca cagaaaacag cacatgagac agataaatca
240gagggaggca agcgcaaagc tgattctgat tctgaagata agggagagga gagcaaacca
300aagaagaaga aagaagagtc agaaaagcca cgaggctttg ctcgaggttt ggagccggag
360cggattattg gagctacaga ctccagtgga gagctcatgt tcctgatgaa atggaaaaac
420tctgatgagg ctgacctggt ccctgccaag gaagccaatg tcaagtgccc acaggttgtc
480atatccttct atgaggaaag gctgacgtgg cattcctacc cctcggagga tgatgacaaa
540aaagatgaca agaactaa
55835257PRTHomo sapiens 35Met Val Ala Glu Lys Glu Thr Leu Ser Leu Asn Lys
Cys Pro Asp Lys1 5 10
15Met Pro Lys Arg Thr Lys Leu Leu Ala Gln Gln Pro Leu Pro Val His
20 25 30Gln Pro His Ser Leu Val Ser
Glu Gly Phe Thr Val Lys Ala Met Met 35 40
45Lys Asn Ser Val Val Arg Gly Pro Pro Ala Ala Gly Ala Phe Lys
Glu 50 55 60Arg Pro Thr Lys Pro Thr
Ala Phe Arg Lys Phe Tyr Glu Arg Gly Asp65 70
75 80Phe Pro Ile Ala Leu Glu His Asp Ser Lys Gly
Asn Lys Ile Ala Trp 85 90
95Lys Val Glu Ile Glu Lys Leu Asp Tyr His His Tyr Leu Pro Leu Phe
100 105 110Phe Asp Gly Leu Cys Glu
Met Thr Phe Pro Tyr Glu Phe Phe Ala Arg 115 120
125Gln Gly Ile His Asp Met Leu Glu His Gly Gly Asn Lys Ile
Leu Pro 130 135 140Val Leu Pro Gln Leu
Ile Ile Pro Ile Lys Asn Ala Leu Asn Leu Arg145 150
155 160Asn Arg Gln Val Ile Cys Val Thr Leu Lys
Val Leu Gln His Leu Val 165 170
175Val Ser Ala Glu Met Val Gly Lys Thr Leu Val Pro Tyr Tyr Arg Gln
180 185 190Ile Leu Pro Val Leu
Asn Ile Phe Lys Asn Met Asn Val Asn Ser Gly 195
200 205Asp Gly Ile Asp Tyr Ser Gln Gln Lys Arg Glu Asn
Ile Gly Asp Leu 210 215 220Ile Gln Glu
Thr Leu Glu Ala Phe Glu Arg Tyr Gly Gly Glu Asn Ala225
230 235 240Phe Ile Asn Ile Lys Tyr Val
Val Pro Thr Tyr Glu Ser Cys Leu Leu 245
250 255Asn36774DNAHomo sapiens 36atggtggcag aaaaagagac
cctgagctta aacaaatgcc cagacaagat gccgaagagg 60accaagctgc tggcacaaca
gccgctcccg gtgcaccagc ctcactctct ggtttctgag 120ggtttcacag tcaaagccat
gatgaaaaac tcagtcgtga gaggccctcc agctgcaggg 180gcatttaaag aaagaccaac
caagcccaca gcatttcgaa aattctatga gcgaggtgac 240ttcccaattg cccttgagca
tgattcgaaa ggaaacaaaa tcgcctggaa ggtagaaatt 300gagaagctgg attaccatca
ttatctgcct ctgttttttg atgggctttg tgaaatgaca 360tttccctatg agttttttgc
tcggcaagga atccacgaca tgctggaaca cggtgggaac 420aagatcctac ctgtccttcc
acagctcatt atcccgataa aaaatgcctt gaacctccga 480aaccgacagg tcatctgtgt
cactctcaag gtcctccagc atctggttgt gtcagctgag 540atggtgggca agaccttggt
gccttattac cgtcaaatcc tccctgtcct gaacatcttt 600aagaatatga atgtgaactc
cggagacggc attgactaca gccagcagaa gagggagaac 660attggggact tgatccagga
gacactggag gccttcgagc gctacggagg agaaaatgcc 720tttatcaaca ttaagtacgt
ggtcccaacc tacgagtctt gcttgctaaa ctaa 774
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