Abstract:
A novel gene, dubbed “YS68”, involved in primitive hematopoiesis was successfully isolated from cDNA derived from mouse yolk sacs. In addition, a human gene corresponding to this gene was successfully isolated. Expression characteristics of these genes suggested their involvement in primitive hematopoiesis. The proteins of this invention and genes encoding the proteins may be utilized as tools for drug development against diseases, such as hematological disorders.

Description:
[0001]    This application is a continuation-in-part of International Patent Application PCT/JP00/05756, filed Aug. 25, 2000, which claims priority to Japanese Patent Application Nos. 11/288738, filed Oct. 8, 1999; 11/288739, filed Oct. 8, 1999; and 2000-123721, filed Apr. 19, 2000.  
         TECHNICAL FIELD  
         [0002]    The present invention relates to novel proteins involved in primitive hematopoiesis and genes encoding the proteins. These molecules may be utilized, for example, in the field of drug development.  
         BACKGROUND  
         [0003]    There are two kinds of hematopoiesis: one is the transient primitive hematopoiesis (embryonic hematopoiesis) that functions only during the embryonic stage, and the other is the definitive hematopoiesis (adult hematopoiesis) that contributes to lifelong hematopoiesis. Research by Medvinsky et al. (Medvinsky et al., Cell 86:897-906, 1996; Cumano et al., Cell 86:907-916) revealed that, in contrast to primitive hematopoiesis that develops within the yolk sac on around embryonic day 9, definitive hematopoiesis is initiated within the AGM (Aorta-Gonad-Mesonephros) region on around embryonic day 10. Furthermore, regarding the origin of hematocytes, various studies have suggested that definitive hematopoiesis originates from hemangioblasts, thought to be precursor cells common to hematopoietic cells and vascular endothelium cells.  
           [0004]    While the mainly accepted view was that hemangioblasts, which are the origin of definitive hematopoiesis, exist in the AGM region, Yorder et al. argued against the existing theory and demonstrated that hemangioblasts, which may contribute to definitive hematopoiesis, also exist in the yolk sac (Yoder et al., Immunity 7:335-344, 1997). Therefore, it is now generally accepted that the surrounding environment is important for the differentiation of hemangioblasts to hematopoietic cells.  
           [0005]    Thus, while the origin of hematopoietic cells and the site of development have been gradually elucidated by phenomenological research, the molecular mechanism of hematopoietic development remains unclear. The isolation of a novel molecule involved with primitive hematopoiesis is thought to be an important step for the development of unprecedented drugs associated with hematological disorders.  
         SUMMARY  
         [0006]    The subject of the present invention is to provide novel proteins involved in primitive hematopoiesis and genes encoding the proteins, as well as production and use of the same.  
           [0007]    Although the existence of hemangioblasts has been reported in the mouse AGM (Aorta-Gonad-Mesonephros) region on embryonic day 9 to day 12, Yorder and Nishikawa et al. have reported that hemangioblasts exist in embryonic day 9 yolk sacs, but no longer exist in embryonic day 13 yolk sacs (Yoder et al., Immunity 7:335-344, 1997; Nishikawa et al., Immunity 8:761-769, 1998). The present inventors conducted cloning of genes to identify molecules involved with primitive hematopoiesis by subtracting the cDNA derived from embryonic day 13 mouse yolk sac in which hemangioblasts are assumed to be absent, from the cDNA derived from embryonic day 9 mouse yolk sac in which hemangioblast is suggested to be present. Inventors succeeded in isolating a novel gene that was named “YS68”. In addition, a primer was constructed based on the nucleotide sequence of the mouse gene, and, by performing 5′-RACE and 3′-RACE using human fetal liver Marathon-Ready cDNA as a template, the corresponding human gene was successfully isolated.  
           [0008]    Determination and comparison of the full-length human and mouse cDNA sequences showed a very high sequence homology of 87% in the N-terminal region (human 1-1137, mouse 1-1137); whereas the homology in the central region (human 1138-1683, mouse 1138-1679) was 57%; and the homology in the C-terminal region (human 1684-2266, mouse 1680-2243) was very low at 45%. Many nuclear transport signals were found to exist in the low-homology C-terminal region. On the other hand, two WD repeats that are known to be necessary for interaction with proteins were found to exist in the high-homology N-terminal region.  
           [0009]    To investigate the role of “YS68” in hematopoiesis, RT-PCR analysis of the expression pattern of “YS68” in mouse hematopoietic tissue was performed; the results revealed that the expression pattern of “YS68” correlated with the transport of hematopoietic tissues during the embryonic stage. In addition, “YS68” was expressed in CD34-positive undifferentiated hematocytes. Therefore, “YS68” is suggested to have an important function in primitive hematopoiesis.  
           [0010]    The “YS68” protein of this invention is useful as a tool for elucidating the mechanism of primitive hematopoiesis, furthermore, its application to drug development for various diseases related to hematopoietic system is anticipated.  
           [0011]    This invention relates to novel proteins involved in primitive hematopoiesis and genes encoding the proteins, as well as the production and use of the same. More specifically, this invention provides the following:  
           [0012]    (1) a DNA selected from the group of:  
           [0013]    (a) a DNA encoding a protein comprising the amino acid sequence of SEQ ID NO:12 or 14;  
           [0014]    (b) a DNA comprising the coding region of the nucleotide sequence of SEQ ID NO:11 or 13;  
           [0015]    (c) a DNA encoding a protein comprising of the amino acid sequence of SEQ ID NO:12 or 14, in which one or more amino acids are modified by substitution, deletion, insertion and/or addition, wherein said protein is functionally equivalent to the protein consisting of the amino acid sequence of SEQ ID NO:12 or 14; and  
           [0016]    (d) a DNA hybridizing under stringent conditions with a DNA consisting of the nucleotide sequence of SEQ ID NO:11 or 13, and encoding a protein that is functionally equivalent to a protein consisting of the amino acid sequence of SEQ ID NO:12 or 14;  
           [0017]    (2) a DNA encoding a partial peptide of a protein consisting of the amino acid sequence of SEQ ID NO:12 or 14;  
           [0018]    (3) a protein or a peptide encoded by the DNA of any one of (1) or (2);  
           [0019]    (4) a vector into which the DNA of any one of (1) or (2) is inserted;  
           [0020]    (5) a host cell retaining the vector of (4);  
           [0021]    (6) a method for producing the proteins or peptides of (3); comprising the step of culturing the host cells of (5), and recovering expressed protein from said host cell or the culture supernatant;  
           [0022]    (7) a polynucleotide comprising at least 15 nucleotides that are complementary to a DNA consisting of the nucleotide sequence of SEQ ID NO:11 or 13 or to a complementary strand thereof;  
           [0023]    (8) a method of screening for a compound that binds to the protein of (3), comprising the steps of:  
           [0024]    (a) contacting a test sample, containing at least one compound, with the protein or partial peptide of (3);  
           [0025]    (b) detecting the binding activity between the compound and the protein or partial peptide thereof; and  
           [0026]    (c) selecting the compound that has the activity to bind to the protein or partial peptide thereof;  
           [0027]    (9) a compound binding to the protein of (3);  
           [0028]    (10) the compound of (9), which is an antibody; and  
           [0029]    (11) a compound binding to the protein of (3), which may be isolated by the method of (8).  
           [0030]    The present invention provides novel proteins involved in primitive hematopoiesis and DNA encoding these proteins. The nucleotide sequence of the full-length cDNA of mouse “YS68” isolated by the present inventors is indicated in SEQ ID NO:11, and the amino acid sequence of the protein encoded by this cDNA is indicated in SEQ ID NO:12. In addition, the nucleotide sequence of the full-length cDNA of human “YS68” isolated by the present inventors is indicated in SEQ ID NO:13, and the amino acid sequence of the protein encoded by this cDNA is indicated in SEQ ID NO:14.  
           [0031]    Hematopoietic stem cells contributing to lifelong hematopoiesis are formed by the differentiation of hemangioblasts, the common mother cells of hematocytes and blood vessels. Several transcription factors thought to be important for primitive hematopoiesis have been reported according to recent gene disruption experiments. Not only angiogenesis but also hematopoiesis was not confirmed in mouse with disruption in SCL (Porcher et al., Cell 86:47-57, 1996; Visvader et al., Genes Dev. 12:473-479, 1998). In addition, AML-1 and c-Myb knockout mice did not show abnormalities in angiogenesis, but they completely lacked definitive hematopoiesis (Okuda et al., Cell 84:321-330, 1996; Lin et al., Curr. Top Microbiol. Immunol. 211:79-87, 1996). However, how these transcription factors interact with each other at the stage of primitive hematopoiesis and become involved in determining the fate of cells remains unknown.  
           [0032]    The mouse “YS68” gene identified by the present inventors was isolated by subtracting cDNA derived from embryonic day 13 mouse yolk sac, which is said to lack the hemangioblast, from cDNA derived from embryonic day 9 yolk sac, which is suggested to have a hemangioblast. The isolated “YS68” gene was expected to encode a protein of 1,265 amino acids, and showed an expression pattern with a high level expression in embryonic day 9 yolk sac followed by a gradual decrease. In addition, an expression of the gene was observed in the AGM region (considered to be the site of hematopoietic stem cell development) from day 10 embryos and in embryonic day 13 livers; the expression then shifted to strong expression at the thymus and spleen of day 16 embryos. Furthermore, expression in these regions considerably diminished in adult mice. Thus, the “YS68” cloned by the present inventors with such an expression pattern in the developmental stage can be considered as a new member of molecules involved in primitive hematopoiesis.  
           [0033]    Although “YS68” is expected to be a nuclear protein because it has multiple nuclear transport signals in its C-terminal region, strong expression was observed not only in the nucleus but also around the nucleus in hepatocytes (Example 6). The finding that WD repeats necessary for binding to proteins existed in the N-terminus, and immunoprecipitation caused coprecipitation of multiple proteins (Example 4) suggested that transport of this protein to the nucleus is regulated by interactions with other proteins.  
           [0034]    The idea that blood cells develop from the vascular endothelium has existed for a relatively long time, but was actually proven only recently. Jaffredo et al. stained the entire avian blood vessel with fluorescence-labeled LDL and revealed that the stained vascular endothelium differentiated into hematocytes (Jaffredo et al., Development 125:4575-4783, 1998). In addition, Hara et al. found that hemangioblasts can be concentrated by sorting the cells of the AGM region by PCLP-1 (podocalyxin-like protein 1). Localization of hemangioblasts in the vascular endothelium was suggested by the localized PCLP-1 expression in the AGM region in the vascular endothelium (Hara et al., Immunity 11:567-578, 1999). As shown in Example 5, the expression site of YS68 in the AGM region was the same vascular endothelium as PCLP-1. In addition, this expression pattern is the same as those of AML-1 and SCL, both of which are known to be important for primitive hematopoiesis. Considering that expression of YS68 in the hematocyte of CD34 positive cells, which are thought to be a group of relatively immature hematocytes (Example 6), is strong, YS68 is suggested to function in the process of differentiation from hemangioblasts to hematocytes.  
           [0035]    The “YS68” proteins of this invention and DNAs encoding the proteins are useful as differentiation markers and as regulating factors of developmental differentiation and the hematopoietic function of hematopoietic stem cells. Additionally, they may be applicable for diagnosis, prevention, and treatment of diseases in which a protein of this invention is involved. In current medicine, means for artificial amplification of hematopoietic stem cells does not exist. Artificial in vitro proliferation of hematopoietic stem cells may be enabled by forced expression of YS68 using a virus vector in hemangioblasts that are the origin of hematopoietic cells, or by administration of cytokines or compounds that induces the expression of YS68. Therefore, YS68 may be applied to medical treatment, as a new alternative to bone marrow transplant.  
           [0036]    In addition, many human blood cell tumors, such as myeloid leukemia and lymphoid leukemia, are often caused by abnormalities in transcription factors, and human “YS68” gene of this invention is likely to be one of the causative genes of these diseases. Therefore, human “YS68” may be particularly applied to genetic diagnosis or gene therapy of such diseases. Furthermore, drug development targeting the human “YS68” gene and protein themselves or molecules that regulate them, or molecules or genes that are regulated by the human “YS68” protein may be useful in the treatment and prevention of the above-mentioned diseases.  
           [0037]    Furthermore, this invention includes proteins that are functionally equivalent to the “YS68” protein (SEQ ID NO:12 and 14). For example, mutant forms of the “YS68” protein are included in such proteins. The term “functionally equivalent” herein means that the protein of interest has the function of regulating the development and/or differentiation of hematopoietic cells or has the function of interacting with other proteins.  
           [0038]    For example, the function of a protein to regulate the development and/or differentiation of hematopoietic cells can be evaluated using as an index the expression characteristics within the hematopoietic tissues, such as those described in Example 2. On the other hand, the function of a protein to interact with other proteins can be determined, for example, by utilizing immunoprecipitation, such as those described in Example 4.  
           [0039]    As a method well known by a person skilled in the art for preparing a protein functionally equivalent to a given protein, methods for introducing mutations into proteins are known. For example, one skilled in the art can prepare proteins functionally equivalent to the “YS68” proteins (SEQ ID NO:12 and 14) by introducing an appropriate mutation in the amino acid sequence of the protein by site-directed mutagenesis (Hashimoto-Gotoh et al., Gene 152:271-275, 1995; Zoller et al., Methods Enzymol. 100:468-500, 1983; Kramer et al., Nucleic Acids Res. 12:9441-9456, 1984; Kramer et al., Methods. Enzymol. 154:350-367, 1987; Kunkel, Proc. Natl. Acad. Sci. USA 82:488-492, 1985; Kunkel, Methods Enzymol. 85:2763-2766, 1988). Mutation of amino acids can occur in nature, too. The proteins of the present invention include those proteins that comprise the amino acid sequences of the “YS68” protein (SEQ ID NO:12 and 14), wherein one or more amino acids are mutated and yet are functionally equivalent to the protein comprising the sequence of “YS68” protein. It is considered that the number of amino acids to be mutated in such a mutant, is generally 100 amino acids or less, preferably 50 amino acids or less, more preferably 20 amino acids or less, and more preferably 5 amino acid or less.  
           [0040]    As for the amino acid residue to be mutated, it is preferable that it is mutated into a different amino acid such that the properties of the amino acid side-chain are conserved. Examples of properties of amino acid side chains are, hydrophobic amino acids (A, I, L, M, F, P, W, Y, V), hydrophilic amino acids (R, D, N, C, E, Q, G, H, K, S, T), and amino acids comprising the following side chains: an aliphatic side-chain (G, A, V, L, I, P); a hydroxyl group containing side-chain (S, T, Y); a sulfur atom containing side-chain (C, M); a carboxylic acid and amide containing side-chain (D, N, E, Q); a base containing side-chain (R, K, H); and an aromatic containing side-chain (H, F, Y, W) (The parenthetic letters indicate the one-letter codes of amino acids).  
           [0041]    It is well known that a protein having deletion, addition, and/or substitution of one or more amino acid residues in the sequence of a protein can retain the original biological activity (Mark et al., Proc. Natl. Acad. Sci. USA 81:5662-5666, 1984; Zoller et al., Nucleic Acids Res. 10:6487-6500, 1982; Wang et al., Science 224:1431-1433; Dalbadie-McFarland et al., Proc. Natl. Acad. Sci. USA 79:6409-6413, 1982).  
           [0042]    The term “substantially pure” as used herein in reference to a given polypeptide means that the polypeptide is substantially free from other biological macromolecules. For example, the substantially pure polypeptide is at least 75%, 80, 85, 95, or 99% pure by dry weight. Purity can be measured by any appropriate standard method known in the art, for example, by column chromatography, polyacrylamide gel electrophoresis, or HPLC analysis.  
           [0043]    Accordingly, the invention includes a polypeptide having a sequence shown as SEQ ID NO:12 or 14. The invention also includes a polypeptide, or fragment thereof, that differs from the corresponding sequence shown as SEQ ID NO:12 or 14. The polypeptide can differ from the sequence of SEQ ID NO:12 or 14 by having one or more amino acids substituted, deleted, inserted and/or added. For example, the polypeptide can be a fusion protein, having an additional amino acid sequence at the N- or C-terminus of SEQ ID NO:12 or 14. In preferred embodiments, the protein has no more than 50, 30, 20, 10 or 5 amino acids substituted, deleted, inserted and/or added. Preferably, the difference is a difference or change at one or more non-essential residues or one or more conservative amino acid substitutions, as defined above. In one embodiment, the polypeptide includes an amino acid sequence at least about 60% identical to a sequence shown as SEQ ID NO:12 or 14, or a fragment thereof. Preferably, the polypeptide is at least 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more identical to SEQ ID NO:12 or 14 and has at least one YS68 activity described herein, e.g., the protein can regulate development or differentiation of hematopoietic cells. Preferred polypeptide fragments of the invention are at least 10%, preferably at least 20%, 30%, 40%, 50%, 60%, 70%, or more, of the length of the sequence shown as SEQ ID NO:12 or 14 and have at least one YS68 activity described herein. Or alternatively, the fragment can be merely an immunogenic fragment.  
           [0044]    A fusion protein comprising “YS68” protein is encompassed in the protein, wherein one or more amino acids residues are added to the amino acid sequence of “YS68”. Fusion proteins are fusions of the “YS68” protein and other peptides or proteins, and are included in the present invention. Fusion proteins can be made by techniques well known to a person skilled in the art, such as by linking the DNA encoding the “YS68” protein (SEQ ID NO:12 and 14) with DNA encoding other peptides or proteins so as the frames match, inserting this linked DNA into an expression vector, and expressing it in a host. There is no restriction as to the peptides or proteins to be fused to a protein of the present invention.  
           [0045]    Known peptides, for example, FLAG (Hopp et al., Biotechnology 6:1204-1210, 1988), 6×His consisting of six His (histidine) residues, 10×His, Influenza agglutinin (HA), human c-myc fragment, VSV-GP fragment, p18HIV fragment, T7-tag, HSV-tag, E-tag, SV40T antigen fragment, lck tag, α-tubulin fragment, B-tag, Protein C fragment, and such, can be used as peptides to be fused to a protein of the present invention. Examples of proteins that may be fused to a protein of the present invention are, GST (glutathione-S-transferase), Influenza agglutinin (HA), immunoglobulin constant region, β-galactosidase, MBP (maltose-binding protein), and such. Fusion proteins can be prepared by fusing commercially available DNA encoding these peptides or proteins with a DNA encoding a protein of the present invention and expressing the fused DNA prepared.  
           [0046]    Furthermore, a protein, in which multiple amino acid residues have been added to the amino acid sequence of the “YS68” protein, includes a protein encoded by the nucleotide sequence starting from “a” at position 98 to “g” at position 6922 of SEQ ID NO:15 (protein comprising the amino acid sequence, wherein an amino acid sequence comprising “Met-Ala-Ala-Glu-Arg-Arg-Cys-Gly-Ser” is added to the N terminus of the amino acid sequence of SEQ ID NO:14).  
           [0047]    In addition, as a method well known to those skilled in the art for preparing proteins that are functionally equivalent to a known protein, methods that utilize hybridization techniques (Sambrook et al., Molecular Cloning 2nd ed., 9.47-9.58, Cold Spring Harbor Lab. Press, 1989) can be mentioned. More specifically, those skilled in the art may readily isolate DNAs having high homology to the DNA sequences (SEQ ID NO:11 and 13) encoding the “YS68” protein, based on the entire DNA sequence or parts thereof, and isolate DNA encoding proteins functionally equivalent to the “YS68” protein from these DNAs. The present invention includes proteins that are functionally equivalent to the “YS68” protein, and which are encoded by DNAs that hybridize under stringent conditions with DNA encoding the “YS68” protein. When isolating a cDNA that has high sequence homology to the DNA encoding the “YS68” protein, it is considered to be preferable to use embryonic stage hematopoietic tissues (for example, tissues such as the AGM region and yolk sac during early development; and thymus, spleen, and liver during mid to late development).  
           [0048]    Hybridization conditions for isolating DNAs encoding proteins that are functionally equivalent to the “YS68” protein can be appropriately selected by those skilled in the art. Conditions for hybridization, for example, may be those with low stringency. Low stringency conditions means that the washing conditions after hybridization are, for example, 42° C., 2×SSC, and 0.1% SDS, or preferably 50° C., 2×SSC, and 0.1% SDS. Examples of hybridization conditions that are more preferable are conditions with high stringency. An example of high stringency conditions is 65° C., 0.1×SSC and 0.1% SDS. Under these conditions, the higher the temperature, the higher the homology of the obtained DNA will be. However, several factors such as temperature and salt concentration can influence the stringency of hybridization and one skilled in the art can appropriately select such factors to accomplish a similar stringency.  
           [0049]    In addition, instead of hybridization, DNA encoding functionally equivalent proteins to “YS68” protein can be isolated by gene amplification methods, for example, by polymerase chain reaction (PCR), which uses primers that are synthesized based on sequence information of DNA encoding the “YS68” protein (SEQ ID NO:11 and 13).  
           [0050]    A protein that is functionally equivalent to a “YS68” protein, encoded by a DNA that is isolated by such hybridization techniques and gene amplification techniques, will normally have a high amino acid sequence homology to the “YS68” protein (SEQ ID NO:12 and 14). The proteins of this invention also include proteins that are functionally equivalent to a “YS68” protein and at the same time have a high sequence homology to the amino acid sequence of SEQ ID NO:12 or 14. High sequence homology typically means a homology of 30% or more, preferably a homology of 50% or more, more preferably a homology of 70% or more, and even more preferably a homology of 90% or more (for example, homology of 95% or more). To determine the homology of a protein, an algorithm described in the literature (Wilbur et al., Proc. Natl. Acad. Sci. USA 80:726-730, 1983) can be used.  
           [0051]    The proteins of this invention may have different amino acid sequences, molecular weights, and isoelectric points, as well as differences in the presence or absence of sugar chains and their forms, depending on the cells or hosts to produce the protein or production method, which will be described later. However, so long as the obtained protein has the same function as the “YS68” protein, it is included in this invention. For example, if a protein of this invention is expressed in a prokaryotic cell such as  E. coli,  a methionine residue will be added to the N terminus of the amino acid sequence of the original protein. The proteins of this invention will also include such proteins.  
           [0052]    The proteins of the present invention can be prepared as recombinant proteins or naturally occurring proteins, by methods well known by those skilled in the art. A recombinant DNA can be prepared by inserting a DNA (for example, the DNA comprising the nucleotide sequence of SEQ ID NOs:11 or 13) which encodes a protein of the present invention into an appropriate vector, collecting the recombinant obtained by introducing the vector into appropriate host cells, obtaining the extract, and purifying by subjecting the extract to chromatography such as ion exchange, reverse, gel filtration, or affinity chromatography in which an antibody against a protein of the present invention is fixed on column or by combining more than one of these columns.  
           [0053]    Also when a protein of the present invention is expressed within host cells (for example, animal cells and  E. coli ) as a fusion protein with glutathione-S-transferase protein or as a recombinant protein supplemented with multiple histidines, the expressed recombinant protein can be purified using a glutathione column or nickel column.  
           [0054]    After purifying the fusion protein, it is also possible to exclude regions other than the objective protein by cutting with thrombin or factor-Xa as required.  
           [0055]    A naturally occurring protein can be isolated by methods known by a person skilled in the art, for example, by using an affinity column in which the antibody binding to a protein of the present invention (described below) is bound against an extract of tissues or cells expressing a protein of the present invention is expressed. An antibody can be a polyclonal or a monoclonal antibody.  
           [0056]    The present invention also contains partial peptides of the proteins of the present invention. A partial peptide of the present invention comprises at least 7 amino acids or more, preferably 8 amino acids or more, and more preferably 9 amino acids or more. The partial peptides can be used, for example, for preparing an antibody against a protein of the present invention, screening a compound binding to a protein of the present invention, and for screening accelerators or inhibitors of a protein of the present invention. The partial peptides can be also used as antagonists or a competitive inhibitors against a protein of the present invention.  
           [0057]    A partial peptide of the invention can be produced by genetic engineering, known methods of peptide synthesis, or by digesting a protein of the invention with an appropriate peptidase. For peptide synthesis, for example, solid phase synthesis or liquid phase synthesis may be used.  
           [0058]    As used herein, an “isolated nucleic acid” is a nucleic acid, the structure of which is not identical to that of any naturally occurring nucleic acid or to that of any fragment of a naturally occurring genomic nucleic acid spanning more than three genes. The term therefore covers, for example, (a) a DNA which has the sequence of part of a naturally occurring genomic DNA molecule but is not flanked by both of the coding sequences that flank that part of the molecule in the genome of the organism in which it naturally occurs; (b) a nucleic acid incorporated into a vector or into the genomic DNA of a prokaryote or eukaryote in a manner such that the resulting molecule is not identical to any naturally occurring vector or genomic DNA; (c) a separate molecule such as a cDNA, a genomic fragment, a fragment produced by polymerase chain reaction (PCR), or a restriction fragment; and (d) a recombinant nucleotide sequence that is part of a hybrid gene, i.e., a gene encoding a fusion protein. Specifically excluded from this definition are nucleic acids present in random, uncharacterized mixtures of different DNA molecules, transfected cells, or cell clones, e.g., as these occur in a DNA library such as a cDNA or genomic DNA library.  
           [0059]    Accordingly, in one aspect, the invention provides an isolated or purified nucleic acid molecule that encodes a polypeptide described herein or a fragment thereof. Preferably, the isolated nucleic acid molecule includes a nucleotide sequence that is at least 60% identical to the nucleotide sequence shown in SEQ ID NO:11 or 13. More preferably, the isolated nucleic acid molecule is at least 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, identical to the nucleotide sequence shown in SEQ ID NO:11 or 13. In the case of an isolated nucleic acid molecule which is longer than or equivalent in length to the reference sequence, e.g., SEQ ID NO:11 or 13, the comparison is made with the full length of the reference sequence. Where the isolated nucleic acid molecule is shorter that the reference sequence, e.g., shorter than SEQ ID NO:11 or 13, the comparison is made to a segment of the reference sequence of the same length (excluding any loop required by the homology calculation).  
           [0060]    As used herein, “% identity” of two amino acid sequences, or of two nucleic acid sequences, is determined using the algorithm of Karlin and Altschul (Proc. Natl. Acad. Sci. USA 87:2264-2268, 1990), modified as in Karlin and Altschul, Proc. Natl. Acad. Sci. USA 90:5873-5877, 1993). Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul et al. (J. Mol. Biol. 215:403-410, 1990). BLAST nucleotide searches are performed with the NBLAST program, score=100, wordlength=12. BLAST protein searches are performed with the XBLAST program, score=50, wordlength=3. To obtain gapped alignment for comparison purposes GappedBLAST is utilized as described in Altschul et al. (Nucleic Acids Res. 25:3389-3402, 1997). When utilizing BLAST and GappedBLAST programs the default parameters of the respective programs (e.g., XBLAST and NBLAST) are used to obtain nucleotide sequences homologous to a nucleic acid molecule of the invention.  
           [0061]    A DNA encoding a protein of the present invention can be used for the production of the protein in vivo or in vitro as described above as well as for, for example, application to gene therapy for diseases attributed to genetic abnormality in the gene encoding the protein of the present invention. Any form of the DNA can be used, so long as it encodes a protein of the present invention. Specifically, cDNA synthesized from mRNA, genomic DNA, or chemically synthesized DNA can be used. The present invention includes a DNA comprising a given nucleotide sequence based on degeneracy of genetic codons, as long as it encodes a protein of the present invention.  
           [0062]    A DNA of the present invention can be prepared by methods known to those skilled in the art. For example, a DNA of the present invention can be prepared from a cDNA library from cells which express a protein of the present invention by conducting hybridization using a partial sequence of the DNA of the present invention (e.g., SEQ ID NO:11 and 13) as a probe. A cDNA library can be prepared, for example, by the method described in Sambrook et al., Molecular Cloning, Cold Spring Harbor Laboratory Press, 1989, or using commercially available cDNA libraries. A cDNA library can be also prepared by extracting RNA from cells expressing a protein of the present invention, synthesizing cDNA using reverse transcriptase, synthesizing an oligo DNA base on the sequence of the DNA of the present invention (for example, SEQ ID NOs:11 and 13), conducting PCR by using these as primers, and amplifying cDNA encoding the protein of the present invention.  
           [0063]    In addition, by sequencing the nucleotides of the obtained cDNA, a translation region encoded by the cDNA can be determined, and the amino acid sequence of a protein of the present invention can be obtained. Moreover, by screening the genomic DNA library using the obtained cDNA as a probe, genomic DNA can be isolated.  
           [0064]    More specifically, mRNAs may first be prepared from a cell, tissue, or organ (for example, embryonic stage hematopoietic tissues suchas AGM region and yolk sac of early development; thymus, spleen, and liver of mid to late development) in which a protein of the invention is expressed. Known methods can be used to isolate mRNAs; for instance, total RNA is prepared by the guanidine ultracentrifugation (Chirgwin et al., Biochemistry 18:5294-5299, 1979) or the AGPC method (Chomczynski et al., Anal. Biochem. 162:156-159, 1987), and mRNA is purified from total RNA using mRNA Purification Kit (Pharmacia) and such. Alternatively, mRNA may be directly purified by QuickPrep mRNA Purification Kit (Pharmacia).  
           [0065]    The obtained mRNA is used to synthesize cDNA using reverse transcriptase. A cDNA may be synthesized using kits, such as the AMV Reverse Transcriptase First-strand cDNA Synthesis Kit (Seikagaku Kogyo). Alternatively, a cDNA may be synthesized and amplified following the 5′-RACE method (Frohman et al., Proc. Natl. Acad. Sci. USA 85:8998-9002, 1988; Belyavsky et al., Nucleic Acids Res. 17:2919-2932, 1989) which uses a primer and such, described herein, the 5′-Ampli FINDER RACE Kit (Clontech), and polymerase chain reaction (PCR).  
           [0066]    A desired DNA fragment is prepared from the PCR products and ligated with a vector DNA. The recombinant vectors are used to transform  E. coli  and such, and a desired recombinant vector is prepared from a selected colony. The nucleotide sequence of the desired DNA can be verified by conventional methods, such as the dideoxynucleotide chain termination method.  
           [0067]    A DNA of the invention may be also designed to have a sequence that is expressed more efficiently by taking into account the frequency of codon usage in the host to be used for expression (Grantham et al., Nucleic Acids Res. 9:43-74, 1981). A DNA of the present invention may be altered by a commercially available kit or a conventional method. For instance, a DNA may be altered by digestion with restriction enzymes, insertion of synthetic oligonucleotides or appropriate DNA fragments, addition of linkers, or insertion of the initiation codon (ATG) and/or the stop codon (TAA, TGA, or TAG).  
           [0068]    The DNAs of this invention include a DNA that (a) hybridizes under stringent conditions with a DNA consisting of the nucleotide sequence of SEQ ID NO:11 or 13 and (b) encodes a protein that is functionally equivalent to a protein of this invention mentioned above. Stringent conditions for hybridization can be selected appropriately by those skilled in the art, and those conditions specifically mentioned above may be used. Under these conditions, DNA having higher homology are obtained as the temperature is raised. The above-mentioned DNA to be hybridized is preferably a naturally occurring DNA, for example, a cDNA or chromosomal DNA.  
           [0069]    The present invention also provides vectors into which a DNA of the present invention is inserted. The vectors of the present invention are useful to retain a DNA of the present invention in host cell, or to express a protein of the present invention.  
           [0070]    When  E. coli  is used as the host cell and a vector is amplified therein to produce a large amount in  E. coli  (e.g., JM109, DH5α, HB101, or XL1Blue), the vector should have an “ori” that may be amplified in  E. coli  and a marker gene for selecting transformed  E. coil  (e.g., a drug-resistance gene selected by a drug (e.g., ampicillin, tetracycline, kanamycin, or chloramphenicol)). For example, the M13-series vectors, the pUC-series vectors, pBR322, pBluescript, pCR-Script, and so on can be used. In addition to the vectors described above, pGEM-T, pDIRECT, and pT7, for example can also be used for subcloning and extracting cDNA. When a vector is used to produce a protein of the present invention, an expression vector is especially useful. For example, an expression vector to be expressed in  E. coli  should have the above characteristics to be amplified in  E. coli.  When  E. coli,  such as JM109, DH5α, HB101, or XL1 Blue, are used as the host cell, the vector should, in addition to the above characteristics, have a promoter so that the vector is copied in the host, for example, the lacZ promoter (Ward et al., Nature 341:544-546, 1989; FASEB J. 6:2422-2427, 1992), the araB promoter (Better et al., Science 240:1041-1043, 1988), or the T7 promoter and such, that can efficiently express the desired gene in  E. coli.  As such a vector, for example, pGFX-5X-1 (Pharmacia), “QIAexpress system” (Qiagen), pEGFP or pET (in this case, the host is preferably BL21 which expresses T7 RNA polymerase) can be used in addition to the above vectors.  
           [0071]    A vector also may contain a signal sequence for polypeptide secretion. As a signal sequence for protein secretion, the pelB signal sequence (Lei et al., J. Bacteriol. 169:4379, 1987) can be used in the case of producing proteins into the periplasm of  E. coli.  For introducing a vector into host cells, for example, the calcium chloride method, and the electroporation method can be used.  
           [0072]    Besides  E. coli,  for example, expression vectors derived from mammals (for example, pcDNA3 (Invitrogen) and pEGF-BOS (Nucleic Acids. Res. 18(17):5322, 1990), pEF, pCDM8); expression vectors derived from insect cells (for example, “Bac-to-BAC baculovirus expression system” (GIBCO BRL), pBacPAK8); expression vectors derived from plants (for example pMH1, pMH2); expression vectors derived from animal viruses (for example, pHSV, pMV, pAdexLcw); expression vectors derived from retroviruses (for example, pZIPneo); expression vector derived from yeast (for example, “Pichia Expression Kit” (Invitrogen), pNV11, SP-Q01); expression vectors derived from  Bacillus subtilis  (for example, pPL608, pKTH50) can be used as vectors for producing a protein of the present invention.  
           [0073]    In order to express a vector in animal cells, such as CHO, COS, or NIH3T3 cells, the vector should have a promoter necessary for expression in such cells, for example, the SV40 promoter (Mulligan et al., Nature 277:108, 1979), the MMLV-LTR promoter, the EF1α promotor (Mizushima et al., Nucleic Acids Res. 18:5322, 1990), or the CMV promoter, and such, and preferably a marker gene for selecting transformants (for example, a drug resistance gene selected by a drug (e.g., neomycin, G418)). Examples of vectors with these characteristics include pMAM, pDR2, pBK-RSV, pBK-CMV, pOPRSV, pOp13, and so on.  
           [0074]    In addition, for the purpose of stably expressing a gene and amplifying the copy number of the gene in cells, for example, a method wherein a vector comprising the complementary DHFR gene (for example pCHO I) is introduced into CHO cells in which the nuclei acid synthesizing pathway is deleted and amplified by methotrexate (MTX) can be used. On the other hand, in the case of transient expression of a gene, a method wherein a vector (e.g., pcD) comprising replication origin of SV40 is transformed using COS cells comprising the SV40 T antigen expressing gene on chromosomes can be used. The origin used for replication may be those of polyomavirus, adenovirus, bovine papilloma virus (BPV), and the like. In addition, the expression vector may include a selection marker gene for amplification of the gene copies in host cells. Examples of such markers include, but are not limited to, the aminoglycoside transferase (APH) gene, the thymidine kinase (TK) gene, the  E. coli  xanthine-guanine phosphoribosyl transferase (Ecogpt) gene, and the dihydrofolate reductase (dhfr) gene.  
           [0075]    On the other hand, a DNA of the present invention can be expressed in vivo in animals, for example, by inserting a DNA of the present invention into an appropriate vector and introducing it in vivo by a conventional method, such as the retrovirus method, the liposome method, the cationic liposome method, and the adenovirus method. By using these methods, gene therapy against diseases attributed to mutation of ‘YS68’ gene of the present invention can be effected. As a vector, for example, adenovirus vector (for example pAdexlcw), and retrovirus vector (for example, pZIPneo) can be used, but the present invention is not restricted thereto. Common gene manipulation, for example, insertion of a DNA of the present invention to a vector, can be performed according to any standard method (Molecular Cloning, 5.61-5.63). Administration into a living body can be either an ex vivo method, or in vivo method.  
           [0076]    The present invention relates to a host cell into which a vector of the present invention has been introduced. The host cell into which a vector of the invention is introduced is not particularly limited.  E. coli  or various animal cells can be used. The host cells of the present invention can be used, for example, as production system for producing or expressing a protein of the present invention. The present invention provides methods of producing a protein of the invention both in vitro or in vivo. For in vitro production, eukaryotic cells or prokaryotic cells can be used as host cells.  
           [0077]    Useful eukaryotic cells as host include animal, plant, or fungi cells. As animal cells, mammalian cells, such as CHO (J. Exp. Med. 108:945, 1995), COS, 3T3, myeloma, baby hamster kidney (BHK), HeLa, and Vero cells; amphibian cells, such as Xenopus oocytes (Valle et al., Nature 291:340-358, 1981); or insect cells, such as Sf9, Sf21, and Tn5 cells can be used. CHO cells lacking the DHFR gene (dhfr-CHO) (Proc. Natl. Acad. Sci. USA 77:4216-4220, 1980) or CHO K-1 (Proc. Natl. Acad. Sci. USA 60:1275, 1968) may be also used. In animal cells, CHO cells are particularly preferable for mass expression. A vector can be introduced into host cells by, for example, the calcium phosphate method, the DEAE dextran method, the cationic liposome DOTAP (Boehringer Mannheim), the electroporation method, or the lipofection method.  
           [0078]    As plant cells, plant cells originating from  Nicotiana tabacum  are known as a protein-production system, and may be used as callus cultures. As fungi cells, yeast cells such as Saccharomyces, including  Saccharomyces cerevisiae,  or filamentous fungi such as Aspergillus, including  Aspergillus niger,  are known and may be used herein.  
           [0079]    Useful prokaryotic cells include bacterial cells, such as  E. coli,  for example, JM109, DH5α, HB101 are known. Regarding others,  Bacillus subtilis  is known.  
           [0080]    These host cells are transformed by a desired DNA, and the resulting transformants are cultured in vitro to obtain a protein. Transformants can be cultured using known methods. Culture medium for animal cell, for example, DMEM, MEM, RPMI1640, or IMDM may be used with or without serum supplement such as fetal calf serum (FCS). The pH of the culture medium is preferably between about pH 6 to 8. Such cells are typically cultured at about 30 to 40° C. for about 15 to 200 hr, and the culture medium may be replaced, aerated, or stirred if necessary.  
           [0081]    Animal and plant hosts may be used for in vivo production. For example, a desired DNA can be introduced into an animal or plant host. Encoded proteins are produced in vivo, and then recovered. These animal and plant hosts are included in the host cells of the present invention.  
           [0082]    Animals to be used for the production systems described above include, but are not limited to, mammals and insects. Mammals, such as goat, porcine, sheep, mouse, and bovine, may be used (Vicki Glaser, SPECTRUM Biotechnology Applications (1993)). Alternatively, the mammals may be transgenic animals.  
           [0083]    For instance, a desired DNA may be prepared as a fusion gene with a gene encoding a protein specifically produced into milk, such as goat β casein. DNA fragments comprising a fusion gene having the desired DNA are injected into goat embryos, which are then introduced back to female goats. Proteins are recovered from milk produced by the transgenic goats (i.e., those born from the goats that had received the modified embryos) or from their offspring. To increase the amount of milk containing the proteins produced by transgenic goats, appropriate hormones may be administered to them (Ebert et al., Bio/Technology 12:699-702, 1994).  
           [0084]    Alternatively, insects, such as the silkworm, may be used. A desired DNA inserted into baculovirus can be used to infect silkworms, and a desired protein is then recovered from their body fluid (Susumu et al., Nature 315:592-594, 1985).  
           [0085]    As plants, for example, tobacco can be used. In use of tobacco, a desired DNA is inserted into a plant expression vector, such as pMON530, which is then introduced into a bacteria, such as  Agrobacterium tumefaciens.  Then, the bacteria is used to infect tobacco, such as  Nicotiana tabacum,  and a desired polypeptide is recovered from the leaves of the plant (Julian et al., Eur. J. Immunol. 24:131-138, 1994).  
           [0086]    A protein of the present invention obtained as above may be isolated from the interior or exterior (e.g. medium) of the cells or hosts, and purified as a substantially pure homogeneous protein. The method for protein isolation and purification is not limited to any specific method; in fact, any standard method may be used. For instance, column chromatography, filter, ultrafiltration, salt precipitation, solvent precipitation, solvent extraction, distillation, immunoprecipitation, SDS-polyacrylamide gel electrophoresis, isoelectric point electrophoresis, dialysis, and recrystallization may be appropriately selected and combined to isolate and purify the protein.  
           [0087]    For chromatography, for example, affinity chromatography, ion-exchange chromatography, hydrophobic chromatography, gel filtration, reverse phase chromatography, adsorption chromatography, and such may be used (Strategies for Protein Purification and Characterization: A Laboratory Course Manual. Ed. Daniel R. Marshak et al., Cold Spring Harbor Laboratory Press, 1996). These chromatographies may be performed by liquid chromatography, such as HPLC and FPLC. Thus, the present invention provides for highly purified proteins, produced by the above methods.  
           [0088]    A protein of the present invention may be optionally modified or partially deleted by treating it with an appropriate protein modification enzyme before or after purification. Useful protein modification enzymes include, but are not limited to, trypsin, chymotrypsin, lysylendopeptidase, protein kinase, and glucosidase.  
           [0089]    The present invention provides an antibody that binds to a protein of the invention. The antibody of the invention can be used in any form, such as monoclonal or polyclonal antibodies, and includes antiserum obtained by immunizing a rabbit with a protein of the invention, all classes of polyclonal and monoclonal antibodies, human antibodies, and humanized antibodies produced by genetic recombination.  
           [0090]    A protein of the invention used as an antigen to obtain an antibody may be derived from any animal species, but is preferably derived from a mammal such as a human, mouse, or rat, or more preferably from a human. A human-derived protein may be obtained from the nucleotide or amino acid sequences disclosed herein.  
           [0091]    In the present invention, a protein to be used as an immunization antigen may be a complete protein or a partial peptide of a protein. A partial peptide may be, for example, an amino (N)-terminal or carboxy (C)-terminal fragment of the protein. Herein, “an antibody” is defined as an antibody that specifically reacts with either the full-length or a fragment of a protein.  
           [0092]    A gene encoding a protein of the invention or its fragment may be inserted into a known expression vector, which is then used to transform a host cell as described herein. The desired protein or its fragment may be recovered from the exterior or interior of the host cells by any standard method, and may be used as an antigen. Alternatively, cells expressing the protein or their lysates, or a chemically synthesized protein may be used as an antigen. Short peptides are preferably bound with carrier proteins such as bovine serum albumin, ovalbumin, and keyhole limpet hemocyanin to be used as the antigen.  
           [0093]    Any mammalian animal may be immunized with the antigen, but preferably the compatibility with parental cells used for cell fusion is taken into account. In general, animals of the orders Rodentia, Lagomorpha, or Primate are used.  
           [0094]    Rodents include, for example, mouse, rat, and hamster. Lagomorphs include, for example, rabbit. Primates include, for example, a monkey of catarrhine (old world monkey) such as  Macaca fascicularis,  rhesus monkey, sacred baboon, or chimpanzee.  
           [0095]    Methods for immunizing animals against antigens are known in the art. Intraperitoneal injection or subcutaneous injection of antigens is used as a standard method for immunization of mammals. More specifically, antigens may be diluted and suspended in an appropriate amount with phosphate buffered saline (PBS), physiological saline, etc. If desired, the antigen suspension may be mixed with an appropriate amount of a standard adjuvant, such as Freund&#39;s complete adjuvant, made into emulsion, and then administered to mammalian animals. Preferably, it is followed by several administrations of antigen mixed with an appropriately amount of Freund&#39;s incomplete adjuvant every 4 to 21 days. An appropriate carrier may also be used for immunization. After immunization as above, serum is examined for increase of the amount of desired antibodies by a standard method.  
           [0096]    Polyclonal antibodies against a protein of the present invention may be prepared by collecting blood from the immunized mammal examined for the increase of desired antibodies in the serum, and separating serum from the blood by any conventional method. Polyclonal antibodies may be used as serum containing the polyclonal antibodies, or if necessary, a fraction containing the polyclonal antibodies may be isolated from the serum. Immunoglobulin G or M can be prepared by obtaining a fraction which recognizes only a protein of the present invention using an affinity column coupled with the protein of the present invention and further purifying this fraction by using protein A or protein G column.  
           [0097]    To prepare monoclonal antibodies, immune cells are collected from the mammal immunized against an antigen and checked for the increased level of desired antibodies in the serum as described above, and are subjected to cell fusion. The immune cells used for cell fusion are preferably obtained from spleen. Other parental cells can be fused with the above immunocyte; for example, preferably myeloma cells of mammalians, and more preferably myeloma cells which acquired the property for selecting fused cells by drugs can be used.  
           [0098]    The above immunocyte and myeloma cells can be fused by known methods, for example, the method by Milstein et al. (Galfre et al., Methods Enzymol. 73:3-46, 1981).  
           [0099]    Resulting hybridomas obtained by the cell fusion may be selected by cultivating them in a standard selection medium, such as the HAT medium (medium containing hypoxanthine, aminopterin, and thymidine). The cell culture is typically continued in the HAT medium for several days to several weeks, a sufficient time to allow all the other cells, except desired hybridoma (non-fused cells), to die. Then, by the standard limiting dilution method, a hybridoma cell producing the desired antibody is screened and cloned.  
           [0100]    In addition to the above method, in which a non human animal is immunized against an antigen for preparing hybridoma, human lymphocytes, such as that infected by EB virus, may be immunized with a protein, protein expressing cells, or their lysates in vitro. Then, the immunized lymphocytes are fused with human-derived myeloma cells capable of indefinitely dividing, such as U266, to yield a hybridoma producing a desired human antibody having binding ability to the protein can be obtained (Unexamined Published Japanese Patent Application (JP-A) No. Sho 63-17688).  
           [0101]    Next, the monoclonal antibody, obtained by transplanting the obtained hybridomas into the abdominal cavity of a mouse and by extracting ascites, can be purified by, for example, ammonium sulfate precipitation, protein A or protein G column, DEAE ion exchange chromatography, or an affinity column to which a protein of the present invention is coupled. An antibody of the present invention can be used not only for purification and detection of a protein of the present invention, but also as a candidate for agonists and antagonists of a protein of the present invention. In addition, an antibody can be applied to antibody treatment for diseases associated with a protein of the present invention. When the obtained antibody is used for the administration to the human body (antibody treatment), a human antibody or a humanized antibody is preferable for reducing immunogenicity.  
           [0102]    For example, transgenic animals having a repertory of human antibody genes may be immunized against a protein, protein expressing cells, or their lysates as an antigen. Antibody producing cells are collected from the animals, and fused with myeloma cells to obtain hybridoma, from which human antibodies against a protein can be prepared (see WO92-03918, WO93-2227, WO94-02602, WO94-25585, WO96-33735, and WO96-34096).  
           [0103]    Alternatively, an immune cell, such as an immunized lymphocyte, producing antibodies may be immortalized by an oncogene and used for preparing monoclonal antibodies.  
           [0104]    Monoclonal antibodies thus obtained can be also recombinantly prepared using genetic engineering techniques (see, for example, Borrebaeck C. A. K. and Larrick, J. W., THERAPEUTIC MONOCLONAL ANTIBODIES, published in the United Kingdom by MACMILLAN PUBLISHERS LTD, 1990). A DNA encoding an antibody may be cloned from an immune cell, such as a hybridoma or an immunized lymphocyte producing the antibody, inserted into an appropriate vector, and introduced into host cells to prepare a recombinant antibody. The present invention also provides recombinant antibodies prepared as described above.  
           [0105]    Furthermore, an antibody of the present invention may be a fragment of an antibody or modified antibody, so long as it binds to one or more of the proteins of the invention. For instance, the antibody fragment may be Fab, F(ab′) 2 , Fv, or single chain Fv (scFv), in which Fv fragments from H and L chains are ligated by an appropriate linker (Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883, 1988). More specifically, an antibody fragment may be generated by treating an antibody with enzymes such as papain or pepsin. Alternatively, a gene encoding an antibody fragment may be constructed, inserted into an expression vector, and expressed in an appropriate host cell (see, for example, Co et al., J. Immunol. 152:2968-2976, 1994; Better et al., Methods Enzymol. 178:476-496, 1989; Pluckthun et al., Methods Enzymol. 178:497-515, 1989; Lamoyi, Methods Enzymol. 121:652-663, 1986; Rousseaux et al., Methods Enzymol. 121:663-669, 1986; Bird et al., Trends Biotechnol. 9:132-137, 1991).  
           [0106]    An antibody may be modified by conjugation with a variety of molecules, such as polyethylene glycol (PEG). The present invention provides such modified antibodies. The modified antibody can be obtained by chemically modifying an antibody. These modification methods are conventional in this field.  
           [0107]    Alternatively, an antibody of the present invention may be obtained as a chimeric antibody, between a variable region derived from nonhuman antibody and the constant region derived from human antibody; or as a humanized antibody, comprising the complementarity determining region (CDR) derived from nonhuman antibody, the frame work region (FR) derived from human antibody, and the constant region.  
           [0108]    Obtained antibodies may be purified into homogeneity. An antibody used in the present invention can be separated and purified by conventional methods used for separating and purifying usual proteins. For example, the separation and purification of a protein can be performed by an appropriately selected and combined use of column chromatography, such as affinity chromatography, filter, ultrafiltration, salting-out, dialysis, SDS polyacrylamide gel electrophoresis, isoelectric focusing, and others (Antibodies: A Laboratory Manual. Ed Harlow and David Lane, Cold Spring Harbor Laboratory, 1988); however, the present invention is not limited thereto. The concentration of antibodies obtained above can be determined by measuring absorbance, by the enzyme-linked immunosorbent assay (ELISA), and so on.  
           [0109]    Examples of columns used for affinity chromatography include protein A columns and protein G columns. Examples of columns using protein A column include Hyper D, POROS, Sepharose F. F. (Pharmacia), etc.  
           [0110]    In addition to affinity chromatography, the chromatography includes, for example, ion-exchange chromatography, hydrophobic chromatography, gel filtration, reverse-phase chromatography, adsorption chromatography, and the like (Strategies for Protein Purification and Characterization: A Laboratory Course Manual. Ed Daniel R. Marshak et al., Cold Spring Harbor Laboratory Press, 1996). The chromatographic procedures can be carried out by liquid-phase chromatography such as HPLC, FPLC, or the like.  
           [0111]    For example, measurement of absorbance, enzyme-linked immunosorbent assay (ELISA), enzyme immunoassay (EIA), radioimmunoassay (RIA), and/or immunofluorescence may be used to measure the antigen binding activity of an antibody of the invention. In ELISA, an antibody of the present invention is immobilized on a plate, a protein of the invention is applied to the plate, and then a sample containing a desired antibody, such as culture supernatant of antibody producing cells or purified antibodies, is applied. Then, a secondary antibody that recognizes the primary antibody and is labeled with an enzyme, such as alkaline phosphatase, is applied, and the plate is incubated. Next, after washing, an enzyme substrate, such as p-nitrophenyl phosphate, is added to the plate, and the absorbance is measured to evaluate the antigen binding activity of the sample. A fragment of a protein, such as a C-terminal fragment, may be used as a protein. BIAcore (Pharmacia) may be used to evaluate the activity of an antibody according to the present invention.  
           [0112]    The above methods allow for the detection or measurement of the proteins of the invention, by exposing an antibody of the invention to a sample assumed to contain a protein of the invention, and detecting or measuring the immune complex formed by the antibody and the protein. Because the method of detection or measurement of proteins according to the invention can specifically detect or measure proteins, the method may be useful in a variety of experiments in which the protein is used.  
           [0113]    The present invention provides a polynucleotide having at least 15 nucleotides that is complementary to the DNA that encodes the “YS68” protein (SEQ ID NO:11 or 13) or the complementary strand thereof.  
           [0114]    Herein, the term “complementary strand” is defined as one strand of a double strand DNA composed of A:T and G:C base pairs to the other strand. In addition, “complementary” is defined as not only those completely matching within a continuous region of at least 15 nucleotides, but also having a homology of at least 70%, preferably at least 80%, more preferably 90%, and even more preferably 95% or higher within that region. The homology may be determined using the algorithm described herein.  
           [0115]    Probes or primers for detection and amplification of a DNA encoding a protein of this invention, or nucleotides or nucleotide derivatives for suppressing protein expression (for example, antisense oligonucleotides and ribozymes, or DNA encoding them) are included in these polynucleotides. In addition, such polynucleotides may be also used for preparing DNA chips.  
           [0116]    When used as a primer, the region on the 3′ side is designed to be complementary to a DNA encoding a protein of the invention, and restriction enzyme recognition sequence and tags can be added to the 5′ side.  
           [0117]    For example, an antisense oligonucleotide that hybridizes with a portion of the nucleotide sequence of SEQ ID NO:11 or 13 is also included in the antisense oligonucleotides of the present invention. An antisense oligonucleotide is preferably one against at least 15 continuous nucleotides in the nucleotide sequence of SEQ ID NO:11 or 13. More preferably, it is an antisense oligonucleotide having at least 15 continuous nucleotides that contains the translation initiation codon.  
           [0118]    Derivatives or modified products of antisense oligonucleotides can be used as antisense oligonucleotides. Examples of such modified products are, lower alkyl phosphonate modifications such as methyl-phosphonate-type or ethyl-phosphonate-type, phosphothioate modifications and phosphoamidate modifications.  
           [0119]    The term “antisense oligonucleotides” as used herein means, not only those in which the entire nucleotides corresponding to those constituting a specified region of a DNA or mRNA are complementary, but also those having a mismatch of one or more nucleotides, so long as DNA or mRNA and an oligonucleotide can specifically hybridize with the nucleotide sequence of SEQ ID NO:11 or 13.  
           [0120]    An antisense oligonucleotide derivative of the present invention has inhibitory effect on the function of a protein of the present invention as a result that the derivative inhibits the expression of the protein of the invention by acting upon cells producing the protein of the invention and by binding to the DNA or mRNA encoding the protein to inhibit its transcription or translation or to promote the degradation of the mRNA.  
           [0121]    An antisense oligonucleotide derivative of the present invention can be made into an external preparation, such as a liniment and a poultice, by mixing with a suitable base material which is inactive against the derivatives.  
           [0122]    Also, as necessary, the derivatives can be formulated into tablets, powders, granules, capsules, liposome capsules, injections, solutions, nose-drops, and freeze-drying agents and such by adding excipients, isotonic agents, solubilizing agents, stabilizers, preservative substance, pain-killers, and such. These can be prepared by following usual methods.  
           [0123]    An antisense oligonucleotide derivative is given to a patient by directly applying onto the ailing site or by injecting into a blood vessel so that it will reach the site of ailment. An antisense-mounting medium can also be used to increase durability and membrane-permeability. Examples are, liposome, poly-L-lysine, lipid, cholesterol, lipofectin or derivatives of these.  
           [0124]    The dosage of an antisense oligonucleotide derivative of the present invention can be adjusted suitably according to the patient&#39;s condition and used in desired amounts. For example, a dose range of 0. 1 to 100 mg/kg, preferably 0.1 to 50 mg/kg can be administered.  
           [0125]    An antisense oligonucleotide of the invention inhibits the expression of a protein of the invention and thereby is useful for suppressing the biological activity of the protein of the invention. Also, expression-inhibitors comprising an antisense oligonucleotide of the invention are useful in that they can inhibit the biological activity of a protein of the invention. It is thought that it is possible to use an antisense oligonucleotides of this invention for the purpose of suppressing biological activities of a protein of the invention.  
           [0126]    A protein of the invention may be used for screening compounds binding to the protein. Specifically, a protein may be used in methods of screening for compounds comprising the steps of: (1) exposing a protein of the present invention to a test sample in which a compound binding to the protein is expected to be contained; (2) detecting the binding activity of the protein to the test sample; and (3) selecting the compound having the binding activity to the protein.  
           [0127]    A protein of the present invention to be used for screening may be a recombinant protein, a protein derived from the nature, or partial peptide thereof. Alternatively, the protein may be in a form expressed on a cell surface or in a form of cell membrane fraction. Any test sample, for example, cell extracts, cell culture supernatant, products of fermenting microorganism, extracts from marine organism, plant extracts, purified or crude proteins, peptides, non-peptide compounds, synthetic low molecular compounds and naturally occurring compounds, can be used. A protein of the present invention to be contacted with a test sample can be contacted, for example, as a purified protein, a soluble protein, a form bound to a carrier, a fusion protein with another protein, a form expressed on cell membrane, or a cell membrane fraction.  
           [0128]    By using a protein of the present invention, for example, in a method for screening for proteins binding to the protein thereof, many methods well known by a person skilled in the art can be used. Such a screening can be conducted by, for example, the immunoprecipitation method, specifically, in the following manner. A gene encoding a protein of the present invention is expressed in a host cell, such as an animal cell, by inserting the gene into an expression vector for foreign gene, such as pSV2neo, pcDNA I, pCD8. As a promoter to be used for the expression, any promoter which can be generally used can be selected; for example, the SV40 early promoter (Rigby in Williamson (ed.), Genetic engineering, vol. 3. Academic Press, London, p. 83-141, 1982), the EF-1α promoter (Kim et al., Gene 91:217-223, 1990), the CAG promoter (Niwa et al., Gene 108:193-200, 1991), the RSV LTR promoter (Cullen Methods in Enzymology 152:684-704, 1987), the SRα promoter (Takebe et al., Mol. Cell. Biol. 8:466, 1988), the CMV immediate early promoter (Seed et al., Proc. Natl. Acad. Sci. USA 84:3365-3369, 1987), the SV40 late promoter (Gheysen et al., J. Mol. Appl. Genet. 1:385-394, 1982), the Adenovirus late promoter (Kaufman et al., Mol. Cell. Biol. 9:946, 1989), the HSV TK promoter, and so on may be used.  
           [0129]    To express a foreign gene by introducing the gene into animal cells, the electroporation method (Chu et al., Nucl. Acid Res. 15:1311-1326, 1987), the calcium phosphate method (Chen et al., Mol Cell. Biol. 7:2745-2752, 1987), the DEAE dextran method (Lopata et al., Nucl. Acids Res. 12:5707-5717, 1984; Sussman et al., Mol. Cell. Biol. 4:1642-1643, 1985), the Lipofectin method (Derijard, Cell 7:1025-1037, 1994; Lamb et al., Nature Genetics 5:22-30, 1993; Rabindran et al., Science 259:230-234, 1993), and such can be exemplified, and any method can be used.  
           [0130]    A protein of the present invention can be expressed as a fusion protein comprising a recognition site (epitope) of a monoclonal antibody by introducing the epitope of the monoclonal antibody, whose property has been revealed, to N or C terminus of the protein of the present invention. A commercially available epitope-antibody system can be used (Experimental Med. 13:85-90, 1995). Through a multiple cloning site, a vector which can express a fusion protein with, for example, β-galactosidase, maltose binding protein, glutathione S-transferase, green florescence protein (GFP), is available in the market.  
           [0131]    Methods have been reported in which fusion proteins are prepared by introducing only small epitopes comprising several to a dozen of amino acids, so that the properties of the proteins of the present invention may not change by making the proteins fusion proteins. Epitopes, for example, polyhistidine (His-tag), influenza aggregate HA, human c-myc, FLAG, Vesicular stomatitis virus glycoprotein (VSV-GP), T7 gene 10 protein (T7-tag), human simple herpes virus glycoprotein (HSV-tag), epitope such as E-tag (an epitope on monoclonal phage), and monoclonal antibodies recognizing these can be used as an epitope-antibody system for screening a protein binding to a protein of the present invention (Experimental Med. 13:85-90, 1995).  
           [0132]    In the immunoprecipitation, an immune complex is formed by adding these antibodies to cell eluate prepared by using an appropriate detergent. This immune complex comprises a protein of the present invention, a protein having a binding affinity for the protein, and an antibody. Immunoprecipitation can be conducted by an antibody against a protein of the present invention, besides using antibodies against the above epitopes. An antibody against a protein of the present invention can be prepared, for example, by introducing a gene encoding the protein of the present invention into an appropriate  E. coli  expression vector; expressing the gene in  E. coli;  purifying the expressed protein; and immunizing animals, for example, rabbits, mice, rats, goats, domestic fowls, and such, with such protein. The antibody can be prepared also by immunizing the above animals against a synthesized partial peptide of a protein of the present invention.  
           [0133]    An immune complex can be precipitated, for example, by Protein A Sepharose or Protein G Sepharose when the antibody is mouse IgG antibody. When a protein of the present invention is prepared as a fusion protein with an epitope, for example GST, an immune complex can be formed by using a substance specifically binding to these epitopes, such as glutathione-Sepharose 4B, in the same manner as in the use of an antibody against a protein of the present invention.  
           [0134]    Popular Immunoprecipitation can be performed by following or according to, for example, the reference (Harlow, E. and Lane, D.: Antibodies pp. 511-552, Cold Spring Harbor Laboratory publications, New York (1988)).  
           [0135]    SDS-PAGE is commonly used for analysis of immunoprecipitated proteins and the binding protein can be analyzed depending on the molecular weight of the protein by using gel with an appropriate concentration. In general, because it is difficult to detect a protein binding to a protein of the present invention by a common staining method, such as Coomassie staining or silver staining, the detection sensitivity for the protein can be improved by culturing in a culture medium containing radioactive isomer,  35 S-methionine or  35 S-cystein, labeling proteins in the cells, and detecting the proteins. The target protein can be purified from the SDS-polyacrylamide gel and its sequence can be determined directly after the molecular weight of the protein is determined.  
           [0136]    The present inventors have detected multiple proteins that bind to a protein of this invention by immunoprecipitation in the Example (Example 4).  
           [0137]    To isolate proteins that bind to a protein of the present invention by using the protein, for example, West western blotting (Skolnik et al., Cell 65:83-90, 1991) may be used. More specifically, it is conducted as follows: (1) constructing a cDNA library using a phage vector (λgt11, ZAP, etc.) from cells, tissues, and organs (for example, AGM region and yolk sac during early development; thymus, spleen, and liver during mid to late development, and such) that are expected to express binding proteins that bind to the protein of this invention; (2) expressing the cDNA library on LB-agarose and immobilizing the expressed protein onto a filter; (3) reacting the purified and labeled protein of this invention with the filter; and (4) detecting the plaque expressing the protein that binds to the protein of this invention by the label. Methods to label a protein of this invention may be a method that utilizes the binding characteristics of biotin and avidin; a method utilizing antibodies that bind specifically to the protein of this invention or to peptides or polypeptides fused to the protein of this invention (for example GST and such); a method that utilizes radioisotopes; a method that utilizes fluorescence; and such.  
           [0138]    Further, another embodiment of the screening method of this invention is exemplified by a method utilizing the two-hybrid system using cells (Fields et al., Trends. Genet. 10:286-292, 1994; Dalton et al., Cell 68:597-612; “MATCHMAKER Two-Hybrid System”, “Mammalian MATCHMAKER Two-Hybrid Assay Kit”, “MATCHMAKER One-Hybrid System” (all manufactured by Clonetech); and “HybriZAP Two-Hybrid Vector System” (manufactured by Stratagene)). In the two-hybrid system, a protein of this invention or a partial peptide thereof may be fused to the DNA binding region of SRF or GAL4, and expressed in yeast. A cDNA library is constructed from cells predicted to express proteins that bind to the protein of this invention, wherein the cDNA library is constructed in such a way that the proteins are expressed as fusion proteins with transcription activation regions of VP16 or GAL4. The cDNA library is transfected into the above yeast, and then positive clones are detected to isolate the cDNA derived from the library (expression of a protein that binds to the protein of the invention in yeast leads to the binding of the two proteins, and results in the activation of the reporter gene, which allows to detect positive clones). The protein encoded by the isolated cDNA may be obtained by introducing the cDNA into  E. coli  and expressing it therein. Thus, it is possible to prepare proteins that bind to a protein of this invention and genes encoding them. The reporter gene used in the two-hybrid system may be such as Ade2 gene, Lac Z gene, CAT gene, luciferase gene, PAI-1 (Plasminogen activator inhibitor type 1) gene, and such besides HIS3 gene, but are not limited to these examples.  
           [0139]    A protein binding to a protein of the present invention can be screened using affinity chromatography. For example, a preferred method for screening of the present invention utilizes affinity chromatography. A protein of the invention is immobilized on a carrier of an affinity column, and a test sample, in which a protein capable of binding to the protein of the invention is supposed to be expressed, is applied to the column. A test sample herein may be, for example, cell extracts, cell lysates, etc. After loading the test sample, the column is washed, and proteins bound to the protein of the invention can be prepared.  
           [0140]    The amino acid sequence of the obtained protein is analyzed, an oligo DNA was synthesized based on the sequence, and cDNA libraries are screened using the DNA as a probe to obtain a DNA encoding the protein.  
           [0141]    A biosensor using the Surface Plasmon Resonance phenomenon may be used as a means for detecting or quantifying the bound compound in the present invention. When such a biosensor is used, the interaction between a protein of the invention and a test compound can be observed in real-time as a surface plasmon resonance signal, using only a minute amount of proteins without labeling (for example, BIAcore, Pharmacia). Therefore, it is possible to evaluate the binding between a protein of the invention and a test compound using a biosensor such as BIAcore.  
           [0142]    Methods of screening molecules that bind when an immobilized protein of the present invention is exposed to synthetic chemical compounds, natural substance banks, or a random phage peptide display library, and methods of screening using high-throughput based on combinatorial chemistry techniques (Wrighton et al., Science 273:458-64, 1996; Verdine, Nature 384:11-13, 1996; Hogan, Jr., Nature 384:17-9, 1996) are well known to those skilled in the art as methods for isolating not only proteins but also chemical compounds that bind to a protein of the present invention (including agonist and antagonist).  
           [0143]    Compounds that bind to a protein of this invention serve as drug candidates for promoting or inhibiting the activity of the protein of this invention, and may be applied to treatment of diseases caused by expressional or functional abnormalities of the protein of this invention, or diseases that may be treated by regulating the activity of the protein of this invention. Compounds obtained by using the screening method of this invention, wherein the structure of compounds having binding activity toward a protein of this invention is partially altered by addition, deletion, and/or replacement, are also included as compounds that bind to a protein of this invention.  
           [0144]    When a compound binding to a protein of the present invention is used as a pharmaceutical for humans and other mammals, such as, mice, rats, guinea pigs, rabbits, chicken, cats, dogs, sheep, pigs, bovines, monkeys, baboons, chimpanzees, the isolated compound can be administered not only directly, but also as dosage forms using known pharmaceutical preparation methods. For example, according to the need, the drugs can be taken orally as sugarcoated tablets, capsules, elixirs and microcapsules; or non-orally in the form of injections of sterile solutions or suspensions with water or any other pharmaceutically acceptable liquid. For example, the compounds can be mixed with pharmacologically acceptable carriers or medium, specifically, sterilized water, physiological saline, plant-oil, emulsifiers, suspending agent, surface-active agent, stabilizers, flavoring agents, excipients, vehicles, preservatives and binders, into a unit dose form required for generally accepted drug implementation. The amount of active ingredient in these preparations makes a suitable dosage within the indicated range acquirable.  
           [0145]    Examples of additives which can be mixed to tablets and capsules are, binders such as gelatin, corn starch, tragacanth gum and gum acacia; excipients such as crystalline cellulose; swelling agents such as corn starch, gelatin and alginic acid; lubricants such as magnesium stearate; sweeteners such as sucrose, lactose or saccharin; flavoring agents such as peppermint,  Gaultheria adenothrix  oil and cherry. When the unit dosage form is a capsule, a liquid carrier such as oil can also be included in the above ingredients. Sterile composites for injection can be formulated following normal drug implementations using vehicles such as distilled water used for injections.  
           [0146]    Physiological saline, glucose, and other isotonic liquids including adjuvants, such as D-sorbitol, D-mannose, D-mannitol, and sodium chloride, can be used as aqueous solutions for injections. These can be used in conjunction with suitable solubilizers, such as alcohol, specifically ethanol; polyalcohols such as propylene glycol and polyethylene glycol; and non-ionic surfactants such as Polysorbate 80 (TM) and HCO-50.  
           [0147]    Sesame oil or Soy-bean oil can be used as a oleaginous liquid and may be used in conjunction with benzyl benzoate or benzyl alcohol as solubilizers; they further may be formulated with a buffer such as phosphate buffer and sodium acetate buffer, a pain-killer such as procaine hydrochloride, a stabilizer such as benzyl alcohol and phenol, and an anti-oxidant. The prepared injection may be filled into a suitable ampule.  
           [0148]    Methods well known to one skilled in the art may be used to administer the pharmaceutical compounds of the present invention to patients, for example as intraarterial, intravenous, percutaneous injections and also as intranasal, transbronchial, intramuscular percutaneous, or oral administrations. The dosage varies according to the body-weight and age of a patient and the administration method, but one skilled in the art can suitably select them. If the compound can be encoded by a DNA, the DNA can be inserted into a vector for gene therapy to perform the therapy. The dosage and method of administration vary according to the body-weight, age, and symptoms of a patient, but one skilled in the art can select them suitably.  
           [0149]    Although there are some differences according to the symptoms, the dose of a compound that binds with a transcriptional regulatory factor of the present invention and inhibits its activity is about 0.1 mg to about 100 mg per day, preferably about 1.0 mg to about 50 mg per day and more preferably about 1.0 mg to about 20 mg per day, when administered orally to a normal adult (weight 60 kg).  
           [0150]    When administering parenterally in the form of an injection to a normal adult (weight 60 kg), although there are some differences according to the patient, target organ, symptoms and method of administration, it is convenient to intravenously inject a dose of about 0.01 mg to about 30 mg per day, preferably about 0.1 to about 20 mg per day and more preferably about 0.1 to about 10 mg per day. Also, in the case of other animals too, it is possible to administer an amount converted to 60 kgs of body-weight or an amount converted to body surface.  
           [0151]    All publications and patents cited herein are incorporated by reference in their entirety. 
       
    
    
     DESCRIPTION OF DRAWINGS  
       [0152]    [0152]FIG. 1 depicts photomicrographs indicating the localization of YS68 within cells. YS68 tagged with a flag epitope is expressed in COS7 cells, and upon staining with anti-Flag antibodies, the expression sites of YS68 were investigated (right). In addition, the same cells were treated with Hoechst to selectively stain the nucleus (left).  
         [0153]    [0153]FIG. 2 depicts photographs demonstrating the result of electrophoresis showing the expression distribution of YS68 in tissues. RNA was prepared from liver, thymus, or spleen tissues of an embryonic day 14 (E14) or embryonic day 18 (E18) mouse embryo, respectively, or from the tissues of an adult mouse to perform Northern hybridization. The lower panel shows 18S ribosomal RNA before blotting as a control.  
         [0154]    [0154]FIG. 3 depicts photographs demonstrating the result of electrophoresis showing the result of analyzing YS68 expression by RT-PCR in the yolk sac at each stage of a developing embryo.  
         [0155]    [0155]FIG. 4 depicts photographs demonstrating the result of electrophoresis showing the result of analyzing YS68 expression by RT-PCR in the AGM region at each stage of a developing embryo is shown in (A); and in (B) the E10.5 AGM region was cultivated in the presence or absence of oncostatin M (OSM), and RNA was prepared on the 5th day of cultivation. Expression of YS 68 was then compared to those of uncultivated AGM region by RT-PCR.  
         [0156]    [0156]FIG. 5 depicts photographs demonstrating the result of electrophoresis showing the result of comparison of the expression level of YS68 by RT-PCR upon extraction of RNA from liver, thymus and spleen of embryonic (E11.5 to E16.5), 7-day-old, and adult mice, respectively.  
         [0157]    [0157]FIG. 6 depicts photographs showing the result of in situ hybridization on slices prepared from an E11.5 embryo. A is an autoradiogram, and B is an image obtained by staining the same slice by hematoxylin. Li: liver.  
         [0158]    [0158]FIG. 7 depicts photographs showing the result of in situ hybridization on slices prepared from an E14.5 embryo. A and C are autoradiograms, while B and D are images obtained by staining the same slices by hematoxylin. Li: liver, Lu: lung, Th: thymus, and N: neural tube.  
         [0159]    [0159]FIG. 8 depicts a comparison of the amino acid sequences between human and mouse YS68.  
         [0160]    [0160]FIG. 9 depicts the comparison of the amino acid structures of human and mouse YS68.  
         [0161]    [0161]FIG. 10 depicts a photograph showing the result of analysis on proteins that coprecipitate with YS68. After primary cultivation of E14.5 liver, cell lysate was prepared. Then, the lysate was subjected to immunoprecipitation with anti-YS68 antibody and protein A (Lane  1 ), rabbit IgG and protein A (Lane  2 ), and protein A alone (Lane  3 ). Following SDS-PAGE, the gel was visualized by silver staining. Arrow: YS68; and *: protein that coprecipitated with YS68.  
         [0162]    [0162]FIG. 11 depicts photographs showing the result of immunostaining of YS68 in tissues. The dorsal aorta (A, B, C, D, and E), the umbilical artery (F) of an E11.5 mouse; and the blood vessels within an E9 yolk sac (H) were stained with erythroid marker TER119 (A, B, and G) and with anti-YS68 antibody (C, D, E, and H). B and D are enlargements of A and C, respectively, and E shows a different view of the aorta. The site where the hematocyte is budding from the vascular endothelium is indicated by an arrow.  
         [0163]    [0163]FIG. 12 depicts photographs showing the result of staining primary culture cells of E14.5 liver with anti-YS68 antibodies (A), or with rabbit IgG (B). The expression of YS68 was strong at the nucleus and around the nucleus.  
         [0164]    [0164]FIG. 13 depicts photographs showing the result of investigation on the expression of YS68 in hematocytes isolated from E14 liver. The Giemsa stained hematocytes of the liver (A); hematocytes of the E14.5 liver (B); CD34 negative cells (C); and CD34 positive cells (D) were stained with anti-YS68 antibodies. Whether the sorted cells are CD34 positive or not was confirmed (E-H). E-F and G-H are taken from the same views, E and G are fluorescence photographs, and F and H are visual photographs. Most of the cells sorted by CD34 were weakly CD34 positive to strongly positive (E and F). Cells that passed through the CD34 column were hardly expressing any CD34 (G and H).  
         [0165]    [0165]FIG. 14 depicts photographs showing the localization of YS68 within cells. A slightly magnified photograph is shown on the left, and a largely magnified photograph is shown on the right. Cells derived from fetal liver were stained with anti-YS68 antibodies to investigate endogenous expression sites of YS68 (top row). In addition, pEFBOSE-F-YS68 (5-1148) that expresses the N-terminal region of YS68 (middle row), or pEFBOSE-F-YS68 (981-2243) that expresses the C-terminal region of YS68 (bottom row) were transfected to COS7 cells, and these cells were stained with anti-Flag antigens to investigate the localization within the cell. 
     
    
     DETAILED DESCRIPTION  
       [0166]    The present invention will be described specifically by way of examples below, however this invention is not restricted in any way to these examples.  
       EXAMPLE 1  
     Isolation of YS68 Gene  
       [0167]    To obtain molecules that are expressed specifically in hemangioblasts, an experiment was carried out in which cDNA of an E14 yolk sac was subtracted from the cDNA of an E9 yolk sac. Poly A RNAs were purified from each of the E9 and E14 yolk sacs, respectively; then PCR-Select cDNA Subtraction Kit (Clonetech) was used for the subtraction. The obtained cDNA fragments were subcloned into pGEM-T vectors (Promega), and then, after selecting highly expressed cDNAs in E9 yolk sacs by dot blotting, selected cDNA were sequenced. The clone #68 was a novel gene fragment that was not registered in the database. Thus, a primer was designed from the sequence of this gene fragment, and using mouse 15-day Embryo Marathon-Ready cDNA (Clonetech) as a template, a full-length cDNA was isolated by the 5′-RACE method. Mouse YS68 encodes 1,265 amino acids, but is expected to have further upstream sequence.  
         [0168]    The obtained YS68 did not have a characteristic motif within its amino acid sequence. However, existence of multiple nuclear transport signals was confirmed. Consequently, YS68 was anticipated to be a protein that functions in the nucleus. Therefore, to confirm the hypothesis, a vector (pEFBOSE-Flag (Nakashima et al., FEBS Let. 403:79-82, 1997) that expresses the mouse YS68 protein (1265 amino acids) tagged with Flag was transfected to COS7 cells. After 24 hours, the cells were fixed with 4% formalin, and was treated with 0.1% Triton-X 100. Then, this was reacted with anti-Flag antibodies, followed by FITC-labeled anti-mouse IgG, and was observed through a fluorescence microscope. Consequently, expression of YS68 was strong in the nucleus, as expected (FIG. 1). Since the cell nucleus is the site where DNA transcription occurs, YS68 is anticipated to be a transcription factor involved with DNA transcription.  
         [0169]    Human YS68 gene was isolated by 5′-RACE and 3′-RACE by designing a primer based on the genetic sequence of mouse YS68. More specifically, based on the genetic sequence of mouse YS68, EST fragments that are thought to be YS68 homologues in humans were searched in the EST database. Primers were designed based on this EST fragment, and using human fetal liver Marathon-Ready cDNA (Clonetech) as a template, the 5′ region and the 3′ region cDNA were isolated by 5′-RACE and 3′-RACE according to the instructed procedure. The isolated cDNA nucleotide sequence is described in SEQ ID NO:11, and the amino acid sequence of the protein encoded by this cDNA is described in SEQ ID NO:12. A comparison of human and mouse YS68 amino acid sequences is shown in FIG. 8.  
       EXAMPLE 2  
     Expression Pattern Analysis of YS68  
       [0170]    The expression distribution of YS68 within tissues was analyzed by Northern blotting. Total RNA was prepared from each tissues of embryonic or adult mice using ISOGEN (Wako). 25 μg/lane of these samples were electrophoresed. After blotting onto a nylon membrane, hybridization was performed with YS68 cDNA fragments labeled with  32 P. Hybridization was performed in ExpressHyb solution (Clonetech) at 68° C. for 2 hours; then, after several washings with 2×SSC and 0.1% SDS at room temperature, followed by several washings with 0.1×SSC and 0.1% SDS at 65° C., autoradiography was performed.  
         [0171]    The expression of YS68 in adult tissue was the strongest in testis, followed those in kidney and lung. Observation of YS68 expression in hematopoietic tissues showed that expression was very strong in liver, thymus and spleen that function as hematopoietic tissues during the embryonic stage. However, expression in these tissues rapidly decreased or was absent in those of adult (FIG. 2).  
         [0172]    Further, the expression pattern in tissues known to be involved in primitive hematopoiesis was investigated in detail. The site of hematopoiesis is known to shift during the embryonic stage as described below from previous studies. First, primitive hematopoiesis starts in the yolk sac at E8, and definitive hematopoiesis begins later in the AGM region at E10.5. Hematocytes that developed in AGM are immediately transported to liver that is formed around E11.5, then differentiate and proliferate at this site until immediately after birth. Meanwhile, hematopoiesis begins to take place in thymus and spleen that are formed around E16.5. After birth, the site of hematopoiesis changes to bone marrow. Based on these facts, the expression pattern of YS68 in these tissues was analyzed in further detail by RT-PCR. Total RNA was extracted from each tissue of mouse embryos at each developmental stage, or an adult mouse; and 1 μg of each total RNA was reverse transcribed to cDNA using SUPERSCRIPT II preamplification system (Gibco). This was used as a template and a YS68-specific primer (68 3:5′-CACCCGTGAAGAAACAAATAGGCA-3′/SEQ ID NO:3, 68 4:5′-CCTTTGGTACATGAGCTTCTATTT-5′/SEQ ID NO:4) or a G3PDH-specific primer was used to perform PCR (25 cycles of 94° C. for 30 seconds, 62° C. for 30 seconds, and 72° C. for 30 seconds). Then was electrophoresed on 1% agarose gel, and the gel was stained with ethidium bromide.  
         [0173]    Expression of YS68 decreased gradually in the yolk sac, as development proceeded (FIG. 3). Against expectations, expression of YS68 was low in the AGM region at E10.5, when definitive hematopoiesis begins (FIG. 5A). On the other hand, in liver, thymus, and spleen known to function as sites for hematopoiesis in the embryonic stage, expression of YS68 was very high (FIG. 4) and correlated to the period when these tissues function as hematopoietic organs.  
         [0174]    Furthermore, the expression distribution of YS68 in mouse embryo was analyzed by in situ hybridization. A vector constructed by inserting a 545 bp cDNA of the 5′-region of YS68 (positions 898 to 1443) into pBluescript II was used as a template to perform in vitro transcription using T7 RNA polymerase or T3 RNA polymerase (Boeringer Mannheim), and to synthesize sense or antisense  35 S-labeled RNA, respectively. The mouse embryo was removed and frozen to produce slices using a cryostat. After immobilization and acetylation with 4% paraformaldehyde/PBT, hybridization was performed overnight at 55° C. with the above-mentioned RNA probe. After treating the reaction solution with RNase A, it was washed several times and autoradiography was performed.  
         [0175]    The expression of YS68 was the strongest in liver at E11.5 (FIG. 6). YS68 was mainly strongly expressed in liver and in the developing thymus, and expression was also confirmed in lungs and neural tube at E14.5 (FIG. 7).  
         [0176]    These results indicate that the expression of YS68 is localized in tissues where active hematopoiesis takes place in a period-specific manner, and strongly suggests that YS68 is a molecule involved in primitive hematopoiesis. Its expression was low in the E10.5 AGM region, which is thought to be the site of development for hematopoietic cells. However this may be due to the absolute number of cells involved in hematopoiesis within the entire AGM region, which is not so high. In fact, Suda et al. revealed that the percentage of hemangioblasts in the AGM region at E10.5 is 5% or less using TEK as a marker for hemangioblasts (Hamaguchi et al., Blood 93:1549-1556, 1999). On the other hand, when E10.5 AGM region is dispersed and cultivated on a dish, the emergence of hematocytes can be confirmed around the 5th day of cultivation (Mukouyama et al., Immunity 8:105-114, 1998). Interestingly, the expression of YS68 had increased in AGM derived cells cultivated for 5 days (FIG. 4B). According to these results, the expression of YS68 is expected to rise in cells that have acquired hematopoietic ability, or in immature hematocytes.  
       EXAMPLE 3  
     Full-Length Cloning of Mouse and Human YS68  
       [0177]    Using primers constructed from the YS68 gene sequence obtained so far, 5′-RACE was performed using the mouse 15-day Embryo Marathon-Ready cDNA and human fetal liver Marathon-Ready cDNA (Clonetech) as templates, to clone the upstream 5′ region of mouse and human YS68 gene. Full-length human and mouse cDNA sequences were determined by repeating this 5′-RACE protocol.  
         [0178]    Consequently, human and mouse YS68 were anticipated to encode 2,266 and 2,243 amino acids, respectively (FIG. 9). Comparing the human and mouse amino acid sequences, interestingly, the N-terminal region (human 1-1137, mouse 1-1137) had a very high homology of 87%; whereas the homology in the central region (human 1138-1683, mouse 1138-1679) was 57%, and that in the C-terminal region (human 1684-2266, mouse 1680-2243) was very low showing a homology of 45%. In the C-terminal region with low homology, many nuclear transport signals existed. On the other hand, in the N-terminal region with high homology, two WD repeats existed, which repeats are known to be necessary for interaction among proteins. Since the homology in this region is very high between humans and mice, this region is anticipated to be important for the function of YS68.  
       EXAMPLE 4  
     Proteins Binding to YS68  
       [0179]    It was expected that YS68 is bound to some protein in vivo because a protein-binding site (WD repeats) exists in the N-terminal region of YS68. Therefore, cell lysate was prepared from cultivated cells of embryonic liver and immunoprecipitation with anti-YS68 antibody was performed. Then, SDS polyacrylamide gel electrophoresis was performed to investigate whether a protein that coprecipitates with YS68 exists. Specifically, cultivated mouse liver cells at E14.5 were solubilized with lysis buffer (0.5% NP-40, 10 mM Tris-HCl pH7.6, 150 mM NaCl, 5 mM EDTA, 2 mM Na 3 VO 4 , 1 mM phenylmethylsulfonyl fluoride, and 5 μg/ml aprotinin). After incubation overnight at 4° C. with anti-YS68 antibodies, protein G was added and was further incubated for 1 hour. SDS polyacrylamide gel electrophoresis was conducted after immunoprecipitation, and the gel was stained with silver.  
         [0180]    Consequently, existence of multiple molecules that coprecipitate with YS68 within cells of embryonic liver was confirmed (FIG. 10). This suggested that YS68 functions by binding to several types of proteins within the cell.  
       EXAMPLE 5  
     Expression Site of YS68 Within Tissues  
       [0181]    For detailed analysis of the YS68 expression site, the YS68 protein was used to immunize rabbits to produce polyclonal antibodies against YS68. The protein encoding the 1208-1482 amino acid region of mouse YS68 was expressed in  E. coli,  was purified according to standard procedures, and was used as the antigen in the production of YS68 polyclonal antibodies. Immunization was carried out on rabbits (New Zealand White, 2.5 kg, female) using 200 μg antigen for 1 immunization, with an interval of 10 days for 4 immunizations. Then upon collection of whole blood, antiserum was obtained. Furthermore, an affinity column with immobilized antigens was prepared, and anti-YS68 polyclonal antibodies were purified from the antiserum.  
         [0182]    Using these antibodies, the expression site in the AGM region of E11.5 embryo was investigated by immunostaining. Immunostaining was conducted as follows. First, slices of frozen mouse embryo were prepared using a cryostat (Leica). This was immobilized with 4% formaldehyde and was treated with methanol. After treatment with 0.3% aqueous hydrogen peroxide, blocking was carried out with 3% BSA, then upon reaction with primary antibodies overnight at 4° C. and with secondary antibodies (HRP-labeled anti-rabbit IgG) at room temperature for 1 hour, washing was repeated 3 times with PBS, and visualization was accomplished by the addition of substrate (Metal Enhanced DAB substrate kit, Pierce).  
         [0183]    Consequently, the hematocytes existing in the endothelium were stained using red blood cell marker TER119 (used as a control; FIGS. 11A, B), whereas, the vascular endothelium was stained specifically using anti-YS68 antibody (FIGS. 11C, D, and E). Interestingly, YS68 was darkly stained in the hematocytes emerging from the endothelium cells (FIG. 11E, arrow). In addition, strong expression of YS68 was indicated in the vascular endothelium of the umbilical vein (FIG. 11F). In contrast to TER119, which selectively stained hematocytes in the blood vessel, YS68 expression was stronger in vascular endothelium than in hematocytes in E9.5 yolk sacs (FIGS. 11G and H).  
       EXAMPLE 6  
     Expression of YS68 Within Cells  
       [0184]    A liver was surgically removed from an embryo (E14.5), cut into small pieces with tweezers, and incubated in cell dissociation buffer (Gibco) at 37° C. for 30 minutes. The cells were further treated with 0.1% collagenase at 37° C. for 1 hour, and were loosened by pipetting. After washing several times with PBS, the cells were suspended in DMEM containing 10% FCS, and were cultivated on a 10-cm dish.  
         [0185]    To investigate the localization of endogenous YS68 within cells, cultured hepatic cells were stained with anti-YS68 antibodies. First, the cells were fixed with 4% formalin, and then treated with 0.1% Triton-X 100 for cell staining. Next, cells were reacted with the primary antibodies, and then with secondary antibodies. The cells were visualized in the same manner as in Example 5.  
         [0186]    Consequently, although YS68 has multiple nuclear transport signals, strong expression was found not only in the nucleus, but also around the nucleus, which expression depended on cells (FIG. 12). Next, similar analysis for the expression in hematocytes was carried out. YS68 expression in hematocytes separated from embryonic liver was found to have varied strengths of expression depending on the cell type (FIG. 13B).  
         [0187]    Therefore, the group of hematocytes was sorted using CD34, which is a marker for immature hematocytes, and YS68 expression in CD34-positive cells was investigated. To collect CD34-positive cells, embryonic liver (E14.5) was incubated in a dissociation buffer at 37° C. for 30 minutes, and then the cells were dissociated by pipetting in PBS. After passing through a nylon mesh filter (Falcon), the cells were suspended in a sample buffer (0.5% BSA, 2 mM EDTA in PBS). The cells were reacted with biotin labeled anti-CD34 antibodies (Pharmingen), followed by FITC labeled streptavidin at 4° C., and then were incubated with anti-FITC microbeads. CD34 positive cells were eluted using MACS (Magnetic Cell Sorting) column according to the instructed protocol. The cells were centrifuged on a slide glass at 400 rpm for 5 minutes to fix them onto the slide glass. Cell staining was performed in the same manner as described above.  
         [0188]    Consequently, hematocytes that were concentrated using anti-CD34 antibodies (FIG. 12D) showed a higher expression of YS68 compared to hematocytes that passed through the CD34 column (FIG. 12C). Therefore, YS68 expression is anticipated in less differentiated CD34 positive hematocytes.  
       EXAMPLE 7  
     Localization of Each Domain of YS68 Within Cells  
       [0189]    Using cDNA prepared from mouse embryonic liver as a template, cDNA encoding the N-terminal region (amino acids 5-1148) and C-terminal region (amino acids 981-2243) of mouse YS68 were amplified by PCR. The amplified cDNAs were inserted downstream of the Flag region of animal cell expression vector pEFBOSE-F to produce pEFBOSE-F-YS68(5-1148) and pEFBOSE-F-YS68(981-2243) that expresses the N-terminal region of YS68 and the C-terminal region of YS68, respectively. The expression vectors were then transfected into COS-7 cells using lipofectamine 2000 (Gibco), and 24 hours later, the cells were immobilized with methanol. To investigate the localizations of each YS68 expressed within the cells, the cells were reacted with anti-Flag antibody, followed by peroxidase-labeled anti-mouse IgG, and finally substrate was added for visualization.  
         [0190]    Due to the multiple nuclear transport signals in the YS68 C-terminal region (FIG. 9), localization of YS68 in the nucleus was anticipated; however, endogenous YS68 was localized not only in the nucleus but also around the nucleus (FIG. 12). Additionally, constructs lacking the YS68 N-terminal region or the C-terminal region were prepared and were expressed in COS cells, and their localizations were investigated. The results confirmed that YS68 lacking the C-terminal region had strong tendency to localize in the cytoplasm, and YS68 lacking the N-terminal region in the nucleus (FIG. 14). These results suggested the possibility that the N-terminal region is inhibiting the transfer of YS68 into the nucleus. Since two WD repeats necessary for protein interaction exist in the N-terminal region, it was speculated that binding of this region to some molecule might possibly inhibit the transfer into the nucleus.  
       INDUSTRIAL APPLICABILITY  
       [0191]    The present invention provides novel “YS68” proteins predicted to be involved in primitive hematopoiesis and genes encoding the proteins. The genes may be utilized as markers for hematopoietic cells involved in primitive hematopoiesis and as factors regulating hematopoiesis. In addition, they may be utilized for purification and cloning of new factors involved in hematopoiesis, and even as tools for drug development for various diseases arising due to abnormalities in expression of the genes of this invention caused by abnormalities in expression regulation in vivo. Further, the “YS68” genes of this invention may be involved in blood tumors. Therefore, drug development against tumors utilizing the proteins of this invention is anticipated. By designing medicaments that target the genes of this invention, development of drugs that have new mechanisms of action may be enabled. Proteins and genes derived from humans are especially preferred in drug development compared to those derived from other organisms  
     
       
       
         1 
         
           
             15  
           
           
             1  
             4115  
             DNA  
             Mus musculus  
             
               CDS  
               (2)..(3817)  
             
             
               misc_feature  
               3101  
               n = A,T,C or G  
             
           
            1 

t cag att ctg aag aat aat ctc atg agt gat cgt gac cct cga ttg cgg     49 
  Gln Ile Leu Lys Asn Asn Leu Met Ser Asp Arg Asp Pro Arg Leu Arg 
    1               5                  10                  15 

gaa aga tcg gtg act cga aat tct ata tta gac cag tat ggg aaa atc       97 
Glu Arg Ser Val Thr Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile 
             20                  25                  30 

cta cct aga gtc cag aga aag tta gct gtt gag cga gct aag cct tac      145 
Leu Pro Arg Val Gln Arg Lys Leu Ala Val Glu Arg Ala Lys Pro Tyr 
         35                  40                  45 

cac ctg tcg aca tcc tca gtt ttt cat gaa gtt tct aga ccc aaa ccg      193 
His Leu Ser Thr Ser Ser Val Phe His Glu Val Ser Arg Pro Lys Pro 
     50                  55                  60 

tta tcg gca ttt cca aag aaa gct ata act gga aca gtg tta acc cga      241 
Leu Ser Ala Phe Pro Lys Lys Ala Ile Thr Gly Thr Val Leu Thr Arg 
 65                  70                  75                  80 

tct acg ttc atc agc aat gtt tta tct aaa att gga gag gtg tgg gca      289 
Ser Thr Phe Ile Ser Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala 
                 85                  90                  95 

agt cat gag cct aga aat ggc gtc tca ctt ttt aac agt cct aaa aca      337 
Ser His Glu Pro Arg Asn Gly Val Ser Leu Phe Asn Ser Pro Lys Thr 
            100                 105                 110 

gaa cag cca tct cct gta gta cac tct ttc cca cac cca gag ctt cct      385 
Glu Gln Pro Ser Pro Val Val His Ser Phe Pro His Pro Glu Leu Pro 
        115                 120                 125 

gag gcg ttt gtt gga act cca att tca aat aca tcc cag aga att tct      433 
Glu Ala Phe Val Gly Thr Pro Ile Ser Asn Thr Ser Gln Arg Ile Ser 
    130                 135                 140 

aga tta ctg gat ttg gtt gtc cat cct gta ccc cag cct tct cag tgt      481 
Arg Leu Leu Asp Leu Val Val His Pro Val Pro Gln Pro Ser Gln Cys 
145                 150                 155                 160 

ttg gag ttt att caa caa agt ccc aca aga tct cct ttg tgt ctg ctg      529 
Leu Glu Phe Ile Gln Gln Ser Pro Thr Arg Ser Pro Leu Cys Leu Leu 
                165                 170                 175 

tcc agt tcg tta cca tta agt tca cag ttt aaa agg cca cat cag aat      577 
Ser Ser Ser Leu Pro Leu Ser Ser Gln Phe Lys Arg Pro His Gln Asn 
            180                 185                 190 

acc tcc agg cct tca gag ttg ctt tta ctt gag act cct ctc ata gtt      625 
Thr Ser Arg Pro Ser Glu Leu Leu Leu Leu Glu Thr Pro Leu Ile Val 
        195                 200                 205 

aag aaa gct aaa tct ttg gct ctg tca gcc acg tct tct gga ttt gcc      673 
Lys Lys Ala Lys Ser Leu Ala Leu Ser Ala Thr Ser Ser Gly Phe Ala 
    210                 215                 220 

gag ttt act cct cca tcc atc ctt agg tct ggt ttt cga aca aca cct      721 
Glu Phe Thr Pro Pro Ser Ile Leu Arg Ser Gly Phe Arg Thr Thr Pro 
225                 230                 235                 240 

tta gca tct ccc tct ttg tca cct gga aga tct ctc act ccg cct ttc      769 
Leu Ala Ser Pro Ser Leu Ser Pro Gly Arg Ser Leu Thr Pro Pro Phe 
                245                 250                 255 

aga gtt aaa gaa aca agg att tca ttc atg gaa gaa ggc atg aat aca      817 
Arg Val Lys Glu Thr Arg Ile Ser Phe Met Glu Glu Gly Met Asn Thr 
            260                 265                 270 

cac tgg act gat aga gct aca gat gac cga aat aca aaa gcg ttt gtt      865 
His Trp Thr Asp Arg Ala Thr Asp Asp Arg Asn Thr Lys Ala Phe Val 
        275                 280                 285 

agc aca tct ttc cat aaa tgt gga ctt cca gca gaa act gag tgg atg      913 
Ser Thr Ser Phe His Lys Cys Gly Leu Pro Ala Glu Thr Glu Trp Met 
    290                 295                 300 

aag acc agt gat aag aat aca tat ttt cct ctg gat gtc cct gca aag      961 
Lys Thr Ser Asp Lys Asn Thr Tyr Phe Pro Leu Asp Val Pro Ala Lys 
305                 310                 315                 320 

ggc cct cag aaa gtg gtg gca gag tca ctg gct acc cat tca gga agg     1009 
Gly Pro Gln Lys Val Val Ala Glu Ser Leu Ala Thr His Ser Gly Arg 
                325                 330                 335 

ctg gag aaa ctg gat gtg agc aaa gaa gac agc aca gct tcc acc agg     1057 
Leu Glu Lys Leu Asp Val Ser Lys Glu Asp Ser Thr Ala Ser Thr Arg 
            340                 345                 350 

tca gac cag acc tcc tta gag tat cat gac gca cca tca cca gaa gac     1105 
Ser Asp Gln Thr Ser Leu Glu Tyr His Asp Ala Pro Ser Pro Glu Asp 
        355                 360                 365 

ttg gaa ggt gct gtt ttt gtg tct ccc aag cca gca tct tcc tcc act     1153 
Leu Glu Gly Ala Val Phe Val Ser Pro Lys Pro Ala Ser Ser Ser Thr 
    370                 375                 380 

gaa cta act act aat tca act cta caa aca gag agg gat aat gat aaa     1201 
Glu Leu Thr Thr Asn Ser Thr Leu Gln Thr Glu Arg Asp Asn Asp Lys 
385                 390                 395                 400 

gat gcg ttt aag tca gaa ggt act cct tca ccc gtg aag aaa caa ata     1249 
Asp Ala Phe Lys Ser Glu Gly Thr Pro Ser Pro Val Lys Lys Gln Ile 
                405                 410                 415 

ggc acg gga gac gct gca gtg gaa gca ttt tca gaa ctg agt cgc tta     1297 
Gly Thr Gly Asp Ala Ala Val Glu Ala Phe Ser Glu Leu Ser Arg Leu 
            420                 425                 430 

gac cct gtt gaa aga gct gaa gct tct ttt ggt gtg tcg tca gtc tgt     1345 
Asp Pro Val Glu Arg Ala Glu Ala Ser Phe Gly Val Ser Ser Val Cys 
        435                 440                 445 

gaa ggg gaa acc tcc act tca aac tcc aag acg tca gtt ctg gat gga     1393 
Glu Gly Glu Thr Ser Thr Ser Asn Ser Lys Thr Ser Val Leu Asp Gly 
    450                 455                 460 

atc gtg cct att gag agc cga acc tcc ata ctt aca gca gac cac aaa     1441 
Ile Val Pro Ile Glu Ser Arg Thr Ser Ile Leu Thr Ala Asp His Lys 
465                 470                 475                 480 

gag tct gtg gcc aac acg gtt gca gat gtt gaa agc tct ggg tcc acc     1489 
Glu Ser Val Ala Asn Thr Val Ala Asp Val Glu Ser Ser Gly Ser Thr 
                485                 490                 495 

agc tcc aag tgc ccg gtt acc tct gaa cgc agc ctc ggc caa aaa cta     1537 
Ser Ser Lys Cys Pro Val Thr Ser Glu Arg Ser Leu Gly Gln Lys Leu 
            500                 505                 510 

aca tta aac tta aaa gaa gat gaa ata gaa gct cat gta cca aag gag     1585 
Thr Leu Asn Leu Lys Glu Asp Glu Ile Glu Ala His Val Pro Lys Glu 
        515                 520                 525 

aac gtt ggt tta cca gaa gaa agc cct cga att tct gct gct cct tct     1633 
Asn Val Gly Leu Pro Glu Glu Ser Pro Arg Ile Ser Ala Ala Pro Ser 
    530                 535                 540 

gat act cac gag att cat cta att gga tgt gaa aat ctt gaa gtt caa     1681 
Asp Thr His Glu Ile His Leu Ile Gly Cys Glu Asn Leu Glu Val Gln 
545                 550                 555                 560 

aat tca gaa gag gag gcc aag aat ctt tca ttt gat gag ttg tat ccc     1729 
Asn Ser Glu Glu Glu Ala Lys Asn Leu Ser Phe Asp Glu Leu Tyr Pro 
                565                 570                 575 

tta ggg gca gag aaa ctt gag tat aat ctc agt act att gag cag cag     1777 
Leu Gly Ala Glu Lys Leu Glu Tyr Asn Leu Ser Thr Ile Glu Gln Gln 
            580                 585                 590 

ttt tgt gac ttg cct gat gac aaa gac tct gct gaa tgt gat gct gct     1825 
Phe Cys Asp Leu Pro Asp Asp Lys Asp Ser Ala Glu Cys Asp Ala Ala 
        595                 600                 605 

gaa gta gac ggg gaa ctt ttt gtg gcc cag agc aac ttt acc ctg att     1873 
Glu Val Asp Gly Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile 
    610                 615                 620 

tta gaa ggt gaa gaa gga gaa gct gag gca agc gac tct gca gca cct     1921 
Leu Glu Gly Glu Glu Gly Glu Ala Glu Ala Ser Asp Ser Ala Ala Pro 
625                 630                 635                 640 

aat atg tta ccg aaa tcg acc aag gaa aaa cct gtg tgc tac agg gaa     1969 
Asn Met Leu Pro Lys Ser Thr Lys Glu Lys Pro Val Cys Tyr Arg Glu 
                645                 650                 655 

ccc cat aat cag gag cgc gtt aca gat ttg cca tct gct gtg act gct     2017 
Pro His Asn Gln Glu Arg Val Thr Asp Leu Pro Ser Ala Val Thr Ala 
            660                 665                 670 

gac caa gaa tcc cac aag gta gag act tta ccg tat gtg cct gaa ccg     2065 
Asp Gln Glu Ser His Lys Val Glu Thr Leu Pro Tyr Val Pro Glu Pro 
        675                 680                 685 

gtt aaa gtg gca att gca gaa aat ctg ttg gat gta att aaa gac acc     2113 
Val Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr 
    690                 695                 700 

aga agt aag gaa gca act ccc gtg gca gca ggt gag gct ggt gat gag     2161 
Arg Ser Lys Glu Ala Thr Pro Val Ala Ala Gly Glu Ala Gly Asp Glu 
705                 710                 715                 720 

gac gga gca gtg ata gtc tca aag gct gca cat tcg tcc agg ctg aca     2209 
Asp Gly Ala Val Ile Val Ser Lys Ala Ala His Ser Ser Arg Leu Thr 
                725                 730                 735 

aac tct aca ccg aag act gtt aag gaa cca cgt gca gag act gta aat     2257 
Asn Ser Thr Pro Lys Thr Val Lys Glu Pro Arg Ala Glu Thr Val Asn 
            740                 745                 750 

acc agc cag agt gat gac atg gtt tct tct aga act ctc aca aga agg     2305 
Thr Ser Gln Ser Asp Asp Met Val Ser Ser Arg Thr Leu Thr Arg Arg 
        755                 760                 765 

cag cat gcc cta agc ctg aat gtc aca tca gaa caa gag cct tca gca     2353 
Gln His Ala Leu Ser Leu Asn Val Thr Ser Glu Gln Glu Pro Ser Ala 
    770                 775                 780 

gtt gcc act cct aag aag aga act aga aaa att aaa gaa act cct gag     2401 
Val Ala Thr Pro Lys Lys Arg Thr Arg Lys Ile Lys Glu Thr Pro Glu 
785                 790                 795                 800 

tct tct gaa agg acc tgt tct gac cta aaa gta gca cct gag aac caa     2449 
Ser Ser Glu Arg Thr Cys Ser Asp Leu Lys Val Ala Pro Glu Asn Gln 
                805                 810                 815 

ctg aca gct cag aat cct ccc gct cct agg aga aga aag aag aag gac     2497 
Leu Thr Ala Gln Asn Pro Pro Ala Pro Arg Arg Arg Lys Lys Lys Asp 
            820                 825                 830 

gtt agc caa ggc aca ctg cca agt tct ggt gct gtg gag ccg gag ccg     2545 
Val Ser Gln Gly Thr Leu Pro Ser Ser Gly Ala Val Glu Pro Glu Pro 
        835                 840                 845 

gaa cct cag ggt acg ccg gga aga ctg agg ctg aga acg cag cca ccc     2593 
Glu Pro Gln Gly Thr Pro Gly Arg Leu Arg Leu Arg Thr Gln Pro Pro 
    850                 855                 860 

gag cca gca gct gaa gaa act cct tct aga aca aaa gtc agg ctt tca     2641 
Glu Pro Ala Ala Glu Glu Thr Pro Ser Arg Thr Lys Val Arg Leu Ser 
865                 870                 875                 880 

tct gtt aga aag gga acc cct aga aga ctt aag aag tct gta gaa aat     2689 
Ser Val Arg Lys Gly Thr Pro Arg Arg Leu Lys Lys Ser Val Glu Asn 
                885                 890                 895 

ggg caa agt ata gaa att cta gat gat ctc aaa ggg agt gag gca gca     2737 
Gly Gln Ser Ile Glu Ile Leu Asp Asp Leu Lys Gly Ser Glu Ala Ala 
            900                 905                 910 

agt cat gac ggg act gtc aca gag ctg agg aat gcc aat tta gaa gat     2785 
Ser His Asp Gly Thr Val Thr Glu Leu Arg Asn Ala Asn Leu Glu Asp 
        915                 920                 925 

act cag aat atg gag tat aaa caa gat gaa cac agt gac cag caa ccg     2833 
Thr Gln Asn Met Glu Tyr Lys Gln Asp Glu His Ser Asp Gln Gln Pro 
    930                 935                 940 

cct cta aaa cga aag agg gtc aga gag aga gaa gtt agt gtg tca agt     2881 
Pro Leu Lys Arg Lys Arg Val Arg Glu Arg Glu Val Ser Val Ser Ser 
945                 950                 955                 960 

gtg aca gaa gag cca aag ctt gac tca tcc cag ttg cct ctt cag aca     2929 
Val Thr Glu Glu Pro Lys Leu Asp Ser Ser Gln Leu Pro Leu Gln Thr 
                965                 970                 975 

gga ctc gat gta cct gcc acc cct agg aaa cgt ggt aga ccc agg aag     2977 
Gly Leu Asp Val Pro Ala Thr Pro Arg Lys Arg Gly Arg Pro Arg Lys 
            980                 985                 990 

gta gtt ccc tta gaa gct gac ggt ggc aca act ggt aag gaa cag aca     3025 
Val Val Pro Leu Glu Ala Asp Gly Gly Thr Thr Gly Lys Glu Gln Thr 
        995                1000                1005 

agt cct cag aag aaa gat gtt ccg gtt gtc cgg aga tct aca cgg aac     3073 
Ser Pro Gln Lys Lys Asp Val Pro Val Val Arg Arg Ser Thr Arg Asn 
   1010                1015                1020 

acc cca gct aga aat gtg agt act tta naa aaa tca gtt tta gtg cca     3121 
Thr Pro Ala Arg Asn Val Ser Thr Leu Xaa Lys Ser Val Leu Val Pro 
1025               1030                1035                1040 

aat aag gaa gct gct cta gtg gtg aca tct aag agg aga cct aca aag     3169 
Asn Lys Glu Ala Ala Leu Val Val Thr Ser Lys Arg Arg Pro Thr Lys 
               1045                1050                1055 

aag tct gca gag gaa agc tca aaa gat cca tca gcg gca gtc tca gac     3217 
Lys Ser Ala Glu Glu Ser Ser Lys Asp Pro Ser Ala Ala Val Ser Asp 
           1060                1065                1070 

tgg gcg ggt gga gca gcc cac aca gag tcc gct gac cga agg gac gga     3265 
Trp Ala Gly Gly Ala Ala His Thr Glu Ser Ala Asp Arg Arg Asp Gly 
       1075                1080                1085 

ctg ctt gcc gcc gct gct ctc acg cca tct gcc cag ggc aca agg act     3313 
Leu Leu Ala Ala Ala Ala Leu Thr Pro Ser Ala Gln Gly Thr Arg Thr 
   1090                1095                1100 

agg tct aga agg acc atg ttg ttg acg gac att tct gaa ccc aaa act     3361 
Arg Ser Arg Arg Thr Met Leu Leu Thr Asp Ile Ser Glu Pro Lys Thr 
1105               1110                1115                1120 

gag cct tta ttt cct cct cct tca gtg aag gtt cca aag aaa aaa tca     3409 
Glu Pro Leu Phe Pro Pro Pro Ser Val Lys Val Pro Lys Lys Lys Ser 
               1125                1130                1135 

aaa gct gag aac atg gag gcc gca gcc cag ctg aaa gaa ttg gtg tca     3457 
Lys Ala Glu Asn Met Glu Ala Ala Ala Gln Leu Lys Glu Leu Val Ser 
           1140                1145                1150 

gat tta tct tct cag ttt gtt gtt tcc cct cct gcc ttg aga acc agg     3505 
Asp Leu Ser Ser Gln Phe Val Val Ser Pro Pro Ala Leu Arg Thr Arg 
       1155                1160                1165 

cag aaa agt ata tcc aat act tcc aag ctt cta ggt gaa ctg gag agt     3553 
Gln Lys Ser Ile Ser Asn Thr Ser Lys Leu Leu Gly Glu Leu Glu Ser 
   1170                1175                1180 

gac cct aaa cca tta gag atc ata gaa caa aaa cca aaa aga agc agg     3601 
Asp Pro Lys Pro Leu Glu Ile Ile Glu Gln Lys Pro Lys Arg Ser Arg 
1185               1190                1195                1200 

act gtg aag aca aga gca agc aga aac aca gga aaa gga agt tct tgg     3649 
Thr Val Lys Thr Arg Ala Ser Arg Asn Thr Gly Lys Gly Ser Ser Trp 
               1205                1210                1215 

tca cct cct cct gta gaa att aag ctg gtt tct ccc ttg gcg agt cca     3697 
Ser Pro Pro Pro Val Glu Ile Lys Leu Val Ser Pro Leu Ala Ser Pro 
           1220                1225                1230 

gtg gat gaa ata aag acc ggc aag cca aga aaa act gca gaa ata gca     3745 
Val Asp Glu Ile Lys Thr Gly Lys Pro Arg Lys Thr Ala Glu Ile Ala 
       1235                1240                1245 

gga aaa act ctt gga agg ggc aga aag aag cca tct tct ttt cca aag     3793 
Gly Lys Thr Leu Gly Arg Gly Arg Lys Lys Pro Ser Ser Phe Pro Lys 
   1250                1255                1260 

caa att tta cgc agg aaa atg ctg taatttttag cccaagattt taacacgcac    3847 
Gln Ile Leu Arg Arg Lys Met Leu 
1265               1270 

ctgtttgtaa aagtcaacag tatttgtgtg gattattaaa gtcaccaatt tggatgaaaa   3907 

tactttatat aaattgtaca attttgtaag cagtaaatga gtaactccac atggagtgca   3967 

gttcttgtag tgcaggcgtt ttatacgact tgatgcgttt atatcaatgt aaatatgact   4027 

tatcattggg aggttaaata aactactgta aagtaaaaaa aaaaaaaaaa aaaaaaaaaa   4087 

aaaaaaaaaa aaaaaaaaaa aaaaaaaa                                      4115 

 
           
             2  
             1272  
             PRT  
             Mus musculus  
             
               VARIANT  
               1034  
               Xaa = Any Amino Acid  
             
           
            2 

Gln Ile Leu Lys Asn Asn Leu Met Ser Asp Arg Asp Pro Arg Leu Arg 
  1               5                  10                  15 

Glu Arg Ser Val Thr Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile 
             20                  25                  30 

Leu Pro Arg Val Gln Arg Lys Leu Ala Val Glu Arg Ala Lys Pro Tyr 
         35                  40                  45 

His Leu Ser Thr Ser Ser Val Phe His Glu Val Ser Arg Pro Lys Pro 
     50                  55                  60 

Leu Ser Ala Phe Pro Lys Lys Ala Ile Thr Gly Thr Val Leu Thr Arg 
 65                  70                  75                  80 

Ser Thr Phe Ile Ser Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala 
                 85                  90                  95 

Ser His Glu Pro Arg Asn Gly Val Ser Leu Phe Asn Ser Pro Lys Thr 
            100                 105                 110 

Glu Gln Pro Ser Pro Val Val His Ser Phe Pro His Pro Glu Leu Pro 
        115                 120                 125 

Glu Ala Phe Val Gly Thr Pro Ile Ser Asn Thr Ser Gln Arg Ile Ser 
    130                 135                 140 

Arg Leu Leu Asp Leu Val Val His Pro Val Pro Gln Pro Ser Gln Cys 
145                 150                 155                 160 

Leu Glu Phe Ile Gln Gln Ser Pro Thr Arg Ser Pro Leu Cys Leu Leu 
                165                 170                 175 

Ser Ser Ser Leu Pro Leu Ser Ser Gln Phe Lys Arg Pro His Gln Asn 
            180                 185                 190 

Thr Ser Arg Pro Ser Glu Leu Leu Leu Leu Glu Thr Pro Leu Ile Val 
        195                 200                 205 

Lys Lys Ala Lys Ser Leu Ala Leu Ser Ala Thr Ser Ser Gly Phe Ala 
    210                 215                 220 

Glu Phe Thr Pro Pro Ser Ile Leu Arg Ser Gly Phe Arg Thr Thr Pro 
225                 230                 235                 240 

Leu Ala Ser Pro Ser Leu Ser Pro Gly Arg Ser Leu Thr Pro Pro Phe 
                245                 250                 255 

Arg Val Lys Glu Thr Arg Ile Ser Phe Met Glu Glu Gly Met Asn Thr 
            260                 265                 270 

His Trp Thr Asp Arg Ala Thr Asp Asp Arg Asn Thr Lys Ala Phe Val 
        275                 280                 285 

Ser Thr Ser Phe His Lys Cys Gly Leu Pro Ala Glu Thr Glu Trp Met 
    290                 295                 300 

Lys Thr Ser Asp Lys Asn Thr Tyr Phe Pro Leu Asp Val Pro Ala Lys 
305                 310                 315                 320 

Gly Pro Gln Lys Val Val Ala Glu Ser Leu Ala Thr His Ser Gly Arg 
                325                 330                 335 

Leu Glu Lys Leu Asp Val Ser Lys Glu Asp Ser Thr Ala Ser Thr Arg 
            340                 345                 350 

Ser Asp Gln Thr Ser Leu Glu Tyr His Asp Ala Pro Ser Pro Glu Asp 
        355                 360                 365 

Leu Glu Gly Ala Val Phe Val Ser Pro Lys Pro Ala Ser Ser Ser Thr 
    370                 375                 380 

Glu Leu Thr Thr Asn Ser Thr Leu Gln Thr Glu Arg Asp Asn Asp Lys 
385                 390                 395                 400 

Asp Ala Phe Lys Ser Glu Gly Thr Pro Ser Pro Val Lys Lys Gln Ile 
                405                 410                 415 

Gly Thr Gly Asp Ala Ala Val Glu Ala Phe Ser Glu Leu Ser Arg Leu 
            420                 425                 430 

Asp Pro Val Glu Arg Ala Glu Ala Ser Phe Gly Val Ser Ser Val Cys 
        435                 440                 445 

Glu Gly Glu Thr Ser Thr Ser Asn Ser Lys Thr Ser Val Leu Asp Gly 
    450                 455                 460 

Ile Val Pro Ile Glu Ser Arg Thr Ser Ile Leu Thr Ala Asp His Lys 
465                 470                 475                 480 

Glu Ser Val Ala Asn Thr Val Ala Asp Val Glu Ser Ser Gly Ser Thr 
                485                 490                 495 

Ser Ser Lys Cys Pro Val Thr Ser Glu Arg Ser Leu Gly Gln Lys Leu 
            500                 505                 510 

Thr Leu Asn Leu Lys Glu Asp Glu Ile Glu Ala His Val Pro Lys Glu 
        515                 520                 525 

Asn Val Gly Leu Pro Glu Glu Ser Pro Arg Ile Ser Ala Ala Pro Ser 
    530                 535                 540 

Asp Thr His Glu Ile His Leu Ile Gly Cys Glu Asn Leu Glu Val Gln 
545                 550                 555                 560 

Asn Ser Glu Glu Glu Ala Lys Asn Leu Ser Phe Asp Glu Leu Tyr Pro 
                565                 570                 575 

Leu Gly Ala Glu Lys Leu Glu Tyr Asn Leu Ser Thr Ile Glu Gln Gln 
            580                 585                 590 

Phe Cys Asp Leu Pro Asp Asp Lys Asp Ser Ala Glu Cys Asp Ala Ala 
        595                 600                 605 

Glu Val Asp Gly Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile 
    610                 615                 620 

Leu Glu Gly Glu Glu Gly Glu Ala Glu Ala Ser Asp Ser Ala Ala Pro 
625                 630                 635                 640 

Asn Met Leu Pro Lys Ser Thr Lys Glu Lys Pro Val Cys Tyr Arg Glu 
                645                 650                 655 

Pro His Asn Gln Glu Arg Val Thr Asp Leu Pro Ser Ala Val Thr Ala 
            660                 665                 670 

Asp Gln Glu Ser His Lys Val Glu Thr Leu Pro Tyr Val Pro Glu Pro 
        675                 680                 685 

Val Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr 
    690                 695                 700 

Arg Ser Lys Glu Ala Thr Pro Val Ala Ala Gly Glu Ala Gly Asp Glu 
705                 710                 715                 720 

Asp Gly Ala Val Ile Val Ser Lys Ala Ala His Ser Ser Arg Leu Thr 
                725                 730                 735 

Asn Ser Thr Pro Lys Thr Val Lys Glu Pro Arg Ala Glu Thr Val Asn 
            740                 745                 750 

Thr Ser Gln Ser Asp Asp Met Val Ser Ser Arg Thr Leu Thr Arg Arg 
        755                 760                 765 

Gln His Ala Leu Ser Leu Asn Val Thr Ser Glu Gln Glu Pro Ser Ala 
    770                 775                 780 

Val Ala Thr Pro Lys Lys Arg Thr Arg Lys Ile Lys Glu Thr Pro Glu 
785                 790                 795                 800 

Ser Ser Glu Arg Thr Cys Ser Asp Leu Lys Val Ala Pro Glu Asn Gln 
                805                 810                 815 

Leu Thr Ala Gln Asn Pro Pro Ala Pro Arg Arg Arg Lys Lys Lys Asp 
            820                 825                 830 

Val Ser Gln Gly Thr Leu Pro Ser Ser Gly Ala Val Glu Pro Glu Pro 
        835                 840                 845 

Glu Pro Gln Gly Thr Pro Gly Arg Leu Arg Leu Arg Thr Gln Pro Pro 
    850                 855                 860 

Glu Pro Ala Ala Glu Glu Thr Pro Ser Arg Thr Lys Val Arg Leu Ser 
865                 870                 875                 880 

Ser Val Arg Lys Gly Thr Pro Arg Arg Leu Lys Lys Ser Val Glu Asn 
                885                 890                 895 

Gly Gln Ser Ile Glu Ile Leu Asp Asp Leu Lys Gly Ser Glu Ala Ala 
            900                 905                 910 

Ser His Asp Gly Thr Val Thr Glu Leu Arg Asn Ala Asn Leu Glu Asp 
        915                 920                 925 

Thr Gln Asn Met Glu Tyr Lys Gln Asp Glu His Ser Asp Gln Gln Pro 
    930                 935                 940 

Pro Leu Lys Arg Lys Arg Val Arg Glu Arg Glu Val Ser Val Ser Ser 
945                 950                 955                 960 

Val Thr Glu Glu Pro Lys Leu Asp Ser Ser Gln Leu Pro Leu Gln Thr 
                965                 970                 975 

Gly Leu Asp Val Pro Ala Thr Pro Arg Lys Arg Gly Arg Pro Arg Lys 
            980                 985                 990 

Val Val Pro Leu Glu Ala Asp Gly Gly Thr Thr Gly Lys Glu Gln Thr 
        995                1000                1005 

Ser Pro Gln Lys Lys Asp Val Pro Val Val Arg Arg Ser Thr Arg Asn 
   1010                1015                1020 

Thr Pro Ala Arg Asn Val Ser Thr Leu Xaa Lys Ser Val Leu Val Pro 
1025               1030                1035                1040 

Asn Lys Glu Ala Ala Leu Val Val Thr Ser Lys Arg Arg Pro Thr Lys 
               1045                1050                1055 

Lys Ser Ala Glu Glu Ser Ser Lys Asp Pro Ser Ala Ala Val Ser Asp 
           1060                1065                1070 

Trp Ala Gly Gly Ala Ala His Thr Glu Ser Ala Asp Arg Arg Asp Gly 
       1075                1080                1085 

Leu Leu Ala Ala Ala Ala Leu Thr Pro Ser Ala Gln Gly Thr Arg Thr 
   1090                1095                1100 

Arg Ser Arg Arg Thr Met Leu Leu Thr Asp Ile Ser Glu Pro Lys Thr 
1105               1110                1115                1120 

Glu Pro Leu Phe Pro Pro Pro Ser Val Lys Val Pro Lys Lys Lys Ser 
               1125                1130                1135 

Lys Ala Glu Asn Met Glu Ala Ala Ala Gln Leu Lys Glu Leu Val Ser 
           1140                1145                1150 

Asp Leu Ser Ser Gln Phe Val Val Ser Pro Pro Ala Leu Arg Thr Arg 
       1155                1160                1165 

Gln Lys Ser Ile Ser Asn Thr Ser Lys Leu Leu Gly Glu Leu Glu Ser 
   1170                1175                1180 

Asp Pro Lys Pro Leu Glu Ile Ile Glu Gln Lys Pro Lys Arg Ser Arg 
1185               1190                1195                1200 

Thr Val Lys Thr Arg Ala Ser Arg Asn Thr Gly Lys Gly Ser Ser Trp 
               1205                1210                1215 

Ser Pro Pro Pro Val Glu Ile Lys Leu Val Ser Pro Leu Ala Ser Pro 
           1220                1225                1230 

Val Asp Glu Ile Lys Thr Gly Lys Pro Arg Lys Thr Ala Glu Ile Ala 
       1235                1240                1245 

Gly Lys Thr Leu Gly Arg Gly Arg Lys Lys Pro Ser Ser Phe Pro Lys 
   1250                1255                1260 

Gln Ile Leu Arg Arg Lys Met Leu 
1265               1270 

 
           
             3  
             24  
             DNA  
             Artificial Sequence  
             
               Description of Artificial SequenceArtificially 
      Synthesized Primer Sequence  
             
           
            3 

cacccgtgaa gaaacaaata ggca                                            24 

 
           
             4  
             24  
             DNA  
             Artificial Sequence  
             
               Description of Artificial SequenceArtificially 
      Synthesized Primer Sequence  
             
           
            4 

cctttggtac atgagcttct attt                                            24 

 
           
             5  
             4883  
             DNA  
             Homo sapiens  
             
               CDS  
               (1)..(4590)  
             
           
            5 

gag aag ttg tgg aaa cga gat gaa gga ggc aca gga aaa tat cct cct       48 
Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Lys Tyr Pro Pro 
  1               5                  10                  15 

gct agt ctg cat gca gta ctt gat atg tac cta tta gac ggc gtt act       96 
Ala Ser Leu His Ala Val Leu Asp Met Tyr Leu Leu Asp Gly Val Thr 
             20                  25                  30 

gaa gca gcc aaa cac tct att acc att tat ttg cta ctt gat att atg      144 
Glu Ala Ala Lys His Ser Ile Thr Ile Tyr Leu Leu Leu Asp Ile Met 
         35                  40                  45 

tat tcc ttt ccc aac aaa aca gac act ccc att gaa tct ttc cca act      192 
Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser Phe Pro Thr 
     50                  55                  60 

gta ttt gcc att tct tgg ggc caa gtt aaa ctt att cag ggg ttt tgg      240 
Val Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Ile Gln Gly Phe Trp 
 65                  70                  75                  80 

ttg ata gat cat aat gac tat gag agt ggt ttg gat ctt ttg ttt cat      288 
Leu Ile Asp His Asn Asp Tyr Glu Ser Gly Leu Asp Leu Leu Phe His 
                 85                  90                  95 

cca gct act gca aaa cct ttg tca tgg caa cat tca aag att att cag      336 
Pro Ala Thr Ala Lys Pro Leu Ser Trp Gln His Ser Lys Ile Ile Gln 
            100                 105                 110 

gca ttc atg agt cag ggc gag cac aga caa gcc ctc aga tat att cag      384 
Ala Phe Met Ser Gln Gly Glu His Arg Gln Ala Leu Arg Tyr Ile Gln 
        115                 120                 125 

aca atg aag cca aca gtg tcc agt ggt aac gat gtt atc ctt cac ctc      432 
Thr Met Lys Pro Thr Val Ser Ser Gly Asn Asp Val Ile Leu His Leu 
    130                 135                 140 

act gtt ttg ctt ttt aat agg tgt atg gtt gaa gcc tgg aat ttt ttg      480 
Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp Asn Phe Leu 
145                 150                 155                 160 

cgg caa cat tgc aat agg ttg aat ata gag gag tta ctg aag cac atg      528 
Arg Gln His Cys Asn Arg Leu Asn Ile Glu Glu Leu Leu Lys His Met 
                165                 170                 175 

tat gaa gtc tgt cag gaa atg ggc ttg atg gaa gat tta ctg aag tta      576 
Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu Leu Lys Leu 
            180                 185                 190 

cca ttt aca gac act gag cag gaa tgt tta gtg aaa ttt ttg cag tcc      624 
Pro Phe Thr Asp Thr Glu Gln Glu Cys Leu Val Lys Phe Leu Gln Ser 
        195                 200                 205 

agt gcc agc gtt cag aat cat gaa ttc ctt tta gtg cac cat ttg cag      672 
Ser Ala Ser Val Gln Asn His Glu Phe Leu Leu Val His His Leu Gln 
    210                 215                 220 

cgt gcc aat tat gtg cct gcc ttg aag ctg aac caa act ctg aag att      720 
Arg Ala Asn Tyr Val Pro Ala Leu Lys Leu Asn Gln Thr Leu Lys Ile 
225                 230                 235                 240 

aat gtt atg aat gat cgt gat cct cgt ttg cgg gag aga tca ctg gct      768 
Asn Val Met Asn Asp Arg Asp Pro Arg Leu Arg Glu Arg Ser Leu Ala 
                245                 250                 255 

cga aat tct ata tta gac cag tat gga aaa atc ctt cct aga gtc cat      816 
Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro Arg Val His 
            260                 265                 270 

cga aaa tta gcc att gaa cga gct aag cct tat cat ctg tca aca tca      864 
Arg Lys Leu Ala Ile Glu Arg Ala Lys Pro Tyr His Leu Ser Thr Ser 
        275                 280                 285 

tca gtt ttt cga tta gtt tct aga ccc aaa cca tta tca gca gtt cca      912 
Ser Val Phe Arg Leu Val Ser Arg Pro Lys Pro Leu Ser Ala Val Pro 
    290                 295                 300 

aag caa gtt gta aca gga act gtg ttg aca aga tct gtt ttc atc aac      960 
Lys Gln Val Val Thr Gly Thr Val Leu Thr Arg Ser Val Phe Ile Asn 
305                 310                 315                 320 

aat gtg tta tct aaa att gga gaa gtt tgg gca agc aaa gaa cct ata     1008 
Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser Lys Glu Pro Ile 
                325                 330                 335 

aat agc acc aca cct ttc aat agt tct aaa ata gaa gaa cca tct cct     1056 
Asn Ser Thr Thr Pro Phe Asn Ser Ser Lys Ile Glu Glu Pro Ser Pro 
            340                 345                 350 

ata gtg tat tcg ctc cca gct cca gag ctg cct gag gca ttt ttt gga     1104 
Ile Val Tyr Ser Leu Pro Ala Pro Glu Leu Pro Glu Ala Phe Phe Gly 
        355                 360                 365 

aca cca att tca aaa gca tca caa aaa att tct aga ctg cta gat ttg     1152 
Thr Pro Ile Ser Lys Ala Ser Gln Lys Ile Ser Arg Leu Leu Asp Leu 
    370                 375                 380 

gtt gtt cag cct gtc ccc cgg cct tct cag tgt tcg gag ttt att cag     1200 
Val Val Gln Pro Val Pro Arg Pro Ser Gln Cys Ser Glu Phe Ile Gln 
385                 390                 395                 400 

caa agc tcc atg aaa tct cct ttg tac cta gta tcc cgt tca ctg ccc     1248 
Gln Ser Ser Met Lys Ser Pro Leu Tyr Leu Val Ser Arg Ser Leu Pro 
                405                 410                 415 

tca agt tcg caa tta aaa gga tcg cct cag gcc atc tcc agg gct tca     1296 
Ser Ser Ser Gln Leu Lys Gly Ser Pro Gln Ala Ile Ser Arg Ala Ser 
            420                 425                 430 

gaa tta cat ttg ctt gaa act cct ctt gta gtt aag aaa gct aaa agt     1344 
Glu Leu His Leu Leu Glu Thr Pro Leu Val Val Lys Lys Ala Lys Ser 
        435                 440                 445 

ttg gcc atg tca gtt act act tct gga ttt tct gag ttc act cct cag     1392 
Leu Ala Met Ser Val Thr Thr Ser Gly Phe Ser Glu Phe Thr Pro Gln 
    450                 455                 460 

tcc atc ctg agg tct act cct cga tca aca cct tta gca tct ccc tct     1440 
Ser Ile Leu Arg Ser Thr Pro Arg Ser Thr Pro Leu Ala Ser Pro Ser 
465                 470                 475                 480 

cca tca cct gga agg tct cct caa cga ctt aaa gaa act aga att tca     1488 
Pro Ser Pro Gly Arg Ser Pro Gln Arg Leu Lys Glu Thr Arg Ile Ser 
                485                 490                 495 

ttt gtg gaa gaa gat gtc cac cca aaa tgg att cct ggg gct gca gat     1536 
Phe Val Glu Glu Asp Val His Pro Lys Trp Ile Pro Gly Ala Ala Asp 
            500                 505                 510 

gat agc aaa tta gaa gta ttt act aca cct aaa aaa tgt gca gtt cca     1584 
Asp Ser Lys Leu Glu Val Phe Thr Thr Pro Lys Lys Cys Ala Val Pro 
        515                 520                 525 

gtg gaa act gaa tgg ccg aag agc aaa gat agg acc aca tct ttt ttc     1632 
Val Glu Thr Glu Trp Pro Lys Ser Lys Asp Arg Thr Thr Ser Phe Phe 
    530                 535                 540 

ctg aac agc cct gaa aag gag cat caa gaa atg gat gag ggg tca caa     1680 
Leu Asn Ser Pro Glu Lys Glu His Gln Glu Met Asp Glu Gly Ser Gln 
545                 550                 555                 560 

agt tta gag aaa ctg gat gtg agc aaa gga aac agc agt gtt tca atc     1728 
Ser Leu Glu Lys Leu Asp Val Ser Lys Gly Asn Ser Ser Val Ser Ile 
                565                 570                 575 

aca tcc gat gag act acc tta gag tat cag gat gca ccg tca ccg gaa     1776 
Thr Ser Asp Glu Thr Thr Leu Glu Tyr Gln Asp Ala Pro Ser Pro Glu 
            580                 585                 590 

gac ctt gaa gag act gtt ttc acg gcc tct aag ccc aaa agc tct tcc     1824 
Asp Leu Glu Glu Thr Val Phe Thr Ala Ser Lys Pro Lys Ser Ser Ser 
        595                 600                 605 

act gca cta act act aat gta act gaa caa act gaa aag gat gga gat     1872 
Thr Ala Leu Thr Thr Asn Val Thr Glu Gln Thr Glu Lys Asp Gly Asp 
    610                 615                 620 

aaa gat gta ttt gca tca gaa gta act cct tca gac cta cag aaa caa     1920 
Lys Asp Val Phe Ala Ser Glu Val Thr Pro Ser Asp Leu Gln Lys Gln 
625                 630                 635                 640 

atg ggc aat tta gaa gat gca gaa aca aag gat ctc tta gtt gca gca     1968 
Met Gly Asn Leu Glu Asp Ala Glu Thr Lys Asp Leu Leu Val Ala Ala 
                645                 650                 655 

gag gca ttt tca gaa ttg aat cac tta agc ccg gtt caa gga act gaa     2016 
Glu Ala Phe Ser Glu Leu Asn His Leu Ser Pro Val Gln Gly Thr Glu 
            660                 665                 670 

gct tct ctt tgt gca cca tca gtc tat gaa ggg aaa atc ttc acc cag     2064 
Ala Ser Leu Cys Ala Pro Ser Val Tyr Glu Gly Lys Ile Phe Thr Gln 
        675                 680                 685 

aag tcc aag gta cca gtg ttg gac gaa gga tta aca tct gtt gaa acc     2112 
Lys Ser Lys Val Pro Val Leu Asp Glu Gly Leu Thr Ser Val Glu Thr 
    690                 695                 700 

tac acc cct gca att aga gca aat gac aat aaa tct atg gct gat gtc     2160 
Tyr Thr Pro Ala Ile Arg Ala Asn Asp Asn Lys Ser Met Ala Asp Val 
705                 710                 715                 720 

ctt ggt gat ggt gga aac tcc tcg ctc act atc tct gaa ggt cct att     2208 
Leu Gly Asp Gly Gly Asn Ser Ser Leu Thr Ile Ser Glu Gly Pro Ile 
                725                 730                 735 

gtc tct gag cgc agg ctt aac cag gaa gta gcg ctg aac tta aaa gaa     2256 
Val Ser Glu Arg Arg Leu Asn Gln Glu Val Ala Leu Asn Leu Lys Glu 
            740                 745                 750 

gat cat gaa gta gaa gtt ggt gta cta aaa gaa agt gtt gac tta cca     2304 
Asp His Glu Val Glu Val Gly Val Leu Lys Glu Ser Val Asp Leu Pro 
        755                 760                 765 

gaa gaa aag ctt cca att tct gac agc cct cct gat act caa gaa att     2352 
Glu Glu Lys Leu Pro Ile Ser Asp Ser Pro Pro Asp Thr Gln Glu Ile 
    770                 775                 780 

cat gtg att gaa caa gaa aag ctt gaa gct caa gat tca gga gaa gag     2400 
His Val Ile Glu Gln Glu Lys Leu Glu Ala Gln Asp Ser Gly Glu Glu 
785                 790                 795                 800 

gct agg aat ctt tca ttt aat gag tta tat ccc tct gga aca ctt aag     2448 
Ala Arg Asn Leu Ser Phe Asn Glu Leu Tyr Pro Ser Gly Thr Leu Lys 
                805                 810                 815 

ctt cag tac aat ttt gat act att gac caa cag ttt tgt gac tta gct     2496 
Leu Gln Tyr Asn Phe Asp Thr Ile Asp Gln Gln Phe Cys Asp Leu Ala 
            820                 825                 830 

gat aac aaa gac act gct gaa tgt gac att gct gaa gta gat ggg gaa     2544 
Asp Asn Lys Asp Thr Ala Glu Cys Asp Ile Ala Glu Val Asp Gly Glu 
        835                 840                 845 

ctt ttt gtg gct caa agc aac ttt acc ttg ata ttg gaa ggt gaa gaa     2592 
Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu Gly Glu Glu 
    850                 855                 860 

gga gaa gtt gag cca ggt gat ttt gca tca tct gat gtg tta cct aaa     2640 
Gly Glu Val Glu Pro Gly Asp Phe Ala Ser Ser Asp Val Leu Pro Lys 
865                 870                 875                 880 

gca gct aac aca gca act gaa gaa aaa ctt gta tgc agt ggg gaa aat     2688 
Ala Ala Asn Thr Ala Thr Glu Glu Lys Leu Val Cys Ser Gly Glu Asn 
                885                 890                 895 

gat aat cat gga caa att gca aat ttg cca tct gcc gta act agt gac     2736 
Asp Asn His Gly Gln Ile Ala Asn Leu Pro Ser Ala Val Thr Ser Asp 
            900                 905                 910 

caa aag tcc caa aaa gta gac act tta cca tat gtg cct gaa cct att     2784 
Gln Lys Ser Gln Lys Val Asp Thr Leu Pro Tyr Val Pro Glu Pro Ile 
        915                 920                 925 

aaa gta gca att gca gaa aat tta cta gat gta att aaa gac aca aga     2832 
Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr Arg 
    930                 935                 940 

agt aaa gaa att act tca gat aca atg gaa cag tcc att cat gaa aca     2880 
Ser Lys Glu Ile Thr Ser Asp Thr Met Glu Gln Ser Ile His Glu Thr 
945                 950                 955                 960 

ata cct tta gtg agc caa aac ata atg tgt ccc act aaa ttg gtc aaa     2928 
Ile Pro Leu Val Ser Gln Asn Ile Met Cys Pro Thr Lys Leu Val Lys 
                965                 970                 975 

tct gca ttt aag act gct cag gaa aca agc aca atg act atg aat gtc     2976 
Ser Ala Phe Lys Thr Ala Gln Glu Thr Ser Thr Met Thr Met Asn Val 
            980                 985                 990 

agc cag gtt gat gac gtg gtt tcc tcc aaa act cgt acg aga ggt caa     3024 
Ser Gln Val Asp Asp Val Val Ser Ser Lys Thr Arg Thr Arg Gly Gln 
        995                1000                1005 

cgt atc caa aac gtg aat gtc aaa tca gca caa cag gaa gca tca gca     3072 
Arg Ile Gln Asn Val Asn Val Lys Ser Ala Gln Gln Glu Ala Ser Ala 
   1010                1015                1020 

gat gtt gct act cct aag atg cca ggg cag tca gtc agg aag aaa act     3120 
Asp Val Ala Thr Pro Lys Met Pro Gly Gln Ser Val Arg Lys Lys Thr 
1025               1030                1035                1040 

agg aag gca aaa gaa att tct gaa gct tct gaa aac atc tat tct gat     3168 
Arg Lys Ala Lys Glu Ile Ser Glu Ala Ser Glu Asn Ile Tyr Ser Asp 
               1045                1050                1055 

gtc aga gga cta ttt cag aac cag caa ata cct caa aat tct gtt acg     3216 
Val Arg Gly Leu Phe Gln Asn Gln Gln Ile Pro Gln Asn Ser Val Thr 
           1060                1065                1070 

cct agg aga gga agg aga aag aaa gaa gtt aat cag gac ata cta gaa     3264 
Pro Arg Arg Gly Arg Arg Lys Lys Glu Val Asn Gln Asp Ile Leu Glu 
       1075                1080                1085 

aac acc agt tct gtg gaa caa gaa tta cag atc act aca ggt agg gaa     3312 
Asn Thr Ser Ser Val Glu Gln Glu Leu Gln Ile Thr Thr Gly Arg Glu 
   1090                1095                1100 

tca aaa aga tta aaa tca tct cag ctg ttg gaa cca gca gtt gaa gaa     3360 
Ser Lys Arg Leu Lys Ser Ser Gln Leu Leu Glu Pro Ala Val Glu Glu 
1105               1110                1115                1120 

act act aaa aaa gaa gtt aag gtt tca tct gtt aca aaa agg act cct     3408 
Thr Thr Lys Lys Glu Val Lys Val Ser Ser Val Thr Lys Arg Thr Pro 
               1125                1130                1135 

aga aga att aaa aga tct gta gaa aat cag gaa agt gtt gaa att ata     3456 
Arg Arg Ile Lys Arg Ser Val Glu Asn Gln Glu Ser Val Glu Ile Ile 
           1140                1145                1150 

aat gat cta aaa gtt agt acg gta aca agt cct agc aga atg atc aga     3504 
Asn Asp Leu Lys Val Ser Thr Val Thr Ser Pro Ser Arg Met Ile Arg 
       1155                1160                1165 

aaa ttg aga agt act aat tta gat gct tct gaa aat aca gga aat aag     3552 
Lys Leu Arg Ser Thr Asn Leu Asp Ala Ser Glu Asn Thr Gly Asn Lys 
   1170                1175                1180 

caa gat gat aaa tcc agt gac aag cag ctg cgt att aaa cat gtt aga     3600 
Gln Asp Asp Lys Ser Ser Asp Lys Gln Leu Arg Ile Lys His Val Arg 
1185               1190                1195                1200 

agg gtc aga ggg aga gaa gtt agt cca tca gat gtg aga gaa gac tcc     3648 
Arg Val Arg Gly Arg Glu Val Ser Pro Ser Asp Val Arg Glu Asp Ser 
               1205                1210                1215 

aac ctt gag tca tct cag ttg act gtt caa gca gaa ttt gat atg tct     3696 
Asn Leu Glu Ser Ser Gln Leu Thr Val Gln Ala Glu Phe Asp Met Ser 
           1220                1225                1230 

gcc ata cct aga aaa cgt ggt aga cca aga aaa atc aat cca tct gaa     3744 
Ala Ile Pro Arg Lys Arg Gly Arg Pro Arg Lys Ile Asn Pro Ser Glu 
       1235                1240                1245 

gat gta gga tct aag gct gtt aag gaa gag aga agc ccc aag aag aaa     3792 
Asp Val Gly Ser Lys Ala Val Lys Glu Glu Arg Ser Pro Lys Lys Lys 
   1250                1255                1260 

gaa gct ccc agc att aga agg aga tct aca aga aat acc cca gct aaa     3840 
Glu Ala Pro Ser Ile Arg Arg Arg Ser Thr Arg Asn Thr Pro Ala Lys 
1265               1270                1275                1280 

agt gaa aat gtt gat gtt gga aaa cca gct tta gga aaa tcc att tta     3888 
Ser Glu Asn Val Asp Val Gly Lys Pro Ala Leu Gly Lys Ser Ile Leu 
               1285                1290                1295 

gtg cca aac gag gaa ctt tcg atg gtg atg agc tct aag aaa aaa ctt     3936 
Val Pro Asn Glu Glu Leu Ser Met Val Met Ser Ser Lys Lys Lys Leu 
           1300                1305                1310 

aca aaa aag act gaa agt caa agc caa aaa cgt tca ttg cac tca gta     3984 
Thr Lys Lys Thr Glu Ser Gln Ser Gln Lys Arg Ser Leu His Ser Val 
       1315                1320                1325 

tca gaa gaa cgc aca gat gaa atg aca cat aaa gaa aca aat gag cag     4032 
Ser Glu Glu Arg Thr Asp Glu Met Thr His Lys Glu Thr Asn Glu Gln 
   1330                1335                1340 

gaa gaa aga ttg ctc gcc aca gct tcc ttc act aaa tca tcc cgc agc     4080 
Glu Glu Arg Leu Leu Ala Thr Ala Ser Phe Thr Lys Ser Ser Arg Ser 
1345               1350                1355                1360 

agc agg act cgg tct agc aag gcc atc ttg ttg ccg gac ctt tct gaa     4128 
Ser Arg Thr Arg Ser Ser Lys Ala Ile Leu Leu Pro Asp Leu Ser Glu 
               1365                1370                1375 

cca aac aat gag cct tta ttt tct cca gcg tca gaa gtt cca agg aaa     4176 
Pro Asn Asn Glu Pro Leu Phe Ser Pro Ala Ser Glu Val Pro Arg Lys 
           1380                1385                1390 

gca aaa gct aaa aaa ata gag gtt cct gca cag ctg aaa gaa tta gtt     4224 
Ala Lys Ala Lys Lys Ile Glu Val Pro Ala Gln Leu Lys Glu Leu Val 
       1395                1400                1405 

tcg gat tta tct tct cag ttt gtc atc tca cct cct gct tta agg agc     4272 
Ser Asp Leu Ser Ser Gln Phe Val Ile Ser Pro Pro Ala Leu Arg Ser 
   1410                1415                1420 

aga caa aaa aac aca tcc aat aag aac aag ctt gaa gat gaa ctg aaa     4320 
Arg Gln Lys Asn Thr Ser Asn Lys Asn Lys Leu Glu Asp Glu Leu Lys 
1425               1430                1435                1440 

gat gat gca caa tca gta gaa act ctg gga aag cca aaa gcg aaa cga     4368 
Asp Asp Ala Gln Ser Val Glu Thr Leu Gly Lys Pro Lys Ala Lys Arg 
               1445                1450                1455 

atc agg acg tca aaa aca aaa caa gca agc aaa aac aca gaa aaa gaa     4416 
Ile Arg Thr Ser Lys Thr Lys Gln Ala Ser Lys Asn Thr Glu Lys Glu 
           1460                1465                1470 

agt gct tgg tca ctt cct ccc ata gaa att cgg ctg att tcc ccc ttg     4464 
Ser Ala Trp Ser Leu Pro Pro Ile Glu Ile Arg Leu Ile Ser Pro Leu 
       1475                1480                1485 

gct agc cca gct gac gga gtc aag agc aaa cca aga aaa act aca gaa     4512 
Ala Ser Pro Ala Asp Gly Val Lys Ser Lys Pro Arg Lys Thr Thr Glu 
   1490                1495                1500 

gtg aca gga aca ggt ctt gga agg aac aga aag aaa ctg tct tcc tat     4560 
Val Thr Gly Thr Gly Leu Gly Arg Asn Arg Lys Lys Leu Ser Ser Tyr 
1505               1510                1515                1520 

cca aag caa att tta cgc aga aaa atg ctg taatttcttg ggaagatttt       4610 
Pro Lys Gln Ile Leu Arg Arg Lys Met Leu 
               1525                1530 

aatgtacacc tatttgtaaa gtcatcagaa tagtgtggat tattaaatat ctagtttgga   4670 

agaaaataat ttatataaat tattgtaaat ttttatgtaa acagaaggtc ttcaataagt   4730 

aaagtaactc catatggagt gattgtttca gtccaggcaa tttttctatt ttatattaag   4790 

acttcataca tttatatatg taaatatggc ttattaatgg aatgttaaat aaaatgtata   4850 

cttctcaaaa aaaaaaaaaa aaaaaaaaaa aaa                                4883 

 
           
             6  
             1530  
             PRT  
             Homo sapiens  
           
            6 

Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Lys Tyr Pro Pro 
  1               5                  10                  15 

Ala Ser Leu His Ala Val Leu Asp Met Tyr Leu Leu Asp Gly Val Thr 
             20                  25                  30 

Glu Ala Ala Lys His Ser Ile Thr Ile Tyr Leu Leu Leu Asp Ile Met 
         35                  40                  45 

Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser Phe Pro Thr 
     50                  55                  60 

Val Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Ile Gln Gly Phe Trp 
 65                  70                  75                  80 

Leu Ile Asp His Asn Asp Tyr Glu Ser Gly Leu Asp Leu Leu Phe His 
                 85                  90                  95 

Pro Ala Thr Ala Lys Pro Leu Ser Trp Gln His Ser Lys Ile Ile Gln 
            100                 105                 110 

Ala Phe Met Ser Gln Gly Glu His Arg Gln Ala Leu Arg Tyr Ile Gln 
        115                 120                 125 

Thr Met Lys Pro Thr Val Ser Ser Gly Asn Asp Val Ile Leu His Leu 
    130                 135                 140 

Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp Asn Phe Leu 
145                 150                 155                 160 

Arg Gln His Cys Asn Arg Leu Asn Ile Glu Glu Leu Leu Lys His Met 
                165                 170                 175 

Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu Leu Lys Leu 
            180                 185                 190 

Pro Phe Thr Asp Thr Glu Gln Glu Cys Leu Val Lys Phe Leu Gln Ser 
        195                 200                 205 

Ser Ala Ser Val Gln Asn His Glu Phe Leu Leu Val His His Leu Gln 
    210                 215                 220 

Arg Ala Asn Tyr Val Pro Ala Leu Lys Leu Asn Gln Thr Leu Lys Ile 
225                 230                 235                 240 

Asn Val Met Asn Asp Arg Asp Pro Arg Leu Arg Glu Arg Ser Leu Ala 
                245                 250                 255 

Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro Arg Val His 
            260                 265                 270 

Arg Lys Leu Ala Ile Glu Arg Ala Lys Pro Tyr His Leu Ser Thr Ser 
        275                 280                 285 

Ser Val Phe Arg Leu Val Ser Arg Pro Lys Pro Leu Ser Ala Val Pro 
    290                 295                 300 

Lys Gln Val Val Thr Gly Thr Val Leu Thr Arg Ser Val Phe Ile Asn 
305                 310                 315                 320 

Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser Lys Glu Pro Ile 
                325                 330                 335 

Asn Ser Thr Thr Pro Phe Asn Ser Ser Lys Ile Glu Glu Pro Ser Pro 
            340                 345                 350 

Ile Val Tyr Ser Leu Pro Ala Pro Glu Leu Pro Glu Ala Phe Phe Gly 
        355                 360                 365 

Thr Pro Ile Ser Lys Ala Ser Gln Lys Ile Ser Arg Leu Leu Asp Leu 
    370                 375                 380 

Val Val Gln Pro Val Pro Arg Pro Ser Gln Cys Ser Glu Phe Ile Gln 
385                 390                 395                 400 

Gln Ser Ser Met Lys Ser Pro Leu Tyr Leu Val Ser Arg Ser Leu Pro 
                405                 410                 415 

Ser Ser Ser Gln Leu Lys Gly Ser Pro Gln Ala Ile Ser Arg Ala Ser 
            420                 425                 430 

Glu Leu His Leu Leu Glu Thr Pro Leu Val Val Lys Lys Ala Lys Ser 
        435                 440                 445 

Leu Ala Met Ser Val Thr Thr Ser Gly Phe Ser Glu Phe Thr Pro Gln 
    450                 455                 460 

Ser Ile Leu Arg Ser Thr Pro Arg Ser Thr Pro Leu Ala Ser Pro Ser 
465                 470                 475                 480 

Pro Ser Pro Gly Arg Ser Pro Gln Arg Leu Lys Glu Thr Arg Ile Ser 
                485                 490                 495 

Phe Val Glu Glu Asp Val His Pro Lys Trp Ile Pro Gly Ala Ala Asp 
            500                 505                 510 

Asp Ser Lys Leu Glu Val Phe Thr Thr Pro Lys Lys Cys Ala Val Pro 
        515                 520                 525 

Val Glu Thr Glu Trp Pro Lys Ser Lys Asp Arg Thr Thr Ser Phe Phe 
    530                 535                 540 

Leu Asn Ser Pro Glu Lys Glu His Gln Glu Met Asp Glu Gly Ser Gln 
545                 550                 555                 560 

Ser Leu Glu Lys Leu Asp Val Ser Lys Gly Asn Ser Ser Val Ser Ile 
                565                 570                 575 

Thr Ser Asp Glu Thr Thr Leu Glu Tyr Gln Asp Ala Pro Ser Pro Glu 
            580                 585                 590 

Asp Leu Glu Glu Thr Val Phe Thr Ala Ser Lys Pro Lys Ser Ser Ser 
        595                 600                 605 

Thr Ala Leu Thr Thr Asn Val Thr Glu Gln Thr Glu Lys Asp Gly Asp 
    610                 615                 620 

Lys Asp Val Phe Ala Ser Glu Val Thr Pro Ser Asp Leu Gln Lys Gln 
625                 630                 635                 640 

Met Gly Asn Leu Glu Asp Ala Glu Thr Lys Asp Leu Leu Val Ala Ala 
                645                 650                 655 

Glu Ala Phe Ser Glu Leu Asn His Leu Ser Pro Val Gln Gly Thr Glu 
            660                 665                 670 

Ala Ser Leu Cys Ala Pro Ser Val Tyr Glu Gly Lys Ile Phe Thr Gln 
        675                 680                 685 

Lys Ser Lys Val Pro Val Leu Asp Glu Gly Leu Thr Ser Val Glu Thr 
    690                 695                 700 

Tyr Thr Pro Ala Ile Arg Ala Asn Asp Asn Lys Ser Met Ala Asp Val 
705                 710                 715                 720 

Leu Gly Asp Gly Gly Asn Ser Ser Leu Thr Ile Ser Glu Gly Pro Ile 
                725                 730                 735 

Val Ser Glu Arg Arg Leu Asn Gln Glu Val Ala Leu Asn Leu Lys Glu 
            740                 745                 750 

Asp His Glu Val Glu Val Gly Val Leu Lys Glu Ser Val Asp Leu Pro 
        755                 760                 765 

Glu Glu Lys Leu Pro Ile Ser Asp Ser Pro Pro Asp Thr Gln Glu Ile 
    770                 775                 780 

His Val Ile Glu Gln Glu Lys Leu Glu Ala Gln Asp Ser Gly Glu Glu 
785                 790                 795                 800 

Ala Arg Asn Leu Ser Phe Asn Glu Leu Tyr Pro Ser Gly Thr Leu Lys 
                805                 810                 815 

Leu Gln Tyr Asn Phe Asp Thr Ile Asp Gln Gln Phe Cys Asp Leu Ala 
            820                 825                 830 

Asp Asn Lys Asp Thr Ala Glu Cys Asp Ile Ala Glu Val Asp Gly Glu 
        835                 840                 845 

Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu Gly Glu Glu 
    850                 855                 860 

Gly Glu Val Glu Pro Gly Asp Phe Ala Ser Ser Asp Val Leu Pro Lys 
865                 870                 875                 880 

Ala Ala Asn Thr Ala Thr Glu Glu Lys Leu Val Cys Ser Gly Glu Asn 
                885                 890                 895 

Asp Asn His Gly Gln Ile Ala Asn Leu Pro Ser Ala Val Thr Ser Asp 
            900                 905                 910 

Gln Lys Ser Gln Lys Val Asp Thr Leu Pro Tyr Val Pro Glu Pro Ile 
        915                 920                 925 

Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr Arg 
    930                 935                 940 

Ser Lys Glu Ile Thr Ser Asp Thr Met Glu Gln Ser Ile His Glu Thr 
945                 950                 955                 960 

Ile Pro Leu Val Ser Gln Asn Ile Met Cys Pro Thr Lys Leu Val Lys 
                965                 970                 975 

Ser Ala Phe Lys Thr Ala Gln Glu Thr Ser Thr Met Thr Met Asn Val 
            980                 985                 990 

Ser Gln Val Asp Asp Val Val Ser Ser Lys Thr Arg Thr Arg Gly Gln 
        995                1000                1005 

Arg Ile Gln Asn Val Asn Val Lys Ser Ala Gln Gln Glu Ala Ser Ala 
   1010                1015                1020 

Asp Val Ala Thr Pro Lys Met Pro Gly Gln Ser Val Arg Lys Lys Thr 
1025               1030                1035                1040 

Arg Lys Ala Lys Glu Ile Ser Glu Ala Ser Glu Asn Ile Tyr Ser Asp 
               1045                1050                1055 

Val Arg Gly Leu Phe Gln Asn Gln Gln Ile Pro Gln Asn Ser Val Thr 
           1060                1065                1070 

Pro Arg Arg Gly Arg Arg Lys Lys Glu Val Asn Gln Asp Ile Leu Glu 
       1075                1080                1085 

Asn Thr Ser Ser Val Glu Gln Glu Leu Gln Ile Thr Thr Gly Arg Glu 
   1090                1095                1100 

Ser Lys Arg Leu Lys Ser Ser Gln Leu Leu Glu Pro Ala Val Glu Glu 
1105               1110                1115                1120 

Thr Thr Lys Lys Glu Val Lys Val Ser Ser Val Thr Lys Arg Thr Pro 
               1125                1130                1135 

Arg Arg Ile Lys Arg Ser Val Glu Asn Gln Glu Ser Val Glu Ile Ile 
           1140                1145                1150 

Asn Asp Leu Lys Val Ser Thr Val Thr Ser Pro Ser Arg Met Ile Arg 
       1155                1160                1165 

Lys Leu Arg Ser Thr Asn Leu Asp Ala Ser Glu Asn Thr Gly Asn Lys 
   1170                1175                1180 

Gln Asp Asp Lys Ser Ser Asp Lys Gln Leu Arg Ile Lys His Val Arg 
1185               1190                1195                1200 

Arg Val Arg Gly Arg Glu Val Ser Pro Ser Asp Val Arg Glu Asp Ser 
               1205                1210                1215 

Asn Leu Glu Ser Ser Gln Leu Thr Val Gln Ala Glu Phe Asp Met Ser 
           1220                1225                1230 

Ala Ile Pro Arg Lys Arg Gly Arg Pro Arg Lys Ile Asn Pro Ser Glu 
       1235                1240                1245 

Asp Val Gly Ser Lys Ala Val Lys Glu Glu Arg Ser Pro Lys Lys Lys 
   1250                1255                1260 

Glu Ala Pro Ser Ile Arg Arg Arg Ser Thr Arg Asn Thr Pro Ala Lys 
1265               1270                1275                1280 

Ser Glu Asn Val Asp Val Gly Lys Pro Ala Leu Gly Lys Ser Ile Leu 
               1285                1290                1295 

Val Pro Asn Glu Glu Leu Ser Met Val Met Ser Ser Lys Lys Lys Leu 
           1300                1305                1310 

Thr Lys Lys Thr Glu Ser Gln Ser Gln Lys Arg Ser Leu His Ser Val 
       1315                1320                1325 

Ser Glu Glu Arg Thr Asp Glu Met Thr His Lys Glu Thr Asn Glu Gln 
   1330                1335                1340 

Glu Glu Arg Leu Leu Ala Thr Ala Ser Phe Thr Lys Ser Ser Arg Ser 
1345               1350                1355                1360 

Ser Arg Thr Arg Ser Ser Lys Ala Ile Leu Leu Pro Asp Leu Ser Glu 
               1365                1370                1375 

Pro Asn Asn Glu Pro Leu Phe Ser Pro Ala Ser Glu Val Pro Arg Lys 
           1380                1385                1390 

Ala Lys Ala Lys Lys Ile Glu Val Pro Ala Gln Leu Lys Glu Leu Val 
       1395                1400                1405 

Ser Asp Leu Ser Ser Gln Phe Val Ile Ser Pro Pro Ala Leu Arg Ser 
   1410                1415                1420 

Arg Gln Lys Asn Thr Ser Asn Lys Asn Lys Leu Glu Asp Glu Leu Lys 
1425               1430                1435                1440 

Asp Asp Ala Gln Ser Val Glu Thr Leu Gly Lys Pro Lys Ala Lys Arg 
               1445                1450                1455 

Ile Arg Thr Ser Lys Thr Lys Gln Ala Ser Lys Asn Thr Glu Lys Glu 
           1460                1465                1470 

Ser Ala Trp Ser Leu Pro Pro Ile Glu Ile Arg Leu Ile Ser Pro Leu 
       1475                1480                1485 

Ala Ser Pro Ala Asp Gly Val Lys Ser Lys Pro Arg Lys Thr Thr Glu 
   1490                1495                1500 

Val Thr Gly Thr Gly Leu Gly Arg Asn Arg Lys Lys Leu Ser Ser Tyr 
1505               1510                1515                1520 

Pro Lys Gln Ile Leu Arg Arg Lys Met Leu 
               1525                1530 

 
           
             7  
             4115  
             DNA  
             Mus musculus  
             
               CDS  
               (2)..(3817)  
             
             
               misc_feature  
               3101  
               n = A,T,C or G  
             
           
            7 

t cag att ctg aag aat aat ctc atg agt gat cgt gac cct cga ttg cgg     49 
  Gln Ile Leu Lys Asn Asn Leu Met Ser Asp Arg Asp Pro Arg Leu Arg 
    1               5                  10                  15 

gaa aga tcg gtg act cga aat tct ata tta gac cag tat ggg aaa atc       97 
Glu Arg Ser Val Thr Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile 
             20                  25                  30 

cta cct aga gtc cag aga aag tta gct gtt gag cga gct aag cct tac      145 
Leu Pro Arg Val Gln Arg Lys Leu Ala Val Glu Arg Ala Lys Pro Tyr 
         35                  40                  45 

cac ctg tcg aca tcc tca gtt ttt cat gaa gtt tct aga ccc aaa ccg      193 
His Leu Ser Thr Ser Ser Val Phe His Glu Val Ser Arg Pro Lys Pro 
     50                  55                  60 

tta tcg gca ttt cca aag aaa gct ata act gga aca gtg tta acc cga      241 
Leu Ser Ala Phe Pro Lys Lys Ala Ile Thr Gly Thr Val Leu Thr Arg 
 65                  70                  75                  80 

tct acg ttc atc agc aat gtt tta tct aaa att gga gag gtg tgg gca      289 
Ser Thr Phe Ile Ser Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala 
                 85                  90                  95 

agt cat gag cct aga aat ggc gtc tca ctt ttt aac agt cct aaa aca      337 
Ser His Glu Pro Arg Asn Gly Val Ser Leu Phe Asn Ser Pro Lys Thr 
            100                 105                 110 

gaa cag cca tct cct gta gta cac tct ttc cca cac cca gag ctt cct      385 
Glu Gln Pro Ser Pro Val Val His Ser Phe Pro His Pro Glu Leu Pro 
        115                 120                 125 

gag gcg ttt gtt gga act cca att tca aat aca tcc cag aga att tct      433 
Glu Ala Phe Val Gly Thr Pro Ile Ser Asn Thr Ser Gln Arg Ile Ser 
    130                 135                 140 

aga tta ctg gat ttg gtt gtc cat cct gta ccc cag cct tct cag tgt      481 
Arg Leu Leu Asp Leu Val Val His Pro Val Pro Gln Pro Ser Gln Cys 
145                 150                 155                 160 

ttg gag ttt att caa caa agt ccc aca aga tct cct ttg tgt ctg ctg      529 
Leu Glu Phe Ile Gln Gln Ser Pro Thr Arg Ser Pro Leu Cys Leu Leu 
                165                 170                 175 

tcc agt tcg tta cca tta agt tca cag ttt aaa agg cca cat cag aat      577 
Ser Ser Ser Leu Pro Leu Ser Ser Gln Phe Lys Arg Pro His Gln Asn 
            180                 185                 190 

acc tcc agg cct tca gag ttg ctt tta ctt gag act cct ctc ata gtt      625 
Thr Ser Arg Pro Ser Glu Leu Leu Leu Leu Glu Thr Pro Leu Ile Val 
        195                 200                 205 

aag aaa gct aaa tct ttg gct ctg tca gcc acg tct tct gga ttt gcc      673 
Lys Lys Ala Lys Ser Leu Ala Leu Ser Ala Thr Ser Ser Gly Phe Ala 
    210                 215                 220 

gag ttt act cct cca tcc atc ctt agg tct ggt ttt cga aca aca cct      721 
Glu Phe Thr Pro Pro Ser Ile Leu Arg Ser Gly Phe Arg Thr Thr Pro 
225                 230                 235                 240 

tta gca tct ccc tct ttg tca cct gga aga tct ctc act ccg cct ttc      769 
Leu Ala Ser Pro Ser Leu Ser Pro Gly Arg Ser Leu Thr Pro Pro Phe 
                245                 250                 255 

aga gtt aaa gaa aca agg att tca ttc atg gaa gaa ggc atg aat aca      817 
Arg Val Lys Glu Thr Arg Ile Ser Phe Met Glu Glu Gly Met Asn Thr 
            260                 265                 270 

cac tgg act gat aga gct aca gat gac cga aat aca aaa gcg ttt gtt      865 
His Trp Thr Asp Arg Ala Thr Asp Asp Arg Asn Thr Lys Ala Phe Val 
        275                 280                 285 

agc aca tct ttc cat aaa tgt gga ctt cca gca gaa act gag tgg atg      913 
Ser Thr Ser Phe His Lys Cys Gly Leu Pro Ala Glu Thr Glu Trp Met 
    290                 295                 300 

aag acc agt gat aag aat aca tat ttt cct ctg gat gtc cct gca aag      961 
Lys Thr Ser Asp Lys Asn Thr Tyr Phe Pro Leu Asp Val Pro Ala Lys 
305                 310                 315                 320 

ggc cct cag aaa gtg gtg gca gag tca ctg gct acc cat tca gga agg     1009 
Gly Pro Gln Lys Val Val Ala Glu Ser Leu Ala Thr His Ser Gly Arg 
                325                 330                 335 

ctg gag aaa ctg gat gtg agc aaa gaa gac agc aca gct tcc acc agg     1057 
Leu Glu Lys Leu Asp Val Ser Lys Glu Asp Ser Thr Ala Ser Thr Arg 
            340                 345                 350 

tca gac cag acc tcc tta gag tat cat gac gca cca tca cca gaa gac     1105 
Ser Asp Gln Thr Ser Leu Glu Tyr His Asp Ala Pro Ser Pro Glu Asp 
        355                 360                 365 

ttg gaa ggt gct gtt ttt gtg tct ccc aag cca gca tct tcc tcc act     1153 
Leu Glu Gly Ala Val Phe Val Ser Pro Lys Pro Ala Ser Ser Ser Thr 
    370                 375                 380 

gaa cta act act aat tca act cta caa aca gag agg gat aat gat aaa     1201 
Glu Leu Thr Thr Asn Ser Thr Leu Gln Thr Glu Arg Asp Asn Asp Lys 
385                 390                 395                 400 

gat gcg ttt aag tca gaa ggt act cct tca ccc gtg aag aaa caa ata     1249 
Asp Ala Phe Lys Ser Glu Gly Thr Pro Ser Pro Val Lys Lys Gln Ile 
                405                 410                 415 

ggc acg gga gac gct gca gtg gaa gca ttt tca gaa ctg agt cgc tta     1297 
Gly Thr Gly Asp Ala Ala Val Glu Ala Phe Ser Glu Leu Ser Arg Leu 
            420                 425                 430 

gac cct gtt gaa aga gct gaa gct tct ttt ggt gtg tcg tca gtc tgt     1345 
Asp Pro Val Glu Arg Ala Glu Ala Ser Phe Gly Val Ser Ser Val Cys 
        435                 440                 445 

gaa ggg gaa acc tcc act tca aac tcc aag acg tca gtt ctg gat gga     1393 
Glu Gly Glu Thr Ser Thr Ser Asn Ser Lys Thr Ser Val Leu Asp Gly 
    450                 455                 460 

atc gtg cct att gag agc cga acc tcc ata ctt aca gca gac cac aaa     1441 
Ile Val Pro Ile Glu Ser Arg Thr Ser Ile Leu Thr Ala Asp His Lys 
465                 470                 475                 480 

gag tct gtg gcc aac acg gtt gca gat gtt gaa agc tct ggg tcc acc     1489 
Glu Ser Val Ala Asn Thr Val Ala Asp Val Glu Ser Ser Gly Ser Thr 
                485                 490                 495 

agc tcc aag tgc ccg gtt acc tct gaa cgc agc ctc ggc caa aaa cta     1537 
Ser Ser Lys Cys Pro Val Thr Ser Glu Arg Ser Leu Gly Gln Lys Leu 
            500                 505                 510 

aca tta aac tta aaa gaa gat gaa ata gaa gct cat gta cca aag gag     1585 
Thr Leu Asn Leu Lys Glu Asp Glu Ile Glu Ala His Val Pro Lys Glu 
        515                 520                 525 

aac gtt ggt tta cca gaa gaa agc cct cga att tct gct gct cct tct     1633 
Asn Val Gly Leu Pro Glu Glu Ser Pro Arg Ile Ser Ala Ala Pro Ser 
    530                 535                 540 

gat act cac gag att cat cta att gga tgt gaa aat ctt gaa gtt caa     1681 
Asp Thr His Glu Ile His Leu Ile Gly Cys Glu Asn Leu Glu Val Gln 
545                 550                 555                 560 

aat tca gaa gag gag gcc aag aat ctt tca ttt gat gag ttg tat ccc     1729 
Asn Ser Glu Glu Glu Ala Lys Asn Leu Ser Phe Asp Glu Leu Tyr Pro 
                565                 570                 575 

tta ggg gca gag aaa ctt gag tat aat ctc agt act att gag cag cag     1777 
Leu Gly Ala Glu Lys Leu Glu Tyr Asn Leu Ser Thr Ile Glu Gln Gln 
            580                 585                 590 

ttt tgt gac ttg cct gat gac aaa gac tct gct gaa tgt gat gct gct     1825 
Phe Cys Asp Leu Pro Asp Asp Lys Asp Ser Ala Glu Cys Asp Ala Ala 
        595                 600                 605 

gaa gta gac ggg gaa ctt ttt gtg gcc cag agc aac ttt acc ctg att     1873 
Glu Val Asp Gly Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile 
    610                 615                 620 

tta gaa ggt gaa gaa gga gaa gct gag gca agc gac tct gca gca cct     1921 
Leu Glu Gly Glu Glu Gly Glu Ala Glu Ala Ser Asp Ser Ala Ala Pro 
625                 630                 635                 640 

aat atg tta ccg aaa tcg acc aag gaa aaa cct gtg tgc tac agg gaa     1969 
Asn Met Leu Pro Lys Ser Thr Lys Glu Lys Pro Val Cys Tyr Arg Glu 
                645                 650                 655 

ccc cat aat cag gag cgc gtt aca gat ttg cca tct gct gtg act gct     2017 
Pro His Asn Gln Glu Arg Val Thr Asp Leu Pro Ser Ala Val Thr Ala 
            660                 665                 670 

gac caa gaa tcc cac aag gta gag act tta ccg tat gtg cct gaa ccg     2065 
Asp Gln Glu Ser His Lys Val Glu Thr Leu Pro Tyr Val Pro Glu Pro 
        675                 680                 685 

gtt aaa gtg gca att gca gaa aat ctg ttg gat gta att aaa gac acc     2113 
Val Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr 
    690                 695                 700 

aga agt aag gaa gca act ccc gtg gca gca ggt gag gct ggt gat gag     2161 
Arg Ser Lys Glu Ala Thr Pro Val Ala Ala Gly Glu Ala Gly Asp Glu 
705                 710                 715                 720 

gac gga gca gtg ata gtc tca aag gct gca cat tcg tcc agg ctg aca     2209 
Asp Gly Ala Val Ile Val Ser Lys Ala Ala His Ser Ser Arg Leu Thr 
                725                 730                 735 

aac tct aca ccg aag act gtt aag gaa cca cgt gca gag act gta aat     2257 
Asn Ser Thr Pro Lys Thr Val Lys Glu Pro Arg Ala Glu Thr Val Asn 
            740                 745                 750 

acc agc cag agt gat gac atg gtt tct tct aga act ctc aca aga agg     2305 
Thr Ser Gln Ser Asp Asp Met Val Ser Ser Arg Thr Leu Thr Arg Arg 
        755                 760                 765 

cag cat gcc cta agc ctg aat gtc aca tca gaa caa gag cct tca gca     2353 
Gln His Ala Leu Ser Leu Asn Val Thr Ser Glu Gln Glu Pro Ser Ala 
    770                 775                 780 

gtt gcc act cct aag aag aga act aga aaa att aaa gaa act cct gag     2401 
Val Ala Thr Pro Lys Lys Arg Thr Arg Lys Ile Lys Glu Thr Pro Glu 
785                 790                 795                 800 

tct tct gaa agg acc tgt tct gac cta aaa gta gca cct gag aac caa     2449 
Ser Ser Glu Arg Thr Cys Ser Asp Leu Lys Val Ala Pro Glu Asn Gln 
                805                 810                 815 

ctg aca gct cag aat cct ccc gct cct agg aga aga aag aag aag gac     2497 
Leu Thr Ala Gln Asn Pro Pro Ala Pro Arg Arg Arg Lys Lys Lys Asp 
            820                 825                 830 

gtt agc caa ggc aca ctg cca agt tct ggt gct gtg gag ccg gag ccg     2545 
Val Ser Gln Gly Thr Leu Pro Ser Ser Gly Ala Val Glu Pro Glu Pro 
        835                 840                 845 

gaa cct cag ggt acg ccg gga aga ctg agg ctg aga acg cag cca ccc     2593 
Glu Pro Gln Gly Thr Pro Gly Arg Leu Arg Leu Arg Thr Gln Pro Pro 
    850                 855                 860 

gag cca gca gct gaa gaa act cct tct aga aca aaa gtc agg ctt tca     2641 
Glu Pro Ala Ala Glu Glu Thr Pro Ser Arg Thr Lys Val Arg Leu Ser 
865                 870                 875                 880 

tct gtt aga aag gga acc cct aga aga ctt aag aag tct gta gaa aat     2689 
Ser Val Arg Lys Gly Thr Pro Arg Arg Leu Lys Lys Ser Val Glu Asn 
                885                 890                 895 

ggg caa agt ata gaa att cta gat gat ctc aaa ggg agt gag gca gca     2737 
Gly Gln Ser Ile Glu Ile Leu Asp Asp Leu Lys Gly Ser Glu Ala Ala 
            900                 905                 910 

agt cat gac ggg act gtc aca gag ctg agg aat gcc aat tta gaa gat     2785 
Ser His Asp Gly Thr Val Thr Glu Leu Arg Asn Ala Asn Leu Glu Asp 
        915                 920                 925 

act cag aat atg gag tat aaa caa gat gaa cac agt gac cag caa ccg     2833 
Thr Gln Asn Met Glu Tyr Lys Gln Asp Glu His Ser Asp Gln Gln Pro 
    930                 935                 940 

cct cta aaa cga aag agg gtc aga gag aga gaa gtt agt gtg tca agt     2881 
Pro Leu Lys Arg Lys Arg Val Arg Glu Arg Glu Val Ser Val Ser Ser 
945                 950                 955                 960 

gtg aca gaa gag cca aag ctt gac tca tcc cag ttg cct ctt cag aca     2929 
Val Thr Glu Glu Pro Lys Leu Asp Ser Ser Gln Leu Pro Leu Gln Thr 
                965                 970                 975 

gga ctc gat gta cct gcc acc cct agg aaa cgt ggt aga ccc agg aag     2977 
Gly Leu Asp Val Pro Ala Thr Pro Arg Lys Arg Gly Arg Pro Arg Lys 
            980                 985                 990 

gta gtt ccc tta gaa gct gac ggt ggc aca act ggt aag gaa cag aca     3025 
Val Val Pro Leu Glu Ala Asp Gly Gly Thr Thr Gly Lys Glu Gln Thr 
        995                1000                1005 

agt cct cag aag aaa gat gtt ccg gtt gtc cgg aga tct aca cgg aac     3073 
Ser Pro Gln Lys Lys Asp Val Pro Val Val Arg Arg Ser Thr Arg Asn 
   1010                1015                1020 

acc cca gct aga aat gtg agt act tta naa aaa tca gtt tta gtg cca     3121 
Thr Pro Ala Arg Asn Val Ser Thr Leu Xaa Lys Ser Val Leu Val Pro 
1025               1030                1035                1040 

aat aag gaa gct gct cta gtg gtg aca tct aag agg aga cct aca aag     3169 
Asn Lys Glu Ala Ala Leu Val Val Thr Ser Lys Arg Arg Pro Thr Lys 
               1045                1050                1055 

aag tct gca gag gaa agc tca aaa gat cca tca gcg gca gtc tca gac     3217 
Lys Ser Ala Glu Glu Ser Ser Lys Asp Pro Ser Ala Ala Val Ser Asp 
           1060                1065                1070 

tgg gcg ggt gga gca gcc cac aca gag tcc gct gac cga agg gac gga     3265 
Trp Ala Gly Gly Ala Ala His Thr Glu Ser Ala Asp Arg Arg Asp Gly 
       1075                1080                1085 

ctg ctt gcc gcc gct gct ctc acg cca tct gcc cag ggc aca agg act     3313 
Leu Leu Ala Ala Ala Ala Leu Thr Pro Ser Ala Gln Gly Thr Arg Thr 
   1090                1095                1100 

agg tct aga agg acc atg ttg ttg acg gac att tct gaa ccc aaa act     3361 
Arg Ser Arg Arg Thr Met Leu Leu Thr Asp Ile Ser Glu Pro Lys Thr 
1105               1110                1115                1120 

gag cct tta ttt cct cct cct tca gtg aag gtt cca aag aaa aaa tca     3409 
Glu Pro Leu Phe Pro Pro Pro Ser Val Lys Val Pro Lys Lys Lys Ser 
               1125                1130                1135 

aaa gct gag aac atg gag gcc gca gcc cag ctg aaa gaa ttg gtg tca     3457 
Lys Ala Glu Asn Met Glu Ala Ala Ala Gln Leu Lys Glu Leu Val Ser 
           1140                1145                1150 

gat tta tct tct cag ttt gtt gtt tcc cct cct gcc ttg aga acc agg     3505 
Asp Leu Ser Ser Gln Phe Val Val Ser Pro Pro Ala Leu Arg Thr Arg 
       1155                1160                1165 

cag aaa agt ata tcc aat act tcc aag ctt cta ggt gaa ctg gag agt     3553 
Gln Lys Ser Ile Ser Asn Thr Ser Lys Leu Leu Gly Glu Leu Glu Ser 
   1170                1175                1180 

gac cct aaa cca tta gag atc ata gaa caa aaa cca aaa aga agc agg     3601 
Asp Pro Lys Pro Leu Glu Ile Ile Glu Gln Lys Pro Lys Arg Ser Arg 
1185               1190                1195                1200 

act gtg aag aca aga gca agc aga aac aca gga aaa gga agt tct tgg     3649 
Thr Val Lys Thr Arg Ala Ser Arg Asn Thr Gly Lys Gly Ser Ser Trp 
               1205                1210                1215 

tca cct cct cct gta gaa att aag ctg gtt tct ccc ttg gcg agt cca     3697 
Ser Pro Pro Pro Val Glu Ile Lys Leu Val Ser Pro Leu Ala Ser Pro 
           1220                1225                1230 

gtg gat gaa ata aag acc ggc aag cca aga aaa act gca gaa ata gca     3745 
Val Asp Glu Ile Lys Thr Gly Lys Pro Arg Lys Thr Ala Glu Ile Ala 
       1235                1240                1245 

gga aaa act ctt gga agg ggc aga aag aag cca tct tct ttt cca aag     3793 
Gly Lys Thr Leu Gly Arg Gly Arg Lys Lys Pro Ser Ser Phe Pro Lys 
   1250                1255                1260 

caa att tta cgc agg aaa atg ctg taatttttag cccaagattt taacacgcac    3847 
Gln Ile Leu Arg Arg Lys Met Leu 
1265               1270 

ctgtttgtaa aagtcaacag tatttgtgtg gattattaaa gtcaccaatt tggatgaaaa   3907 

tactttatat aaattgtaca attttgtaag cagtaaatga gtaactccac atggagtgca   3967 

gttcttgtag tgcaggcgtt ttatacgact tgatgcgttt atatcaatgt aaatatgact   4027 

tatcattggg aggttaaata aactactgta aagtaaaaaa aaaaaaaaaa aaaaaaaaaa   4087 

aaaaaaaaaa aaaaaaaaaa aaaaaaaa                                      4115 

 
           
             8  
             1272  
             PRT  
             Mus musculus  
             
               VARIANT  
               1034  
               Xaa = Any Amino Acid  
             
           
            8 

Gln Ile Leu Lys Asn Asn Leu Met Ser Asp Arg Asp Pro Arg Leu Arg 
  1               5                  10                  15 

Glu Arg Ser Val Thr Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile 
             20                  25                  30 

Leu Pro Arg Val Gln Arg Lys Leu Ala Val Glu Arg Ala Lys Pro Tyr 
         35                  40                  45 

His Leu Ser Thr Ser Ser Val Phe His Glu Val Ser Arg Pro Lys Pro 
     50                  55                  60 

Leu Ser Ala Phe Pro Lys Lys Ala Ile Thr Gly Thr Val Leu Thr Arg 
 65                  70                  75                  80 

Ser Thr Phe Ile Ser Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala 
                 85                  90                  95 

Ser His Glu Pro Arg Asn Gly Val Ser Leu Phe Asn Ser Pro Lys Thr 
            100                 105                 110 

Glu Gln Pro Ser Pro Val Val His Ser Phe Pro His Pro Glu Leu Pro 
        115                 120                 125 

Glu Ala Phe Val Gly Thr Pro Ile Ser Asn Thr Ser Gln Arg Ile Ser 
    130                 135                 140 

Arg Leu Leu Asp Leu Val Val His Pro Val Pro Gln Pro Ser Gln Cys 
145                 150                 155                 160 

Leu Glu Phe Ile Gln Gln Ser Pro Thr Arg Ser Pro Leu Cys Leu Leu 
                165                 170                 175 

Ser Ser Ser Leu Pro Leu Ser Ser Gln Phe Lys Arg Pro His Gln Asn 
            180                 185                 190 

Thr Ser Arg Pro Ser Glu Leu Leu Leu Leu Glu Thr Pro Leu Ile Val 
        195                 200                 205 

Lys Lys Ala Lys Ser Leu Ala Leu Ser Ala Thr Ser Ser Gly Phe Ala 
    210                 215                 220 

Glu Phe Thr Pro Pro Ser Ile Leu Arg Ser Gly Phe Arg Thr Thr Pro 
225                 230                 235                 240 

Leu Ala Ser Pro Ser Leu Ser Pro Gly Arg Ser Leu Thr Pro Pro Phe 
                245                 250                 255 

Arg Val Lys Glu Thr Arg Ile Ser Phe Met Glu Glu Gly Met Asn Thr 
            260                 265                 270 

His Trp Thr Asp Arg Ala Thr Asp Asp Arg Asn Thr Lys Ala Phe Val 
        275                 280                 285 

Ser Thr Ser Phe His Lys Cys Gly Leu Pro Ala Glu Thr Glu Trp Met 
    290                 295                 300 

Lys Thr Ser Asp Lys Asn Thr Tyr Phe Pro Leu Asp Val Pro Ala Lys 
305                 310                 315                 320 

Gly Pro Gln Lys Val Val Ala Glu Ser Leu Ala Thr His Ser Gly Arg 
                325                 330                 335 

Leu Glu Lys Leu Asp Val Ser Lys Glu Asp Ser Thr Ala Ser Thr Arg 
            340                 345                 350 

Ser Asp Gln Thr Ser Leu Glu Tyr His Asp Ala Pro Ser Pro Glu Asp 
        355                 360                 365 

Leu Glu Gly Ala Val Phe Val Ser Pro Lys Pro Ala Ser Ser Ser Thr 
    370                 375                 380 

Glu Leu Thr Thr Asn Ser Thr Leu Gln Thr Glu Arg Asp Asn Asp Lys 
385                 390                 395                 400 

Asp Ala Phe Lys Ser Glu Gly Thr Pro Ser Pro Val Lys Lys Gln Ile 
                405                 410                 415 

Gly Thr Gly Asp Ala Ala Val Glu Ala Phe Ser Glu Leu Ser Arg Leu 
            420                 425                 430 

Asp Pro Val Glu Arg Ala Glu Ala Ser Phe Gly Val Ser Ser Val Cys 
        435                 440                 445 

Glu Gly Glu Thr Ser Thr Ser Asn Ser Lys Thr Ser Val Leu Asp Gly 
    450                 455                 460 

Ile Val Pro Ile Glu Ser Arg Thr Ser Ile Leu Thr Ala Asp His Lys 
465                 470                 475                 480 

Glu Ser Val Ala Asn Thr Val Ala Asp Val Glu Ser Ser Gly Ser Thr 
                485                 490                 495 

Ser Ser Lys Cys Pro Val Thr Ser Glu Arg Ser Leu Gly Gln Lys Leu 
            500                 505                 510 

Thr Leu Asn Leu Lys Glu Asp Glu Ile Glu Ala His Val Pro Lys Glu 
        515                 520                 525 

Asn Val Gly Leu Pro Glu Glu Ser Pro Arg Ile Ser Ala Ala Pro Ser 
    530                 535                 540 

Asp Thr His Glu Ile His Leu Ile Gly Cys Glu Asn Leu Glu Val Gln 
545                 550                 555                 560 

Asn Ser Glu Glu Glu Ala Lys Asn Leu Ser Phe Asp Glu Leu Tyr Pro 
                565                 570                 575 

Leu Gly Ala Glu Lys Leu Glu Tyr Asn Leu Ser Thr Ile Glu Gln Gln 
            580                 585                 590 

Phe Cys Asp Leu Pro Asp Asp Lys Asp Ser Ala Glu Cys Asp Ala Ala 
        595                 600                 605 

Glu Val Asp Gly Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile 
    610                 615                 620 

Leu Glu Gly Glu Glu Gly Glu Ala Glu Ala Ser Asp Ser Ala Ala Pro 
625                 630                 635                 640 

Asn Met Leu Pro Lys Ser Thr Lys Glu Lys Pro Val Cys Tyr Arg Glu 
                645                 650                 655 

Pro His Asn Gln Glu Arg Val Thr Asp Leu Pro Ser Ala Val Thr Ala 
            660                 665                 670 

Asp Gln Glu Ser His Lys Val Glu Thr Leu Pro Tyr Val Pro Glu Pro 
        675                 680                 685 

Val Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr 
    690                 695                 700 

Arg Ser Lys Glu Ala Thr Pro Val Ala Ala Gly Glu Ala Gly Asp Glu 
705                 710                 715                 720 

Asp Gly Ala Val Ile Val Ser Lys Ala Ala His Ser Ser Arg Leu Thr 
                725                 730                 735 

Asn Ser Thr Pro Lys Thr Val Lys Glu Pro Arg Ala Glu Thr Val Asn 
            740                 745                 750 

Thr Ser Gln Ser Asp Asp Met Val Ser Ser Arg Thr Leu Thr Arg Arg 
        755                 760                 765 

Gln His Ala Leu Ser Leu Asn Val Thr Ser Glu Gln Glu Pro Ser Ala 
    770                 775                 780 

Val Ala Thr Pro Lys Lys Arg Thr Arg Lys Ile Lys Glu Thr Pro Glu 
785                 790                 795                 800 

Ser Ser Glu Arg Thr Cys Ser Asp Leu Lys Val Ala Pro Glu Asn Gln 
                805                 810                 815 

Leu Thr Ala Gln Asn Pro Pro Ala Pro Arg Arg Arg Lys Lys Lys Asp 
            820                 825                 830 

Val Ser Gln Gly Thr Leu Pro Ser Ser Gly Ala Val Glu Pro Glu Pro 
        835                 840                 845 

Glu Pro Gln Gly Thr Pro Gly Arg Leu Arg Leu Arg Thr Gln Pro Pro 
    850                 855                 860 

Glu Pro Ala Ala Glu Glu Thr Pro Ser Arg Thr Lys Val Arg Leu Ser 
865                 870                 875                 880 

Ser Val Arg Lys Gly Thr Pro Arg Arg Leu Lys Lys Ser Val Glu Asn 
                885                 890                 895 

Gly Gln Ser Ile Glu Ile Leu Asp Asp Leu Lys Gly Ser Glu Ala Ala 
            900                 905                 910 

Ser His Asp Gly Thr Val Thr Glu Leu Arg Asn Ala Asn Leu Glu Asp 
        915                 920                 925 

Thr Gln Asn Met Glu Tyr Lys Gln Asp Glu His Ser Asp Gln Gln Pro 
    930                 935                 940 

Pro Leu Lys Arg Lys Arg Val Arg Glu Arg Glu Val Ser Val Ser Ser 
945                 950                 955                 960 

Val Thr Glu Glu Pro Lys Leu Asp Ser Ser Gln Leu Pro Leu Gln Thr 
                965                 970                 975 

Gly Leu Asp Val Pro Ala Thr Pro Arg Lys Arg Gly Arg Pro Arg Lys 
            980                 985                 990 

Val Val Pro Leu Glu Ala Asp Gly Gly Thr Thr Gly Lys Glu Gln Thr 
        995                1000                1005 

Ser Pro Gln Lys Lys Asp Val Pro Val Val Arg Arg Ser Thr Arg Asn 
   1010                1015                1020 

Thr Pro Ala Arg Asn Val Ser Thr Leu Xaa Lys Ser Val Leu Val Pro 
1025               1030                1035                1040 

Asn Lys Glu Ala Ala Leu Val Val Thr Ser Lys Arg Arg Pro Thr Lys 
               1045                1050                1055 

Lys Ser Ala Glu Glu Ser Ser Lys Asp Pro Ser Ala Ala Val Ser Asp 
           1060                1065                1070 

Trp Ala Gly Gly Ala Ala His Thr Glu Ser Ala Asp Arg Arg Asp Gly 
       1075                1080                1085 

Leu Leu Ala Ala Ala Ala Leu Thr Pro Ser Ala Gln Gly Thr Arg Thr 
   1090                1095                1100 

Arg Ser Arg Arg Thr Met Leu Leu Thr Asp Ile Ser Glu Pro Lys Thr 
1105               1110                1115                1120 

Glu Pro Leu Phe Pro Pro Pro Ser Val Lys Val Pro Lys Lys Lys Ser 
               1125                1130                1135 

Lys Ala Glu Asn Met Glu Ala Ala Ala Gln Leu Lys Glu Leu Val Ser 
           1140                1145                1150 

Asp Leu Ser Ser Gln Phe Val Val Ser Pro Pro Ala Leu Arg Thr Arg 
       1155                1160                1165 

Gln Lys Ser Ile Ser Asn Thr Ser Lys Leu Leu Gly Glu Leu Glu Ser 
   1170                1175                1180 

Asp Pro Lys Pro Leu Glu Ile Ile Glu Gln Lys Pro Lys Arg Ser Arg 
1185               1190                1195                1200 

Thr Val Lys Thr Arg Ala Ser Arg Asn Thr Gly Lys Gly Ser Ser Trp 
               1205                1210                1215 

Ser Pro Pro Pro Val Glu Ile Lys Leu Val Ser Pro Leu Ala Ser Pro 
           1220                1225                1230 

Val Asp Glu Ile Lys Thr Gly Lys Pro Arg Lys Thr Ala Glu Ile Ala 
       1235                1240                1245 

Gly Lys Thr Leu Gly Arg Gly Arg Lys Lys Pro Ser Ser Phe Pro Lys 
   1250                1255                1260 

Gln Ile Leu Arg Arg Lys Met Leu 
1265               1270 

 
           
             9  
             24  
             DNA  
             Artificial Sequence  
             
               Description of Artificial SequenceArtificially 
      Synthesized Primer Sequence  
             
           
            9 

cacccgtgaa gaaacaaata ggca                                            24 

 
           
             10  
             24  
             DNA  
             Artificial Sequence  
             
               Description of Artificial SequenceArtificially 
      Synthesized Primer Sequence  
             
           
            10 

cctttggtac atgagcttct attt                                            24 

 
           
             11  
             7034  
             DNA  
             Mus musculus  
             
               CDS  
               (8)..(6736)  
             
           
            11 

tggcagt atg caa gac ttg aca gct caa gtg act agt gat ctc ctg cat       49 
        Met Gln Asp Leu Thr Ala Gln Val Thr Ser Asp Leu Leu His 
          1               5                  10 

ttc cca gaa gtg act att gaa gct ctt gga gaa gat gag ata aca tta       97 
Phe Pro Glu Val Thr Ile Glu Ala Leu Gly Glu Asp Glu Ile Thr Leu 
 15                  20                  25                  30 

gag tcc gtg ctt cgt gga aag ttt gct gca ggg aaa aat gga cta gca      145 
Glu Ser Val Leu Arg Gly Lys Phe Ala Ala Gly Lys Asn Gly Leu Ala 
                 35                  40                  45 

tgc tta gct tgt ggt cca caa ctt gaa gtt gta aac tcc tta aca gga      193 
Cys Leu Ala Cys Gly Pro Gln Leu Glu Val Val Asn Ser Leu Thr Gly 
             50                  55                  60 

gag cgg tta tct gca tat aga ttc agt gga gta aat gaa cag cct cct      241 
Glu Arg Leu Ser Ala Tyr Arg Phe Ser Gly Val Asn Glu Gln Pro Pro 
         65                  70                  75 

gta gtc ctt gca gtg aaa gaa ttc tct tgg cat aag agg act gga ttg      289 
Val Val Leu Ala Val Lys Glu Phe Ser Trp His Lys Arg Thr Gly Leu 
     80                  85                  90 

tta ata gga ttg gaa gaa gca gat ggg agt gtt ctt tgt ctt tat gac      337 
Leu Ile Gly Leu Glu Glu Ala Asp Gly Ser Val Leu Cys Leu Tyr Asp 
 95                 100                 105                 110 

ctt ggt ata tca aga gtg gtc aaa gca gtt gtt ctt cct gga agg gta      385 
Leu Gly Ile Ser Arg Val Val Lys Ala Val Val Leu Pro Gly Arg Val 
                115                 120                 125 

aca gct atc gag cct ata att aac cat gga gga gcc agt gcg agt acc      433 
Thr Ala Ile Glu Pro Ile Ile Asn His Gly Gly Ala Ser Ala Ser Thr 
            130                 135                 140 

cag cat tta cat cca agt ctc cgg tgg ctt ttt ggc gtg gcc gct gtg      481 
Gln His Leu His Pro Ser Leu Arg Trp Leu Phe Gly Val Ala Ala Val 
        145                 150                 155 

gtg act gat gtt gga cag atc ctt ctt att gac ctg tgt ttg gat gac      529 
Val Thr Asp Val Gly Gln Ile Leu Leu Ile Asp Leu Cys Leu Asp Asp 
    160                 165                 170 

ttg tcc tgc agt cag aat gaa gtt gag gca tca gac ctt gaa gtt atc      577 
Leu Ser Cys Ser Gln Asn Glu Val Glu Ala Ser Asp Leu Glu Val Ile 
175                 180                 185                 190 

act ggt atc cca gct gaa gta cca cac atc aga gag aga gtg atg aga      625 
Thr Gly Ile Pro Ala Glu Val Pro His Ile Arg Glu Arg Val Met Arg 
                195                 200                 205 

gag ggg cgc cac ctg tgc ttc cag tta gta agc cca ttg gga gta gcc      673 
Glu Gly Arg His Leu Cys Phe Gln Leu Val Ser Pro Leu Gly Val Ala 
            210                 215                 220 

att tct act ctg agt tac atc aac agg aca aat cag ctt gct gtg ggt      721 
Ile Ser Thr Leu Ser Tyr Ile Asn Arg Thr Asn Gln Leu Ala Val Gly 
        225                 230                 235 

ttt tct gat ggc tac tta gca ctt tgg aac atg aaa agc atg aaa aga      769 
Phe Ser Asp Gly Tyr Leu Ala Leu Trp Asn Met Lys Ser Met Lys Arg 
    240                 245                 250 

gaa tac tat aca cag ttg gaa ggt gga agg gtt cct gtc cat gca gtt      817 
Glu Tyr Tyr Thr Gln Leu Glu Gly Gly Arg Val Pro Val His Ala Val 
255                 260                 265                 270 

gcc ttt caa gag cct gag aat gat cct cgt aac tgc tgt tat tta tgg      865 
Ala Phe Gln Glu Pro Glu Asn Asp Pro Arg Asn Cys Cys Tyr Leu Trp 
                275                 280                 285 

gct gtt cag tcc aca caa gat agt gaa ggg gat gtt ttg agt ttg cat      913 
Ala Val Gln Ser Thr Gln Asp Ser Glu Gly Asp Val Leu Ser Leu His 
            290                 295                 300 

ctg ctt cag ctg gct ttt ggt gat aga aaa tgt ttg gca tca ggg caa      961 
Leu Leu Gln Leu Ala Phe Gly Asp Arg Lys Cys Leu Ala Ser Gly Gln 
        305                 310                 315 

att tta tat gag gga tta gaa tac tgc gaa gaa aga tat aca ctg gat     1009 
Ile Leu Tyr Glu Gly Leu Glu Tyr Cys Glu Glu Arg Tyr Thr Leu Asp 
    320                 325                 330 

cta gca ggt ggc acg ttc ccc tta agg gga caa act agt aat acc aaa     1057 
Leu Ala Gly Gly Thr Phe Pro Leu Arg Gly Gln Thr Ser Asn Thr Lys 
335                 340                 345                 350 

ttg ttg gga tgc cag agt ata gag aga ttt cca tct cat gga gac aga     1105 
Leu Leu Gly Cys Gln Ser Ile Glu Arg Phe Pro Ser His Gly Asp Arg 
                355                 360                 365 

gaa gaa agt atg aga gaa gct ctg tct ccc gat acc agc gtt tct gtc     1153 
Glu Glu Ser Met Arg Glu Ala Leu Ser Pro Asp Thr Ser Val Ser Val 
            370                 375                 380 

ttt acc tgg caa gtg aat ata tat gga cag gga aag cct tct gtg tat     1201 
Phe Thr Trp Gln Val Asn Ile Tyr Gly Gln Gly Lys Pro Ser Val Tyr 
        385                 390                 395 

tta ggg cta ttt gac ata aat cgt tgg tat cat gca caa atg ccc gat     1249 
Leu Gly Leu Phe Asp Ile Asn Arg Trp Tyr His Ala Gln Met Pro Asp 
    400                 405                 410 

tct tta aga tca gga gaa tct ctg cat aat tgc tct tat ttt gcg ttg     1297 
Ser Leu Arg Ser Gly Glu Ser Leu His Asn Cys Ser Tyr Phe Ala Leu 
415                 420                 425                 430 

tgg tca ttg gat tcg gtt gta agt agg act tct cca cat cac atc ttg     1345 
Trp Ser Leu Asp Ser Val Val Ser Arg Thr Ser Pro His His Ile Leu 
                435                 440                 445 

gac ata cta gta cat gag agg agt tta aac cga ggg gtt cct cct tcc     1393 
Asp Ile Leu Val His Glu Arg Ser Leu Asn Arg Gly Val Pro Pro Ser 
            450                 455                 460 

tac cca cct cca gag caa ttt ttt aac cca agt act ttt aat ttt gat     1441 
Tyr Pro Pro Pro Glu Gln Phe Phe Asn Pro Ser Thr Phe Asn Phe Asp 
        465                 470                 475 

gcc act tgt ttg tta gac tct gga gtt atc cat gta act tgt gct gga     1489 
Ala Thr Cys Leu Leu Asp Ser Gly Val Ile His Val Thr Cys Ala Gly 
    480                 485                 490 

ttt cag aag gag act ttg aca ttt tta aag aaa tca gga cca act ctt     1537 
Phe Gln Lys Glu Thr Leu Thr Phe Leu Lys Lys Ser Gly Pro Thr Leu 
495                 500                 505                 510 

aat gaa gtc att cct gat agt tat aat cga tgt ctt gtt gct ggt ctc     1585 
Asn Glu Val Ile Pro Asp Ser Tyr Asn Arg Cys Leu Val Ala Gly Leu 
                515                 520                 525 

ctc tca cca aga ctt att gat att cag cct tcc agt tta agt caa gaa     1633 
Leu Ser Pro Arg Leu Ile Asp Ile Gln Pro Ser Ser Leu Ser Gln Glu 
            530                 535                 540 

gaa caa tta gaa gct ata ttg tca gca gca att cag aca agt tcc ttg     1681 
Glu Gln Leu Glu Ala Ile Leu Ser Ala Ala Ile Gln Thr Ser Ser Leu 
        545                 550                 555 

gga ctt ttg act ggt tac atc aga aca tgg ata ata gaa gaa caa cca     1729 
Gly Leu Leu Thr Gly Tyr Ile Arg Thr Trp Ile Ile Glu Glu Gln Pro 
    560                 565                 570 

aat tct gct gct aat cta cga ttt gtt ctt gag tgg aca tgg aat aaa     1777 
Asn Ser Ala Ala Asn Leu Arg Phe Val Leu Glu Trp Thr Trp Asn Lys 
575                 580                 585                 590 

gtg gtt ctc aca aaa gaa gag ttt gat agg ctt tgt gtg ccg ctg ttt     1825 
Val Val Leu Thr Lys Glu Glu Phe Asp Arg Leu Cys Val Pro Leu Phe 
                595                 600                 605 

gac ggt tcg tgt cgt ttt att gac cca cag act att cag tct atc cag     1873 
Asp Gly Ser Cys Arg Phe Ile Asp Pro Gln Thr Ile Gln Ser Ile Gln 
            610                 615                 620 

cag tgc cat tta ctg ctt agc aac ctt agt aca gtc tta agc tgt ttt     1921 
Gln Cys His Leu Leu Leu Ser Asn Leu Ser Thr Val Leu Ser Cys Phe 
        625                 630                 635 

gca atg gag gcc cag ggt atc act gag aga gga ctg gtg gac ttg agc     1969 
Ala Met Glu Ala Gln Gly Ile Thr Glu Arg Gly Leu Val Asp Leu Ser 
    640                 645                 650 

aac aag cac atg gtc acc cag ctt ctc tgt cag tac gca cac atg gtt     2017 
Asn Lys His Met Val Thr Gln Leu Leu Cys Gln Tyr Ala His Met Val 
655                 660                 665                 670 

ctg tgg ttc tgc cac tcg ggg ctt ctg ccc gaa ggc tta gat gat gct     2065 
Leu Trp Phe Cys His Ser Gly Leu Leu Pro Glu Gly Leu Asp Asp Ala 
                675                 680                 685 

ctg cac ctg tca aga cta cgc tac aac tac cct gta att cag aac tac     2113 
Leu His Leu Ser Arg Leu Arg Tyr Asn Tyr Pro Val Ile Gln Asn Tyr 
            690                 695                 700 

tat aca agt cgt cgg cag aag tct gag cgc tca ccc aga ggg aag tgg     2161 
Tyr Thr Ser Arg Arg Gln Lys Ser Glu Arg Ser Pro Arg Gly Lys Trp 
        705                 710                 715 

aac cac gac tgc ttg atg att gat gga tta gtc tct caa cta gga gat     2209 
Asn His Asp Cys Leu Met Ile Asp Gly Leu Val Ser Gln Leu Gly Asp 
    720                 725                 730 

gaa gtt gag aag ttg tgg aag cgg gac gaa ggt ggc aca gga aga tac     2257 
Glu Val Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Arg Tyr 
735                 740                 745                 750 

cct cct gct agc atc cac gca tta ctt gat ata tat tta tta gac aac     2305 
Pro Pro Ala Ser Ile His Ala Leu Leu Asp Ile Tyr Leu Leu Asp Asn 
                755                 760                 765 

att acc gaa gca agc aaa cat gct att acc att tat ttg ctg ctt gat     2353 
Ile Thr Glu Ala Ser Lys His Ala Ile Thr Ile Tyr Leu Leu Leu Asp 
            770                 775                 780 

att atg tat tcc ttt cca aat aaa acg gat acc ccc att gaa tct ttc     2401 
Ile Met Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser Phe 
        785                 790                 795 

ccc act gcc ttt gct att tct tgg ggc caa gtt aag cta gtt caa gga     2449 
Pro Thr Ala Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Val Gln Gly 
    800                 805                 810 

ttt tgg cta cta gat cat aat gac tat gag aat ggt tta gac ctt ctg     2497 
Phe Trp Leu Leu Asp His Asn Asp Tyr Glu Asn Gly Leu Asp Leu Leu 
815                 820                 825                 830 

ttt cac cca gtt act gca aag cct gca tcg tgg caa cat tca aag ata     2545 
Phe His Pro Val Thr Ala Lys Pro Ala Ser Trp Gln His Ser Lys Ile 
                835                 840                 845 

att gaa gct ttt atg agt cag gga gag cac aaa cag gct ctc cgg tat     2593 
Ile Glu Ala Phe Met Ser Gln Gly Glu His Lys Gln Ala Leu Arg Tyr 
            850                 855                 860 

ctt cag aca atg aag cca aca gtg tcc agt agc aat gaa gtt atc ctt     2641 
Leu Gln Thr Met Lys Pro Thr Val Ser Ser Ser Asn Glu Val Ile Leu 
        865                 870                 875 

cac ctc act gtt cta ctt ttt aat aga tgc atg gtt gag gcc tgg aac     2689 
His Leu Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp Asn 
    880                 885                 890 

tta ctg cga cag aat tca aac aga gta aat ata gag gaa tta tta aag     2737 
Leu Leu Arg Gln Asn Ser Asn Arg Val Asn Ile Glu Glu Leu Leu Lys 
895                 900                 905                 910 

cac gct tat gaa gtt tgt cag gag atg ggc tta atg gag gat tta ctg     2785 
His Ala Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu Leu 
                915                 920                 925 

aag ctg cca ttt aca aac act gag cag gaa tgc tta gtg aaa ttt tta     2833 
Lys Leu Pro Phe Thr Asn Thr Glu Gln Glu Cys Leu Val Lys Phe Leu 
            930                 935                 940 

cag tcc agt acc agt gtt gag aat cat gaa ttc ctt cta gtt cac cat     2881 
Gln Ser Ser Thr Ser Val Glu Asn His Glu Phe Leu Leu Val His His 
        945                 950                 955 

tta cag cgt gcc aat tat att tct gcc ttg aaa cta aac cag att ctg     2929 
Leu Gln Arg Ala Asn Tyr Ile Ser Ala Leu Lys Leu Asn Gln Ile Leu 
    960                 965                 970 

aag aat aat ctc atg agt gat cgt gac cct cga ttg cgg gaa aga tcg     2977 
Lys Asn Asn Leu Met Ser Asp Arg Asp Pro Arg Leu Arg Glu Arg Ser 
975                 980                 985                 990 

gtg act cga aat tct ata tta gac cag tat ggg aaa atc cta cct aga     3025 
Val Thr Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro Arg 
                995                1000                1005 

gtc cag aga aag tta gct gtt gag cga gct aag cct tac cac ctg tcg     3073 
Val Gln Arg Lys Leu Ala Val Glu Arg Ala Lys Pro Tyr His Leu Ser 
           1010                1015                1020 

aca tcc tca gtt ttt cat gaa gtt tct aga ccc aaa ccg tta tcg gca     3121 
Thr Ser Ser Val Phe His Glu Val Ser Arg Pro Lys Pro Leu Ser Ala 
       1025                1030                1035 

ttt cca aag aaa gct ata act gga aca gtg tta acc cga tct acg ttc     3169 
Phe Pro Lys Lys Ala Ile Thr Gly Thr Val Leu Thr Arg Ser Thr Phe 
   1040                1045                1050 

atc agc aat gtt tta tct aaa att gga gag gtg tgg gca agt cat gag     3217 
Ile Ser Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser His Glu 
1055               1060                1065                1070 

cct aga aat ggc gtc tca ctt ttt aac agt cct aaa aca gaa cag cca     3265 
Pro Arg Asn Gly Val Ser Leu Phe Asn Ser Pro Lys Thr Glu Gln Pro 
               1075                1080                1085 

tct cct gta gta cac tct ttc cca cac cca gag ctt cct gag gcg ttt     3313 
Ser Pro Val Val His Ser Phe Pro His Pro Glu Leu Pro Glu Ala Phe 
           1090                1095                1100 

gtt gga act cca att tca aat aca tcc cag aga att tct aga tta ctg     3361 
Val Gly Thr Pro Ile Ser Asn Thr Ser Gln Arg Ile Ser Arg Leu Leu 
       1105                1110                1115 

gat ttg gtt gtc cat cct gta ccc cag cct tct cag tgt ttg gag ttt     3409 
Asp Leu Val Val His Pro Val Pro Gln Pro Ser Gln Cys Leu Glu Phe 
   1120                1125                1130 

att caa caa agt ccc aca aga tct cct ttg tgt ctg ctg tcc agt tcg     3457 
Ile Gln Gln Ser Pro Thr Arg Ser Pro Leu Cys Leu Leu Ser Ser Ser 
1135               1140                1145                1150 

tta cca tta agt tca cag ttt aaa agg cca cat cag aat acc tcc agg     3505 
Leu Pro Leu Ser Ser Gln Phe Lys Arg Pro His Gln Asn Thr Ser Arg 
               1155                1160                1165 

cct tca gag ttg ctt tta ctt gag act cct ctc ata gtt aag aaa gct     3553 
Pro Ser Glu Leu Leu Leu Leu Glu Thr Pro Leu Ile Val Lys Lys Ala 
           1170                1175                1180 

aaa tct ttg gct ctg tca gcc acg tct tct gga ttt gcc gag ttt act     3601 
Lys Ser Leu Ala Leu Ser Ala Thr Ser Ser Gly Phe Ala Glu Phe Thr 
       1185                1190                1195 

cct cca tcc atc ctt agg tct ggt ttt cga aca aca cct tta gca tct     3649 
Pro Pro Ser Ile Leu Arg Ser Gly Phe Arg Thr Thr Pro Leu Ala Ser 
   1200                1205                1210 

ccc tct ttg tca cct gga aga tct ctc act ccg cct ttc aga gtt aaa     3697 
Pro Ser Leu Ser Pro Gly Arg Ser Leu Thr Pro Pro Phe Arg Val Lys 
1215               1220                1225                1230 

gaa aca agg att tca ttc atg gaa gaa ggc atg aat aca cac tgg act     3745 
Glu Thr Arg Ile Ser Phe Met Glu Glu Gly Met Asn Thr His Trp Thr 
               1235                1240                1245 

gat aga gct aca gat gac cga aat aca aaa gcg ttt gtt agc aca tct     3793 
Asp Arg Ala Thr Asp Asp Arg Asn Thr Lys Ala Phe Val Ser Thr Ser 
           1250                1255                1260 

ttc cat aaa tgt gga ctt cca gca gaa act gag tgg atg aag acc agt     3841 
Phe His Lys Cys Gly Leu Pro Ala Glu Thr Glu Trp Met Lys Thr Ser 
       1265                1270                1275 

gat aag aat aca tat ttt cct ctg gat gtc cct gca aag ggc cct cag     3889 
Asp Lys Asn Thr Tyr Phe Pro Leu Asp Val Pro Ala Lys Gly Pro Gln 
   1280                1285                1290 

aaa gtg gtg gca gag tca ctg gct acc cat tca gga agg ctg gag aaa     3937 
Lys Val Val Ala Glu Ser Leu Ala Thr His Ser Gly Arg Leu Glu Lys 
1295               1300                1305                1310 

ctg gat gtg agc aaa gaa gac agc aca gct tcc acc agg tca gac cag     3985 
Leu Asp Val Ser Lys Glu Asp Ser Thr Ala Ser Thr Arg Ser Asp Gln 
               1315                1320                1325 

acc tcc tta gag tat cat gac gca cca tca cca gaa gac ttg gaa ggt     4033 
Thr Ser Leu Glu Tyr His Asp Ala Pro Ser Pro Glu Asp Leu Glu Gly 
           1330                1335                1340 

gct gtt ttt gtg tct ccc aag cca gca tct tcc tcc act gaa cta act     4081 
Ala Val Phe Val Ser Pro Lys Pro Ala Ser Ser Ser Thr Glu Leu Thr 
       1345                1350                1355 

act aat tca act cta caa aca gag agg gat aat gat aaa gat gcg ttt     4129 
Thr Asn Ser Thr Leu Gln Thr Glu Arg Asp Asn Asp Lys Asp Ala Phe 
   1360                1365                1370 

aag tca gaa ggt act cct tca ccc gtg aag aaa caa ata ggc acg gga     4177 
Lys Ser Glu Gly Thr Pro Ser Pro Val Lys Lys Gln Ile Gly Thr Gly 
1375               1380                1385                1390 

gac gct gca gtg gaa gca ttt tca gaa ctg agt cgc tta gac cct gtt     4225 
Asp Ala Ala Val Glu Ala Phe Ser Glu Leu Ser Arg Leu Asp Pro Val 
               1395                1400                1405 

gaa aga gct gaa gct tct ttt ggt gtg tcg tca gtc tgt gaa ggg gaa     4273 
Glu Arg Ala Glu Ala Ser Phe Gly Val Ser Ser Val Cys Glu Gly Glu 
           1410                1415                1420 

acc tcc act tca aac tcc aag acg tca gtt ctg gat gga atc gtg cct     4321 
Thr Ser Thr Ser Asn Ser Lys Thr Ser Val Leu Asp Gly Ile Val Pro 
       1425                1430                1435 

att gag agc cga acc tcc ata ctt aca gca gac cac aaa gag tct gtg     4369 
Ile Glu Ser Arg Thr Ser Ile Leu Thr Ala Asp His Lys Glu Ser Val 
   1440                1445                1450 

gcc aac acg gtt gca gat gtt gaa agc tct ggg tcc acc agc tcc aag     4417 
Ala Asn Thr Val Ala Asp Val Glu Ser Ser Gly Ser Thr Ser Ser Lys 
1455               1460                1465                1470 

tgc ccg gtt acc tct gaa cgc agc ctc ggc caa aaa cta aca tta aac     4465 
Cys Pro Val Thr Ser Glu Arg Ser Leu Gly Gln Lys Leu Thr Leu Asn 
               1475                1480                1485 

tta aaa gaa gat gaa ata gaa gct cat gta cca aag gag aac gtt ggt     4513 
Leu Lys Glu Asp Glu Ile Glu Ala His Val Pro Lys Glu Asn Val Gly 
           1490                1495                1500 

tta cca gaa gaa agc cct cga att tct gct gct cct tct gat act cac     4561 
Leu Pro Glu Glu Ser Pro Arg Ile Ser Ala Ala Pro Ser Asp Thr His 
       1505                1510                1515 

gag att cat cta att gga tgt gaa aat ctt gaa gtt caa aat tca gaa     4609 
Glu Ile His Leu Ile Gly Cys Glu Asn Leu Glu Val Gln Asn Ser Glu 
   1520                1525                1530 

gag gag gcc aag aat ctt tca ttt gat gag ttg tat ccc tta ggg gca     4657 
Glu Glu Ala Lys Asn Leu Ser Phe Asp Glu Leu Tyr Pro Leu Gly Ala 
1535               1540                1545                1550 

gag aaa ctt gag tat aat ctc agt act att gag cag cag ttt tgt gac     4705 
Glu Lys Leu Glu Tyr Asn Leu Ser Thr Ile Glu Gln Gln Phe Cys Asp 
               1555                1560                1565 

ttg cct gat gac aaa gac tct gct gaa tgt gat gct gct gaa gta gac     4753 
Leu Pro Asp Asp Lys Asp Ser Ala Glu Cys Asp Ala Ala Glu Val Asp 
           1570                1575                1580 

ggg gaa ctt ttt gtg gcc cag agc aac ttt acc ctg att tta gaa ggt     4801 
Gly Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu Gly 
       1585                1590                1595 

gaa gaa gga gaa gct gag gca agc gac tct gca gca cct aat atg tta     4849 
Glu Glu Gly Glu Ala Glu Ala Ser Asp Ser Ala Ala Pro Asn Met Leu 
   1600                1605                1610 

ccg aaa tcg acc aag gaa aaa cct gtg tgc tac agg gaa ccc cat aat     4897 
Pro Lys Ser Thr Lys Glu Lys Pro Val Cys Tyr Arg Glu Pro His Asn 
1615               1620                1625                1630 

cag gag cgc gtt aca gat ttg cca tct gct gtg act gct gac caa gaa     4945 
Gln Glu Arg Val Thr Asp Leu Pro Ser Ala Val Thr Ala Asp Gln Glu 
               1635                1640                1645 

tcc cac aag gta gag act tta ccg tat gtg cct gaa ccg gtt aaa gtg     4993 
Ser His Lys Val Glu Thr Leu Pro Tyr Val Pro Glu Pro Val Lys Val 
           1650                1655                1660 

gca att gca gaa aat ctg ttg gat gta att aaa gac acc aga agt aag     5041 
Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr Arg Ser Lys 
       1665                1670                1675 

gaa gca act ccc gtg gca gca ggt gag gct ggt gat gag gac gga gca     5089 
Glu Ala Thr Pro Val Ala Ala Gly Glu Ala Gly Asp Glu Asp Gly Ala 
   1680                1685                1690 

gtg ata gtc tca aag gct gca cat tcg tcc agg ctg aca aac tct aca     5137 
Val Ile Val Ser Lys Ala Ala His Ser Ser Arg Leu Thr Asn Ser Thr 
1695               1700                1705                1710 

ccg aag act gtt aag gaa cca cgt gca gag act gta aat acc agc cag     5185 
Pro Lys Thr Val Lys Glu Pro Arg Ala Glu Thr Val Asn Thr Ser Gln 
               1715                1720                1725 

agt gat gac atg gtt tct tct aga act ctc aca aga agg cag cat gcc     5233 
Ser Asp Asp Met Val Ser Ser Arg Thr Leu Thr Arg Arg Gln His Ala 
           1730                1735                1740 

cta agc ctg aat gtc aca tca gaa caa gag cct tca gca gtt gcc act     5281 
Leu Ser Leu Asn Val Thr Ser Glu Gln Glu Pro Ser Ala Val Ala Thr 
       1745                1750                1755 

cct aag aag aga act aga aaa att aaa gaa act cct gag tct tct gaa     5329 
Pro Lys Lys Arg Thr Arg Lys Ile Lys Glu Thr Pro Glu Ser Ser Glu 
   1760                1765                1770 

agg acc tgt tct gac cta aaa gta gca cct gag aac caa ctg aca gct     5377 
Arg Thr Cys Ser Asp Leu Lys Val Ala Pro Glu Asn Gln Leu Thr Ala 
1775               1780                1785                1790 

cag aat cct ccc gct cct agg aga aga aag aag aag gac gtt agc caa     5425 
Gln Asn Pro Pro Ala Pro Arg Arg Arg Lys Lys Lys Asp Val Ser Gln 
               1795                1800                1805 

ggc aca ctg cca agt tct ggt gct gtg gag ccg gag ccg gaa cct cag     5473 
Gly Thr Leu Pro Ser Ser Gly Ala Val Glu Pro Glu Pro Glu Pro Gln 
           1810                1815                1820 

ggt acg ccg gga aga ctg agg ctg aga acg cag cca ccc gag cca gca     5521 
Gly Thr Pro Gly Arg Leu Arg Leu Arg Thr Gln Pro Pro Glu Pro Ala 
       1825                1830                1835 

gct gaa gaa act cct tct aga aca aaa gtc agg ctt tca tct gtt aga     5569 
Ala Glu Glu Thr Pro Ser Arg Thr Lys Val Arg Leu Ser Ser Val Arg 
   1840                1845                1850 

aag gga acc cct aga aga ctt aag aag tct gta gaa aat ggg caa agt     5617 
Lys Gly Thr Pro Arg Arg Leu Lys Lys Ser Val Glu Asn Gly Gln Ser 
1855               1860                1865                1870 

ata gaa att cta gat gat ctc aaa ggg agt gag gca gca agt cat gac     5665 
Ile Glu Ile Leu Asp Asp Leu Lys Gly Ser Glu Ala Ala Ser His Asp 
               1875                1880                1885 

ggg act gtc aca gag ctg agg aat gcc aat tta gaa gat act cag aat     5713 
Gly Thr Val Thr Glu Leu Arg Asn Ala Asn Leu Glu Asp Thr Gln Asn 
           1890                1895                1900 

atg gag tat aaa caa gat gaa cac agt gac cag caa ccg cct cta aaa     5761 
Met Glu Tyr Lys Gln Asp Glu His Ser Asp Gln Gln Pro Pro Leu Lys 
       1905                1910                1915 

cga aag agg gtc aga gag aga gaa gtt agt gtg tca agt gtg aca gaa     5809 
Arg Lys Arg Val Arg Glu Arg Glu Val Ser Val Ser Ser Val Thr Glu 
   1920                1925                1930 

gag cca aag ctt gac tca tcc cag ttg cct ctt cag aca gga ctc gat     5857 
Glu Pro Lys Leu Asp Ser Ser Gln Leu Pro Leu Gln Thr Gly Leu Asp 
1935               1940                1945                1950 

gta cct gcc acc cct agg aaa cgt ggt aga ccc agg aag gta gtt ccc     5905 
Val Pro Ala Thr Pro Arg Lys Arg Gly Arg Pro Arg Lys Val Val Pro 
               1955                1960                1965 

tta gaa gct gac ggt ggc aca act ggt aag gaa cag aca agt cct cag     5953 
Leu Glu Ala Asp Gly Gly Thr Thr Gly Lys Glu Gln Thr Ser Pro Gln 
           1970                1975                1980 

aag aaa gat gtt ccg gtt gtc cgg aga tct aca cgg aac acc cca gct     6001 
Lys Lys Asp Val Pro Val Val Arg Arg Ser Thr Arg Asn Thr Pro Ala 
       1985                1990                1995 

aga aat gtg agt act tta aaa aaa tca gtt tta gtg cca aat aag gaa     6049 
Arg Asn Val Ser Thr Leu Lys Lys Ser Val Leu Val Pro Asn Lys Glu 
   2000                2005                2010 

gct gct cta gtg gtg aca tct aag agg aga cct aca aag aag tct gca     6097 
Ala Ala Leu Val Val Thr Ser Lys Arg Arg Pro Thr Lys Lys Ser Ala 
2015               2020                2025                2030 

gag gaa agc tca aaa gat cca tca gcg gca gtc tca gac tgg gcg ggt     6145 
Glu Glu Ser Ser Lys Asp Pro Ser Ala Ala Val Ser Asp Trp Ala Gly 
               2035                2040                2045 

gga gca gcc cac aca gag tcc gct gac cga agg gac gga ctg ctt gcc     6193 
Gly Ala Ala His Thr Glu Ser Ala Asp Arg Arg Asp Gly Leu Leu Ala 
           2050                2055                2060 

gcc gct gct ctc acg cca tct gcc cag ggc aca agg act agg tct aga     6241 
Ala Ala Ala Leu Thr Pro Ser Ala Gln Gly Thr Arg Thr Arg Ser Arg 
       2065                2070                2075 

agg acc atg ttg ttg acg gac att tct gaa ccc aaa act gag cct tta     6289 
Arg Thr Met Leu Leu Thr Asp Ile Ser Glu Pro Lys Thr Glu Pro Leu 
   2080                2085                2090 

ttt cct cct cct tca gtg aag gtt cca aag aaa aaa tca aaa gct gag     6337 
Phe Pro Pro Pro Ser Val Lys Val Pro Lys Lys Lys Ser Lys Ala Glu 
2095               2100                2105                2110 

aac atg gag gcc gca gcc cag ctg aaa gaa ttg gtg tca gat tta tct     6385 
Asn Met Glu Ala Ala Ala Gln Leu Lys Glu Leu Val Ser Asp Leu Ser 
               2115                2120                2125 

tct cag ttt gtt gtt tcc cct cct gcc ttg aga acc agg cag aaa agt     6433 
Ser Gln Phe Val Val Ser Pro Pro Ala Leu Arg Thr Arg Gln Lys Ser 
           2130                2135                2140 

ata tcc aat act tcc aag ctt cta ggt gaa ctg gag agt gac cct aaa     6481 
Ile Ser Asn Thr Ser Lys Leu Leu Gly Glu Leu Glu Ser Asp Pro Lys 
       2145                2150                2155 

cca tta gag atc ata gaa caa aaa cca aaa aga agc agg act gtg aag     6529 
Pro Leu Glu Ile Ile Glu Gln Lys Pro Lys Arg Ser Arg Thr Val Lys 
   2160                2165                2170 

aca aga gca agc aga aac aca gga aaa gga agt tct tgg tca cct cct     6577 
Thr Arg Ala Ser Arg Asn Thr Gly Lys Gly Ser Ser Trp Ser Pro Pro 
2175               2180                2185                2190 

cct gta gaa att aag ctg gtt tct ccc ttg gcg agt cca gtg gat gaa     6625 
Pro Val Glu Ile Lys Leu Val Ser Pro Leu Ala Ser Pro Val Asp Glu 
               2195                2200                2205 

ata aag acc ggc aag cca aga aaa act gca gaa ata gca gga aaa act     6673 
Ile Lys Thr Gly Lys Pro Arg Lys Thr Ala Glu Ile Ala Gly Lys Thr 
           2210                2215                2220 

ctt gga agg ggc aga aag aag cca tct tct ttt cca aag caa att tta     6721 
Leu Gly Arg Gly Arg Lys Lys Pro Ser Ser Phe Pro Lys Gln Ile Leu 
       2225                2230                2235 

cgc agg aaa atg ctg taatttttag cccaagattt taacacgcac ctgtttgtaa     6776 
Arg Arg Lys Met Leu 
   2240 

aagtcaacag tatttgtgtg gattattaaa gtcaccaatt tggatgaaaa tactttatat   6836 

aaattgtaca attttgtaag cagtaaatga gtaactccac atggagtgca gttcttgtag   6896 

tgcaggcgtt ttatacgact tgatgcgttt atatcaatgt aaatatgact tatcattggg   6956 

aggttaaata aactactgta aagtaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   7016 

aaaaaaaaaa aaaaaaaa                                                 7034 

 
           
             12  
             2243  
             PRT  
             Mus musculus  
           
            12 

Met Gln Asp Leu Thr Ala Gln Val Thr Ser Asp Leu Leu His Phe Pro 
  1               5                  10                  15 

Glu Val Thr Ile Glu Ala Leu Gly Glu Asp Glu Ile Thr Leu Glu Ser 
             20                  25                  30 

Val Leu Arg Gly Lys Phe Ala Ala Gly Lys Asn Gly Leu Ala Cys Leu 
         35                  40                  45 

Ala Cys Gly Pro Gln Leu Glu Val Val Asn Ser Leu Thr Gly Glu Arg 
     50                  55                  60 

Leu Ser Ala Tyr Arg Phe Ser Gly Val Asn Glu Gln Pro Pro Val Val 
 65                  70                  75                  80 

Leu Ala Val Lys Glu Phe Ser Trp His Lys Arg Thr Gly Leu Leu Ile 
                 85                  90                  95 

Gly Leu Glu Glu Ala Asp Gly Ser Val Leu Cys Leu Tyr Asp Leu Gly 
            100                 105                 110 

Ile Ser Arg Val Val Lys Ala Val Val Leu Pro Gly Arg Val Thr Ala 
        115                 120                 125 

Ile Glu Pro Ile Ile Asn His Gly Gly Ala Ser Ala Ser Thr Gln His 
    130                 135                 140 

Leu His Pro Ser Leu Arg Trp Leu Phe Gly Val Ala Ala Val Val Thr 
145                 150                 155                 160 

Asp Val Gly Gln Ile Leu Leu Ile Asp Leu Cys Leu Asp Asp Leu Ser 
                165                 170                 175 

Cys Ser Gln Asn Glu Val Glu Ala Ser Asp Leu Glu Val Ile Thr Gly 
            180                 185                 190 

Ile Pro Ala Glu Val Pro His Ile Arg Glu Arg Val Met Arg Glu Gly 
        195                 200                 205 

Arg His Leu Cys Phe Gln Leu Val Ser Pro Leu Gly Val Ala Ile Ser 
    210                 215                 220 

Thr Leu Ser Tyr Ile Asn Arg Thr Asn Gln Leu Ala Val Gly Phe Ser 
225                 230                 235                 240 

Asp Gly Tyr Leu Ala Leu Trp Asn Met Lys Ser Met Lys Arg Glu Tyr 
                245                 250                 255 

Tyr Thr Gln Leu Glu Gly Gly Arg Val Pro Val His Ala Val Ala Phe 
            260                 265                 270 

Gln Glu Pro Glu Asn Asp Pro Arg Asn Cys Cys Tyr Leu Trp Ala Val 
        275                 280                 285 

Gln Ser Thr Gln Asp Ser Glu Gly Asp Val Leu Ser Leu His Leu Leu 
    290                 295                 300 

Gln Leu Ala Phe Gly Asp Arg Lys Cys Leu Ala Ser Gly Gln Ile Leu 
305                 310                 315                 320 

Tyr Glu Gly Leu Glu Tyr Cys Glu Glu Arg Tyr Thr Leu Asp Leu Ala 
                325                 330                 335 

Gly Gly Thr Phe Pro Leu Arg Gly Gln Thr Ser Asn Thr Lys Leu Leu 
            340                 345                 350 

Gly Cys Gln Ser Ile Glu Arg Phe Pro Ser His Gly Asp Arg Glu Glu 
        355                 360                 365 

Ser Met Arg Glu Ala Leu Ser Pro Asp Thr Ser Val Ser Val Phe Thr 
    370                 375                 380 

Trp Gln Val Asn Ile Tyr Gly Gln Gly Lys Pro Ser Val Tyr Leu Gly 
385                 390                 395                 400 

Leu Phe Asp Ile Asn Arg Trp Tyr His Ala Gln Met Pro Asp Ser Leu 
                405                 410                 415 

Arg Ser Gly Glu Ser Leu His Asn Cys Ser Tyr Phe Ala Leu Trp Ser 
            420                 425                 430 

Leu Asp Ser Val Val Ser Arg Thr Ser Pro His His Ile Leu Asp Ile 
        435                 440                 445 

Leu Val His Glu Arg Ser Leu Asn Arg Gly Val Pro Pro Ser Tyr Pro 
    450                 455                 460 

Pro Pro Glu Gln Phe Phe Asn Pro Ser Thr Phe Asn Phe Asp Ala Thr 
465                 470                 475                 480 

Cys Leu Leu Asp Ser Gly Val Ile His Val Thr Cys Ala Gly Phe Gln 
                485                 490                 495 

Lys Glu Thr Leu Thr Phe Leu Lys Lys Ser Gly Pro Thr Leu Asn Glu 
            500                 505                 510 

Val Ile Pro Asp Ser Tyr Asn Arg Cys Leu Val Ala Gly Leu Leu Ser 
        515                 520                 525 

Pro Arg Leu Ile Asp Ile Gln Pro Ser Ser Leu Ser Gln Glu Glu Gln 
    530                 535                 540 

Leu Glu Ala Ile Leu Ser Ala Ala Ile Gln Thr Ser Ser Leu Gly Leu 
545                 550                 555                 560 

Leu Thr Gly Tyr Ile Arg Thr Trp Ile Ile Glu Glu Gln Pro Asn Ser 
                565                 570                 575 

Ala Ala Asn Leu Arg Phe Val Leu Glu Trp Thr Trp Asn Lys Val Val 
            580                 585                 590 

Leu Thr Lys Glu Glu Phe Asp Arg Leu Cys Val Pro Leu Phe Asp Gly 
        595                 600                 605 

Ser Cys Arg Phe Ile Asp Pro Gln Thr Ile Gln Ser Ile Gln Gln Cys 
    610                 615                 620 

His Leu Leu Leu Ser Asn Leu Ser Thr Val Leu Ser Cys Phe Ala Met 
625                 630                 635                 640 

Glu Ala Gln Gly Ile Thr Glu Arg Gly Leu Val Asp Leu Ser Asn Lys 
                645                 650                 655 

His Met Val Thr Gln Leu Leu Cys Gln Tyr Ala His Met Val Leu Trp 
            660                 665                 670 

Phe Cys His Ser Gly Leu Leu Pro Glu Gly Leu Asp Asp Ala Leu His 
        675                 680                 685 

Leu Ser Arg Leu Arg Tyr Asn Tyr Pro Val Ile Gln Asn Tyr Tyr Thr 
    690                 695                 700 

Ser Arg Arg Gln Lys Ser Glu Arg Ser Pro Arg Gly Lys Trp Asn His 
705                 710                 715                 720 

Asp Cys Leu Met Ile Asp Gly Leu Val Ser Gln Leu Gly Asp Glu Val 
                725                 730                 735 

Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Arg Tyr Pro Pro 
            740                 745                 750 

Ala Ser Ile His Ala Leu Leu Asp Ile Tyr Leu Leu Asp Asn Ile Thr 
        755                 760                 765 

Glu Ala Ser Lys His Ala Ile Thr Ile Tyr Leu Leu Leu Asp Ile Met 
    770                 775                 780 

Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser Phe Pro Thr 
785                 790                 795                 800 

Ala Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Val Gln Gly Phe Trp 
                805                 810                 815 

Leu Leu Asp His Asn Asp Tyr Glu Asn Gly Leu Asp Leu Leu Phe His 
            820                 825                 830 

Pro Val Thr Ala Lys Pro Ala Ser Trp Gln His Ser Lys Ile Ile Glu 
        835                 840                 845 

Ala Phe Met Ser Gln Gly Glu His Lys Gln Ala Leu Arg Tyr Leu Gln 
    850                 855                 860 

Thr Met Lys Pro Thr Val Ser Ser Ser Asn Glu Val Ile Leu His Leu 
865                 870                 875                 880 

Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp Asn Leu Leu 
                885                 890                 895 

Arg Gln Asn Ser Asn Arg Val Asn Ile Glu Glu Leu Leu Lys His Ala 
            900                 905                 910 

Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu Leu Lys Leu 
        915                 920                 925 

Pro Phe Thr Asn Thr Glu Gln Glu Cys Leu Val Lys Phe Leu Gln Ser 
    930                 935                 940 

Ser Thr Ser Val Glu Asn His Glu Phe Leu Leu Val His His Leu Gln 
945                 950                 955                 960 

Arg Ala Asn Tyr Ile Ser Ala Leu Lys Leu Asn Gln Ile Leu Lys Asn 
                965                 970                 975 

Asn Leu Met Ser Asp Arg Asp Pro Arg Leu Arg Glu Arg Ser Val Thr 
            980                 985                 990 

Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro Arg Val Gln 
        995                1000                1005 

Arg Lys Leu Ala Val Glu Arg Ala Lys Pro Tyr His Leu Ser Thr Ser 
   1010                1015                1020 

Ser Val Phe His Glu Val Ser Arg Pro Lys Pro Leu Ser Ala Phe Pro 
1025               1030                1035                1040 

Lys Lys Ala Ile Thr Gly Thr Val Leu Thr Arg Ser Thr Phe Ile Ser 
               1045                1050                1055 

Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser His Glu Pro Arg 
           1060                1065                1070 

Asn Gly Val Ser Leu Phe Asn Ser Pro Lys Thr Glu Gln Pro Ser Pro 
       1075                1080                1085 

Val Val His Ser Phe Pro His Pro Glu Leu Pro Glu Ala Phe Val Gly 
   1090                1095                1100 

Thr Pro Ile Ser Asn Thr Ser Gln Arg Ile Ser Arg Leu Leu Asp Leu 
1105               1110                1115                1120 

Val Val His Pro Val Pro Gln Pro Ser Gln Cys Leu Glu Phe Ile Gln 
               1125                1130                1135 

Gln Ser Pro Thr Arg Ser Pro Leu Cys Leu Leu Ser Ser Ser Leu Pro 
           1140                1145                1150 

Leu Ser Ser Gln Phe Lys Arg Pro His Gln Asn Thr Ser Arg Pro Ser 
       1155                1160                1165 

Glu Leu Leu Leu Leu Glu Thr Pro Leu Ile Val Lys Lys Ala Lys Ser 
   1170                1175                1180 

Leu Ala Leu Ser Ala Thr Ser Ser Gly Phe Ala Glu Phe Thr Pro Pro 
1185               1190                1195                1200 

Ser Ile Leu Arg Ser Gly Phe Arg Thr Thr Pro Leu Ala Ser Pro Ser 
               1205                1210                1215 

Leu Ser Pro Gly Arg Ser Leu Thr Pro Pro Phe Arg Val Lys Glu Thr 
           1220                1225                1230 

Arg Ile Ser Phe Met Glu Glu Gly Met Asn Thr His Trp Thr Asp Arg 
       1235                1240                1245 

Ala Thr Asp Asp Arg Asn Thr Lys Ala Phe Val Ser Thr Ser Phe His 
   1250                1255                1260 

Lys Cys Gly Leu Pro Ala Glu Thr Glu Trp Met Lys Thr Ser Asp Lys 
1265               1270                1275                1280 

Asn Thr Tyr Phe Pro Leu Asp Val Pro Ala Lys Gly Pro Gln Lys Val 
               1285                1290                1295 

Val Ala Glu Ser Leu Ala Thr His Ser Gly Arg Leu Glu Lys Leu Asp 
           1300                1305                1310 

Val Ser Lys Glu Asp Ser Thr Ala Ser Thr Arg Ser Asp Gln Thr Ser 
       1315                1320                1325 

Leu Glu Tyr His Asp Ala Pro Ser Pro Glu Asp Leu Glu Gly Ala Val 
   1330                1335                1340 

Phe Val Ser Pro Lys Pro Ala Ser Ser Ser Thr Glu Leu Thr Thr Asn 
1345               1350                1355                1360 

Ser Thr Leu Gln Thr Glu Arg Asp Asn Asp Lys Asp Ala Phe Lys Ser 
               1365                1370                1375 

Glu Gly Thr Pro Ser Pro Val Lys Lys Gln Ile Gly Thr Gly Asp Ala 
           1380                1385                1390 

Ala Val Glu Ala Phe Ser Glu Leu Ser Arg Leu Asp Pro Val Glu Arg 
       1395                1400                1405 

Ala Glu Ala Ser Phe Gly Val Ser Ser Val Cys Glu Gly Glu Thr Ser 
   1410                1415                1420 

Thr Ser Asn Ser Lys Thr Ser Val Leu Asp Gly Ile Val Pro Ile Glu 
1425               1430                1435                1440 

Ser Arg Thr Ser Ile Leu Thr Ala Asp His Lys Glu Ser Val Ala Asn 
               1445                1450                1455 

Thr Val Ala Asp Val Glu Ser Ser Gly Ser Thr Ser Ser Lys Cys Pro 
           1460                1465                1470 

Val Thr Ser Glu Arg Ser Leu Gly Gln Lys Leu Thr Leu Asn Leu Lys 
       1475                1480                1485 

Glu Asp Glu Ile Glu Ala His Val Pro Lys Glu Asn Val Gly Leu Pro 
   1490                1495                1500 

Glu Glu Ser Pro Arg Ile Ser Ala Ala Pro Ser Asp Thr His Glu Ile 
1505               1510                1515                1520 

His Leu Ile Gly Cys Glu Asn Leu Glu Val Gln Asn Ser Glu Glu Glu 
               1525                1530                1535 

Ala Lys Asn Leu Ser Phe Asp Glu Leu Tyr Pro Leu Gly Ala Glu Lys 
           1540                1545                1550 

Leu Glu Tyr Asn Leu Ser Thr Ile Glu Gln Gln Phe Cys Asp Leu Pro 
       1555                1560                1565 

Asp Asp Lys Asp Ser Ala Glu Cys Asp Ala Ala Glu Val Asp Gly Glu 
   1570                1575                1580 

Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu Gly Glu Glu 
1585               1590                1595                1600 

Gly Glu Ala Glu Ala Ser Asp Ser Ala Ala Pro Asn Met Leu Pro Lys 
               1605                1610                1615 

Ser Thr Lys Glu Lys Pro Val Cys Tyr Arg Glu Pro His Asn Gln Glu 
           1620                1625                1630 

Arg Val Thr Asp Leu Pro Ser Ala Val Thr Ala Asp Gln Glu Ser His 
       1635                1640                1645 

Lys Val Glu Thr Leu Pro Tyr Val Pro Glu Pro Val Lys Val Ala Ile 
   1650                1655                1660 

Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr Arg Ser Lys Glu Ala 
1665               1670                1675                1680 

Thr Pro Val Ala Ala Gly Glu Ala Gly Asp Glu Asp Gly Ala Val Ile 
               1685                1690                1695 

Val Ser Lys Ala Ala His Ser Ser Arg Leu Thr Asn Ser Thr Pro Lys 
           1700                1705                1710 

Thr Val Lys Glu Pro Arg Ala Glu Thr Val Asn Thr Ser Gln Ser Asp 
       1715                1720                1725 

Asp Met Val Ser Ser Arg Thr Leu Thr Arg Arg Gln His Ala Leu Ser 
   1730                1735                1740 

Leu Asn Val Thr Ser Glu Gln Glu Pro Ser Ala Val Ala Thr Pro Lys 
1745               1750                1755                1760 

Lys Arg Thr Arg Lys Ile Lys Glu Thr Pro Glu Ser Ser Glu Arg Thr 
               1765                1770                1775 

Cys Ser Asp Leu Lys Val Ala Pro Glu Asn Gln Leu Thr Ala Gln Asn 
           1780                1785                1790 

Pro Pro Ala Pro Arg Arg Arg Lys Lys Lys Asp Val Ser Gln Gly Thr 
       1795                1800                1805 

Leu Pro Ser Ser Gly Ala Val Glu Pro Glu Pro Glu Pro Gln Gly Thr 
   1810                1815                1820 

Pro Gly Arg Leu Arg Leu Arg Thr Gln Pro Pro Glu Pro Ala Ala Glu 
1825               1830                1835                1840 

Glu Thr Pro Ser Arg Thr Lys Val Arg Leu Ser Ser Val Arg Lys Gly 
               1845                1850                1855 

Thr Pro Arg Arg Leu Lys Lys Ser Val Glu Asn Gly Gln Ser Ile Glu 
           1860                1865                1870 

Ile Leu Asp Asp Leu Lys Gly Ser Glu Ala Ala Ser His Asp Gly Thr 
       1875                1880                1885 

Val Thr Glu Leu Arg Asn Ala Asn Leu Glu Asp Thr Gln Asn Met Glu 
   1890                1895                1900 

Tyr Lys Gln Asp Glu His Ser Asp Gln Gln Pro Pro Leu Lys Arg Lys 
1905               1910                1915                1920 

Arg Val Arg Glu Arg Glu Val Ser Val Ser Ser Val Thr Glu Glu Pro 
               1925                1930                1935 

Lys Leu Asp Ser Ser Gln Leu Pro Leu Gln Thr Gly Leu Asp Val Pro 
           1940                1945                1950 

Ala Thr Pro Arg Lys Arg Gly Arg Pro Arg Lys Val Val Pro Leu Glu 
       1955                1960                1965 

Ala Asp Gly Gly Thr Thr Gly Lys Glu Gln Thr Ser Pro Gln Lys Lys 
   1970                1975                1980 

Asp Val Pro Val Val Arg Arg Ser Thr Arg Asn Thr Pro Ala Arg Asn 
1985               1990                1995                2000 

Val Ser Thr Leu Lys Lys Ser Val Leu Val Pro Asn Lys Glu Ala Ala 
               2005                2010                2015 

Leu Val Val Thr Ser Lys Arg Arg Pro Thr Lys Lys Ser Ala Glu Glu 
           2020                2025                2030 

Ser Ser Lys Asp Pro Ser Ala Ala Val Ser Asp Trp Ala Gly Gly Ala 
       2035                2040                2045 

Ala His Thr Glu Ser Ala Asp Arg Arg Asp Gly Leu Leu Ala Ala Ala 
   2050                2055                2060 

Ala Leu Thr Pro Ser Ala Gln Gly Thr Arg Thr Arg Ser Arg Arg Thr 
2065               2070                2075                2080 

Met Leu Leu Thr Asp Ile Ser Glu Pro Lys Thr Glu Pro Leu Phe Pro 
               2085                2090                2095 

Pro Pro Ser Val Lys Val Pro Lys Lys Lys Ser Lys Ala Glu Asn Met 
           2100                2105                2110 

Glu Ala Ala Ala Gln Leu Lys Glu Leu Val Ser Asp Leu Ser Ser Gln 
       2115                2120                2125 

Phe Val Val Ser Pro Pro Ala Leu Arg Thr Arg Gln Lys Ser Ile Ser 
   2130                2135                2140 

Asn Thr Ser Lys Leu Leu Gly Glu Leu Glu Ser Asp Pro Lys Pro Leu 
2145               2150                2155                2160 

Glu Ile Ile Glu Gln Lys Pro Lys Arg Ser Arg Thr Val Lys Thr Arg 
               2165                2170                2175 

Ala Ser Arg Asn Thr Gly Lys Gly Ser Ser Trp Ser Pro Pro Pro Val 
           2180                2185                2190 

Glu Ile Lys Leu Val Ser Pro Leu Ala Ser Pro Val Asp Glu Ile Lys 
       2195                2200                2205 

Thr Gly Lys Pro Arg Lys Thr Ala Glu Ile Ala Gly Lys Thr Leu Gly 
   2210                2215                2220 

Arg Gly Arg Lys Lys Pro Ser Ser Phe Pro Lys Gln Ile Leu Arg Arg 
2225               2230                2235                2240 

Lys Met Leu 

 
           
             13  
             7215  
             DNA  
             Homo sapiens  
             
               CDS  
               (125)..(6922)  
             
           
            13 

tgcggctcga gggggccagc gctgacggtg gcgggtacgg caggctcgcg ggcgccgggc     60 

ttcgttacat aatctcggac cggaggagcg gtggcacatg gcggcggaac ggcgctgtgg    120 

aagt atg cga gac tta aga gct caa gtg act agt ggt ctc ctg cca ttt     169 
     Met Arg Asp Leu Arg Ala Gln Val Thr Ser Gly Leu Leu Pro Phe 
       1               5                  10                  15 

cca gaa gtg act ctt caa gcc ctt gga gaa gac gaa ata aca tta gaa      217 
Pro Glu Val Thr Leu Gln Ala Leu Gly Glu Asp Glu Ile Thr Leu Glu 
                 20                  25                  30 

tct gtg ctt cgt gga aag ttt gct gcg ggg aaa aat gga ctt gct tgc      265 
Ser Val Leu Arg Gly Lys Phe Ala Ala Gly Lys Asn Gly Leu Ala Cys 
             35                  40                  45 

ttg gct tgt ggt cca caa ctt gag gta gta aac tct ata aca gga gag      313 
Leu Ala Cys Gly Pro Gln Leu Glu Val Val Asn Ser Ile Thr Gly Glu 
         50                  55                  60 

cga ttg tct gct tac aga ttc agt gga gtc aat gaa cag cct cct gta      361 
Arg Leu Ser Ala Tyr Arg Phe Ser Gly Val Asn Glu Gln Pro Pro Val 
     65                  70                  75 

gtt tta gct gtg aaa gaa ttc tct tgg cag aag aga act gga tta tta      409 
Val Leu Ala Val Lys Glu Phe Ser Trp Gln Lys Arg Thr Gly Leu Leu 
 80                  85                  90                  95 

ata gga ttg gaa gaa aca gaa ggg agt gtt ctc tgt ctt tat gac ctt      457 
Ile Gly Leu Glu Glu Thr Glu Gly Ser Val Leu Cys Leu Tyr Asp Leu 
                100                 105                 110 

gga ata tca aaa gta gtt aaa gca gtt gtt ctt cct gga agg gta aca      505 
Gly Ile Ser Lys Val Val Lys Ala Val Val Leu Pro Gly Arg Val Thr 
            115                 120                 125 

gct att gaa cct ata att aat cat gga gga gcc agt gca agc act cag      553 
Ala Ile Glu Pro Ile Ile Asn His Gly Gly Ala Ser Ala Ser Thr Gln 
        130                 135                 140 

cat tta cat cca agt ctg cga tgg ctt ttt gga gtg gca gct gtg gtc      601 
His Leu His Pro Ser Leu Arg Trp Leu Phe Gly Val Ala Ala Val Val 
    145                 150                 155 

act gat gtt gga cag atc ctt ctt att gac cta tgt ttg gat gac ttg      649 
Thr Asp Val Gly Gln Ile Leu Leu Ile Asp Leu Cys Leu Asp Asp Leu 
160                 165                 170                 175 

tca tgc aat caa aat gaa gtt gaa gca tca gat ctt gaa gtt cta act      697 
Ser Cys Asn Gln Asn Glu Val Glu Ala Ser Asp Leu Glu Val Leu Thr 
                180                 185                 190 

ggt atc cca gct gaa gta cca cac att aga gaa agt gtg atg aga gaa      745 
Gly Ile Pro Ala Glu Val Pro His Ile Arg Glu Ser Val Met Arg Glu 
            195                 200                 205 

ggg cgc cat ctg tgt ttc cag tta gta agt cca aca gga aca gcc gtt      793 
Gly Arg His Leu Cys Phe Gln Leu Val Ser Pro Thr Gly Thr Ala Val 
        210                 215                 220 

tca act ctt agt tac ata agc agg aca aat cag ctt gct gca ggt ttt      841 
Ser Thr Leu Ser Tyr Ile Ser Arg Thr Asn Gln Leu Ala Ala Gly Phe 
    225                 230                 235 

tct gat ggc tat cta gca ctt tgg aac atg aaa agc atg aaa aga gaa      889 
Ser Asp Gly Tyr Leu Ala Leu Trp Asn Met Lys Ser Met Lys Arg Glu 
240                 245                 250                 255 

tat tac ata caa ttg gaa agt gga caa gtt cct gta tat gct gtc act      937 
Tyr Tyr Ile Gln Leu Glu Ser Gly Gln Val Pro Val Tyr Ala Val Thr 
                260                 265                 270 

ttt caa gaa cct gag aat gat cgt cgg aat tgc tgc tac ttg tgg gct      985 
Phe Gln Glu Pro Glu Asn Asp Arg Arg Asn Cys Cys Tyr Leu Trp Ala 
            275                 280                 285 

gtt cag tct aca caa gat agt gaa ggg gat gtt ttg agt ttg cat ctg     1033 
Val Gln Ser Thr Gln Asp Ser Glu Gly Asp Val Leu Ser Leu His Leu 
        290                 295                 300 

ctg cag ctg gcc ttt ggt aat aga aag tgt ttg gca tca gga caa atc     1081 
Leu Gln Leu Ala Phe Gly Asn Arg Lys Cys Leu Ala Ser Gly Gln Ile 
    305                 310                 315 

tta tat gag ggg tta gaa tac tgt gaa gaa aga tac acc ctg gac ctg     1129 
Leu Tyr Glu Gly Leu Glu Tyr Cys Glu Glu Arg Tyr Thr Leu Asp Leu 
320                 325                 330                 335 

aca ggt ggc atg ttc cct ttg agg gga cag acg agt aat acc aaa ttg     1177 
Thr Gly Gly Met Phe Pro Leu Arg Gly Gln Thr Ser Asn Thr Lys Leu 
                340                 345                 350 

ttg gga tgc cag agt ata gag aaa ttt cga tct cat ggt gac agg gag     1225 
Leu Gly Cys Gln Ser Ile Glu Lys Phe Arg Ser His Gly Asp Arg Glu 
            355                 360                 365 

gaa ggc gtg aat gaa gct cta tcg cct gac act agt gtt tca gtc ttt     1273 
Glu Gly Val Asn Glu Ala Leu Ser Pro Asp Thr Ser Val Ser Val Phe 
        370                 375                 380 

acc tgg cag gtg aat ata tat gga cag gga aag cct tct gta tat ttg     1321 
Thr Trp Gln Val Asn Ile Tyr Gly Gln Gly Lys Pro Ser Val Tyr Leu 
    385                 390                 395 

ggg ctt ttt gat ata aat cgt tgg tat cat gca caa atg cca gat tcg     1369 
Gly Leu Phe Asp Ile Asn Arg Trp Tyr His Ala Gln Met Pro Asp Ser 
400                 405                 410                 415 

tta agg tca gga gaa tat cta cat aat tgc tct tat ttt gca ctg tgg     1417 
Leu Arg Ser Gly Glu Tyr Leu His Asn Cys Ser Tyr Phe Ala Leu Trp 
                420                 425                 430 

tca ttg gag tct gtt gta agt agg act tct cca cat ggc atc ttg gat     1465 
Ser Leu Glu Ser Val Val Ser Arg Thr Ser Pro His Gly Ile Leu Asp 
            435                 440                 445 

ata tta gta cat gag aga agt tta aat aga gga gtc cct cct tca tat     1513 
Ile Leu Val His Glu Arg Ser Leu Asn Arg Gly Val Pro Pro Ser Tyr 
        450                 455                 460 

cca cct ccc gag cag ttt ttt aat cca agc act tat aat ttt gat gcc     1561 
Pro Pro Pro Glu Gln Phe Phe Asn Pro Ser Thr Tyr Asn Phe Asp Ala 
    465                 470                 475 

act tgt ttg tta aac tcg gga gtt gtt cat tta act tgt act ggc ttt     1609 
Thr Cys Leu Leu Asn Ser Gly Val Val His Leu Thr Cys Thr Gly Phe 
480                 485                 490                 495 

cag aag gag act ttg act ttt tta aag aaa tca ggt cca tca ctc aat     1657 
Gln Lys Glu Thr Leu Thr Phe Leu Lys Lys Ser Gly Pro Ser Leu Asn 
                500                 505                 510 

gaa ctc att cct gat ggt tat aat cga tgt ctt gta gct ggc ctt ctt     1705 
Glu Leu Ile Pro Asp Gly Tyr Asn Arg Cys Leu Val Ala Gly Leu Leu 
            515                 520                 525 

tcc cca aga ttt gtt gat gtt cag cct tcc agt tta agc caa gaa gaa     1753 
Ser Pro Arg Phe Val Asp Val Gln Pro Ser Ser Leu Ser Gln Glu Glu 
        530                 535                 540 

cag tta gaa gct ata ttg tca gca gca att cag act agt tcc ctg gga     1801 
Gln Leu Glu Ala Ile Leu Ser Ala Ala Ile Gln Thr Ser Ser Leu Gly 
    545                 550                 555 

ctt ttg act ggt tat atc cga aga tgg ata aca gaa gaa caa cca aat     1849 
Leu Leu Thr Gly Tyr Ile Arg Arg Trp Ile Thr Glu Glu Gln Pro Asn 
560                 565                 570                 575 

tct gcc act aat ttg cgc ttt gtt ctt gaa tgg acg tgg aat aaa gtg     1897 
Ser Ala Thr Asn Leu Arg Phe Val Leu Glu Trp Thr Trp Asn Lys Val 
                580                 585                 590 

gtt ctc aca aaa gag gaa ttt gac aga cta tgt gtg cca tta ttt gat     1945 
Val Leu Thr Lys Glu Glu Phe Asp Arg Leu Cys Val Pro Leu Phe Asp 
            595                 600                 605 

ggt tcg tgt cat ttc atg gat cca caa act ata cag tct atc cag caa     1993 
Gly Ser Cys His Phe Met Asp Pro Gln Thr Ile Gln Ser Ile Gln Gln 
        610                 615                 620 

tgc tat ttg ctt ctt agc aat ctt aat ata gtc ttg agc tgt ttt gca     2041 
Cys Tyr Leu Leu Leu Ser Asn Leu Asn Ile Val Leu Ser Cys Phe Ala 
    625                 630                 635 

tca gaa gcc cga gag atc gct gag aga gga ctg ata gac tta agc aat     2089 
Ser Glu Ala Arg Glu Ile Ala Glu Arg Gly Leu Ile Asp Leu Ser Asn 
640                 645                 650                 655 

aag ttt gtg gtt tcc cac ctc atc tgt cag tat gca caa gtg gtt ctt     2137 
Lys Phe Val Val Ser His Leu Ile Cys Gln Tyr Ala Gln Val Val Leu 
                660                 665                 670 

tgg ttc tct cat tct ggg ctt tta cca gaa ggc ata gat gat tct gtg     2185 
Trp Phe Ser His Ser Gly Leu Leu Pro Glu Gly Ile Asp Asp Ser Val 
            675                 680                 685 

cag ttg tca agg tta tgc tac aac tac cct gta att cag aac tac tac     2233 
Gln Leu Ser Arg Leu Cys Tyr Asn Tyr Pro Val Ile Gln Asn Tyr Tyr 
        690                 695                 700 

acc agt cgt cga cag aag ttt gag cgt tta tca aga ggg aag tgg aat     2281 
Thr Ser Arg Arg Gln Lys Phe Glu Arg Leu Ser Arg Gly Lys Trp Asn 
    705                 710                 715 

ccc gat tgc ttg atg att gat gga ctg gtt tct cag tta gga gag cga     2329 
Pro Asp Cys Leu Met Ile Asp Gly Leu Val Ser Gln Leu Gly Glu Arg 
720                 725                 730                 735 

att gag aag ttg tgg aaa cga gat gaa gga ggc aca gga aaa tat cct     2377 
Ile Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Lys Tyr Pro 
                740                 745                 750 

cct gct agt ctg cat gca gta ctt gat atg tac cta tta gac ggc gtt     2425 
Pro Ala Ser Leu His Ala Val Leu Asp Met Tyr Leu Leu Asp Gly Val 
            755                 760                 765 

act gaa gca gcc aaa cac tct att acc att tat ttg cta ctt gat att     2473 
Thr Glu Ala Ala Lys His Ser Ile Thr Ile Tyr Leu Leu Leu Asp Ile 
        770                 775                 780 

atg tat tcc ttt ccc aac aaa aca gac act ccc att gaa tct ttc cca     2521 
Met Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser Phe Pro 
    785                 790                 795 

act gta ttt gcc att tct tgg ggc caa gtt aaa ctt att cag ggg ttt     2569 
Thr Val Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Ile Gln Gly Phe 
800                 805                 810                 815 

tgg ttg ata gat cat aat gac tat gag agt ggt ttg gat ctt ttg ttt     2617 
Trp Leu Ile Asp His Asn Asp Tyr Glu Ser Gly Leu Asp Leu Leu Phe 
                820                 825                 830 

cat cca gct act gca aaa cct ttg tca tgg caa cat tca aag att att     2665 
His Pro Ala Thr Ala Lys Pro Leu Ser Trp Gln His Ser Lys Ile Ile 
            835                 840                 845 

cag gca ttc atg agt cag ggc gag cac aga caa gcc ctc aga tat att     2713 
Gln Ala Phe Met Ser Gln Gly Glu His Arg Gln Ala Leu Arg Tyr Ile 
        850                 855                 860 

cag aca atg aag cca aca gtg tcc agt ggt aac gat gtt atc ctt cac     2761 
Gln Thr Met Lys Pro Thr Val Ser Ser Gly Asn Asp Val Ile Leu His 
    865                 870                 875 

ctc act gtt ttg ctt ttt aat agg tgt atg gtt gaa gcc tgg aat ttt     2809 
Leu Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp Asn Phe 
880                 885                 890                 895 

ttg cgg caa cat tgc aat agg ttg aat ata gag gag tta ctg aag cac     2857 
Leu Arg Gln His Cys Asn Arg Leu Asn Ile Glu Glu Leu Leu Lys His 
                900                 905                 910 

atg tat gaa gtc tgt cag gaa atg ggc ttg atg gaa gat tta ctg aag     2905 
Met Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu Leu Lys 
            915                 920                 925 

tta cca ttt aca gac act gag cag gaa tgt tta gtg aaa ttt ttg cag     2953 
Leu Pro Phe Thr Asp Thr Glu Gln Glu Cys Leu Val Lys Phe Leu Gln 
        930                 935                 940 

tcc agt gcc agc gtt cag aat cat gaa ttc ctt tta gtg cac cat ttg     3001 
Ser Ser Ala Ser Val Gln Asn His Glu Phe Leu Leu Val His His Leu 
    945                 950                 955 

cag cgt gcc aat tat gtg cct gcc ttg aag ctg aac caa act ctg aag     3049 
Gln Arg Ala Asn Tyr Val Pro Ala Leu Lys Leu Asn Gln Thr Leu Lys 
960                 965                 970                 975 

att aat gtt atg aat gat cgt gat cct cgt ttg cgg gag aga tca ctg     3097 
Ile Asn Val Met Asn Asp Arg Asp Pro Arg Leu Arg Glu Arg Ser Leu 
                980                 985                 990 

gct cga aat tct ata tta gac cag tat gga aaa atc ctt cct aga gtc     3145 
Ala Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro Arg Val 
            995                1000                1005 

cat cga aaa tta gcc att gaa cga gct aag cct tat cat ctg tca aca     3193 
His Arg Lys Leu Ala Ile Glu Arg Ala Lys Pro Tyr His Leu Ser Thr 
       1010                1015                1020 

tca tca gtt ttt cga tta gtt tct aga ccc aaa cca tta tca gca gtt     3241 
Ser Ser Val Phe Arg Leu Val Ser Arg Pro Lys Pro Leu Ser Ala Val 
   1025                1030                1035 

cca aag caa gtt gta aca gga act gtg ttg aca aga tct gtt ttc atc     3289 
Pro Lys Gln Val Val Thr Gly Thr Val Leu Thr Arg Ser Val Phe Ile 
1040               1045                1050                1055 

aac aat gtg tta tct aaa att gga gaa gtt tgg gca agc aaa gaa cct     3337 
Asn Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser Lys Glu Pro 
               1060                1065                1070 

ata aat agc acc aca cct ttc aat agt tct aaa ata gaa gaa cca tct     3385 
Ile Asn Ser Thr Thr Pro Phe Asn Ser Ser Lys Ile Glu Glu Pro Ser 
           1075                1080                1085 

cct ata gtg tat tcg ctc cca gct cca gag ctg cct gag gca ttt ttt     3433 
Pro Ile Val Tyr Ser Leu Pro Ala Pro Glu Leu Pro Glu Ala Phe Phe 
       1090                1095                1100 

gga aca cca att tca aaa gca tca caa aaa att tct aga ctg cta gat     3481 
Gly Thr Pro Ile Ser Lys Ala Ser Gln Lys Ile Ser Arg Leu Leu Asp 
   1105                1110                1115 

ttg gtt gtt cag cct gtc ccc cgg cct tct cag tgt tcg gag ttt att     3529 
Leu Val Val Gln Pro Val Pro Arg Pro Ser Gln Cys Ser Glu Phe Ile 
1120               1125                1130                1135 

cag caa agc tcc atg aaa tct cct ttg tac cta gta tcc cgt tca ctg     3577 
Gln Gln Ser Ser Met Lys Ser Pro Leu Tyr Leu Val Ser Arg Ser Leu 
               1140                1145                1150 

ccc tca agt tcg caa tta aaa gga tcg cct cag gcc atc tcc agg gct     3625 
Pro Ser Ser Ser Gln Leu Lys Gly Ser Pro Gln Ala Ile Ser Arg Ala 
           1155                1160                1165 

tca gaa tta cat ttg ctt gaa act cct ctt gta gtt aag aaa gct aaa     3673 
Ser Glu Leu His Leu Leu Glu Thr Pro Leu Val Val Lys Lys Ala Lys 
       1170                1175                1180 

agt ttg gcc atg tca gtt act act tct gga ttt tct gag ttc act cct     3721 
Ser Leu Ala Met Ser Val Thr Thr Ser Gly Phe Ser Glu Phe Thr Pro 
   1185                1190                1195 

cag tcc atc ctg agg tct act cct cga tca aca cct tta gca tct ccc     3769 
Gln Ser Ile Leu Arg Ser Thr Pro Arg Ser Thr Pro Leu Ala Ser Pro 
1200               1205                1210                1215 

tct cca tca cct gga agg tct cct caa cga ctt aaa gaa act aga att     3817 
Ser Pro Ser Pro Gly Arg Ser Pro Gln Arg Leu Lys Glu Thr Arg Ile 
               1220                1225                1230 

tca ttt gtg gaa gaa gat gtc cac cca aaa tgg att cct ggg gct gca     3865 
Ser Phe Val Glu Glu Asp Val His Pro Lys Trp Ile Pro Gly Ala Ala 
           1235                1240                1245 

gat gat agc aaa tta gaa gta ttt act aca cct aaa aaa tgt gca gtt     3913 
Asp Asp Ser Lys Leu Glu Val Phe Thr Thr Pro Lys Lys Cys Ala Val 
       1250                1255                1260 

cca gtg gaa act gaa tgg ccg aag agc aaa gat agg acc aca tct ttt     3961 
Pro Val Glu Thr Glu Trp Pro Lys Ser Lys Asp Arg Thr Thr Ser Phe 
   1265                1270                1275 

ttc ctg aac agc cct gaa aag gag cat caa gaa atg gat gag ggg tca     4009 
Phe Leu Asn Ser Pro Glu Lys Glu His Gln Glu Met Asp Glu Gly Ser 
1280               1285                1290                1295 

caa agt tta gag aaa ctg gat gtg agc aaa gga aac agc agt gtt tca     4057 
Gln Ser Leu Glu Lys Leu Asp Val Ser Lys Gly Asn Ser Ser Val Ser 
               1300                1305                1310 

atc aca tcc gat gag act acc tta gag tat cag gat gca ccg tca ccg     4105 
Ile Thr Ser Asp Glu Thr Thr Leu Glu Tyr Gln Asp Ala Pro Ser Pro 
           1315                1320                1325 

gaa gac ctt gaa gag act gtt ttc acg gcc tct aag ccc aaa agc tct     4153 
Glu Asp Leu Glu Glu Thr Val Phe Thr Ala Ser Lys Pro Lys Ser Ser 
       1330                1335                1340 

tcc act gca cta act act aat gta act gaa caa act gaa aag gat gga     4201 
Ser Thr Ala Leu Thr Thr Asn Val Thr Glu Gln Thr Glu Lys Asp Gly 
   1345                1350                1355 

gat aaa gat gta ttt gca tca gaa gta act cct tca gac cta cag aaa     4249 
Asp Lys Asp Val Phe Ala Ser Glu Val Thr Pro Ser Asp Leu Gln Lys 
1360               1365                1370                1375 

caa atg ggc aat tta gaa gat gca gaa aca aag gat ctc tta gtt gca     4297 
Gln Met Gly Asn Leu Glu Asp Ala Glu Thr Lys Asp Leu Leu Val Ala 
               1380                1385                1390 

gca gag gca ttt tca gaa ttg aat cac tta agc ccg gtt caa gga act     4345 
Ala Glu Ala Phe Ser Glu Leu Asn His Leu Ser Pro Val Gln Gly Thr 
           1395                1400                1405 

gaa gct tct ctt tgt gca cca tca gtc tat gaa ggg aaa atc ttc acc     4393 
Glu Ala Ser Leu Cys Ala Pro Ser Val Tyr Glu Gly Lys Ile Phe Thr 
       1410                1415                1420 

cag aag tcc aag gta cca gtg ttg gac gaa gga tta aca tct gtt gaa     4441 
Gln Lys Ser Lys Val Pro Val Leu Asp Glu Gly Leu Thr Ser Val Glu 
   1425                1430                1435 

acc tac acc cct gca att aga gca aat gac aat aaa tct atg gct gat     4489 
Thr Tyr Thr Pro Ala Ile Arg Ala Asn Asp Asn Lys Ser Met Ala Asp 
1440               1445                1450                1455 

gtc ctt ggt gat ggt gga aac tcc tcg ctc act atc tct gaa ggt cct     4537 
Val Leu Gly Asp Gly Gly Asn Ser Ser Leu Thr Ile Ser Glu Gly Pro 
               1460                1465                1470 

att gtc tct gag cgc agg ctt aac cag gaa gta gcg ctg aac tta aaa     4585 
Ile Val Ser Glu Arg Arg Leu Asn Gln Glu Val Ala Leu Asn Leu Lys 
           1475                1480                1485 

gaa gat cat gaa gta gaa gtt ggt gta cta aaa gaa agt gtt gac tta     4633 
Glu Asp His Glu Val Glu Val Gly Val Leu Lys Glu Ser Val Asp Leu 
       1490                1495                1500 

cca gaa gaa aag ctt cca att tct gac agc cct cct gat act caa gaa     4681 
Pro Glu Glu Lys Leu Pro Ile Ser Asp Ser Pro Pro Asp Thr Gln Glu 
   1505                1510                1515 

att cat gtg att gaa caa gaa aag ctt gaa gct caa gat tca gga gaa     4729 
Ile His Val Ile Glu Gln Glu Lys Leu Glu Ala Gln Asp Ser Gly Glu 
1520               1525                1530                1535 

gag gct agg aat ctt tca ttt aat gag tta tat ccc tct gga aca ctt     4777 
Glu Ala Arg Asn Leu Ser Phe Asn Glu Leu Tyr Pro Ser Gly Thr Leu 
               1540                1545                1550 

aag ctt cag tac aat ttt gat act att gac caa cag ttt tgt gac tta     4825 
Lys Leu Gln Tyr Asn Phe Asp Thr Ile Asp Gln Gln Phe Cys Asp Leu 
           1555                1560                1565 

gct gat aac aaa gac act gct gaa tgt gac att gct gaa gta gat ggg     4873 
Ala Asp Asn Lys Asp Thr Ala Glu Cys Asp Ile Ala Glu Val Asp Gly 
       1570                1575                1580 

gaa ctt ttt gtg gct caa agc aac ttt acc ttg ata ttg gaa ggt gaa     4921 
Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu Gly Glu 
   1585                1590                1595 

gaa gga gaa gtt gag cca ggt gat ttt gca tca tct gat gtg tta cct     4969 
Glu Gly Glu Val Glu Pro Gly Asp Phe Ala Ser Ser Asp Val Leu Pro 
1600               1605                1610                1615 

aaa gca gct aac aca gca act gaa gaa aaa ctt gta tgc agt ggg gaa     5017 
Lys Ala Ala Asn Thr Ala Thr Glu Glu Lys Leu Val Cys Ser Gly Glu 
               1620                1625                1630 

aat gat aat cat gga caa att gca aat ttg cca tct gcc gta act agt     5065 
Asn Asp Asn His Gly Gln Ile Ala Asn Leu Pro Ser Ala Val Thr Ser 
           1635                1640                1645 

gac caa aag tcc caa aaa gta gac act tta cca tat gtg cct gaa cct     5113 
Asp Gln Lys Ser Gln Lys Val Asp Thr Leu Pro Tyr Val Pro Glu Pro 
       1650                1655                1660 

att aaa gta gca att gca gaa aat tta cta gat gta att aaa gac aca     5161 
Ile Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr 
   1665                1670                1675 

aga agt aaa gaa att act tca gat aca atg gaa cag tcc att cat gaa     5209 
Arg Ser Lys Glu Ile Thr Ser Asp Thr Met Glu Gln Ser Ile His Glu 
1680               1685                1690                1695 

aca ata cct tta gtg agc caa aac ata atg tgt ccc act aaa ttg gtc     5257 
Thr Ile Pro Leu Val Ser Gln Asn Ile Met Cys Pro Thr Lys Leu Val 
               1700                1705                1710 

aaa tct gca ttt aag act gct cag gaa aca agc aca atg act atg aat     5305 
Lys Ser Ala Phe Lys Thr Ala Gln Glu Thr Ser Thr Met Thr Met Asn 
           1715                1720                1725 

gtc agc cag gtt gat gac gtg gtt tcc tcc aaa act cgt acg aga ggt     5353 
Val Ser Gln Val Asp Asp Val Val Ser Ser Lys Thr Arg Thr Arg Gly 
       1730                1735                1740 

caa cgt atc caa aac gtg aat gtc aaa tca gca caa cag gaa gca tca     5401 
Gln Arg Ile Gln Asn Val Asn Val Lys Ser Ala Gln Gln Glu Ala Ser 
   1745                1750                1755 

gca gat gtt gct act cct aag atg cca ggg cag tca gtc agg aag aaa     5449 
Ala Asp Val Ala Thr Pro Lys Met Pro Gly Gln Ser Val Arg Lys Lys 
1760               1765                1770                1775 

act agg aag gca aaa gaa att tct gaa gct tct gaa aac atc tat tct     5497 
Thr Arg Lys Ala Lys Glu Ile Ser Glu Ala Ser Glu Asn Ile Tyr Ser 
               1780                1785                1790 

gat gtc aga gga cta ttt cag aac cag caa ata cct caa aat tct gtt     5545 
Asp Val Arg Gly Leu Phe Gln Asn Gln Gln Ile Pro Gln Asn Ser Val 
           1795                1800                1805 

acg cct agg aga gga agg aga aag aaa gaa gtt aat cag gac ata cta     5593 
Thr Pro Arg Arg Gly Arg Arg Lys Lys Glu Val Asn Gln Asp Ile Leu 
       1810                1815                1820 

gaa aac acc agt tct gtg gaa caa gaa tta cag atc act aca ggt agg     5641 
Glu Asn Thr Ser Ser Val Glu Gln Glu Leu Gln Ile Thr Thr Gly Arg 
   1825                1830                1835 

gaa tca aaa aga tta aaa tca tct cag ctg ttg gaa cca gca gtt gaa     5689 
Glu Ser Lys Arg Leu Lys Ser Ser Gln Leu Leu Glu Pro Ala Val Glu 
1840               1845                1850                1855 

gaa act act aaa aaa gaa gtt aag gtt tca tct gtt aca aaa agg act     5737 
Glu Thr Thr Lys Lys Glu Val Lys Val Ser Ser Val Thr Lys Arg Thr 
               1860                1865                1870 

cct aga aga att aaa aga tct gta gaa aat cag gaa agt gtt gaa att     5785 
Pro Arg Arg Ile Lys Arg Ser Val Glu Asn Gln Glu Ser Val Glu Ile 
           1875                1880                1885 

ata aat gat cta aaa gtt agt acg gta aca agt cct agc aga atg atc     5833 
Ile Asn Asp Leu Lys Val Ser Thr Val Thr Ser Pro Ser Arg Met Ile 
       1890                1895                1900 

aga aaa ttg aga agt act aat tta gat gct tct gaa aat aca gga aat     5881 
Arg Lys Leu Arg Ser Thr Asn Leu Asp Ala Ser Glu Asn Thr Gly Asn 
   1905                1910                1915 

aag caa gat gat aaa tcc agt gac aag cag ctg cgt att aaa cat gtt     5929 
Lys Gln Asp Asp Lys Ser Ser Asp Lys Gln Leu Arg Ile Lys His Val 
1920               1925                1930                1935 

aga agg gtc aga ggg aga gaa gtt agt cca tca gat gtg aga gaa gac     5977 
Arg Arg Val Arg Gly Arg Glu Val Ser Pro Ser Asp Val Arg Glu Asp 
               1940                1945                1950 

tcc aac ctt gag tca tct cag ttg act gtt caa gca gaa ttt gat atg     6025 
Ser Asn Leu Glu Ser Ser Gln Leu Thr Val Gln Ala Glu Phe Asp Met 
           1955                1960                1965 

tct gcc ata cct aga aaa cgt ggt aga cca aga aaa atc aat cca tct     6073 
Ser Ala Ile Pro Arg Lys Arg Gly Arg Pro Arg Lys Ile Asn Pro Ser 
       1970                1975                1980 

gaa gat gta gga tct aag gct gtt aag gaa gag aga agc ccc aag aag     6121 
Glu Asp Val Gly Ser Lys Ala Val Lys Glu Glu Arg Ser Pro Lys Lys 
   1985                1990                1995 

aaa gaa gct ccc agc att aga agg aga tct aca aga aat acc cca gct     6169 
Lys Glu Ala Pro Ser Ile Arg Arg Arg Ser Thr Arg Asn Thr Pro Ala 
2000               2005                2010                2015 

aaa agt gaa aat gtt gat gtt gga aaa cca gct tta gga aaa tcc att     6217 
Lys Ser Glu Asn Val Asp Val Gly Lys Pro Ala Leu Gly Lys Ser Ile 
               2020                2025                2030 

tta gtg cca aac gag gaa ctt tcg atg gtg atg agc tct aag aaa aaa     6265 
Leu Val Pro Asn Glu Glu Leu Ser Met Val Met Ser Ser Lys Lys Lys 
           2035                2040                2045 

ctt aca aaa aag act gaa agt caa agc caa aaa cgt tca ttg cac tca     6313 
Leu Thr Lys Lys Thr Glu Ser Gln Ser Gln Lys Arg Ser Leu His Ser 
       2050                2055                2060 

gta tca gaa gaa cgc aca gat gaa atg aca cat aaa gaa aca aat gag     6361 
Val Ser Glu Glu Arg Thr Asp Glu Met Thr His Lys Glu Thr Asn Glu 
   2065                2070                2075 

cag gaa gaa aga ttg ctc gcc aca gct tcc ttc act aaa tca tcc cgc     6409 
Gln Glu Glu Arg Leu Leu Ala Thr Ala Ser Phe Thr Lys Ser Ser Arg 
2080               2085                2090                2095 

agc agc agg act cgg tct agc aag gcc atc ttg ttg ccg gac ctt tct     6457 
Ser Ser Arg Thr Arg Ser Ser Lys Ala Ile Leu Leu Pro Asp Leu Ser 
               2100                2105                2110 

gaa cca aac aat gag cct tta ttt tct cca gcg tca gaa gtt cca agg     6505 
Glu Pro Asn Asn Glu Pro Leu Phe Ser Pro Ala Ser Glu Val Pro Arg 
           2115                2120                2125 

aaa gca aaa gct aaa aaa ata gag gtt cct gca cag ctg aaa gaa tta     6553 
Lys Ala Lys Ala Lys Lys Ile Glu Val Pro Ala Gln Leu Lys Glu Leu 
       2130                2135                2140 

gtt tcg gat tta tct tct cag ttt gtc atc tca cct cct gct tta agg     6601 
Val Ser Asp Leu Ser Ser Gln Phe Val Ile Ser Pro Pro Ala Leu Arg 
   2145                2150                2155 

agc aga caa aaa aac aca tcc aat aag aac aag ctt gaa gat gaa ctg     6649 
Ser Arg Gln Lys Asn Thr Ser Asn Lys Asn Lys Leu Glu Asp Glu Leu 
2160               2165                2170                2175 

aaa gat gat gca caa tca gta gaa act ctg gga aag cca aaa gcg aaa     6697 
Lys Asp Asp Ala Gln Ser Val Glu Thr Leu Gly Lys Pro Lys Ala Lys 
               2180                2185                2190 

cga atc agg acg tca aaa aca aaa caa gca agc aaa aac aca gaa aaa     6745 
Arg Ile Arg Thr Ser Lys Thr Lys Gln Ala Ser Lys Asn Thr Glu Lys 
           2195                2200                2205 

gaa agt gct tgg tca ctt cct ccc ata gaa att cgg ctg att tcc ccc     6793 
Glu Ser Ala Trp Ser Leu Pro Pro Ile Glu Ile Arg Leu Ile Ser Pro 
       2210                2215                2220 

ttg gct agc cca gct gac gga gtc aag agc aaa cca aga aaa act aca     6841 
Leu Ala Ser Pro Ala Asp Gly Val Lys Ser Lys Pro Arg Lys Thr Thr 
   2225                2230                2235 

gaa gtg aca gga aca ggt ctt gga agg aac aga aag aaa ctg tct tcc     6889 
Glu Val Thr Gly Thr Gly Leu Gly Arg Asn Arg Lys Lys Leu Ser Ser 
2240               2245                2250                2255 

tat cca aag caa att tta cgc aga aaa atg ctg taatttcttg ggaagatttt   6942 
Tyr Pro Lys Gln Ile Leu Arg Arg Lys Met Leu 
               2260                2265 

aatgtacacc tatttgtaaa gtcatcagaa tagtgtggat tattaaatat ctagtttgga   7002 

agaaaataat ttatataaat tattgtaaat ttttatgtaa acagaaggtc ttcaataagt   7062 

aaagtaactc catatggagt gattgtttca gtccaggcaa tttttctatt ttatattaag   7122 

acttcataca tttatatatg taaatatggc ttattaatgg aatgttaaat aaaatgtata   7182 

cttctcaaaa aaaaaaaaaa aaaaaaaaaa aaa                                7215 

 
           
             14  
             2266  
             PRT  
             Homo sapiens  
           
            14 

Met Arg Asp Leu Arg Ala Gln Val Thr Ser Gly Leu Leu Pro Phe Pro 
  1               5                  10                  15 

Glu Val Thr Leu Gln Ala Leu Gly Glu Asp Glu Ile Thr Leu Glu Ser 
             20                  25                  30 

Val Leu Arg Gly Lys Phe Ala Ala Gly Lys Asn Gly Leu Ala Cys Leu 
         35                  40                  45 

Ala Cys Gly Pro Gln Leu Glu Val Val Asn Ser Ile Thr Gly Glu Arg 
     50                  55                  60 

Leu Ser Ala Tyr Arg Phe Ser Gly Val Asn Glu Gln Pro Pro Val Val 
 65                  70                  75                  80 

Leu Ala Val Lys Glu Phe Ser Trp Gln Lys Arg Thr Gly Leu Leu Ile 
                 85                  90                  95 

Gly Leu Glu Glu Thr Glu Gly Ser Val Leu Cys Leu Tyr Asp Leu Gly 
            100                 105                 110 

Ile Ser Lys Val Val Lys Ala Val Val Leu Pro Gly Arg Val Thr Ala 
        115                 120                 125 

Ile Glu Pro Ile Ile Asn His Gly Gly Ala Ser Ala Ser Thr Gln His 
    130                 135                 140 

Leu His Pro Ser Leu Arg Trp Leu Phe Gly Val Ala Ala Val Val Thr 
145                 150                 155                 160 

Asp Val Gly Gln Ile Leu Leu Ile Asp Leu Cys Leu Asp Asp Leu Ser 
                165                 170                 175 

Cys Asn Gln Asn Glu Val Glu Ala Ser Asp Leu Glu Val Leu Thr Gly 
            180                 185                 190 

Ile Pro Ala Glu Val Pro His Ile Arg Glu Ser Val Met Arg Glu Gly 
        195                 200                 205 

Arg His Leu Cys Phe Gln Leu Val Ser Pro Thr Gly Thr Ala Val Ser 
    210                 215                 220 

Thr Leu Ser Tyr Ile Ser Arg Thr Asn Gln Leu Ala Ala Gly Phe Ser 
225                 230                 235                 240 

Asp Gly Tyr Leu Ala Leu Trp Asn Met Lys Ser Met Lys Arg Glu Tyr 
                245                 250                 255 

Tyr Ile Gln Leu Glu Ser Gly Gln Val Pro Val Tyr Ala Val Thr Phe 
            260                 265                 270 

Gln Glu Pro Glu Asn Asp Arg Arg Asn Cys Cys Tyr Leu Trp Ala Val 
        275                 280                 285 

Gln Ser Thr Gln Asp Ser Glu Gly Asp Val Leu Ser Leu His Leu Leu 
    290                 295                 300 

Gln Leu Ala Phe Gly Asn Arg Lys Cys Leu Ala Ser Gly Gln Ile Leu 
305                 310                 315                 320 

Tyr Glu Gly Leu Glu Tyr Cys Glu Glu Arg Tyr Thr Leu Asp Leu Thr 
                325                 330                 335 

Gly Gly Met Phe Pro Leu Arg Gly Gln Thr Ser Asn Thr Lys Leu Leu 
            340                 345                 350 

Gly Cys Gln Ser Ile Glu Lys Phe Arg Ser His Gly Asp Arg Glu Glu 
        355                 360                 365 

Gly Val Asn Glu Ala Leu Ser Pro Asp Thr Ser Val Ser Val Phe Thr 
    370                 375                 380 

Trp Gln Val Asn Ile Tyr Gly Gln Gly Lys Pro Ser Val Tyr Leu Gly 
385                 390                 395                 400 

Leu Phe Asp Ile Asn Arg Trp Tyr His Ala Gln Met Pro Asp Ser Leu 
                405                 410                 415 

Arg Ser Gly Glu Tyr Leu His Asn Cys Ser Tyr Phe Ala Leu Trp Ser 
            420                 425                 430 

Leu Glu Ser Val Val Ser Arg Thr Ser Pro His Gly Ile Leu Asp Ile 
        435                 440                 445 

Leu Val His Glu Arg Ser Leu Asn Arg Gly Val Pro Pro Ser Tyr Pro 
    450                 455                 460 

Pro Pro Glu Gln Phe Phe Asn Pro Ser Thr Tyr Asn Phe Asp Ala Thr 
465                 470                 475                 480 

Cys Leu Leu Asn Ser Gly Val Val His Leu Thr Cys Thr Gly Phe Gln 
                485                 490                 495 

Lys Glu Thr Leu Thr Phe Leu Lys Lys Ser Gly Pro Ser Leu Asn Glu 
            500                 505                 510 

Leu Ile Pro Asp Gly Tyr Asn Arg Cys Leu Val Ala Gly Leu Leu Ser 
        515                 520                 525 

Pro Arg Phe Val Asp Val Gln Pro Ser Ser Leu Ser Gln Glu Glu Gln 
    530                 535                 540 

Leu Glu Ala Ile Leu Ser Ala Ala Ile Gln Thr Ser Ser Leu Gly Leu 
545                 550                 555                 560 

Leu Thr Gly Tyr Ile Arg Arg Trp Ile Thr Glu Glu Gln Pro Asn Ser 
                565                 570                 575 

Ala Thr Asn Leu Arg Phe Val Leu Glu Trp Thr Trp Asn Lys Val Val 
            580                 585                 590 

Leu Thr Lys Glu Glu Phe Asp Arg Leu Cys Val Pro Leu Phe Asp Gly 
        595                 600                 605 

Ser Cys His Phe Met Asp Pro Gln Thr Ile Gln Ser Ile Gln Gln Cys 
    610                 615                 620 

Tyr Leu Leu Leu Ser Asn Leu Asn Ile Val Leu Ser Cys Phe Ala Ser 
625                 630                 635                 640 

Glu Ala Arg Glu Ile Ala Glu Arg Gly Leu Ile Asp Leu Ser Asn Lys 
                645                 650                 655 

Phe Val Val Ser His Leu Ile Cys Gln Tyr Ala Gln Val Val Leu Trp 
            660                 665                 670 

Phe Ser His Ser Gly Leu Leu Pro Glu Gly Ile Asp Asp Ser Val Gln 
        675                 680                 685 

Leu Ser Arg Leu Cys Tyr Asn Tyr Pro Val Ile Gln Asn Tyr Tyr Thr 
    690                 695                 700 

Ser Arg Arg Gln Lys Phe Glu Arg Leu Ser Arg Gly Lys Trp Asn Pro 
705                 710                 715                 720 

Asp Cys Leu Met Ile Asp Gly Leu Val Ser Gln Leu Gly Glu Arg Ile 
                725                 730                 735 

Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Lys Tyr Pro Pro 
            740                 745                 750 

Ala Ser Leu His Ala Val Leu Asp Met Tyr Leu Leu Asp Gly Val Thr 
        755                 760                 765 

Glu Ala Ala Lys His Ser Ile Thr Ile Tyr Leu Leu Leu Asp Ile Met 
    770                 775                 780 

Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser Phe Pro Thr 
785                 790                 795                 800 

Val Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Ile Gln Gly Phe Trp 
                805                 810                 815 

Leu Ile Asp His Asn Asp Tyr Glu Ser Gly Leu Asp Leu Leu Phe His 
            820                 825                 830 

Pro Ala Thr Ala Lys Pro Leu Ser Trp Gln His Ser Lys Ile Ile Gln 
        835                 840                 845 

Ala Phe Met Ser Gln Gly Glu His Arg Gln Ala Leu Arg Tyr Ile Gln 
    850                 855                 860 

Thr Met Lys Pro Thr Val Ser Ser Gly Asn Asp Val Ile Leu His Leu 
865                 870                 875                 880 

Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp Asn Phe Leu 
                885                 890                 895 

Arg Gln His Cys Asn Arg Leu Asn Ile Glu Glu Leu Leu Lys His Met 
            900                 905                 910 

Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu Leu Lys Leu 
        915                 920                 925 

Pro Phe Thr Asp Thr Glu Gln Glu Cys Leu Val Lys Phe Leu Gln Ser 
    930                 935                 940 

Ser Ala Ser Val Gln Asn His Glu Phe Leu Leu Val His His Leu Gln 
945                 950                 955                 960 

Arg Ala Asn Tyr Val Pro Ala Leu Lys Leu Asn Gln Thr Leu Lys Ile 
                965                 970                 975 

Asn Val Met Asn Asp Arg Asp Pro Arg Leu Arg Glu Arg Ser Leu Ala 
            980                 985                 990 

Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro Arg Val His 
        995                1000                1005 

Arg Lys Leu Ala Ile Glu Arg Ala Lys Pro Tyr His Leu Ser Thr Ser 
   1010                1015                1020 

Ser Val Phe Arg Leu Val Ser Arg Pro Lys Pro Leu Ser Ala Val Pro 
1025               1030                1035                1040 

Lys Gln Val Val Thr Gly Thr Val Leu Thr Arg Ser Val Phe Ile Asn 
               1045                1050                1055 

Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser Lys Glu Pro Ile 
           1060                1065                1070 

Asn Ser Thr Thr Pro Phe Asn Ser Ser Lys Ile Glu Glu Pro Ser Pro 
       1075                1080                1085 

Ile Val Tyr Ser Leu Pro Ala Pro Glu Leu Pro Glu Ala Phe Phe Gly 
   1090                1095                1100 

Thr Pro Ile Ser Lys Ala Ser Gln Lys Ile Ser Arg Leu Leu Asp Leu 
1105               1110                1115                1120 

Val Val Gln Pro Val Pro Arg Pro Ser Gln Cys Ser Glu Phe Ile Gln 
               1125                1130                1135 

Gln Ser Ser Met Lys Ser Pro Leu Tyr Leu Val Ser Arg Ser Leu Pro 
           1140                1145                1150 

Ser Ser Ser Gln Leu Lys Gly Ser Pro Gln Ala Ile Ser Arg Ala Ser 
       1155                1160                1165 

Glu Leu His Leu Leu Glu Thr Pro Leu Val Val Lys Lys Ala Lys Ser 
   1170                1175                1180 

Leu Ala Met Ser Val Thr Thr Ser Gly Phe Ser Glu Phe Thr Pro Gln 
1185               1190                1195                1200 

Ser Ile Leu Arg Ser Thr Pro Arg Ser Thr Pro Leu Ala Ser Pro Ser 
               1205                1210                1215 

Pro Ser Pro Gly Arg Ser Pro Gln Arg Leu Lys Glu Thr Arg Ile Ser 
           1220                1225                1230 

Phe Val Glu Glu Asp Val His Pro Lys Trp Ile Pro Gly Ala Ala Asp 
       1235                1240                1245 

Asp Ser Lys Leu Glu Val Phe Thr Thr Pro Lys Lys Cys Ala Val Pro 
   1250                1255                1260 

Val Glu Thr Glu Trp Pro Lys Ser Lys Asp Arg Thr Thr Ser Phe Phe 
1265               1270                1275                1280 

Leu Asn Ser Pro Glu Lys Glu His Gln Glu Met Asp Glu Gly Ser Gln 
               1285                1290                1295 

Ser Leu Glu Lys Leu Asp Val Ser Lys Gly Asn Ser Ser Val Ser Ile 
           1300                1305                1310 

Thr Ser Asp Glu Thr Thr Leu Glu Tyr Gln Asp Ala Pro Ser Pro Glu 
       1315                1320                1325 

Asp Leu Glu Glu Thr Val Phe Thr Ala Ser Lys Pro Lys Ser Ser Ser 
   1330                1335                1340 

Thr Ala Leu Thr Thr Asn Val Thr Glu Gln Thr Glu Lys Asp Gly Asp 
1345               1350                1355                1360 

Lys Asp Val Phe Ala Ser Glu Val Thr Pro Ser Asp Leu Gln Lys Gln 
               1365                1370                1375 

Met Gly Asn Leu Glu Asp Ala Glu Thr Lys Asp Leu Leu Val Ala Ala 
           1380                1385                1390 

Glu Ala Phe Ser Glu Leu Asn His Leu Ser Pro Val Gln Gly Thr Glu 
       1395                1400                1405 

Ala Ser Leu Cys Ala Pro Ser Val Tyr Glu Gly Lys Ile Phe Thr Gln 
   1410                1415                1420 

Lys Ser Lys Val Pro Val Leu Asp Glu Gly Leu Thr Ser Val Glu Thr 
1425               1430                1435                1440 

Tyr Thr Pro Ala Ile Arg Ala Asn Asp Asn Lys Ser Met Ala Asp Val 
               1445                1450                1455 

Leu Gly Asp Gly Gly Asn Ser Ser Leu Thr Ile Ser Glu Gly Pro Ile 
           1460                1465                1470 

Val Ser Glu Arg Arg Leu Asn Gln Glu Val Ala Leu Asn Leu Lys Glu 
       1475                1480                1485 

Asp His Glu Val Glu Val Gly Val Leu Lys Glu Ser Val Asp Leu Pro 
   1490                1495                1500 

Glu Glu Lys Leu Pro Ile Ser Asp Ser Pro Pro Asp Thr Gln Glu Ile 
1505               1510                1515                1520 

His Val Ile Glu Gln Glu Lys Leu Glu Ala Gln Asp Ser Gly Glu Glu 
               1525                1530                1535 

Ala Arg Asn Leu Ser Phe Asn Glu Leu Tyr Pro Ser Gly Thr Leu Lys 
           1540                1545                1550 

Leu Gln Tyr Asn Phe Asp Thr Ile Asp Gln Gln Phe Cys Asp Leu Ala 
       1555                1560                1565 

Asp Asn Lys Asp Thr Ala Glu Cys Asp Ile Ala Glu Val Asp Gly Glu 
   1570                1575                1580 

Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu Gly Glu Glu 
1585               1590                1595                1600 

Gly Glu Val Glu Pro Gly Asp Phe Ala Ser Ser Asp Val Leu Pro Lys 
               1605                1610                1615 

Ala Ala Asn Thr Ala Thr Glu Glu Lys Leu Val Cys Ser Gly Glu Asn 
           1620                1625                1630 

Asp Asn His Gly Gln Ile Ala Asn Leu Pro Ser Ala Val Thr Ser Asp 
       1635                1640                1645 

Gln Lys Ser Gln Lys Val Asp Thr Leu Pro Tyr Val Pro Glu Pro Ile 
   1650                1655                1660 

Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys Asp Thr Arg 
1665               1670                1675                1680 

Ser Lys Glu Ile Thr Ser Asp Thr Met Glu Gln Ser Ile His Glu Thr 
               1685                1690                1695 

Ile Pro Leu Val Ser Gln Asn Ile Met Cys Pro Thr Lys Leu Val Lys 
           1700                1705                1710 

Ser Ala Phe Lys Thr Ala Gln Glu Thr Ser Thr Met Thr Met Asn Val 
       1715                1720                1725 

Ser Gln Val Asp Asp Val Val Ser Ser Lys Thr Arg Thr Arg Gly Gln 
   1730                1735                1740 

Arg Ile Gln Asn Val Asn Val Lys Ser Ala Gln Gln Glu Ala Ser Ala 
1745               1750                1755                1760 

Asp Val Ala Thr Pro Lys Met Pro Gly Gln Ser Val Arg Lys Lys Thr 
               1765                1770                1775 

Arg Lys Ala Lys Glu Ile Ser Glu Ala Ser Glu Asn Ile Tyr Ser Asp 
           1780                1785                1790 

Val Arg Gly Leu Phe Gln Asn Gln Gln Ile Pro Gln Asn Ser Val Thr 
       1795                1800                1805 

Pro Arg Arg Gly Arg Arg Lys Lys Glu Val Asn Gln Asp Ile Leu Glu 
   1810                1815                1820 

Asn Thr Ser Ser Val Glu Gln Glu Leu Gln Ile Thr Thr Gly Arg Glu 
1825               1830                1835                1840 

Ser Lys Arg Leu Lys Ser Ser Gln Leu Leu Glu Pro Ala Val Glu Glu 
               1845                1850                1855 

Thr Thr Lys Lys Glu Val Lys Val Ser Ser Val Thr Lys Arg Thr Pro 
           1860                1865                1870 

Arg Arg Ile Lys Arg Ser Val Glu Asn Gln Glu Ser Val Glu Ile Ile 
       1875                1880                1885 

Asn Asp Leu Lys Val Ser Thr Val Thr Ser Pro Ser Arg Met Ile Arg 
   1890                1895                1900 

Lys Leu Arg Ser Thr Asn Leu Asp Ala Ser Glu Asn Thr Gly Asn Lys 
1905               1910                1915                1920 

Gln Asp Asp Lys Ser Ser Asp Lys Gln Leu Arg Ile Lys His Val Arg 
               1925                1930                1935 

Arg Val Arg Gly Arg Glu Val Ser Pro Ser Asp Val Arg Glu Asp Ser 
           1940                1945                1950 

Asn Leu Glu Ser Ser Gln Leu Thr Val Gln Ala Glu Phe Asp Met Ser 
       1955                1960                1965 

Ala Ile Pro Arg Lys Arg Gly Arg Pro Arg Lys Ile Asn Pro Ser Glu 
   1970                1975                1980 

Asp Val Gly Ser Lys Ala Val Lys Glu Glu Arg Ser Pro Lys Lys Lys 
1985               1990                1995                2000 

Glu Ala Pro Ser Ile Arg Arg Arg Ser Thr Arg Asn Thr Pro Ala Lys 
               2005                2010                2015 

Ser Glu Asn Val Asp Val Gly Lys Pro Ala Leu Gly Lys Ser Ile Leu 
           2020                2025                2030 

Val Pro Asn Glu Glu Leu Ser Met Val Met Ser Ser Lys Lys Lys Leu 
       2035                2040                2045 

Thr Lys Lys Thr Glu Ser Gln Ser Gln Lys Arg Ser Leu His Ser Val 
   2050                2055                2060 

Ser Glu Glu Arg Thr Asp Glu Met Thr His Lys Glu Thr Asn Glu Gln 
2065               2070                2075                2080 

Glu Glu Arg Leu Leu Ala Thr Ala Ser Phe Thr Lys Ser Ser Arg Ser 
               2085                2090                2095 

Ser Arg Thr Arg Ser Ser Lys Ala Ile Leu Leu Pro Asp Leu Ser Glu 
           2100                2105                2110 

Pro Asn Asn Glu Pro Leu Phe Ser Pro Ala Ser Glu Val Pro Arg Lys 
       2115                2120                2125 

Ala Lys Ala Lys Lys Ile Glu Val Pro Ala Gln Leu Lys Glu Leu Val 
   2130                2135                2140 

Ser Asp Leu Ser Ser Gln Phe Val Ile Ser Pro Pro Ala Leu Arg Ser 
2145               2150                2155                2160 

Arg Gln Lys Asn Thr Ser Asn Lys Asn Lys Leu Glu Asp Glu Leu Lys 
               2165                2170                2175 

Asp Asp Ala Gln Ser Val Glu Thr Leu Gly Lys Pro Lys Ala Lys Arg 
           2180                2185                2190 

Ile Arg Thr Ser Lys Thr Lys Gln Ala Ser Lys Asn Thr Glu Lys Glu 
       2195                2200                2205 

Ser Ala Trp Ser Leu Pro Pro Ile Glu Ile Arg Leu Ile Ser Pro Leu 
   2210                2215                2220 

Ala Ser Pro Ala Asp Gly Val Lys Ser Lys Pro Arg Lys Thr Thr Glu 
2225               2230                2235                2240 

Val Thr Gly Thr Gly Leu Gly Arg Asn Arg Lys Lys Leu Ser Ser Tyr 
               2245                2250                2255 

Pro Lys Gln Ile Leu Arg Arg Lys Met Leu 
           2260                2265 

 
           
             15  
             7215  
             DNA  
             Homo sapiens  
             
               CDS  
               (98)..(6922)  
             
           
            15 

tgcggctcga gggggccagc gctgacggtg gcgggtacgg caggctcgcg ggcgccgggc     60 

ttcgttacat aatctcggac cggaggagcg gtggcac atg gcg gcg gaa cgg cgc     115 
                                         Met Ala Ala Glu Arg Arg 
                                           1               5 

tgt gga agt atg cga gac tta aga gct caa gtg act agt ggt ctc ctg      163 
Cys Gly Ser Met Arg Asp Leu Arg Ala Gln Val Thr Ser Gly Leu Leu 
             10                  15                  20 

cca ttt cca gaa gtg act ctt caa gcc ctt gga gaa gac gaa ata aca      211 
Pro Phe Pro Glu Val Thr Leu Gln Ala Leu Gly Glu Asp Glu Ile Thr 
         25                  30                  35 

tta gaa tct gtg ctt cgt gga aag ttt gct gcg ggg aaa aat gga ctt      259 
Leu Glu Ser Val Leu Arg Gly Lys Phe Ala Ala Gly Lys Asn Gly Leu 
     40                  45                  50 

gct tgc ttg gct tgt ggt cca caa ctt gag gta gta aac tct ata aca      307 
Ala Cys Leu Ala Cys Gly Pro Gln Leu Glu Val Val Asn Ser Ile Thr 
 55                  60                  65                  70 

gga gag cga ttg tct gct tac aga ttc agt gga gtc aat gaa cag cct      355 
Gly Glu Arg Leu Ser Ala Tyr Arg Phe Ser Gly Val Asn Glu Gln Pro 
                 75                  80                  85 

cct gta gtt tta gct gtg aaa gaa ttc tct tgg cag aag aga act gga      403 
Pro Val Val Leu Ala Val Lys Glu Phe Ser Trp Gln Lys Arg Thr Gly 
             90                  95                 100 

tta tta ata gga ttg gaa gaa aca gaa ggg agt gtt ctc tgt ctt tat      451 
Leu Leu Ile Gly Leu Glu Glu Thr Glu Gly Ser Val Leu Cys Leu Tyr 
        105                 110                 115 

gac ctt gga ata tca aaa gta gtt aaa gca gtt gtt ctt cct gga agg      499 
Asp Leu Gly Ile Ser Lys Val Val Lys Ala Val Val Leu Pro Gly Arg 
    120                 125                 130 

gta aca gct att gaa cct ata att aat cat gga gga gcc agt gca agc      547 
Val Thr Ala Ile Glu Pro Ile Ile Asn His Gly Gly Ala Ser Ala Ser 
135                 140                 145                 150 

act cag cat tta cat cca agt ctg cga tgg ctt ttt gga gtg gca gct      595 
Thr Gln His Leu His Pro Ser Leu Arg Trp Leu Phe Gly Val Ala Ala 
                155                 160                 165 

gtg gtc act gat gtt gga cag atc ctt ctt att gac cta tgt ttg gat      643 
Val Val Thr Asp Val Gly Gln Ile Leu Leu Ile Asp Leu Cys Leu Asp 
            170                 175                 180 

gac ttg tca tgc aat caa aat gaa gtt gaa gca tca gat ctt gaa gtt      691 
Asp Leu Ser Cys Asn Gln Asn Glu Val Glu Ala Ser Asp Leu Glu Val 
        185                 190                 195 

cta act ggt atc cca gct gaa gta cca cac att aga gaa agt gtg atg      739 
Leu Thr Gly Ile Pro Ala Glu Val Pro His Ile Arg Glu Ser Val Met 
    200                 205                 210 

aga gaa ggg cgc cat ctg tgt ttc cag tta gta agt cca aca gga aca      787 
Arg Glu Gly Arg His Leu Cys Phe Gln Leu Val Ser Pro Thr Gly Thr 
215                 220                 225                 230 

gcc gtt tca act ctt agt tac ata agc agg aca aat cag ctt gct gca      835 
Ala Val Ser Thr Leu Ser Tyr Ile Ser Arg Thr Asn Gln Leu Ala Ala 
                235                 240                 245 

ggt ttt tct gat ggc tat cta gca ctt tgg aac atg aaa agc atg aaa      883 
Gly Phe Ser Asp Gly Tyr Leu Ala Leu Trp Asn Met Lys Ser Met Lys 
            250                 255                 260 

aga gaa tat tac ata caa ttg gaa agt gga caa gtt cct gta tat gct      931 
Arg Glu Tyr Tyr Ile Gln Leu Glu Ser Gly Gln Val Pro Val Tyr Ala 
        265                 270                 275 

gtc act ttt caa gaa cct gag aat gat cgt cgg aat tgc tgc tac ttg      979 
Val Thr Phe Gln Glu Pro Glu Asn Asp Arg Arg Asn Cys Cys Tyr Leu 
    280                 285                 290 

tgg gct gtt cag tct aca caa gat agt gaa ggg gat gtt ttg agt ttg     1027 
Trp Ala Val Gln Ser Thr Gln Asp Ser Glu Gly Asp Val Leu Ser Leu 
295                 300                 305                 310 

cat ctg ctg cag ctg gcc ttt ggt aat aga aag tgt ttg gca tca gga     1075 
His Leu Leu Gln Leu Ala Phe Gly Asn Arg Lys Cys Leu Ala Ser Gly 
                315                 320                 325 

caa atc tta tat gag ggg tta gaa tac tgt gaa gaa aga tac acc ctg     1123 
Gln Ile Leu Tyr Glu Gly Leu Glu Tyr Cys Glu Glu Arg Tyr Thr Leu 
            330                 335                 340 

gac ctg aca ggt ggc atg ttc cct ttg agg gga cag acg agt aat acc     1171 
Asp Leu Thr Gly Gly Met Phe Pro Leu Arg Gly Gln Thr Ser Asn Thr 
        345                 350                 355 

aaa ttg ttg gga tgc cag agt ata gag aaa ttt cga tct cat ggt gac     1219 
Lys Leu Leu Gly Cys Gln Ser Ile Glu Lys Phe Arg Ser His Gly Asp 
    360                 365                 370 

agg gag gaa ggc gtg aat gaa gct cta tcg cct gac act agt gtt tca     1267 
Arg Glu Glu Gly Val Asn Glu Ala Leu Ser Pro Asp Thr Ser Val Ser 
375                 380                 385                 390 

gtc ttt acc tgg cag gtg aat ata tat gga cag gga aag cct tct gta     1315 
Val Phe Thr Trp Gln Val Asn Ile Tyr Gly Gln Gly Lys Pro Ser Val 
                395                 400                 405 

tat ttg ggg ctt ttt gat ata aat cgt tgg tat cat gca caa atg cca     1363 
Tyr Leu Gly Leu Phe Asp Ile Asn Arg Trp Tyr His Ala Gln Met Pro 
            410                 415                 420 

gat tcg tta agg tca gga gaa tat cta cat aat tgc tct tat ttt gca     1411 
Asp Ser Leu Arg Ser Gly Glu Tyr Leu His Asn Cys Ser Tyr Phe Ala 
        425                 430                 435 

ctg tgg tca ttg gag tct gtt gta agt agg act tct cca cat ggc atc     1459 
Leu Trp Ser Leu Glu Ser Val Val Ser Arg Thr Ser Pro His Gly Ile 
    440                 445                 450 

ttg gat ata tta gta cat gag aga agt tta aat aga gga gtc cct cct     1507 
Leu Asp Ile Leu Val His Glu Arg Ser Leu Asn Arg Gly Val Pro Pro 
455                 460                 465                 470 

tca tat cca cct ccc gag cag ttt ttt aat cca agc act tat aat ttt     1555 
Ser Tyr Pro Pro Pro Glu Gln Phe Phe Asn Pro Ser Thr Tyr Asn Phe 
                475                 480                 485 

gat gcc act tgt ttg tta aac tcg gga gtt gtt cat tta act tgt act     1603 
Asp Ala Thr Cys Leu Leu Asn Ser Gly Val Val His Leu Thr Cys Thr 
            490                 495                 500 

ggc ttt cag aag gag act ttg act ttt tta aag aaa tca ggt cca tca     1651 
Gly Phe Gln Lys Glu Thr Leu Thr Phe Leu Lys Lys Ser Gly Pro Ser 
        505                 510                 515 

ctc aat gaa ctc att cct gat ggt tat aat cga tgt ctt gta gct ggc     1699 
Leu Asn Glu Leu Ile Pro Asp Gly Tyr Asn Arg Cys Leu Val Ala Gly 
    520                 525                 530 

ctt ctt tcc cca aga ttt gtt gat gtt cag cct tcc agt tta agc caa     1747 
Leu Leu Ser Pro Arg Phe Val Asp Val Gln Pro Ser Ser Leu Ser Gln 
535                 540                 545                 550 

gaa gaa cag tta gaa gct ata ttg tca gca gca att cag act agt tcc     1795 
Glu Glu Gln Leu Glu Ala Ile Leu Ser Ala Ala Ile Gln Thr Ser Ser 
                555                 560                 565 

ctg gga ctt ttg act ggt tat atc cga aga tgg ata aca gaa gaa caa     1843 
Leu Gly Leu Leu Thr Gly Tyr Ile Arg Arg Trp Ile Thr Glu Glu Gln 
            570                 575                 580 

cca aat tct gcc act aat ttg cgc ttt gtt ctt gaa tgg acg tgg aat     1891 
Pro Asn Ser Ala Thr Asn Leu Arg Phe Val Leu Glu Trp Thr Trp Asn 
        585                 590                 595 

aaa gtg gtt ctc aca aaa gag gaa ttt gac aga cta tgt gtg cca tta     1939 
Lys Val Val Leu Thr Lys Glu Glu Phe Asp Arg Leu Cys Val Pro Leu 
    600                 605                 610 

ttt gat ggt tcg tgt cat ttc atg gat cca caa act ata cag tct atc     1987 
Phe Asp Gly Ser Cys His Phe Met Asp Pro Gln Thr Ile Gln Ser Ile 
615                 620                 625                 630 

cag caa tgc tat ttg ctt ctt agc aat ctt aat ata gtc ttg agc tgt     2035 
Gln Gln Cys Tyr Leu Leu Leu Ser Asn Leu Asn Ile Val Leu Ser Cys 
                635                 640                 645 

ttt gca tca gaa gcc cga gag atc gct gag aga gga ctg ata gac tta     2083 
Phe Ala Ser Glu Ala Arg Glu Ile Ala Glu Arg Gly Leu Ile Asp Leu 
            650                 655                 660 

agc aat aag ttt gtg gtt tcc cac ctc atc tgt cag tat gca caa gtg     2131 
Ser Asn Lys Phe Val Val Ser His Leu Ile Cys Gln Tyr Ala Gln Val 
        665                 670                 675 

gtt ctt tgg ttc tct cat tct ggg ctt tta cca gaa ggc ata gat gat     2179 
Val Leu Trp Phe Ser His Ser Gly Leu Leu Pro Glu Gly Ile Asp Asp 
    680                 685                 690 

tct gtg cag ttg tca agg tta tgc tac aac tac cct gta att cag aac     2227 
Ser Val Gln Leu Ser Arg Leu Cys Tyr Asn Tyr Pro Val Ile Gln Asn 
695                 700                 705                 710 

tac tac acc agt cgt cga cag aag ttt gag cgt tta tca aga ggg aag     2275 
Tyr Tyr Thr Ser Arg Arg Gln Lys Phe Glu Arg Leu Ser Arg Gly Lys 
                715                 720                 725 

tgg aat ccc gat tgc ttg atg att gat gga ctg gtt tct cag tta gga     2323 
Trp Asn Pro Asp Cys Leu Met Ile Asp Gly Leu Val Ser Gln Leu Gly 
            730                 735                 740 

gag cga att gag aag ttg tgg aaa cga gat gaa gga ggc aca gga aaa     2371 
Glu Arg Ile Glu Lys Leu Trp Lys Arg Asp Glu Gly Gly Thr Gly Lys 
        745                 750                 755 

tat cct cct gct agt ctg cat gca gta ctt gat atg tac cta tta gac     2419 
Tyr Pro Pro Ala Ser Leu His Ala Val Leu Asp Met Tyr Leu Leu Asp 
    760                 765                 770 

ggc gtt act gaa gca gcc aaa cac tct att acc att tat ttg cta ctt     2467 
Gly Val Thr Glu Ala Ala Lys His Ser Ile Thr Ile Tyr Leu Leu Leu 
775                 780                 785                 790 

gat att atg tat tcc ttt ccc aac aaa aca gac act ccc att gaa tct     2515 
Asp Ile Met Tyr Ser Phe Pro Asn Lys Thr Asp Thr Pro Ile Glu Ser 
                795                 800                 805 

ttc cca act gta ttt gcc att tct tgg ggc caa gtt aaa ctt att cag     2563 
Phe Pro Thr Val Phe Ala Ile Ser Trp Gly Gln Val Lys Leu Ile Gln 
            810                 815                 820 

ggg ttt tgg ttg ata gat cat aat gac tat gag agt ggt ttg gat ctt     2611 
Gly Phe Trp Leu Ile Asp His Asn Asp Tyr Glu Ser Gly Leu Asp Leu 
        825                 830                 835 

ttg ttt cat cca gct act gca aaa cct ttg tca tgg caa cat tca aag     2659 
Leu Phe His Pro Ala Thr Ala Lys Pro Leu Ser Trp Gln His Ser Lys 
    840                 845                 850 

att att cag gca ttc atg agt cag ggc gag cac aga caa gcc ctc aga     2707 
Ile Ile Gln Ala Phe Met Ser Gln Gly Glu His Arg Gln Ala Leu Arg 
855                 860                 865                 870 

tat att cag aca atg aag cca aca gtg tcc agt ggt aac gat gtt atc     2755 
Tyr Ile Gln Thr Met Lys Pro Thr Val Ser Ser Gly Asn Asp Val Ile 
                875                 880                 885 

ctt cac ctc act gtt ttg ctt ttt aat agg tgt atg gtt gaa gcc tgg     2803 
Leu His Leu Thr Val Leu Leu Phe Asn Arg Cys Met Val Glu Ala Trp 
            890                 895                 900 

aat ttt ttg cgg caa cat tgc aat agg ttg aat ata gag gag tta ctg     2851 
Asn Phe Leu Arg Gln His Cys Asn Arg Leu Asn Ile Glu Glu Leu Leu 
        905                 910                 915 

aag cac atg tat gaa gtc tgt cag gaa atg ggc ttg atg gaa gat tta     2899 
Lys His Met Tyr Glu Val Cys Gln Glu Met Gly Leu Met Glu Asp Leu 
    920                 925                 930 

ctg aag tta cca ttt aca gac act gag cag gaa tgt tta gtg aaa ttt     2947 
Leu Lys Leu Pro Phe Thr Asp Thr Glu Gln Glu Cys Leu Val Lys Phe 
935                 940                 945                 950 

ttg cag tcc agt gcc agc gtt cag aat cat gaa ttc ctt tta gtg cac     2995 
Leu Gln Ser Ser Ala Ser Val Gln Asn His Glu Phe Leu Leu Val His 
                955                 960                 965 

cat ttg cag cgt gcc aat tat gtg cct gcc ttg aag ctg aac caa act     3043 
His Leu Gln Arg Ala Asn Tyr Val Pro Ala Leu Lys Leu Asn Gln Thr 
            970                 975                 980 

ctg aag att aat gtt atg aat gat cgt gat cct cgt ttg cgg gag aga     3091 
Leu Lys Ile Asn Val Met Asn Asp Arg Asp Pro Arg Leu Arg Glu Arg 
        985                 990                 995 

tca ctg gct cga aat tct ata tta gac cag tat gga aaa atc ctt cct     3139 
Ser Leu Ala Arg Asn Ser Ile Leu Asp Gln Tyr Gly Lys Ile Leu Pro 
   1000                1005                1010 

aga gtc cat cga aaa tta gcc att gaa cga gct aag cct tat cat ctg     3187 
Arg Val His Arg Lys Leu Ala Ile Glu Arg Ala Lys Pro Tyr His Leu 
1015               1020                1025                1030 

tca aca tca tca gtt ttt cga tta gtt tct aga ccc aaa cca tta tca     3235 
Ser Thr Ser Ser Val Phe Arg Leu Val Ser Arg Pro Lys Pro Leu Ser 
               1035                1040                1045 

gca gtt cca aag caa gtt gta aca gga act gtg ttg aca aga tct gtt     3283 
Ala Val Pro Lys Gln Val Val Thr Gly Thr Val Leu Thr Arg Ser Val 
           1050                1055                1060 

ttc atc aac aat gtg tta tct aaa att gga gaa gtt tgg gca agc aaa     3331 
Phe Ile Asn Asn Val Leu Ser Lys Ile Gly Glu Val Trp Ala Ser Lys 
       1065                1070                1075 

gaa cct ata aat agc acc aca cct ttc aat agt tct aaa ata gaa gaa     3379 
Glu Pro Ile Asn Ser Thr Thr Pro Phe Asn Ser Ser Lys Ile Glu Glu 
   1080                1085                1090 

cca tct cct ata gtg tat tcg ctc cca gct cca gag ctg cct gag gca     3427 
Pro Ser Pro Ile Val Tyr Ser Leu Pro Ala Pro Glu Leu Pro Glu Ala 
1095               1100                1105                1110 

ttt ttt gga aca cca att tca aaa gca tca caa aaa att tct aga ctg     3475 
Phe Phe Gly Thr Pro Ile Ser Lys Ala Ser Gln Lys Ile Ser Arg Leu 
               1115                1120                1125 

cta gat ttg gtt gtt cag cct gtc ccc cgg cct tct cag tgt tcg gag     3523 
Leu Asp Leu Val Val Gln Pro Val Pro Arg Pro Ser Gln Cys Ser Glu 
           1130                1135                1140 

ttt att cag caa agc tcc atg aaa tct cct ttg tac cta gta tcc cgt     3571 
Phe Ile Gln Gln Ser Ser Met Lys Ser Pro Leu Tyr Leu Val Ser Arg 
       1145                1150                1155 

tca ctg ccc tca agt tcg caa tta aaa gga tcg cct cag gcc atc tcc     3619 
Ser Leu Pro Ser Ser Ser Gln Leu Lys Gly Ser Pro Gln Ala Ile Ser 
   1160                1165                1170 

agg gct tca gaa tta cat ttg ctt gaa act cct ctt gta gtt aag aaa     3667 
Arg Ala Ser Glu Leu His Leu Leu Glu Thr Pro Leu Val Val Lys Lys 
1175               1180                1185                1190 

gct aaa agt ttg gcc atg tca gtt act act tct gga ttt tct gag ttc     3715 
Ala Lys Ser Leu Ala Met Ser Val Thr Thr Ser Gly Phe Ser Glu Phe 
               1195                1200                1205 

act cct cag tcc atc ctg agg tct act cct cga tca aca cct tta gca     3763 
Thr Pro Gln Ser Ile Leu Arg Ser Thr Pro Arg Ser Thr Pro Leu Ala 
           1210                1215                1220 

tct ccc tct cca tca cct gga agg tct cct caa cga ctt aaa gaa act     3811 
Ser Pro Ser Pro Ser Pro Gly Arg Ser Pro Gln Arg Leu Lys Glu Thr 
       1225                1230                1235 

aga att tca ttt gtg gaa gaa gat gtc cac cca aaa tgg att cct ggg     3859 
Arg Ile Ser Phe Val Glu Glu Asp Val His Pro Lys Trp Ile Pro Gly 
   1240                1245                1250 

gct gca gat gat agc aaa tta gaa gta ttt act aca cct aaa aaa tgt     3907 
Ala Ala Asp Asp Ser Lys Leu Glu Val Phe Thr Thr Pro Lys Lys Cys 
1255               1260                1265                1270 

gca gtt cca gtg gaa act gaa tgg ccg aag agc aaa gat agg acc aca     3955 
Ala Val Pro Val Glu Thr Glu Trp Pro Lys Ser Lys Asp Arg Thr Thr 
               1275                1280                1285 

tct ttt ttc ctg aac agc cct gaa aag gag cat caa gaa atg gat gag     4003 
Ser Phe Phe Leu Asn Ser Pro Glu Lys Glu His Gln Glu Met Asp Glu 
           1290                1295                1300 

ggg tca caa agt tta gag aaa ctg gat gtg agc aaa gga aac agc agt     4051 
Gly Ser Gln Ser Leu Glu Lys Leu Asp Val Ser Lys Gly Asn Ser Ser 
       1305                1310                1315 

gtt tca atc aca tcc gat gag act acc tta gag tat cag gat gca ccg     4099 
Val Ser Ile Thr Ser Asp Glu Thr Thr Leu Glu Tyr Gln Asp Ala Pro 
   1320                1325                1330 

tca ccg gaa gac ctt gaa gag act gtt ttc acg gcc tct aag ccc aaa     4147 
Ser Pro Glu Asp Leu Glu Glu Thr Val Phe Thr Ala Ser Lys Pro Lys 
1335               1340                1345                1350 

agc tct tcc act gca cta act act aat gta act gaa caa act gaa aag     4195 
Ser Ser Ser Thr Ala Leu Thr Thr Asn Val Thr Glu Gln Thr Glu Lys 
               1355                1360                1365 

gat gga gat aaa gat gta ttt gca tca gaa gta act cct tca gac cta     4243 
Asp Gly Asp Lys Asp Val Phe Ala Ser Glu Val Thr Pro Ser Asp Leu 
           1370                1375                1380 

cag aaa caa atg ggc aat tta gaa gat gca gaa aca aag gat ctc tta     4291 
Gln Lys Gln Met Gly Asn Leu Glu Asp Ala Glu Thr Lys Asp Leu Leu 
       1385                1390                1395 

gtt gca gca gag gca ttt tca gaa ttg aat cac tta agc ccg gtt caa     4339 
Val Ala Ala Glu Ala Phe Ser Glu Leu Asn His Leu Ser Pro Val Gln 
   1400                1405                1410 

gga act gaa gct tct ctt tgt gca cca tca gtc tat gaa ggg aaa atc     4387 
Gly Thr Glu Ala Ser Leu Cys Ala Pro Ser Val Tyr Glu Gly Lys Ile 
1415               1420                1425                1430 

ttc acc cag aag tcc aag gta cca gtg ttg gac gaa gga tta aca tct     4435 
Phe Thr Gln Lys Ser Lys Val Pro Val Leu Asp Glu Gly Leu Thr Ser 
               1435                1440                1445 

gtt gaa acc tac acc cct gca att aga gca aat gac aat aaa tct atg     4483 
Val Glu Thr Tyr Thr Pro Ala Ile Arg Ala Asn Asp Asn Lys Ser Met 
           1450                1455                1460 

gct gat gtc ctt ggt gat ggt gga aac tcc tcg ctc act atc tct gaa     4531 
Ala Asp Val Leu Gly Asp Gly Gly Asn Ser Ser Leu Thr Ile Ser Glu 
       1465                1470                1475 

ggt cct att gtc tct gag cgc agg ctt aac cag gaa gta gcg ctg aac     4579 
Gly Pro Ile Val Ser Glu Arg Arg Leu Asn Gln Glu Val Ala Leu Asn 
   1480                1485                1490 

tta aaa gaa gat cat gaa gta gaa gtt ggt gta cta aaa gaa agt gtt     4627 
Leu Lys Glu Asp His Glu Val Glu Val Gly Val Leu Lys Glu Ser Val 
1495               1500                1505                1510 

gac tta cca gaa gaa aag ctt cca att tct gac agc cct cct gat act     4675 
Asp Leu Pro Glu Glu Lys Leu Pro Ile Ser Asp Ser Pro Pro Asp Thr 
               1515                1520                1525 

caa gaa att cat gtg att gaa caa gaa aag ctt gaa gct caa gat tca     4723 
Gln Glu Ile His Val Ile Glu Gln Glu Lys Leu Glu Ala Gln Asp Ser 
           1530                1535                1540 

gga gaa gag gct agg aat ctt tca ttt aat gag tta tat ccc tct gga     4771 
Gly Glu Glu Ala Arg Asn Leu Ser Phe Asn Glu Leu Tyr Pro Ser Gly 
       1545                1550                1555 

aca ctt aag ctt cag tac aat ttt gat act att gac caa cag ttt tgt     4819 
Thr Leu Lys Leu Gln Tyr Asn Phe Asp Thr Ile Asp Gln Gln Phe Cys 
   1560                1565                1570 

gac tta gct gat aac aaa gac act gct gaa tgt gac att gct gaa gta     4867 
Asp Leu Ala Asp Asn Lys Asp Thr Ala Glu Cys Asp Ile Ala Glu Val 
1575               1580                1585                1590 

gat ggg gaa ctt ttt gtg gct caa agc aac ttt acc ttg ata ttg gaa     4915 
Asp Gly Glu Leu Phe Val Ala Gln Ser Asn Phe Thr Leu Ile Leu Glu 
               1595                1600                1605 

ggt gaa gaa gga gaa gtt gag cca ggt gat ttt gca tca tct gat gtg     4963 
Gly Glu Glu Gly Glu Val Glu Pro Gly Asp Phe Ala Ser Ser Asp Val 
           1610                1615                1620 

tta cct aaa gca gct aac aca gca act gaa gaa aaa ctt gta tgc agt     5011 
Leu Pro Lys Ala Ala Asn Thr Ala Thr Glu Glu Lys Leu Val Cys Ser 
       1625                1630                1635 

ggg gaa aat gat aat cat gga caa att gca aat ttg cca tct gcc gta     5059 
Gly Glu Asn Asp Asn His Gly Gln Ile Ala Asn Leu Pro Ser Ala Val 
   1640                1645                1650 

act agt gac caa aag tcc caa aaa gta gac act tta cca tat gtg cct     5107 
Thr Ser Asp Gln Lys Ser Gln Lys Val Asp Thr Leu Pro Tyr Val Pro 
1655               1660                1665                1670 

gaa cct att aaa gta gca att gca gaa aat tta cta gat gta att aaa     5155 
Glu Pro Ile Lys Val Ala Ile Ala Glu Asn Leu Leu Asp Val Ile Lys 
               1675                1680                1685 

gac aca aga agt aaa gaa att act tca gat aca atg gaa cag tcc att     5203 
Asp Thr Arg Ser Lys Glu Ile Thr Ser Asp Thr Met Glu Gln Ser Ile 
           1690                1695                1700 

cat gaa aca ata cct tta gtg agc caa aac ata atg tgt ccc act aaa     5251 
His Glu Thr Ile Pro Leu Val Ser Gln Asn Ile Met Cys Pro Thr Lys 
       1705                1710                1715 

ttg gtc aaa tct gca ttt aag act gct cag gaa aca agc aca atg act     5299 
Leu Val Lys Ser Ala Phe Lys Thr Ala Gln Glu Thr Ser Thr Met Thr 
   1720                1725                1730 

atg aat gtc agc cag gtt gat gac gtg gtt tcc tcc aaa act cgt acg     5347 
Met Asn Val Ser Gln Val Asp Asp Val Val Ser Ser Lys Thr Arg Thr 
1735               1740                1745                1750 

aga ggt caa cgt atc caa aac gtg aat gtc aaa tca gca caa cag gaa     5395 
Arg Gly Gln Arg Ile Gln Asn Val Asn Val Lys Ser Ala Gln Gln Glu 
               1755                1760                1765 

gca tca gca gat gtt gct act cct aag atg cca ggg cag tca gtc agg     5443 
Ala Ser Ala Asp Val Ala Thr Pro Lys Met Pro Gly Gln Ser Val Arg 
           1770                1775                1780 

aag aaa act agg aag gca aaa gaa att tct gaa gct tct gaa aac atc     5491 
Lys Lys Thr Arg Lys Ala Lys Glu Ile Ser Glu Ala Ser Glu Asn Ile 
       1785                1790                1795 

tat tct gat gtc aga gga cta ttt cag aac cag caa ata cct caa aat     5539 
Tyr Ser Asp Val Arg Gly Leu Phe Gln Asn Gln Gln Ile Pro Gln Asn 
   1800                1805                1810 

tct gtt acg cct agg aga gga agg aga aag aaa gaa gtt aat cag gac     5587 
Ser Val Thr Pro Arg Arg Gly Arg Arg Lys Lys Glu Val Asn Gln Asp 
1815               1820                1825                1830 

ata cta gaa aac acc agt tct gtg gaa caa gaa tta cag atc act aca     5635 
Ile Leu Glu Asn Thr Ser Ser Val Glu Gln Glu Leu Gln Ile Thr Thr 
               1835                1840                1845 

ggt agg gaa tca aaa aga tta aaa tca tct cag ctg ttg gaa cca gca     5683 
Gly Arg Glu Ser Lys Arg Leu Lys Ser Ser Gln Leu Leu Glu Pro Ala 
           1850                1855                1860 

gtt gaa gaa act act aaa aaa gaa gtt aag gtt tca tct gtt aca aaa     5731 
Val Glu Glu Thr Thr Lys Lys Glu Val Lys Val Ser Ser Val Thr Lys 
       1865                1870                1875 

agg act cct aga aga att aaa aga tct gta gaa aat cag gaa agt gtt     5779 
Arg Thr Pro Arg Arg Ile Lys Arg Ser Val Glu Asn Gln Glu Ser Val 
   1880                1885                1890 

gaa att ata aat gat cta aaa gtt agt acg gta aca agt cct agc aga     5827 
Glu Ile Ile Asn Asp Leu Lys Val Ser Thr Val Thr Ser Pro Ser Arg 
1895               1900                1905                1910 

atg atc aga aaa ttg aga agt act aat tta gat gct tct gaa aat aca     5875 
Met Ile Arg Lys Leu Arg Ser Thr Asn Leu Asp Ala Ser Glu Asn Thr 
               1915                1920                1925 

gga aat aag caa gat gat aaa tcc agt gac aag cag ctg cgt att aaa     5923 
Gly Asn Lys Gln Asp Asp Lys Ser Ser Asp Lys Gln Leu Arg Ile Lys 
           1930                1935                1940 

cat gtt aga agg gtc aga ggg aga gaa gtt agt cca tca gat gtg aga     5971 
His Val Arg Arg Val Arg Gly Arg Glu Val Ser Pro Ser Asp Val Arg 
       1945                1950                1955 

gaa gac tcc aac ctt gag tca tct cag ttg act gtt caa gca gaa ttt     6019 
Glu Asp Ser Asn Leu Glu Ser Ser Gln Leu Thr Val Gln Ala Glu Phe 
   1960                1965                1970 

gat atg tct gcc ata cct aga aaa cgt ggt aga cca aga aaa atc aat     6067 
Asp Met Ser Ala Ile Pro Arg Lys Arg Gly Arg Pro Arg Lys Ile Asn 
1975               1980                1985                1990 

cca tct gaa gat gta gga tct aag gct gtt aag gaa gag aga agc ccc     6115 
Pro Ser Glu Asp Val Gly Ser Lys Ala Val Lys Glu Glu Arg Ser Pro 
               1995                2000                2005 

aag aag aaa gaa gct ccc agc att aga agg aga tct aca aga aat acc     6163 
Lys Lys Lys Glu Ala Pro Ser Ile Arg Arg Arg Ser Thr Arg Asn Thr 
           2010                2015                2020 

cca gct aaa agt gaa aat gtt gat gtt gga aaa cca gct tta gga aaa     6211 
Pro Ala Lys Ser Glu Asn Val Asp Val Gly Lys Pro Ala Leu Gly Lys 
       2025                2030                2035 

tcc att tta gtg cca aac gag gaa ctt tcg atg gtg atg agc tct aag     6259 
Ser Ile Leu Val Pro Asn Glu Glu Leu Ser Met Val Met Ser Ser Lys 
   2040                2045                2050 

aaa aaa ctt aca aaa aag act gaa agt caa agc caa aaa cgt tca ttg     6307 
Lys Lys Leu Thr Lys Lys Thr Glu Ser Gln Ser Gln Lys Arg Ser Leu 
2055               2060                2065                2070 

cac tca gta tca gaa gaa cgc aca gat gaa atg aca cat aaa gaa aca     6355 
His Ser Val Ser Glu Glu Arg Thr Asp Glu Met Thr His Lys Glu Thr 
               2075                2080                2085 

aat gag cag gaa gaa aga ttg ctc gcc aca gct tcc ttc act aaa tca     6403 
Asn Glu Gln Glu Glu Arg Leu Leu Ala Thr Ala Ser Phe Thr Lys Ser 
           2090                2095                2100 

tcc cgc agc agc agg act cgg tct agc aag gcc atc ttg ttg ccg gac     6451 
Ser Arg Ser Ser Arg Thr Arg Ser Ser Lys Ala Ile Leu Leu Pro Asp 
       2105                2110                2115 

ctt tct gaa cca aac aat gag cct tta ttt tct cca gcg tca gaa gtt     6499 
Leu Ser Glu Pro Asn Asn Glu Pro Leu Phe Ser Pro Ala Ser Glu Val 
   2120                2125                2130 

cca agg aaa gca aaa gct aaa aaa ata gag gtt cct gca cag ctg aaa     6547 
Pro Arg Lys Ala Lys Ala Lys Lys Ile Glu Val Pro Ala Gln Leu Lys 
2135               2140                2145                2150 

gaa tta gtt tcg gat tta tct tct cag ttt gtc atc tca cct cct gct     6595 
Glu Leu Val Ser Asp Leu Ser Ser Gln Phe Val Ile Ser Pro Pro Ala 
               2155                2160                2165 

tta agg agc aga caa aaa aac aca tcc aat aag aac aag ctt gaa gat     6643 
Leu Arg Ser Arg Gln Lys Asn Thr Ser Asn Lys Asn Lys Leu Glu Asp 
           2170                2175                2180 

gaa ctg aaa gat gat gca caa tca gta gaa act ctg gga aag cca aaa     6691 
Glu Leu Lys Asp Asp Ala Gln Ser Val Glu Thr Leu Gly Lys Pro Lys 
       2185                2190                2195 

gcg aaa cga atc agg acg tca aaa aca aaa caa gca agc aaa aac aca     6739 
Ala Lys Arg Ile Arg Thr Ser Lys Thr Lys Gln Ala Ser Lys Asn Thr 
   2200                2205                2210 

gaa aaa gaa agt gct tgg tca ctt cct ccc ata gaa att cgg ctg att     6787 
Glu Lys Glu Ser Ala Trp Ser Leu Pro Pro Ile Glu Ile Arg Leu Ile 
2215               2220                2225                2230 

tcc ccc ttg gct agc cca gct gac gga gtc aag agc aaa cca aga aaa     6835 
Ser Pro Leu Ala Ser Pro Ala Asp Gly Val Lys Ser Lys Pro Arg Lys 
               2235                2240                2245 

act aca gaa gtg aca gga aca ggt ctt gga agg aac aga aag aaa ctg     6883 
Thr Thr Glu Val Thr Gly Thr Gly Leu Gly Arg Asn Arg Lys Lys Leu 
           2250                2255                2260 

tct tcc tat cca aag caa att tta cgc aga aaa atg ctg taatttcttg      6932 
Ser Ser Tyr Pro Lys Gln Ile Leu Arg Arg Lys Met Leu 
       2265                2270                2275 

ggaagatttt aatgtacacc tatttgtaaa gtcatcagaa tagtgtggat tattaaatat   6992 

ctagtttgga agaaaataat ttatataaat tattgtaaat ttttatgtaa acagaaggtc   7052 

ttcaataagt aaagtaactc catatggagt gattgtttca gtccaggcaa tttttctatt   7112 

ttatattaag acttcataca tttatatatg taaatatggc ttattaatgg aatgttaaat   7172 

aaaatgtata cttctcaaaa aaaaaaaaaa aaaaaaaaaa aaa                     7215