Abstract:
A mouse CDNA encoding a protein comprising a serine/threonine protein kinase region was isolated by effecting PCR using a synthetic DNA corresponding to the kinase-conserved region as a primer and a rat cDNA as a template. A mouse cDNA library was screened using the DNA fragment thus obtained as a probe. The multiple human and mouse cDNAs having the similar structure to the isolated mouse cDNA were successfully isolated based on the sequence of the isolated mouse cDNA. An antisense DNA against the isolated mouse cDNA was synthesized, and its effect on a nerve cell was studied to confirm that the antisense DNA inhibits axonal elongation.

Description:
This application is a continuation-in-part of PCT/JP98/01246, filed Mar. 23, 1998, and claims priority from Japanese Application No. 9/124798, filed Apr. 28, 1997. 
    
    
     TECHNICAL FIELD 
     The present invention relates to a useful serine/threonine protein kinase, a DNA encoding the protein kinase, a vector comprising the DNA, a host harboring the vector, and an antibody that binds to the protein kinase. 
     BACKGROUND ART 
     Protein kinase is an enzyme that phosphorylates serine, threonine, or tyrosine residues of substrate proteins, and numerous protein kinase families are known. It is known that protein kinase controls various biological phenomena by regulating the intracellular signal transduction system through protein phosphorylation (Hunter, T., A thousand and one protein kinases, Cell, 50:823-829, 1987). 
     One of a group of nematode ( C. elegans ) mutants (uncoordinated), “unc-51,” causes movement disorder and a responsible gene “UNC-51 ” found in unc-51 reportedly encodes a novel serine/threonine protein kinase (Ogura, K. et al.,  Caenorhabditis elegans  unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase, Genes Dev., 8:2389-2400, 1994). The result of tissue staining confirmed that the unc-51 mutant has axonal elongation disorder, and the UNC-51 kinase gene was thought to be essential for axonal elongation (Ogura, K. et al.,  Caenorhabditis elegans  unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase, Genes Dev., 8:2389-2400, 1994). 
     The mechanism of axonal biosynthesis in mammals has not been revealed yet at the molecular level.  C. elegans  is an excellent experimental model for axonal biosynthesis, and the involvement of similar molecules in both mammals and  C. elegans  has been suggested. The isolation of mammalian molecule having the similar function as the UNC-51 kinase of the nematode has been desired. 
     DISCLOSURE OF THE INVENTION 
     An objective of the present invention is to provide a mammalian serine/threonine protein kinase involved in axonal formation. 
     As a result of research to achieve the above objective, the inventors successfully isolated a mouse cDNA encoding a protein comprising a serine/threonine protein kinase region by effecting PCR using a synthetic DNA corresponding to the kinase-conserved region as a primer and a rat cDNA as a template, and screening a mouse cDNA library using the DNA fragment thus obtained as a probe. The multiple human and mouse cDNAs having the similar structure to the isolated mouse cDNA were successfully isolated based on the sequence of the isolated mouse cDNA. The inventors synthesized an antisense DNA against the isolated mouse cDNA, and its effect on a nerve cell was studied to confirm that the antisense DNA inhibits axonal elongation. 
     The present invention relates to a mammalian serine/threonine protein kinase involved in axonal formation. More specifically, the invention relates to: 
     (1) a protein comprising the amino acid sequence set forth in SEQ ID NO: 2, 4, 14, 16, or 21, or a protein comprising the amino acid sequence set forth in SEQ ID NO: 2, 4, 14, 16, or 21, in which one or more amino acids are substituted, deleted, or added, wherein said protein has activity of serine/threonine protein kinase; 
     (2) a protein encoded by a DNA hybridizing with a DNA comprising the nucleotide sequence set forth in SEQ ID NO: 1, 3, 13, 15, or 20, wherein said protein has the activity of serine/threonine protein kinase; 
     (3) a protein comprising the amino acid sequence set forth in SEQ ID NO: 2, 4, 14, 16, or 21, or a protein comprising the amino acid sequence set forth in SEQ ID NO: 2, 4, 14, 16, or 21, in which one or more amino acids are substituted, deleted, or added, wherein said protein induces axonal elongation; 
     (4) a protein encoded by a DNA hybridizing with a DNA comprising the nucleotide sequence set forth in SEQ ID NO: 1, 3, 13, 15, or 20, wherein said protein induces axonal elongation; 
     (5) the protein of (2) or (4), wherein said protein is derived from a mammal; 
     (6) a DNA encoding any one of the proteins of (1) to (5); 
     (7) an antisense DNA against a DNA comprising the nucleotide sequence set forth in SEQ ID NO: 1, 3, 13, 15, or 20 or a part thereof, wherein said DNA or a part thereof-inhibits axonal elongation; 
     (8) a vector comprising the DNA of (6) or (7); 
     (9) a host cell harboring the vector of (8); and 
     (10) an antibody that binds to the protein of (1) or (2). 
     A “protein” used herein includes a peptide with a short amino acid sequence. 
     The present invention relates to a mammal-derived serine/threonine protein kinase involved in axonal formation. The inventors isolated a mouse cDNA highly homologous to the kinase region of UNC-51, a serine/threonine kinase that induces axonal elongation in a nematode,  C. elegans  (Ogura, K. et al.,  Caenorhabditis elegans  unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase, Genes Dev., 8:2389-2400, 1994) (this clone was named “MUK1”). The nucleotide sequence of the MUK1 cDNA is shown in SEQ ID NO: 1. The inventors also isolated four cDNAs comprising the similar structure to the MUK1 cDNA by screening a human cerebellum library, a mouse cerebellum library, a human NH-2 cell library, and a mouse brain library, based on the sequence of MUK1. The isolated four cDNAs were considered to be a human counterpart (SEQ ID NO: 3), a splicing valiant (SEQ ID NO: 13), a human homologue (SEQ ID NO: 15), and a family gene (SEQ ID NO: 20) (named “MUK2”) of MUK1 considering their structural characteristics. The analysis of structures of the proteins encoded by these isolated cDNAs confirmed that all the proteins possess the kinase-conserved region. This fact indicates that those proteins would be involved in signal transduction through phosphorylation of other proteins. When an antisense DNA against the MUK1 cDNA (SEQ ID NO: 8) was added to Neuro2A cells derived from neuroblast cells, axonal elongation in the cells was inhibited. Those proteins may thus be involved in axonal elongation by signal transduction through phosphorylation of other proteins. 
     Among these proteins, the protein (SEQ ID NO: 4) encoded by cDNA set forth in SEQ ID NO: 3 is a partial sequence comprising the sequence corresponding to the serine/threonine protein kinase region. A protein encoded by the full-length DNA can be obtained by methods well known in the art. For example, the full-length DNA is isolated by screening a library with a partial sequence of the DNA of SEQ ID NO: 3 as probe or by PCR (Current protocols in Molecular Biology ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 6.1-6.4), the isolated full-length DNA is introduced into cultured cells such as COS cells to express the protein in the cells (Current Protocols in Molecular Biology, ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 9.1-9.9), then the protein is purified. The thus-isolated protein is also included in the protein of this invention. 
     Functional equivalents to the protein set forth in SEQ ID NO: 2, 4, 14, 16, or 21 can be obtained by substituting amino acid residue(s) of these proteins using usually used methods such as site-directed mutagenesis (Current Protocols in Molecular Biology, ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 8.1-8.5). This invention also includes proteins functionally equivalent to the protein of SEQ ID NO: 2, 4, 14, 16, or 21, in which one or more amino acids are substituted, deleted, or added. Alternatively, functionally equivalent proteins to the protein of SEQ ID NO: 2, 4, 14, 16, or 21 can be obtained by isolating DNAs highly homologous to DNA sequences (or a part thereof) of SEQ ID NO: 1, 3, 13, 15, and 20, using the known hybridization technique (Current Protocols in Molecular Biology, ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Sections 6.3, 6.4). The protein of the present invention includes such proteins functionally equivalent to the proteins of SEQ ID NO: 2, 4, 14, 16, and 21, encoded by a DNA hybridizing with the DNA of SEQ ID NO: 1, 3, 13, 15, or 20. The functionally equivalent proteins obtained by the hybridization technique are highly homologous in the amino acid sequence to the protein of SEQ ID NO: 2, 4, 14, 16, or 21 in general. High homology is preferably 60% or more, more preferably 80% or more, and most preferably 95% or more. The hybridization and washing conditions for isolating DNA encoding a functionally equivalent protein are defined as low stringency: 37° C., 1×SSC, 0.1% SDS; moderate stringency: 42° C., 0.5×SSC, 0.1% SDS; and high stringency: 65° C., 0.2×SSC, 0.1% SDS. The “DNA hybridizing with” used herein include not only full-length DNAs hybridizing with the DNA of SEQ ID NO: 1, 3, 13, 15, or 20, but also DNAs comprising a region hybridizing with the above DNA. A “functionally equivalent protein” means a protein that having the serine/threonine protein kinase activity similar to that of the protein of SEQ ID NO: 2, 4, 14, 16, or 21, and/or induces axonal elongation. “Serine/threonine protein kinase activity” means biochemical activity to phosphorylate substrate proteins and cellular biological activity induced by this biochemical activity. The biochemical activity of the serine/threonine protein kinase can be detected as autophosphorylation—and phosphorylation of basic proteins (such as a myelin basic protein, histone, or tau protein) in the presence of magnesium ions and ATP (Protein Kinase and Phosphatase, D. G. Hardie, translated by H. Hidaka, Medical Science International, p101-120). On the other hand, the biological activity can be detected as the cellular change when a DNA encoding serine/threonine protein kinase or its variant is expressed in cells (Muramatsu, M. et al., Protein Kinase and Signal Transduction: Studies with mutant protein kinases (1993) p185-192, The mechanism and new approach on drug resistance of cancer cells, The Elsevier Science Publishers). The “axonal elongation-inducing activity” can be detected by, for example, by introducing a DNA encoding the protein of the invention into cultured nerve cells such as Nero2A cells, PC12 cells, and NT-2 cells (Stratagene) and observing the cells under a phase-contrast microscope (Ulloa, et al., Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells, EMBO. J., 12:1633-1640, 1993). 
     The protein of the present invention can be prepared as a recombinant protein or a natural protein. A recombinant protein can be prepared, for example, by inserting a DNA encoding the protein of the invention (e.g., the DNA of SEQ ID NO: 1, 3, 13, 15, or 20) into an appropriate expression vector, introducing the vector into a host cell, expressing the protein in the transformant, and purifying the protein, as described later. A natural protein can be prepared by the standard methods, for example, using an affinity column with an antibody (Current Protocols in Molecular Biology ed. by Ausubel et al. (1987) published by John and Wiley &amp; Sons, Section 16.1-16.19). The antibody can be either a monoclonal antibody or a polyclonal antibody. A polyclonal antibody can be obtained by synthesizing oligopeptides corresponding to the amino acid sequence of interest and immunizing a rabbit with it, following the standard method (Current Protocols in Molecular Biology ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 11.12-11.13). A monoclonal antibody can be prepared by immunizing a mouse with a purified protein of interest expressed in  E. coli  by a standard method, fusing a spleen cell and a myeloma cell to produce hybridoma cells, and then obtaining a monoclonal antibody from the hybridoma (Current Protocols in Molecular Biology ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 11.4-11.11). When an antibody that binds to the protein of the invention is used for antibody therapy, a human antibody or a humanized antibody that has low immunogenicity is preferably used. A human antibody can be prepared, for example, by immunizing a mouse whose immune system is replaced by the human system in the same manner as described above for producing the monoclonal antibody. A humanized antibody can be prepared by the recombinant DNA technology using hypervariable region of the monoclonal antibody (Methods in Enzymology, 203:99-121, 1991). 
     This invention also relates to the DNA encoding the above-described protein of the invention. The form of the DNA of the invention is not particularly limited as long as it encodes the protein of the invention, including cDNA, genomic DNA, chemically synthesized DNA, etc. The DNA of the present invention can be isolated by the standard method, such as the hybridization method using the DNA sequence of SEQ ID NO: 1, 3, 13, 15, or 20 as a probe, or PCR using the primers synthesized based on these DNA sequences. The DNA of the invention can be used to prepare recombinant proteins. That is, the protein of the invention can be prepared as a recombinant protein by inserting the DNA of this invention in an appropriate vector, introducing the vector into a host cell, and culturing the transformant. Any vector capable of stably maintaining the inserted DNA can be used without limitation. For example, Bluescript vector (Stratagene) is preferable when a host cell is  E. coli . When a vector is used to produce the protein of the invention, an expression vector is especially useful. Any expression vector can be used without limitation as long as it expresses the protein of this invention in vitro, in  E. coli , in a cultured cell line, or in vivo. For example, pBEST vector (Promega) is preferably used for expression in vitro, and pET vector (Invitrogen) for  E. coli , pME18S vector (Mol Cell Biol. 8:466-472, 1988) for cultured cell lines and in vivo. The DNA of the invention can be inserted into a vector by the methods well known in the art, for example, ligation at the restriction enzyme site (Current Protocols in Molecular Biology ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 11. 4-11.11). A vector can be introduced into any host cell without limitation. For example, a cell capable of overexpressing the protein, such as COS cells and CHO cells, can be used. A vector can be introduced into a host cell by the method well known in the art, such as calcium phosphate precipitation, electroporation (Current Protocols in Molecular Biology ed. by Ausubel et al. (1987) published by John Wiley &amp; Sons, Section 9.1-9.9), the lipofectamine method (GIBCO-BRL), or microinjection. 
     The DNA and its antisense DNA of the present invention can be used for promoting or inhibiting axonal elongation. Therefore, those DNAs are useful for diagnosis and gene therapy of various inherited neuropathy, senile dementia, Alzheimer&#39;s disease, and psychoneurosis, which cause axonal elongation disorder. For gene therapy, the above DNA or antisense DNA is inserted into a retrovirus vector or an adenovirus vector- and administered to a patient by the in vivo or ex vivo method. The antisense DNA can be prepared, for example, by the phosphorothioate method (Stein, 1988 Physicochemical properties of phosphorothioate oligodeoxynucleotides, Nucleic Acids Res. 16:3209-3221, 1988) based on the DNA sequence information of the invention (for example, the DNA of SEQ ID NO: 1, 3, 13, 15, or 20). The axonal elongation-inhibitory activity of the thus-prepared antisense DNA can be detected by observing cultured nerve cells such as Nero2A cells, PC12 cells, and NT-2 cells (Stratagene), into which the antisense DNA was introduced, under a phase-contrast microscope (Ulloa et al., Depletion of casein kinase II by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells, EMBO. J., 12:1633-1640, 1993). 
     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 separate 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 mixtures of different (i) DNA molecules, (ii) transfected cells, or (iii) cell clones: e.g., as these occur in a DNA library such as a cDNA or genomic DNA library. 
     The term “substantially pure” as used herein in reference to a given polypeptide means that the polypeptide is substantially free from other biological compounds, such as those in cellular material, viral material, or culture medium, with which the polypeptide was associated (e.g., in the course of production by recombinant DNA techniques or before purification from a natural biological source). The substantially pure polypeptide is at least 75% (e.g., at least 80, 85, 95, or 99%) pure by dry weight. Purity can be measured by any appropriate standard method, for example, by column chromatography, polyacrylamide gel electrophoresis, or HPLC analysis. 
     A “conservative amino acid substitution” is one in which an amino acid residue is replaced with another residue having a chemically similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). 
     As used herein, “percent identity” of two amino acid sequences or of two nucleic acids 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 to obtain nucleotide sequences homologous to a nucleic acid molecules of the invention. BLAST protein searches are performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to a reference polypeptide. To obtain gapped alignments for comparison purposes, Gapped BLAST is utilized as described in Altschul et al. (Nucleic Acids Res. 25:3389-3402, 1997). When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) are used. See http://www.ncbi.nlm.nih.gov. 
     By “inhibiting” is meant any measurable level of inhibition, including, for example, 100% or 10% inhibition. 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present application, including definitions, will control. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference. The materials, methods, and examples are illustrative only and not intended to be limiting. Other features and advantages of the invention will be apparent from the detailed description, and from the claims. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a fluorescent film image showing the MUK1 protein detected by immunoblotting. Lane  1  detects the control using the protein extracted from COS cells without the MUK1 protein expression vector, “pME-MUK1.” Lane  2  detects the protein extracted from COS cells carrying pME-MUK1. 
     FIGS. 2A and 2B are micrographs detecting effects of MUK1 on axonal elongation. FIG. 2A is the control without MUK1. FIG. 2B shows the effect of the MUK1 antisense DNA. FIG. 2C shows the effect of the MUK1 sense DNA. 
     FIG. 3 compares the amino acid sequence of MUK1 and that of MUK2. The amino acid positions from 1 to 550 are shown. 
     FIG. 4 compares the amino acid sequence of MUK1 and that of MUK2. The amino acid positions from 551 to 1100 are shown. 
    
    
     DETAILED DESCRIPTION 
     The present invention is illustrated in detail below with reference to examples, but is not to be construed as being limited thereto. 
     EXAMPLE 1 
     Screening a Mouse Serine/threonine Protein Kinase Gene 
     In order to obtain a novel serine/threonine protein kinase, PCR was conducted using synthetic DNA comprising the codons corresponding to the kinase-conserved region VIb (Ile-Ser-His-Arg-Glu-Leu-Gln) (SEQ ID NO: 5) and the kinase-conserved region VIII (Arg-Tyr-Met-Ala-Pro-Glu) (SEQ ID NO: 6) as the primers, and the single-stranded cDNA prepared by oligo-dT primers from rat fetal brain mRNA as a template. The fragment of 114 bp (SEQ ID NO: 9) was obtained. Subsequently, a mouse cerebellum library (Clontech) was screened using the fragment obtained above, and cDNA of 2673 bp (SEQ ID NO: 1) was isolated. The amino acid sequence deduced from the obtained cDNA showed 60% homology to the kinase region of serine/threonine kinase UNC-51 of a nematode,  C. elegans  (Ogura, K. et al.,  Caenorhabditis elegans  unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase, Genes Dev., 8:2389-2400, 1994). Homology in regions except the kinase region is low in general. However, four highly homologous regions comprising motif-like continuous 7 to 10 amino acids were found. 
     UNC-51 is a serine/threonine protein kinase identified in a nematode “ C. elegans ,” mutant suffering from movement disorders. The mutant has axonal elongation disorder, which was confirmed by tissue staining (Hedgecock, E. M. et al., Axonal guidance of mutants of  C. elegans  identified by filling sensory neurons with fluorescein dyes, Dev. Biol. 111:158-170, 1985). Mutation was identified on the coding region of UNC-51 in multiple unc-51 mutants examined, and UNC-51 in which mutation was introduced into the ATP binding site of the kinase region causes dominant negative mutation.—Therefore, the function of UNC-51 as a protein kinase is considered to be essential for axonal formation (Ogura, K et al.,  Caenorhabditis elegans  unc-51 gene required for axonal elongation encodes a novel serine/threonine kinase, Genes Dev., 8:2389-2400, 1994). The inventors named the obtained clone “Mammalian homologue of Unc-51 Kinase-1” (abbreviated as MUK1). 
     EXAMPLE 2 
     Screening Human MUK1 cDNA 
     MUK1 cDNA (SEQ ID NO: 1) was labeled with  32 P using “Megaprime kit” (Amersham) to serve as a probe—for screening a human cerebellum cDNA (Clontech). 10 6  clones from the library were transferred onto a nylon membrane (Amersham) and fixed by UV. The  32 P-labeled probe was hybridized with the clones on the membrane in QuikHyb solution (Stratagene) overnight. The membrane was washed twice in 2×SSC and 0.1% SDS at room temperature for 20 min once in 0.2×SSC and 0.1% SDS at 65° C. for 10 min to detect positive clones using Kodak XO-mat (primary screening). The positive clones were subjected to the secondary and tertiary screenings using the same method as above. Consequently, a human cDNA hybridizing with the probe was obtained (SEQ ID NO: 3). The amino acid sequence deduced from the obtained human cDNA (SEQ ID NO: 4) showed 90% or more homology to MUK1. 
     EXAMPLE 3 
     Preparing an Antibody Against the MUK1 Protein and Determining the Molecular Weight of the MUK1 Protein 
     The MUK1 cDNA of SEQ ID NO: 1 was inserted into the EcoRI site of pME18S expression vector (Mol. Cell Biol. 8:466-472, 1988) to prepare plasmid pME-MUK1. PME-MUK1 was introduced into COS cells using lipofectamine (BRL) to—temporarily express the cDNA. After 48 hours, the cells were lysed in a buffer solution (Tris-HCl (pH 7.5), 50 mM KCl, 5 mM EDTA) containing 0.2% Triton X-100. The solubilized protein was subjected to—SDS-PAGE (10% polyacrylamide) and transferred onto PVDF membrane (Immobilon) for immunoblotting. Polyclonal antibodies obtained by immunizing a rabbit with a peptide (SEQ ID NO: 10) corresponding to a part of the amino acid sequence derived from the MUK1 translation region were used as the primary antibody. Anti-rabbit Ig antibody (Amersham) was used as the secondary antibody. ECL kit (Amersham) was used for the detection. The band of the protein was obtained at about the molecular weight of 80 kD (FIG.  1 ). 
     EXAMPLE 4 
     Analyzing the MUK1 Function in Nerve Cells 
     In order to determine whether MUK1 elongates axon or not, the antisense DNA (SEQ ID NO: 11) was synthesized based on the nucleotide sequence of SEQ ID NO: 1 by the phosphorothioate (S-oligo) method. Similarly, the sense DNA (SEQ ID NO: 12) was synthesized. 
     Neuro2A cells derived from neuroblastoma cells were transferred into ITS medium containing DMEM medium (Nikken Biology Medicine Laboratory), 5 mg/ml insulin, 5 mg/ml transferrin, and 5 ng/ml selenic acid to confirm that axon elongated. The antisense DNA (SEQ ID NO: 11) was then added to the ITS medium to determine whether axonal elongation of Neuro2A cells was inhibited or not. The addition of 10 μM antisense DNA (SEQ ID NO: 11) significantly inhibited axonal elongation (FIG.  2 B), compared to the control (FIG.  2 A). In contrast, axonal elongation was not inhibited when the same concentration of the sense DNA (SEQ ID NO: 12) was added (FIG.  2 C). 
     EXAMPLE 5 
     Screening a Mouse Cerebellum Library Using the MUK1 cDNA as a Probe 
     The MUK1 cDNA (SEQ ID NO: 1) was labeled with  32 P by Megaprime kit (Amersham) to screen a mouse cerebellum library (Clontech). 10 6  clones from the library were transferred onto a nylon membrane (Amersham) and fixed by UV. The  32 P-labeled probe was hybridized with the clones on the membrane in QuikHyb solution (Stratagene) overnight. The membrane was washed twice in 2×SSC and 0.1% SDS at room temperature for 20 min and once in 0.2×SSC and 0.1% SDS at 65° C. for 10 min to detect positive clones using Kodak XO-mat (primary screening). The positive clones were subjected to the secondary and tertiary screenings using the same method as above. Consequently, a 3995 bp DNA fragment (SEQ ID NO: 13) was cloned. The amino acid sequence (SEQ ID NO: 14) deduced from ORF of SEQ ID NO: 13 has 575 N-terminal amino acids that are the same as the MUK1 protein (SEQ ID NO: 2), but the different carboxyl-terminal amino acids. This DNA fragment was thus considered to encode the splicing variant of MUK1. 
     EXAMPLE 6 
     Screening a Human NT-2 Cell Library Using the MUK1 cDNA as a Probe 
     The MUK1 cDNA (SEQ ID NO: 1) was labeled with  32 P using Megaprime Kit (Amersham) to screen a human NT-2 cell library. 10 6  clones from the library were transferred onto a nylon membrane (Amersham) and fixed by UV. The 32P-labeled probe was hybridized with the clones on the membrane in QuikHyb solution (Stratagene) overnight. The membrane was washed twice in 2×SSC and 0.1% SDS at room temperature for 20 min and once in 0.2×SSC and 0.1% SDS at 65° C. for 10 min to detect positive clones using Kodak XO-mat (primary screening). The positive clones were subjected to the secondary and tertiary screenings using the same method as above. Consequently, a 5228 bp DNA fragment (SEQ ID NO: 15) was cloned. The amino acid sequence (SEQ ID NO: 16) deduced from ORF of this DNA fragment is 91% identical to the splicing variant of MUK1 (SEQ ID NO: 14). 
     EXAMPLE 7 
     Searching GenBank based on the deduced amino acid sequence of the MUK1 protein (SEQ ID NO: 2) found similar expressed sequence tag (EST) (GenBank Accession No. W29537). A DNA was synthesized based on this information (SEQ ID NO: 17 and SEQ ID NO: 18), and PCR was performed using the synthetic DNA and using a mouse brain cDNA library (GIBCO-BRL) as a template to obtain a 445 bp DNA fragment (SEQ ID NO: 19). This DNA fragment was  32 P labeled with Megaprime kit (Amersham) and used to screen a mouse brain library (GIBCO-BRL). 10 6  clones from the library were transferred onto a nylon membrane (Amersham) and fixed by UV. The  32 P-labeled probe was hybridized with the clones on the membrane in QuikHyb solution (Stratagene) overnight. The membrane was washed twice in 2×SSC and 0.1% SDS at room temperature for 20 min and once in 0.2×SSC and 0.1% SDS at 65° C. for 10 min once to detect positive clones using Kodak XO-mat (primary screening). The positive clones were subjected to the secondary and tertiary screenings using the same method as above. Consequently, a 3455 bp DNA fragment (SEQ ID NO: 20) was successfully cloned. This clone was named MUK2. 
     The amino acid sequence (SEQ ID NO: 21) deduced from ORF of this DNA fragment is 82% identical to the kinase region of the MUK1 protein, and 44% to its control region, indicating that this clone is a family gene (FIGS.  3  and  4 ). 
     INDUSTRIAL APPLICABILITY 
     The present invention provides a serine/threonine protein kinase that is industrially highly useful. The serine/threonine protein kinase of this invention is involved in axonal elongation of mammals. Therefore, the serine/threonine protein kinase or its gene of the invention is useful for diagnosis and treatment of various inherited neuropathy, senile dementia, Alzheimer&#39;s disease, and psychoneurosis, which cause axonal elongation disorder. Low molecular weight molecules controlling kinase activity and biological activity of the serine/threonine protein kinase of the invention can be screened by assaying these activities 
     
       
         
               
             
           
               
                   
               
               
                                                SEQUENCE LISTING 
               
               
                   
               
               
                   
               
               
                 &lt;160&gt; NUMBER OF SEQ ID NOS:  21 
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 1 
               
               
                 &lt;211&gt; LENGTH: 2673 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;221&gt; NAME/KEY: CDS 
               
               
                 &lt;222&gt; LOCATION: (1)...(1746) 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 1 
               
               
                   
               
               
                 atg gag ccg ggc cgc ggc ggc gtc gag acc gtg ggc aag ttc gag ttc       48 
               
               
                 Met Glu Pro Gly Arg Gly Gly Val Glu Thr Val Gly Lys Phe Glu Phe 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 tct cgc aag gac ctg att gga cac ggc gcc ttc gcg gtg gtc ttc aag       96 
               
               
                 Ser Arg Lys Asp Leu Ile Gly His Gly Ala Phe Ala Val Val Phe Lys 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 ggt cga cac cgc gag aag cac gac ctg gag gtg gcc gtc aaa tgc att      144 
               
               
                 Gly Arg His Arg Glu Lys His Asp Leu Glu Val Ala Val Lys Cys Ile 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 aac aag aag aac ctt gcc aag tcc caa aca ctg ctg gga aag gaa atc      192 
               
               
                 Asn Lys Lys Asn Leu Ala Lys Ser Gln Thr Leu Leu Gly Lys Glu Ile 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 aaa atc ctg aag gaa cta aag cac gaa aac atc gtg gcg ctg tat gac      240 
               
               
                 Lys Ile Leu Lys Glu Leu Lys His Glu Asn Ile Val Ala Leu Tyr Asp 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 ttc cag gaa atg gct aat tct gtc tac ctg gtc atg gag tat tgt aat      288 
               
               
                 Phe Gln Glu Met Ala Asn Ser Val Tyr Leu Val Met Glu Tyr Cys Asn 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 ggt gga gac ctg gct gac tac ctg cac act atg cgc aca ctg agt gaa      336 
               
               
                 Gly Gly Asp Leu Ala Asp Tyr Leu His Thr Met Arg Thr Leu Ser Glu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 gac act gtc agg ctt ttc cta cag cag atc gct ggc gcc atg cgg ctg      384 
               
               
                 Asp Thr Val Arg Leu Phe Leu Gln Gln Ile Ala Gly Ala Met Arg Leu 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 ctg cac agc aag ggc atc atc cac cgg gac ctg aag ccc cag aac atc      432 
               
               
                 Leu His Ser Lys Gly Ile Ile His Arg Asp Leu Lys Pro Gln Asn Ile 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 ctg ctg tcc aac cct ggg ggc cgc cgg gcc aac ccc agc aac atc cga      480 
               
               
                 Leu Leu Ser Asn Pro Gly Gly Arg Arg Ala Asn Pro Ser Asn Ile Arg 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 gtc aag att gct gac ttt gga ttc gct cgg tac ctc cag agc aac atg      528 
               
               
                 Val Lys Ile Ala Asp Phe Gly Phe Ala Arg Tyr Leu Gln Ser Asn Met 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 atg gcg gcc aca ctc tgt ggt tct cct atg tac atg gct cct gag gtc      576 
               
               
                 Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met Ala Pro Glu Val 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 att atg tcc cag cac tac gat gga aag gct gac ctg tgg agc att ggc      624 
               
               
                 Ile Met Ser Gln His Tyr Asp Gly Lys Ala Asp Leu Trp Ser Ile Gly 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 acc att gtc tac cag tgt ctg aca ggg aag gcc cct ttt cag gcc agc      672 
               
               
                 Thr Ile Val Tyr Gln Cys Leu Thr Gly Lys Ala Pro Phe Gln Ala Ser 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 agc cct cag gat ttg cgc ctg ttt tat gag aag aac aag aca cta gtt      720 
               
               
                 Ser Pro Gln Asp Leu Arg Leu Phe Tyr Glu Lys Asn Lys Thr Leu Val 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 cct gcc atc ccc cgg gag aca tca gct ccc ctg cgg cag ctg ctc ctg      768 
               
               
                 Pro Ala Ile Pro Arg Glu Thr Ser Ala Pro Leu Arg Gln Leu Leu Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 gct ctg ttg cag cgg aac cac aag gac cgc atg gac ttt gat gaa ttt      816 
               
               
                 Ala Leu Leu Gln Arg Asn His Lys Asp Arg Met Asp Phe Asp Glu Phe 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 ttc cac cac cct ttc ttg gat gcc agc acc ccc atc aag aaa tcc cca      864 
               
               
                 Phe His His Pro Phe Leu Asp Ala Ser Thr Pro Ile Lys Lys Ser Pro 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 cct gtg cct gtg ccc tca tat cca agc tca ggg tct ggc agc agc tcc      912 
               
               
                 Pro Val Pro Val Pro Ser Tyr Pro Ser Ser Gly Ser Gly Ser Ser Ser 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 agc agc agc tct gcc tcc cac ctg gcc tct cca ccg tcc ctg ggg gag      960 
               
               
                 Ser Ser Ser Ser Ala Ser His Leu Ala Ser Pro Pro Ser Leu Gly Glu 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 atg cca cag cta cag aag acc ctt acc tcc cca gcc gat gct gct ggc     1008 
               
               
                 Met Pro Gln Leu Gln Lys Thr Leu Thr Ser Pro Ala Asp Ala Ala Gly 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 ttt ctt cag ggc tcc cgg gac tct ggt ggc agc agc aaa gac tcc tgt     1056 
               
               
                 Phe Leu Gln Gly Ser Arg Asp Ser Gly Gly Ser Ser Lys Asp Ser Cys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 gac aca gat gac ttt gtc atg gtc cca gcc cag ttt cca ggt gat cta     1104 
               
               
                 Asp Thr Asp Asp Phe Val Met Val Pro Ala Gln Phe Pro Gly Asp Leu 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 gtt gct gag gca gcc agt gcc aag ccc cca cct gat agc ctg ctg tgt     1152 
               
               
                 Val Ala Glu Ala Ala Ser Ala Lys Pro Pro Pro Asp Ser Leu Leu Cys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 agt ggg agc tca ttg gtg gcc tct gct ggc cta gag agc cac ggc cgt     1200 
               
               
                 Ser Gly Ser Ser Leu Val Ala Ser Ala Gly Leu Glu Ser His Gly Arg 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 acc ccc tct ccc tct ccg acc tgc agc agc tct ccc agc ccc tct ggc     1248 
               
               
                 Thr Pro Ser Pro Ser Pro Thr Cys Ser Ser Ser Pro Ser Pro Ser Gly 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 cgg cct ggc ccc ttc tcc agc aac agg tac ggt gcc tcg gtc ccc att     1296 
               
               
                 Arg Pro Gly Pro Phe Ser Ser Asn Arg Tyr Gly Ala Ser Val Pro Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 cct gtc ccc act cag gtg cac aat tac cag cgc atc gag caa aac ctg     1344 
               
               
                 Pro Val Pro Thr Gln Val His Asn Tyr Gln Arg Ile Glu Gln Asn Leu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 caa tcg ccc act caa cag cag aca gcc cgg tcc tct gcc atc cga agg     1392 
               
               
                 Gln Ser Pro Thr Gln Gln Gln Thr Ala Arg Ser Ser Ala Ile Arg Arg 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 tca ggg agc acc agc ccc ctg ggc ttt ggc cgg gcc agc cca tca ccc     1440 
               
               
                 Ser Gly Ser Thr Ser Pro Leu Gly Phe Gly Arg Ala Ser Pro Ser Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 ccc tcc cac acc gat ggg gcc atg ctg gcc agg aag ctg tca ctt gga     1488 
               
               
                 Pro Ser His Thr Asp Gly Ala Met Leu Ala Arg Lys Leu Ser Leu Gly 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 ggt ggc cgt ccc tac aca cct tct ccc caa gtg gga acc atc cca gag     1536 
               
               
                 Gly Gly Arg Pro Tyr Thr Pro Ser Pro Gln Val Gly Thr Ile Pro Glu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 cga ccc agc tgg agc aga gtg ccc tcc cca caa gga gct gat gtg cgg     1584 
               
               
                 Arg Pro Ser Trp Ser Arg Val Pro Ser Pro Gln Gly Ala Asp Val Arg 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 gtt ggc agg tca cca cga ccc ggt tcc tct gtg cct gag cac tct cca     1632 
               
               
                 Val Gly Arg Ser Pro Arg Pro Gly Ser Ser Val Pro Glu His Ser Pro 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 aga acc act ggg ctg ggc tgc cgc ctg cac agt gcc cct aac ctg tcc     1680 
               
               
                 Arg Thr Thr Gly Leu Gly Cys Arg Leu His Ser Ala Pro Asn Leu Ser 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 gac ttc cat gtt gtg cgt ccc aag ctg cct aag ccc cca aca gac ccc     1728 
               
               
                 Asp Phe His Val Val Arg Pro Lys Leu Pro Lys Pro Pro Thr Asp Pro 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 cgt act aac aaa aat ggc taataacgaa atggctaatg catggtcaat            1776 
               
               
                 Arg Thr Asn Lys Asn Gly 
               
               
                             580 
               
               
                   
               
               
                 ccccggcccc cgttttttcg cattccaagc cgcattgaag ataatgaagc ctatcatcgc   1836 
               
               
                   
               
               
                 cagcgttagc cacaaattgt tgactcggaa aatatacttt agcaagtaac ccacgataaa   1896 
               
               
                   
               
               
                 tagttgtaca acagcccgca cgacaccaat gacgatgtcc ctatctaagc caagtttctg   1956 
               
               
                   
               
               
                 ccacaaacta attcctaacg cgacgagcac taacattgcc gccaaaaata gtgacgtatt   2016 
               
               
                   
               
               
                 attaactgct aaattcatgc gtgtacctcc aatctgccag caaccacttt cgctaactga   2076 
               
               
                   
               
               
                 tctgccgcag caatctctgt cgcgtcatga gtaatcatga tcgttgtcac gtgatcctgc   2136 
               
               
                   
               
               
                 tcatttaact gtcgtaacca ggcgtgcacg atttgcttat tattttcatc caaaccagct   2196 
               
               
                   
               
               
                 gtcacctcat ctaataacaa cacttttggt aagaataaga tgttgcgaag cagcgcgacc   2256 
               
               
                   
               
               
                 cgctgccgtt caccaccgga aagctcgata atcggctgat gcagggttcg ttcggacagc   2316 
               
               
                   
               
               
                 ccaacattat ttaacgccgt taccactcgt tgcgtatcca tgacttgctt acgaatttgg   2376 
               
               
                   
               
               
                 tacgggaaag ctaagttatc tgctaccgtc tcaccaaata acgtcggttg ttggaaacaa   2436 
               
               
                   
               
               
                 tatgagactt gccgccgata catgattggg tcataacttt caatcggctg cccatcaaaa   2496 
               
               
                   
               
               
                 atcaaggtcc cacttgtttt agaaatcatg gccgcaatga tccgtaataa cgtacttttc   2556 
               
               
                   
               
               
                 ccaccaccgg atggtcccgt caatgtaata tgagccccag ctggaatctg ccaatcaaca   2616 
               
               
                   
               
               
                 tcatgtaaaa tatgttgatc agcgatttga taattaactt tttctaaact aatcaat      2673 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 2 
               
               
                 &lt;211&gt; LENGTH: 582 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 2 
               
               
                   
               
               
                 Met Glu Pro Gly Arg Gly Gly Val Glu Thr Val Gly Lys Phe Glu Phe 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Ser Arg Lys Asp Leu Ile Gly His Gly Ala Phe Ala Val Val Phe Lys 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Gly Arg His Arg Glu Lys His Asp Leu Glu Val Ala Val Lys Cys Ile 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Asn Lys Lys Asn Leu Ala Lys Ser Gln Thr Leu Leu Gly Lys Glu Ile 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Lys Ile Leu Lys Glu Leu Lys His Glu Asn Ile Val Ala Leu Tyr Asp 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Phe Gln Glu Met Ala Asn Ser Val Tyr Leu Val Met Glu Tyr Cys Asn 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gly Gly Asp Leu Ala Asp Tyr Leu His Thr Met Arg Thr Leu Ser Glu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Asp Thr Val Arg Leu Phe Leu Gln Gln Ile Ala Gly Ala Met Arg Leu 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Leu His Ser Lys Gly Ile Ile His Arg Asp Leu Lys Pro Gln Asn Ile 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Leu Leu Ser Asn Pro Gly Gly Arg Arg Ala Asn Pro Ser Asn Ile Arg 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Val Lys Ile Ala Asp Phe Gly Phe Ala Arg Tyr Leu Gln Ser Asn Met 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met Ala Pro Glu Val 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Met Ser Gln His Tyr Asp Gly Lys Ala Asp Leu Trp Ser Ile Gly 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Thr Ile Val Tyr Gln Cys Leu Thr Gly Lys Ala Pro Phe Gln Ala Ser 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ser Pro Gln Asp Leu Arg Leu Phe Tyr Glu Lys Asn Lys Thr Leu Val 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Pro Ala Ile Pro Arg Glu Thr Ser Ala Pro Leu Arg Gln Leu Leu Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Leu Leu Gln Arg Asn His Lys Asp Arg Met Asp Phe Asp Glu Phe 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Phe His His Pro Phe Leu Asp Ala Ser Thr Pro Ile Lys Lys Ser Pro 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Pro Val Pro Val Pro Ser Tyr Pro Ser Ser Gly Ser Gly Ser Ser Ser 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Ser Ser Ser Ser Ala Ser His Leu Ala Ser Pro Pro Ser Leu Gly Glu 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Met Pro Gln Leu Gln Lys Thr Leu Thr Ser Pro Ala Asp Ala Ala Gly 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Phe Leu Gln Gly Ser Arg Asp Ser Gly Gly Ser Ser Lys Asp Ser Cys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Asp Thr Asp Asp Phe Val Met Val Pro Ala Gln Phe Pro Gly Asp Leu 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Ala Glu Ala Ala Ser Ala Lys Pro Pro Pro Asp Ser Leu Leu Cys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Ser Gly Ser Ser Leu Val Ala Ser Ala Gly Leu Glu Ser His Gly Arg 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Thr Pro Ser Pro Ser Pro Thr Cys Ser Ser Ser Pro Ser Pro Ser Gly 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Arg Pro Gly Pro Phe Ser Ser Asn Arg Tyr Gly Ala Ser Val Pro Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Pro Val Pro Thr Gln Val His Asn Tyr Gln Arg Ile Glu Gln Asn Leu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Gln Ser Pro Thr Gln Gln Gln Thr Ala Arg Ser Ser Ala Ile Arg Arg 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Ser Gly Ser Thr Ser Pro Leu Gly Phe Gly Arg Ala Ser Pro Ser Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Pro Ser His Thr Asp Gly Ala Met Leu Ala Arg Lys Leu Ser Leu Gly 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Gly Gly Arg Pro Tyr Thr Pro Ser Pro Gln Val Gly Thr Ile Pro Glu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Arg Pro Ser Trp Ser Arg Val Pro Ser Pro Gln Gly Ala Asp Val Arg 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Val Gly Arg Ser Pro Arg Pro Gly Ser Ser Val Pro Glu His Ser Pro 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 Arg Thr Thr Gly Leu Gly Cys Arg Leu His Ser Ala Pro Asn Leu Ser 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 Asp Phe His Val Val Arg Pro Lys Leu Pro Lys Pro Pro Thr Asp Pro 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 Arg Thr Asn Lys Asn Gly 
               
               
                             580 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 3 
               
               
                 &lt;211&gt; LENGTH: 423 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Homo sapiens 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;221&gt; NAME/KEY: CDS 
               
               
                 &lt;222&gt; LOCATION: (1)...(423) 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 3 
               
               
                   
               
               
                 gac aac atc ctg ctg tcc aac ccc gcc ggc cgc cgc gcc aac ccc aac       48 
               
               
                 Asp Asn Ile Leu Leu Ser Asn Pro Ala Gly Arg Arg Ala Asn Pro Asn 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 agc atc cgc gtc aag atc gct gac ttc ggc ttc cgg cgg tac ctc cag       96 
               
               
                 Ser Ile Arg Val Lys Ile Ala Asp Phe Gly Phe Arg Arg Tyr Leu Gln 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 agc aac atg atg gcg gcc aca ctc tgc ggc tcc ccc atg tac atg gcc      144 
               
               
                 Ser Asn Met Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met Ala 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 ccc gag gtc atc atg tcc cag cac tac gac ggg aag gcg gac ctg tgg      192 
               
               
                 Pro Glu Val Ile Met Ser Gln His Tyr Asp Gly Lys Ala Asp Leu Trp 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 agc atc ggc acc atc gta tac cag tgc ctg acg ggg aag gcg ccc ttt      240 
               
               
                 Ser Ile Gly Thr Ile Val Tyr Gln Cys Leu Thr Gly Lys Ala Pro Phe 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 cag gcc agc agc cca gac ctg cgc ctg ttt tac gag aag aac aag acg      288 
               
               
                 Gln Ala Ser Ser Pro Asp Leu Arg Leu Phe Tyr Glu Lys Asn Lys Thr 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 ttg gtc ccc acc atc ccc cgg gag acc tcg gcc ccg ctg cgg cag ctg      336 
               
               
                 Leu Val Pro Thr Ile Pro Arg Glu Thr Ser Ala Pro Leu Arg Gln Leu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 ctc ctg gcc cta ctg caa cgc aac cac aag gac cgc atg gac ttc gat      384 
               
               
                 Leu Leu Ala Leu Leu Gln Arg Asn His Lys Asp Arg Met Asp Phe Asp 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 gag ttt ttt cat cac cct ttc ctc gat gcc agc ccc tcg                  423 
               
               
                 Glu Phe Phe His His Pro Phe Leu Asp Ala Ser Pro Ser 
               
               
                     130                 135                 140 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 4 
               
               
                 &lt;211&gt; LENGTH: 141 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Homo sapiens 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 4 
               
               
                   
               
               
                 Asp Asn Ile Leu Leu Ser Asn Pro Ala Gly Arg Arg Ala Asn Pro Asn 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Ser Ile Arg Val Lys Ile Ala Asp Phe Gly Phe Arg Arg Tyr Leu Gln 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Ser Asn Met Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met Ala 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Pro Glu Val Ile Met Ser Gln His Tyr Asp Gly Lys Ala Asp Leu Trp 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Ser Ile Gly Thr Ile Val Tyr Gln Cys Leu Thr Gly Lys Ala Pro Phe 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Gln Ala Ser Ser Pro Asp Leu Arg Leu Phe Tyr Glu Lys Asn Lys Thr 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Leu Val Pro Thr Ile Pro Arg Glu Thr Ser Ala Pro Leu Arg Gln Leu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Leu Leu Ala Leu Leu Gln Arg Asn His Lys Asp Arg Met Asp Phe Asp 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Glu Phe Phe His His Pro Phe Leu Asp Ala Ser Pro Ser 
               
               
                     130                 135                 140 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 5 
               
               
                 &lt;211&gt; LENGTH: 7 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Kinase-conserved region VIb 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 5 
               
               
                   
               
               
                 Ile Ser His Arg Glu Leu Gln 
               
               
                   1               5 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 6 
               
               
                 &lt;211&gt; LENGTH: 6 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Kinase-conserved region VIII 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 6 
               
               
                   
               
               
                 Arg Tyr Met Ala Pro Glu 
               
               
                   1               5 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 7 
               
               
                 &lt;211&gt; LENGTH: 20 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated primer 
               
               
                 &lt;221&gt; NAME/KEY: misc_feature 
               
               
                 &lt;222&gt; LOCATION: (1)...(20) 
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 7 
               
               
                   
               
               
                 athtcncayc gngayttraa                                                 20 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 8 
               
               
                 &lt;211&gt; LENGTH: 17 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated DNA 
               
               
                 &lt;221&gt; NAME/KEY: misc_feature 
               
               
                 &lt;222&gt; LOCATION: (1)...(17) 
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 8 
               
               
                   
               
               
                 ctnggngcca trtayct                                                    17 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 9 
               
               
                 &lt;211&gt; LENGTH: 114 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Rattus norvegicus 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 9 
               
               
                   
               
               
                 gccatgtacc tattacatct tctaatgtgt caccctgatt atataaattt aactagacac     60 
               
               
                   
               
               
                 taccttccaa agtttgtatc agtgctcata tttgaattca agtcccggtg cgag          114 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 10 
               
               
                 &lt;211&gt; LENGTH: 16 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated protein 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 10 
               
               
                   
               
               
                 Cys Ala Arg Ser Ser Ala Ile Arg Arg Ser Gly Ser Thr Ser Pro Leu 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 11 
               
               
                 &lt;211&gt; LENGTH: 21 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated DNA 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 11 
               
               
                   
               
               
                 gaacttgccc acggtctcga c                                               21 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 12 
               
               
                 &lt;211&gt; LENGTH: 21 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated DNA 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 12 
               
               
                   
               
               
                 gtcgagaccg tgggcaagtt c                                               21 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 13 
               
               
                 &lt;211&gt; LENGTH: 3995 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;221&gt; NAME/KEY: CDS 
               
               
                 &lt;222&gt; LOCATION: (388)...(3540) 
               
               
                 &lt;221&gt; NAME/KEY: misc_feature 
               
               
                 &lt;222&gt; LOCATION: (1)...(3995) 
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 13 
               
               
                   
               
               
                 gtccgcctcn acgcagtgct gcgccggcac ctcgggctcc gaggcccggg tgccgcggat     60 
               
               
                   
               
               
                 cttttgtttc tgcggggctc cgagccgcat cgtcagtcag gcccggactt ggagctggag    120 
               
               
                   
               
               
                 tgtgtcagag ctgagtcccg agtcgaccgg tcccgactgt cagcgccgga gggtaccgag    180 
               
               
                   
               
               
                 nagnacgccg agggagcgcg cccctcngtc cgccggcctg tgggactggg acccggctca    240 
               
               
                   
               
               
                 ggcctgcccg atggggcacg gggccctggc gatgagcccg cgcctccgtc cccgtacgcg    300 
               
               
                   
               
               
                 gcccggccgg cctccgcctg agcccagcgc accccgtagc gccgccccgg ggcccgagcc    360 
               
               
                   
               
               
                 cgctcgcgcc cccggcccgc gcgcgct atg gag ccg ggc cgc ggc ggc gtc gag    414 
               
               
                                               Met Glu Pro Gly Arg Gly Gly Val Glu 
               
               
                                                 1               5 
               
               
                   
               
               
                 acc gtg ggc aag ttc gag ttc tct cgc aag gac ctg att gga cac ggc      462 
               
               
                 Thr Val Gly Lys Phe Glu Phe Ser Arg Lys Asp Leu Ile Gly His Gly 
               
               
                  10                  15                  20                  25 
               
               
                   
               
               
                 gcc ttc gcg gtg gtc ttc aag ggt cga cac cgc gag aag cac gac ctg      510 
               
               
                 Ala Phe Ala Val Val Phe Lys Gly Arg His Arg Glu Lys His Asp Leu 
               
               
                                  30                  35                  40 
               
               
                   
               
               
                 gag gtg gcc gtc aaa tgc att aac aag aag aac ctt gcc aag tcc caa      558 
               
               
                 Glu Val Ala Val Lys Cys Ile Asn Lys Lys Asn Leu Ala Lys Ser Gln 
               
               
                              45                  50                  55 
               
               
                   
               
               
                 aca ctg ctg gga aag gaa atc aaa atc ctg aag gaa cta aag cac gaa      606 
               
               
                 Thr Leu Leu Gly Lys Glu Ile Lys Ile Leu Lys Glu Leu Lys His Glu 
               
               
                          60                  65                  70 
               
               
                   
               
               
                 aac atc gtg gcg ctg tat gac ttc cag gaa atg gct aat tct gtc tac      654 
               
               
                 Asn Ile Val Ala Leu Tyr Asp Phe Gln Glu Met Ala Asn Ser Val Tyr 
               
               
                      75                  80                  85 
               
               
                   
               
               
                 ctg gtc atg gag tat tgt aat ggt gga gac ctg gct gac tac ctg cac      702 
               
               
                 Leu Val Met Glu Tyr Cys Asn Gly Gly Asp Leu Ala Asp Tyr Leu His 
               
               
                  90                  95                 100                 105 
               
               
                   
               
               
                 act atg cgc aca ctg agt gaa gac act gtc agg ctt ttc cta cag cag      750 
               
               
                 Thr Met Arg Thr Leu Ser Glu Asp Thr Val Arg Leu Phe Leu Gln Gln 
               
               
                                 110                 115                 120 
               
               
                   
               
               
                 atc gct ggc gcc atg cgg ctg ctg cac agc aag ggc atc atc cac cgg      798 
               
               
                 Ile Ala Gly Ala Met Arg Leu Leu His Ser Lys Gly Ile Ile His Arg 
               
               
                             125                 130                 135 
               
               
                   
               
               
                 gac ctg aag ccc cag aac atc ctg ctg tcc aat cct ggg ggc cgc cgg      846 
               
               
                 Asp Leu Lys Pro Gln Asn Ile Leu Leu Ser Asn Pro Gly Gly Arg Arg 
               
               
                         140                 145                 150 
               
               
                   
               
               
                 gcc aac ccc agc aac atc cga gtc aag att gct gac ttt gga ttc gct      894 
               
               
                 Ala Asn Pro Ser Asn Ile Arg Val Lys Ile Ala Asp Phe Gly Phe Ala 
               
               
                     155                 160                 165 
               
               
                   
               
               
                 cgg tac ctc cag agc aac atg atg gcg gcc aca ctc tgt ggt tct cct      942 
               
               
                 Arg Tyr Leu Gln Ser Asn Met Met Ala Ala Thr Leu Cys Gly Ser Pro 
               
               
                 170                 175                 180                 185 
               
               
                   
               
               
                 atg tac atg gct cct gag gtc att atg tcc cag cac tac gat gga aag      990 
               
               
                 Met Tyr Met Ala Pro Glu Val Ile Met Ser Gln His Tyr Asp Gly Lys 
               
               
                                 190                 195                 200 
               
               
                   
               
               
                 gct gac ctg tgg agc att ggc acc att gtc tac cag tgt ctg aca ggg     1038 
               
               
                 Ala Asp Leu Trp Ser Ile Gly Thr Ile Val Tyr Gln Cys Leu Thr Gly 
               
               
                             205                 210                 215 
               
               
                   
               
               
                 aag gcc cct ttt cag gcc agc agc cct cag gat ttg cgc ctg ttt tat     1086 
               
               
                 Lys Ala Pro Phe Gln Ala Ser Ser Pro Gln Asp Leu Arg Leu Phe Tyr 
               
               
                         220                 225                 230 
               
               
                   
               
               
                 gag aag aac aag aca cta gtt cct gcc atc ccc cgg gag aca tca gct     1134 
               
               
                 Glu Lys Asn Lys Thr Leu Val Pro Ala Ile Pro Arg Glu Thr Ser Ala 
               
               
                     235                 240                 245 
               
               
                   
               
               
                 ccc ctg cgg cag ctg ctc ctg gct ctg ttg cag cgg aac cac aag gac     1182 
               
               
                 Pro Leu Arg Gln Leu Leu Leu Ala Leu Leu Gln Arg Asn His Lys Asp 
               
               
                 250                 255                 260                 265 
               
               
                   
               
               
                 cgc atg gac ttt gat gaa ttt ttc cac cac cct ttc ttg gat gcc agc     1230 
               
               
                 Arg Met Asp Phe Asp Glu Phe Phe His His Pro Phe Leu Asp Ala Ser 
               
               
                                 270                 275                 280 
               
               
                   
               
               
                 acc ccc atc aag aaa tcc cca cct gtg cct gtg ccc tca tat cca agc     1278 
               
               
                 Thr Pro Ile Lys Lys Ser Pro Pro Val Pro Val Pro Ser Tyr Pro Ser 
               
               
                             285                 290                 295 
               
               
                   
               
               
                 tca ggg tct ggc agc agc tcc agc agc agc tct gcc tcc cac ctg gcc     1326 
               
               
                 Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Ala Ser His Leu Ala 
               
               
                         300                 305                 310 
               
               
                   
               
               
                 tct cca ccg tcc ctg ggg gag atg cca cag cta cag aag acc ctt acc     1374 
               
               
                 Ser Pro Pro Ser Leu Gly Glu Met Pro Gln Leu Gln Lys Thr Leu Thr 
               
               
                     315                 320                 325 
               
               
                   
               
               
                 tcc cca gcc gat gct gct ggc ttt ctt cag ggc tcc cgg gac tct ggt     1422 
               
               
                 Ser Pro Ala Asp Ala Ala Gly Phe Leu Gln Gly Ser Arg Asp Ser Gly 
               
               
                 330                 335                 340                 345 
               
               
                   
               
               
                 ggc agc agc aaa gac tcc tgt gac aca gat gac ttt gtc atg gtc cca     1470 
               
               
                 Gly Ser Ser Lys Asp Ser Cys Asp Thr Asp Asp Phe Val Met Val Pro 
               
               
                                 350                 355                 360 
               
               
                   
               
               
                 gcc cag ttt cca ggt gat cta gtt gct gag gca gcc agt gcc aag ccc     1518 
               
               
                 Ala Gln Phe Pro Gly Asp Leu Val Ala Glu Ala Ala Ser Ala Lys Pro 
               
               
                             365                 370                 375 
               
               
                   
               
               
                 cca cct gat agc ctg ctg tgt agt ggg agc tca ttg gtg gcc tct gct     1566 
               
               
                 Pro Pro Asp Ser Leu Leu Cys Ser Gly Ser Ser Leu Val Ala Ser Ala 
               
               
                         380                 385                 390 
               
               
                   
               
               
                 ggc cta gag agc cac ggc cgt acc ccc tct ccc tct ccg acc tgc agc     1614 
               
               
                 Gly Leu Glu Ser His Gly Arg Thr Pro Ser Pro Ser Pro Thr Cys Ser 
               
               
                     395                 400                 405 
               
               
                   
               
               
                 agc tct ccc agc ccc tct ggc cgg cct ggc ccc ttc tcc agc aac agg     1662 
               
               
                 Ser Ser Pro Ser Pro Ser Gly Arg Pro Gly Pro Phe Ser Ser Asn Arg 
               
               
                 410                 415                 420                 425 
               
               
                   
               
               
                 tac ggt gcc tcg gtc ccc att cct gtc ccc act cag gtg cac aat tac     1710 
               
               
                 Tyr Gly Ala Ser Val Pro Ile Pro Val Pro Thr Gln Val His Asn Tyr 
               
               
                                 430                 435                 440 
               
               
                   
               
               
                 cag cgc atc gag caa aac ctg caa tcg ccc act caa cag cag aca gcc     1758 
               
               
                 Gln Arg Ile Glu Gln Asn Leu Gln Ser Pro Thr Gln Gln Gln Thr Ala 
               
               
                             445                 450                 455 
               
               
                   
               
               
                 cgg tcc tct gcc atc cga agg tca ggg agc acc acc ccc ctg ggc ttt     1806 
               
               
                 Arg Ser Ser Ala Ile Arg Arg Ser Gly Ser Thr Thr Pro Leu Gly Phe 
               
               
                         460                 465                 470 
               
               
                   
               
               
                 ggc cgg gcc agc cca tca ccc ccc tcc cac acc gat ggg gcc atg ctg     1854 
               
               
                 Gly Arg Ala Ser Pro Ser Pro Pro Ser His Thr Asp Gly Ala Met Leu 
               
               
                     475                 480                 485 
               
               
                   
               
               
                 gcc agg aag ctg tca ctt gga ggt ggc cgt ccc tac aca cct tct ccc     1902 
               
               
                 Ala Arg Lys Leu Ser Leu Gly Gly Gly Arg Pro Tyr Thr Pro Ser Pro 
               
               
                 490                 495                 500                 505 
               
               
                   
               
               
                 caa gtg gga acc atc cca gag cga ccc agc tgg agc aga gtg ccc tcc     1950 
               
               
                 Gln Val Gly Thr Ile Pro Glu Arg Pro Ser Trp Ser Arg Val Pro Ser 
               
               
                                 510                 515                 520 
               
               
                   
               
               
                 cca caa gga gct gat gtg cgg gtt ggc agg tca cca cga ccc ggt tcc     1998 
               
               
                 Pro Gln Gly Ala Asp Val Arg Val Gly Arg Ser Pro Arg Pro Gly Ser 
               
               
                             525                 530                 535 
               
               
                   
               
               
                 tct gtg cct gag cac tct cca aga acc act ggg ctg ggc tgc cgc ctg     2046 
               
               
                 Ser Val Pro Glu His Ser Pro Arg Thr Thr Gly Leu Gly Cys Arg Leu 
               
               
                         540                 545                 550 
               
               
                   
               
               
                 cac agt gcc cct aac ctg tcc gac ttc cat gtt gtg cgt ccc aag ctg     2094 
               
               
                 His Ser Ala Pro Asn Leu Ser Asp Phe His Val Val Arg Pro Lys Leu 
               
               
                     555                 560                 565 
               
               
                   
               
               
                 cct aag ccc cca aca gac cca ctg gga gcc acc ttt agc cca ccc cag     2142 
               
               
                 Pro Lys Pro Pro Thr Asp Pro Leu Gly Ala Thr Phe Ser Pro Pro Gln 
               
               
                 570                 575                 580                 585 
               
               
                   
               
               
                 acc agc gca ccc cag cca tgc cca ggg cta cag tct tgc cgg cca ctg     2190 
               
               
                 Thr Ser Ala Pro Gln Pro Cys Pro Gly Leu Gln Ser Cys Arg Pro Leu 
               
               
                                 590                 595                 600 
               
               
                   
               
               
                 cgt ggc tca cct aag ctg cct gac ttc cta cag cgg agt ccc cta ccc     2238 
               
               
                 Arg Gly Ser Pro Lys Leu Pro Asp Phe Leu Gln Arg Ser Pro Leu Pro 
               
               
                             605                 610                 615 
               
               
                   
               
               
                 ccc atc cta ggc tct cct acc aag gcc ggg ccc tcc ttt gac ttc ccc     2286 
               
               
                 Pro Ile Leu Gly Ser Pro Thr Lys Ala Gly Pro Ser Phe Asp Phe Pro 
               
               
                         620                 625                 630 
               
               
                   
               
               
                 aaa acc ccc agc tct cag aat ttg ctg acc ctg ttg gct agg cag ggg     2334 
               
               
                 Lys Thr Pro Ser Ser Gln Asn Leu Leu Thr Leu Leu Ala Arg Gln Gly 
               
               
                     635                 640                 645 
               
               
                   
               
               
                 gta gta atg aca cca cct cgg aac cgt aca ctg cct gac ctc tcc gag     2382 
               
               
                 Val Val Met Thr Pro Pro Arg Asn Arg Thr Leu Pro Asp Leu Ser Glu 
               
               
                 650                 655                 660                 665 
               
               
                   
               
               
                 gcc agt cct ttc cat ggc cag cag ctg ggc tct ggc ctt cgg ccc gct     2430 
               
               
                 Ala Ser Pro Phe His Gly Gln Gln Leu Gly Ser Gly Leu Arg Pro Ala 
               
               
                                 670                 675                 680 
               
               
                   
               
               
                 gaa gac acc cgg ggt ccc ttt gga cgg tcc ttc agc acc agc cgc att     2478 
               
               
                 Glu Asp Thr Arg Gly Pro Phe Gly Arg Ser Phe Ser Thr Ser Arg Ile 
               
               
                             685                 690                 695 
               
               
                   
               
               
                 acg gac ctg ctg ctt aag gct gca ttt ggg act cag gcc tct gac tca     2526 
               
               
                 Thr Asp Leu Leu Leu Lys Ala Ala Phe Gly Thr Gln Ala Ser Asp Ser 
               
               
                         700                 705                 710 
               
               
                   
               
               
                 ggc agc aca gac agc cta cag gag aaa cct atg gag att gct ccc tct     2574 
               
               
                 Gly Ser Thr Asp Ser Leu Gln Glu Lys Pro Met Glu Ile Ala Pro Ser 
               
               
                     715                 720                 725 
               
               
                   
               
               
                 gct ggc ttt gga ggg act ctg cat cca gga gct cgt ggt gga ggg gcc     2622 
               
               
                 Ala Gly Phe Gly Gly Thr Leu His Pro Gly Ala Arg Gly Gly Gly Ala 
               
               
                 730                 735                 740                 745 
               
               
                   
               
               
                 agc agc cca gca cct gtg gta ttt act gta ggc tcc cca ccc agt ggt     2670 
               
               
                 Ser Ser Pro Ala Pro Val Val Phe Thr Val Gly Ser Pro Pro Ser Gly 
               
               
                                 750                 755                 760 
               
               
                   
               
               
                 gcc acc cca ccc cag agt acc cgt acc aga atg ttc tca gtg ggc tct     2718 
               
               
                 Ala Thr Pro Pro Gln Ser Thr Arg Thr Arg Met Phe Ser Val Gly Ser 
               
               
                             765                 770                 775 
               
               
                   
               
               
                 tcc agc tcc ctg ggc tct act ggc tcc tcc tct gcc cgc cac tta gtg     2766 
               
               
                 Ser Ser Ser Leu Gly Ser Thr Gly Ser Ser Ser Ala Arg His Leu Val 
               
               
                         780                 785                 790 
               
               
                   
               
               
                 cct ggg gcc tgt gga gag gcc ccg gag ctt tct gcc cca ggc cac tgc     2814 
               
               
                 Pro Gly Ala Cys Gly Glu Ala Pro Glu Leu Ser Ala Pro Gly His Cys 
               
               
                     795                 800                 805 
               
               
                   
               
               
                 tgt agc ctt gct gac ccc ctt gct gcc aac ttg gag ggg gct gtg acc     2862 
               
               
                 Cys Ser Leu Ala Asp Pro Leu Ala Ala Asn Leu Glu Gly Ala Val Thr 
               
               
                 810                 815                 820                 825 
               
               
                   
               
               
                 ttc gag gct cct gac ctc cca gag gag acc ctc atg gag caa gag cac     2910 
               
               
                 Phe Glu Ala Pro Asp Leu Pro Glu Glu Thr Leu Met Glu Gln Glu His 
               
               
                                 830                 835                 840 
               
               
                   
               
               
                 acg gaa acc cta cac agt ctg cgc ttc aca cta gcg ttt gca cag caa     2958 
               
               
                 Thr Glu Thr Leu His Ser Leu Arg Phe Thr Leu Ala Phe Ala Gln Gln 
               
               
                             845                 850                 855 
               
               
                   
               
               
                 gtt ctg gag att gca gcc ctg aag gga agt gcc agt gag gcc gcc ggt     3006 
               
               
                 Val Leu Glu Ile Ala Ala Leu Lys Gly Ser Ala Ser Glu Ala Ala Gly 
               
               
                         860                 865                 870 
               
               
                   
               
               
                 ggc cct gag tac cag ctc cag gaa agt gtg gtg gct gac cag atc agt     3054 
               
               
                 Gly Pro Glu Tyr Gln Leu Gln Glu Ser Val Val Ala Asp Gln Ile Ser 
               
               
                     875                 880                 885 
               
               
                   
               
               
                 cag ttg agc cga gag tgg ggc ttt gca gag caa ctg gtt ctg tac ttg     3102 
               
               
                 Gln Leu Ser Arg Glu Trp Gly Phe Ala Glu Gln Leu Val Leu Tyr Leu 
               
               
                 890                 895                 900                 905 
               
               
                   
               
               
                 aag gtg gct gag ctg ctg tcc tca ggc cta cag act gcc att gac cag     3150 
               
               
                 Lys Val Ala Glu Leu Leu Ser Ser Gly Leu Gln Thr Ala Ile Asp Gln 
               
               
                                 910                 915                 920 
               
               
                   
               
               
                 att cga gct ggc aaa ctc tgc ctt tca tct act gtg aag cag gtg gta     3198 
               
               
                 Ile Arg Ala Gly Lys Leu Cys Leu Ser Ser Thr Val Lys Gln Val Val 
               
               
                             925                 930                 935 
               
               
                   
               
               
                 cgc aga cta aat gag ctg tac aag gcc agc gtg gta tcc tgc cag ggc     3246 
               
               
                 Arg Arg Leu Asn Glu Leu Tyr Lys Ala Ser Val Val Ser Cys Gln Gly 
               
               
                         940                 945                 950 
               
               
                   
               
               
                 ctc agc ttg cga ctt cag cgc ttc ttt ctg gac aaa caa cgg ctg ctg     3294 
               
               
                 Leu Ser Leu Arg Leu Gln Arg Phe Phe Leu Asp Lys Gln Arg Leu Leu 
               
               
                     955                 960                 965 
               
               
                   
               
               
                 gac ggg atc cat ggt gtc act gca gag cgg ctc atc ctc agc cat gct     3342 
               
               
                 Asp Gly Ile His Gly Val Thr Ala Glu Arg Leu Ile Leu Ser His Ala 
               
               
                 970                 975                 980                 985 
               
               
                   
               
               
                 gtg caa atg gta caa tca gct gcc ctt gat gag atg ttc cag cac cga     3390 
               
               
                 Val Gln Met Val Gln Ser Ala Ala Leu Asp Glu Met Phe Gln His Arg 
               
               
                                  990                 995                1000 
               
               
                   
               
               
                 gag ggc tgt gta ccg aga tat cac aaa gcc ctg cta ttg ctg gag ggg     3438 
               
               
                 Glu Gly Cys Val Pro Arg Tyr His Lys Ala Leu Leu Leu Leu Glu Gly 
               
               
                             1005                1010                1015 
               
               
                   
               
               
                 ttg cag cac act ctc acg gac cag gca gac att gag aac att gcc aaa     3486 
               
               
                 Leu Gln His Thr Leu Thr Asp Gln Ala Asp Ile Glu Asn Ile Ala Lys 
               
               
                         1020                1025                1030 
               
               
                   
               
               
                 tgc aag ctg tgc att gag agg aga ctc tcg gcc ctg ctg agt ggt gtc     3534 
               
               
                 Cys Lys Leu Cys Ile Glu Arg Arg Leu Ser Ala Leu Leu Ser Gly Val 
               
               
                     1035                1040                1045 
               
               
                   
               
               
                 tat gcc tgactacctg ctgccaacct gcagggtagg gtctgagacc tggcagactg      3590 
               
               
                 Tyr Ala 
               
               
                 1050 
               
               
                   
               
               
                 tcctcaacac tgatcagatc cgatggtgct gagactgctg ccagccaact ccagcaggga   3650 
               
               
                   
               
               
                 tgctccacag tggacctgtg cagactggtg caactcttgc ttcctagact gccagtctct   3710 
               
               
                   
               
               
                 gctggcaggt agacatcaga gtgccagggg tcccttgccc actgggacag gagtttctga   3770 
               
               
                   
               
               
                 acatattctt cctagctggc tccctggcaa gcaggtatgg tgccgagaag tggcacctgc   3830 
               
               
                   
               
               
                 cacctgaaga gcccatggca gccctgtgtc aggcaagggc ctgagaccgt tgctgactcc   3890 
               
               
                   
               
               
                 aagccaaagc aagcttttcc tcacagttca cttgccccat tgcttgtcca agaaaaaagg   3950 
               
               
                   
               
               
                 gtatggtctt ctggccccct gttctctcta ggaactccgg aattc                   3995 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 14 
               
               
                 &lt;211&gt; LENGTH: 1051 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 14 
               
               
                   
               
               
                 Met Glu Pro Gly Arg Gly Gly Val Glu Thr Val Gly Lys Phe Glu Phe 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Ser Arg Lys Asp Leu Ile Gly His Gly Ala Phe Ala Val Val Phe Lys 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Gly Arg His Arg Glu Lys His Asp Leu Glu Val Ala Val Lys Cys Ile 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Asn Lys Lys Asn Leu Ala Lys Ser Gln Thr Leu Leu Gly Lys Glu Ile 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Lys Ile Leu Lys Glu Leu Lys His Glu Asn Ile Val Ala Leu Tyr Asp 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Phe Gln Glu Met Ala Asn Ser Val Tyr Leu Val Met Glu Tyr Cys Asn 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gly Gly Asp Leu Ala Asp Tyr Leu His Thr Met Arg Thr Leu Ser Glu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Asp Thr Val Arg Leu Phe Leu Gln Gln Ile Ala Gly Ala Met Arg Leu 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Leu His Ser Lys Gly Ile Ile His Arg Asp Leu Lys Pro Gln Asn Ile 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Leu Leu Ser Asn Pro Gly Gly Arg Arg Ala Asn Pro Ser Asn Ile Arg 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Val Lys Ile Ala Asp Phe Gly Phe Ala Arg Tyr Leu Gln Ser Asn Met 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met Ala Pro Glu Val 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Met Ser Gln His Tyr Asp Gly Lys Ala Asp Leu Trp Ser Ile Gly 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Thr Ile Val Tyr Gln Cys Leu Thr Gly Lys Ala Pro Phe Gln Ala Ser 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ser Pro Gln Asp Leu Arg Leu Phe Tyr Glu Lys Asn Lys Thr Leu Val 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Pro Ala Ile Pro Arg Glu Thr Ser Ala Pro Leu Arg Gln Leu Leu Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Leu Leu Gln Arg Asn His Lys Asp Arg Met Asp Phe Asp Glu Phe 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Phe His His Pro Phe Leu Asp Ala Ser Thr Pro Ile Lys Lys Ser Pro 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Pro Val Pro Val Pro Ser Tyr Pro Ser Ser Gly Ser Gly Ser Ser Ser 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Ser Ser Ser Ser Ala Ser His Leu Ala Ser Pro Pro Ser Leu Gly Glu 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Met Pro Gln Leu Gln Lys Thr Leu Thr Ser Pro Ala Asp Ala Ala Gly 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Phe Leu Gln Gly Ser Arg Asp Ser Gly Gly Ser Ser Lys Asp Ser Cys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Asp Thr Asp Asp Phe Val Met Val Pro Ala Gln Phe Pro Gly Asp Leu 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Ala Glu Ala Ala Ser Ala Lys Pro Pro Pro Asp Ser Leu Leu Cys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Ser Gly Ser Ser Leu Val Ala Ser Ala Gly Leu Glu Ser His Gly Arg 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Thr Pro Ser Pro Ser Pro Thr Cys Ser Ser Ser Pro Ser Pro Ser Gly 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Arg Pro Gly Pro Phe Ser Ser Asn Arg Tyr Gly Ala Ser Val Pro Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Pro Val Pro Thr Gln Val His Asn Tyr Gln Arg Ile Glu Gln Asn Leu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Gln Ser Pro Thr Gln Gln Gln Thr Ala Arg Ser Ser Ala Ile Arg Arg 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Ser Gly Ser Thr Thr Pro Leu Gly Phe Gly Arg Ala Ser Pro Ser Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Pro Ser His Thr Asp Gly Ala Met Leu Ala Arg Lys Leu Ser Leu Gly 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Gly Gly Arg Pro Tyr Thr Pro Ser Pro Gln Val Gly Thr Ile Pro Glu 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Arg Pro Ser Trp Ser Arg Val Pro Ser Pro Gln Gly Ala Asp Val Arg 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Val Gly Arg Ser Pro Arg Pro Gly Ser Ser Val Pro Glu His Ser Pro 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 Arg Thr Thr Gly Leu Gly Cys Arg Leu His Ser Ala Pro Asn Leu Ser 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 Asp Phe His Val Val Arg Pro Lys Leu Pro Lys Pro Pro Thr Asp Pro 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 Leu Gly Ala Thr Phe Ser Pro Pro Gln Thr Ser Ala Pro Gln Pro Cys 
               
               
                             580                 585                 590 
               
               
                   
               
               
                 Pro Gly Leu Gln Ser Cys Arg Pro Leu Arg Gly Ser Pro Lys Leu Pro 
               
               
                         595                 600                 605 
               
               
                   
               
               
                 Asp Phe Leu Gln Arg Ser Pro Leu Pro Pro Ile Leu Gly Ser Pro Thr 
               
               
                     610                 615                 620 
               
               
                   
               
               
                 Lys Ala Gly Pro Ser Phe Asp Phe Pro Lys Thr Pro Ser Ser Gln Asn 
               
               
                 625                 630                 635                 640 
               
               
                   
               
               
                 Leu Leu Thr Leu Leu Ala Arg Gln Gly Val Val Met Thr Pro Pro Arg 
               
               
                                 645                 650                 655 
               
               
                   
               
               
                 Asn Arg Thr Leu Pro Asp Leu Ser Glu Ala Ser Pro Phe His Gly Gln 
               
               
                             660                 665                 670 
               
               
                   
               
               
                 Gln Leu Gly Ser Gly Leu Arg Pro Ala Glu Asp Thr Arg Gly Pro Phe 
               
               
                         675                 680                 685 
               
               
                   
               
               
                 Gly Arg Ser Phe Ser Thr Ser Arg Ile Thr Asp Leu Leu Leu Lys Ala 
               
               
                     690                 695                 700 
               
               
                   
               
               
                 Ala Phe Gly Thr Gln Ala Ser Asp Ser Gly Ser Thr Asp Ser Leu Gln 
               
               
                 705                 710                 715                 720 
               
               
                   
               
               
                 Glu Lys Pro Met Glu Ile Ala Pro Ser Ala Gly Phe Gly Gly Thr Leu 
               
               
                                 725                 730                 735 
               
               
                   
               
               
                 His Pro Gly Ala Arg Gly Gly Gly Ala Ser Ser Pro Ala Pro Val Val 
               
               
                             740                 745                 750 
               
               
                   
               
               
                 Phe Thr Val Gly Ser Pro Pro Ser Gly Ala Thr Pro Pro Gln Ser Thr 
               
               
                         755                 760                 765 
               
               
                   
               
               
                 Arg Thr Arg Met Phe Ser Val Gly Ser Ser Ser Ser Leu Gly Ser Thr 
               
               
                     770                 775                 780 
               
               
                   
               
               
                 Gly Ser Ser Ser Ala Arg His Leu Val Pro Gly Ala Cys Gly Glu Ala 
               
               
                 785                 790                 795                 800 
               
               
                   
               
               
                 Pro Glu Leu Ser Ala Pro Gly His Cys Cys Ser Leu Ala Asp Pro Leu 
               
               
                                 805                 810                 815 
               
               
                   
               
               
                 Ala Ala Asn Leu Glu Gly Ala Val Thr Phe Glu Ala Pro Asp Leu Pro 
               
               
                             820                 825                 830 
               
               
                   
               
               
                 Glu Glu Thr Leu Met Glu Gln Glu His Thr Glu Thr Leu His Ser Leu 
               
               
                         835                 840                 845 
               
               
                   
               
               
                 Arg Phe Thr Leu Ala Phe Ala Gln Gln Val Leu Glu Ile Ala Ala Leu 
               
               
                     850                 855                 860 
               
               
                   
               
               
                 Lys Gly Ser Ala Ser Glu Ala Ala Gly Gly Pro Glu Tyr Gln Leu Gln 
               
               
                 865                 870                 875                 880 
               
               
                   
               
               
                 Glu Ser Val Val Ala Asp Gln Ile Ser Gln Leu Ser Arg Glu Trp Gly 
               
               
                                 885                 890                 895 
               
               
                   
               
               
                 Phe Ala Glu Gln Leu Val Leu Tyr Leu Lys Val Ala Glu Leu Leu Ser 
               
               
                             900                 905                 910 
               
               
                   
               
               
                 Ser Gly Leu Gln Thr Ala Ile Asp Gln Ile Arg Ala Gly Lys Leu Cys 
               
               
                         915                 920                 925 
               
               
                   
               
               
                 Leu Ser Ser Thr Val Lys Gln Val Val Arg Arg Leu Asn Glu Leu Tyr 
               
               
                     930                 935                 940 
               
               
                   
               
               
                 Lys Ala Ser Val Val Ser Cys Gln Gly Leu Ser Leu Arg Leu Gln Arg 
               
               
                 945                 950                 955                 960 
               
               
                   
               
               
                 Phe Phe Leu Asp Lys Gln Arg Leu Leu Asp Gly Ile His Gly Val Thr 
               
               
                                 965                 970                 975 
               
               
                   
               
               
                 Ala Glu Arg Leu Ile Leu Ser His Ala Val Gln Met Val Gln Ser Ala 
               
               
                             980                 985                 990 
               
               
                   
               
               
                 Ala Leu Asp Glu Met Phe Gln His Arg Glu Gly Cys Val Pro Arg Tyr 
               
               
                         995                 1000                1005 
               
               
                   
               
               
                 His Lys Ala Leu Leu Leu Leu Glu Gly Leu Gln His Thr Leu Thr Asp 
               
               
                     1010                1015                1020 
               
               
                   
               
               
                 Gln Ala Asp Ile Glu Asn Ile Ala Lys Cys Lys Leu Cys Ile Glu Arg 
               
               
                 1025                1030                1035                1040 
               
               
                   
               
               
                 Arg Leu Ser Ala Leu Leu Ser Gly Val Tyr Ala 
               
               
                                 1045                1050 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 15 
               
               
                 &lt;211&gt; LENGTH: 5228 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Homo sapiens 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;221&gt; NAME/KEY: CDS 
               
               
                 &lt;222&gt; LOCATION: (269)...(3418) 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 15 
               
               
                   
               
               
                 ggatccggat tcggattagc agcccgggaa gagtgccgtg gcacaggcgc cggagggagc     60 
               
               
                   
               
               
                 gcgaccctcg gaccccgcct ggcccgcggg gctgggaccc ggccccggcc tgcccgatgg    120 
               
               
                   
               
               
                 ggcgcgcggc cccggagatg cgccctcgcc cggccccgcg cccccggccc cgcgcccccg    180 
               
               
                   
               
               
                 gcccgcccgc cccggcccgc gcctccgcct gagtcccccg cgccttggcc cgccaccccc    240 
               
               
                   
               
               
                 cgccccgcgc ccccggcccg cctgcgcc atg gag ccc ggc cgc ggc ggc aca       292 
               
               
                                                Met Glu Pro Gly Arg Gly Gly Thr 
               
               
                                                  1               5 
               
               
                   
               
               
                 gag acc gtg ggc aag ttc gag ttc tcc cgc aag gac ctg atc ggc cac      340 
               
               
                 Glu Thr Val Gly Lys Phe Glu Phe Ser Arg Lys Asp Leu Ile Gly His 
               
               
                      10                  15                  20 
               
               
                   
               
               
                 ggc gcc ttc gcg gtg gtc ttc aag ggc cgc cac cgc gag aag cac gat      388 
               
               
                 Gly Ala Phe Ala Val Val Phe Lys Gly Arg His Arg Glu Lys His Asp 
               
               
                  25                  30                  35                  40 
               
               
                   
               
               
                 ttg gag gtc gcc gtc aag tgc att aac aag aag aac ctc gcc aag tct      436 
               
               
                 Leu Glu Val Ala Val Lys Cys Ile Asn Lys Lys Asn Leu Ala Lys Ser 
               
               
                                  45                  50                  55 
               
               
                   
               
               
                 cag acg ctg ctg ggg aag gaa atc aaa atc ctg aag gaa ctg aaa cat      484 
               
               
                 Gln Thr Leu Leu Gly Lys Glu Ile Lys Ile Leu Lys Glu Leu Lys His 
               
               
                              60                  65                  70 
               
               
                   
               
               
                 gaa aac atc gtg gcc ctg tac gac ttc cag gaa atg gct aat tct gtc      532 
               
               
                 Glu Asn Ile Val Ala Leu Tyr Asp Phe Gln Glu Met Ala Asn Ser Val 
               
               
                          75                  80                  85 
               
               
                   
               
               
                 tac ctg gtt atg gag tac tgc aac ggt ggg gac ctg gcc gac tac ctg      580 
               
               
                 Tyr Leu Val Met Glu Tyr Cys Asn Gly Gly Asp Leu Ala Asp Tyr Leu 
               
               
                      90                  95                 100 
               
               
                   
               
               
                 cac gcc atg cgc acg ctg agc gag gac acc atc agg ctc ttc ctg cag      628 
               
               
                 His Ala Met Arg Thr Leu Ser Glu Asp Thr Ile Arg Leu Phe Leu Gln 
               
               
                 105                 110                 115                 120 
               
               
                   
               
               
                 cag atc gcg ggc gcc atg cgg ctt ctg cac agc aaa ggc atc atc cac      676 
               
               
                 Gln Ile Ala Gly Ala Met Arg Leu Leu His Ser Lys Gly Ile Ile His 
               
               
                                 125                 130                 135 
               
               
                   
               
               
                 cgc gac ctg aaa ccg cag aac atc ctg ctg tcc aac ccc gcc ggc cgc      724 
               
               
                 Arg Asp Leu Lys Pro Gln Asn Ile Leu Leu Ser Asn Pro Ala Gly Arg 
               
               
                             140                 145                 150 
               
               
                   
               
               
                 cgc gcc aac ccc aac agc atc cgc gtc aag atc gct gac ttc ggc ttc      772 
               
               
                 Arg Ala Asn Pro Asn Ser Ile Arg Val Lys Ile Ala Asp Phe Gly Phe 
               
               
                         155                 160                 165 
               
               
                   
               
               
                 gcg cgg tac ctc cag agc aac atg atg gcg gcc aca ctc tgc ggc tcc      820 
               
               
                 Ala Arg Tyr Leu Gln Ser Asn Met Met Ala Ala Thr Leu Cys Gly Ser 
               
               
                     170                 175                 180 
               
               
                   
               
               
                 ccc atg tac atg gcc ccc gag gtc atc atg tcc cag cac tac gac ggg      868 
               
               
                 Pro Met Tyr Met Ala Pro Glu Val Ile Met Ser Gln His Tyr Asp Gly 
               
               
                 185                 190                 195                 200 
               
               
                   
               
               
                 aag gcg gac ctg tgg agc atc ggc acc atc gtc tac cag tgc ctg acg      916 
               
               
                 Lys Ala Asp Leu Trp Ser Ile Gly Thr Ile Val Tyr Gln Cys Leu Thr 
               
               
                                 205                 210                 215 
               
               
                   
               
               
                 ggg aag gcg ccc ttc cag gcc agc agc ccc cag gac ctg cgc ctg ttc      964 
               
               
                 Gly Lys Ala Pro Phe Gln Ala Ser Ser Pro Gln Asp Leu Arg Leu Phe 
               
               
                             220                 225                 230 
               
               
                   
               
               
                 tac gag aag aac aag acg ttg gtc ccc acc atc ccc cgg gag acc tcg     1012 
               
               
                 Tyr Glu Lys Asn Lys Thr Leu Val Pro Thr Ile Pro Arg Glu Thr Ser 
               
               
                         235                 240                 245 
               
               
                   
               
               
                 gcc ccg ctg cgg cag ctg ctc ctg gcc cta ctg caa cgc aac cac aag     1060 
               
               
                 Ala Pro Leu Arg Gln Leu Leu Leu Ala Leu Leu Gln Arg Asn His Lys 
               
               
                     250                 255                 260 
               
               
                   
               
               
                 gac cgc atg gac ttc gat gag ttt ttt cat cac cct ttc ctc gat gcc     1108 
               
               
                 Asp Arg Met Asp Phe Asp Glu Phe Phe His His Pro Phe Leu Asp Ala 
               
               
                 265                 270                 275                 280 
               
               
                   
               
               
                 agc ccc tcg gtc agg aaa tcc cca ccc gtg cct gtg ccc tcg tac cca     1156 
               
               
                 Ser Pro Ser Val Arg Lys Ser Pro Pro Val Pro Val Pro Ser Tyr Pro 
               
               
                                 285                 290                 295 
               
               
                   
               
               
                 agc tcg ggg tcc ggc agc agc tcc agc agc agc tcc acc tcc cac ctg     1204 
               
               
                 Ser Ser Gly Ser Gly Ser Ser Ser Ser Ser Ser Ser Thr Ser His Leu 
               
               
                             300                 305                 310 
               
               
                   
               
               
                 gcc tcc ccg ccg tcc ctg ggc gag atg cag cag ctg cag aag acc ctg     1252 
               
               
                 Ala Ser Pro Pro Ser Leu Gly Glu Met Gln Gln Leu Gln Lys Thr Leu 
               
               
                         315                 320                 325 
               
               
                   
               
               
                 gcc tcc ccg gct gac acc gct ggc ttc ctg cac agc tcc cgg gac tct     1300 
               
               
                 Ala Ser Pro Ala Asp Thr Ala Gly Phe Leu His Ser Ser Arg Asp Ser 
               
               
                     330                 335                 340 
               
               
                   
               
               
                 ggt ggc agc aag gac tct tcc tgt gac aca gac gac ttc gtc atg gtc     1348 
               
               
                 Gly Gly Ser Lys Asp Ser Ser Cys Asp Thr Asp Asp Phe Val Met Val 
               
               
                 345                 350                 355                 360 
               
               
                   
               
               
                 ccc gcg cag ttt cca ggt gac ctg gtg gct gag gcg ccc agt gcc aaa     1396 
               
               
                 Pro Ala Gln Phe Pro Gly Asp Leu Val Ala Glu Ala Pro Ser Ala Lys 
               
               
                                 365                 370                 375 
               
               
                   
               
               
                 ccc ccg cca gac agc ctg atg tgc agt ggg agc tca ctg gtg gcc tct     1444 
               
               
                 Pro Pro Pro Asp Ser Leu Met Cys Ser Gly Ser Ser Leu Val Ala Ser 
               
               
                             380                 385                 390 
               
               
                   
               
               
                 gcg ggc ttg gag agc cac ggc cgg acc cca tct cca tcc cca ccc tgc     1492 
               
               
                 Ala Gly Leu Glu Ser His Gly Arg Thr Pro Ser Pro Ser Pro Pro Cys 
               
               
                         395                 400                 405 
               
               
                   
               
               
                 agc agc tcc ccc agt ccc tca ggc cgg gct ggc ccg ttc tcc agc agc     1540 
               
               
                 Ser Ser Ser Pro Ser Pro Ser Gly Arg Ala Gly Pro Phe Ser Ser Ser 
               
               
                     410                 415                 420 
               
               
                   
               
               
                 agg tgc ggc gcc tct gtc ccc atc cca gtc ccc acg cag gtg cag aac     1588 
               
               
                 Arg Cys Gly Ala Ser Val Pro Ile Pro Val Pro Thr Gln Val Gln Asn 
               
               
                 425                 430                 435                 440 
               
               
                   
               
               
                 tac cag cgc att gag cga aac ctg cag tca ccc acc cag ttc caa aca     1636 
               
               
                 Tyr Gln Arg Ile Glu Arg Asn Leu Gln Ser Pro Thr Gln Phe Gln Thr 
               
               
                                 445                 450                 455 
               
               
                   
               
               
                 cct cgg tcc tct gcc atc cgc agg tca ggc agc acc agc ccc ctg ggc     1684 
               
               
                 Pro Arg Ser Ser Ala Ile Arg Arg Ser Gly Ser Thr Ser Pro Leu Gly 
               
               
                             460                 465                 470 
               
               
                   
               
               
                 ttt gca agg gcc agc ccc tcg ccc cct gcc cac gct gag cat gga ggc     1732 
               
               
                 Phe Ala Arg Ala Ser Pro Ser Pro Pro Ala His Ala Glu His Gly Gly 
               
               
                         475                 480                 485 
               
               
                   
               
               
                 gtc ctg gcc agg aag atg tct ctg ggt gga ggc cgg ccc tac acg cca     1780 
               
               
                 Val Leu Ala Arg Lys Met Ser Leu Gly Gly Gly Arg Pro Tyr Thr Pro 
               
               
                     490                 495                 500 
               
               
                   
               
               
                 tct cct caa gtt gga acc atc cct gag cgg cca ggc tgg agc ggg acg     1828 
               
               
                 Ser Pro Gln Val Gly Thr Ile Pro Glu Arg Pro Gly Trp Ser Gly Thr 
               
               
                 505                 510                 515                 520 
               
               
                   
               
               
                 ccc tcc cca cag gga gct gag atg cgg ggt ggc agg tcc cct cgt cca     1876 
               
               
                 Pro Ser Pro Gln Gly Ala Glu Met Arg Gly Gly Arg Ser Pro Arg Pro 
               
               
                                 525                 530                 535 
               
               
                   
               
               
                 ggc tcc tct gca ccc gag cac tct ccc cgc act tcc ggg ctg ggc tgc     1924 
               
               
                 Gly Ser Ser Ala Pro Glu His Ser Pro Arg Thr Ser Gly Leu Gly Cys 
               
               
                             540                 545                 550 
               
               
                   
               
               
                 cgc ctg cac agc gcc ccc aac ctg tct gac ttg cac gtc gtc cgc ccc     1972 
               
               
                 Arg Leu His Ser Ala Pro Asn Leu Ser Asp Leu His Val Val Arg Pro 
               
               
                         555                 560                 565 
               
               
                   
               
               
                 aag ctg ccc aaa ccc ccc acg gac ccc ctg gga gct gtg ttc agc cca     2020 
               
               
                 Lys Leu Pro Lys Pro Pro Thr Asp Pro Leu Gly Ala Val Phe Ser Pro 
               
               
                     570                 575                 580 
               
               
                   
               
               
                 cca cag gcc agc cct ccc cag ccg tcc cac ggc ctg cag tcc tgc cgg     2068 
               
               
                 Pro Gln Ala Ser Pro Pro Gln Pro Ser His Gly Leu Gln Ser Cys Arg 
               
               
                 585                 590                 595                 600 
               
               
                   
               
               
                 aac ctg cgg ggc tca ccc aag ctg ccc gac ttc ctg cag cga aac ccc     2116 
               
               
                 Asn Leu Arg Gly Ser Pro Lys Leu Pro Asp Phe Leu Gln Arg Asn Pro 
               
               
                                 605                 610                 615 
               
               
                   
               
               
                 ctg ccc ccc atc ctg ggc tcc ccc acc aag gct gtg ccc tcc ttt gac     2164 
               
               
                 Leu Pro Pro Ile Leu Gly Ser Pro Thr Lys Ala Val Pro Ser Phe Asp 
               
               
                             620                 625                 630 
               
               
                   
               
               
                 ttc ccg aag acc ccc agc tcc cag aac ctg ctg gcc ctc cta gcc cgg     2212 
               
               
                 Phe Pro Lys Thr Pro Ser Ser Gln Asn Leu Leu Ala Leu Leu Ala Arg 
               
               
                         635                 640                 645 
               
               
                   
               
               
                 cag ggc gtg gtg atg acg ccc cct cga aac cgg acg ctg ccc gac ctc     2260 
               
               
                 Gln Gly Val Val Met Thr Pro Pro Arg Asn Arg Thr Leu Pro Asp Leu 
               
               
                     650                 655                 660 
               
               
                   
               
               
                 tcg gag gtg gga ccc ttc cat ggt cag ccg ttg ggc cct ggc ctg cgg     2308 
               
               
                 Ser Glu Val Gly Pro Phe His Gly Gln Pro Leu Gly Pro Gly Leu Arg 
               
               
                 665                 670                 675                 680 
               
               
                   
               
               
                 cca ggc gag gac ccc aag ggc ccc ttt ggc cgg tct ttc agc acc agc     2356 
               
               
                 Pro Gly Glu Asp Pro Lys Gly Pro Phe Gly Arg Ser Phe Ser Thr Ser 
               
               
                                 685                 690                 695 
               
               
                   
               
               
                 cgc ctc act gac ctg ctc ctt aag gcg gcg ttt ggg aca caa gcc ccg     2404 
               
               
                 Arg Leu Thr Asp Leu Leu Leu Lys Ala Ala Phe Gly Thr Gln Ala Pro 
               
               
                             700                 705                 710 
               
               
                   
               
               
                 gac ccg ggc agc acg gag agc ctg cag gag aag ccc atg gag atc gca     2452 
               
               
                 Asp Pro Gly Ser Thr Glu Ser Leu Gln Glu Lys Pro Met Glu Ile Ala 
               
               
                         715                 720                 725 
               
               
                   
               
               
                 ccc tca gct ggc ttt gga ggg agc ctg cac cca gga gcc cgt gct ggg     2500 
               
               
                 Pro Ser Ala Gly Phe Gly Gly Ser Leu His Pro Gly Ala Arg Ala Gly 
               
               
                     730                 735                 740 
               
               
                   
               
               
                 ggc acc agc agc ccc tcc ccg gtg gtc ttc acc gtg ggc tct ccc ccg     2548 
               
               
                 Gly Thr Ser Ser Pro Ser Pro Val Val Phe Thr Val Gly Ser Pro Pro 
               
               
                 745                 750                 755                 760 
               
               
                   
               
               
                 agc ggg agc acg ccc ccc cag ggc ccc cgc acc agg atg ttc tca gcg     2596 
               
               
                 Ser Gly Ser Thr Pro Pro Gln Gly Pro Arg Thr Arg Met Phe Ser Ala 
               
               
                                 765                 770                 775 
               
               
                   
               
               
                 ggc ccc act ggc tct gcc agc tct tct gcc cgc cac ctg gtg cct ggg     2644 
               
               
                 Gly Pro Thr Gly Ser Ala Ser Ser Ser Ala Arg His Leu Val Pro Gly 
               
               
                             780                 785                 790 
               
               
                   
               
               
                 ccc tgc agc gag gcc cca gcc cct gag ctc cct gct cca gga cac ggc     2692 
               
               
                 Pro Cys Ser Glu Ala Pro Ala Pro Glu Leu Pro Ala Pro Gly His Gly 
               
               
                         795                 800                 805 
               
               
                   
               
               
                 tgc agc ttt gcc gac ccc att gct gcg aac ctg gag ggg gct gtg acc     2740 
               
               
                 Cys Ser Phe Ala Asp Pro Ile Ala Ala Asn Leu Glu Gly Ala Val Thr 
               
               
                     810                 815                 820 
               
               
                   
               
               
                 ttc gag gcc ccc gac ctc cct gag gag acc ctc atg gag caa gag cac     2788 
               
               
                 Phe Glu Ala Pro Asp Leu Pro Glu Glu Thr Leu Met Glu Gln Glu His 
               
               
                 825                 830                 835                 840 
               
               
                   
               
               
                 acg gag atc ctg cgt ggc ctg cgc ttc acg ctg ctg ttc gtg cag cac     2836 
               
               
                 Thr Glu Ile Leu Arg Gly Leu Arg Phe Thr Leu Leu Phe Val Gln His 
               
               
                                 845                 850                 855 
               
               
                   
               
               
                 gtc ctg gag atc gca gcc ctg aag ggc agc gcc agt gag gcg gcg ggg     2884 
               
               
                 Val Leu Glu Ile Ala Ala Leu Lys Gly Ser Ala Ser Glu Ala Ala Gly 
               
               
                             860                 865                 870 
               
               
                   
               
               
                 ggc cct gag tac cag ctg cag gag agt gtg gtg gcc gac cag atc agc     2932 
               
               
                 Gly Pro Glu Tyr Gln Leu Gln Glu Ser Val Val Ala Asp Gln Ile Ser 
               
               
                         875                 880                 885 
               
               
                   
               
               
                 ctg ctg agc cga gaa tgg ggc ttc gcg gaa cag ctg gtg ctg tac ctg     2980 
               
               
                 Leu Leu Ser Arg Glu Trp Gly Phe Ala Glu Gln Leu Val Leu Tyr Leu 
               
               
                     890                 895                 900 
               
               
                   
               
               
                 aag gtg gcc gag cta ctg tcc tcc ggc ctg caa agt gcc atc gac cag     3028 
               
               
                 Lys Val Ala Glu Leu Leu Ser Ser Gly Leu Gln Ser Ala Ile Asp Gln 
               
               
                 905                 910                 915                 920 
               
               
                   
               
               
                 atc cgg gcc ggc aag ctc tgc ctg tcg tcc act gtg aag cag gtg gtg     3076 
               
               
                 Ile Arg Ala Gly Lys Leu Cys Leu Ser Ser Thr Val Lys Gln Val Val 
               
               
                                 925                 930                 935 
               
               
                   
               
               
                 cgc agg ctg aat gag ctg tac aag gcc agc gtg gtg tcc tgc cag ggc     3124 
               
               
                 Arg Arg Leu Asn Glu Leu Tyr Lys Ala Ser Val Val Ser Cys Gln Gly 
               
               
                             940                 945                 950 
               
               
                   
               
               
                 ctg agc ctg cgg ctg cag cgc ttc ttc ctg gac aag cag cgg ctc ctg     3172 
               
               
                 Leu Ser Leu Arg Leu Gln Arg Phe Phe Leu Asp Lys Gln Arg Leu Leu 
               
               
                         955                 960                 965 
               
               
                   
               
               
                 gac cgc att cac agc atc act gcc gag agg ctc atc ttc agc cac gct     3220 
               
               
                 Asp Arg Ile His Ser Ile Thr Ala Glu Arg Leu Ile Phe Ser His Ala 
               
               
                     970                 975                 980 
               
               
                   
               
               
                 gtg cag atg gtg cag tcg gct gcc ctg gac gag atg ttc cag cac cgt     3268 
               
               
                 Val Gln Met Val Gln Ser Ala Ala Leu Asp Glu Met Phe Gln His Arg 
               
               
                  985                 990                 995                1000 
               
               
                   
               
               
                 gag ggc tgc gtc cca cgc tac cac aag gcc ctg ctg ctc ctg gag ggg     3316 
               
               
                 Glu Gly Cys Val Pro Arg Tyr His Lys Ala Leu Leu Leu Leu Glu Gly 
               
               
                                 1005                1010                1015 
               
               
                   
               
               
                 ctg cag cac atg ctc tcg gac cag gcc gac atc gag aac gtc acc aag     3364 
               
               
                 Leu Gln His Met Leu Ser Asp Gln Ala Asp Ile Glu Asn Val Thr Lys 
               
               
                             1020                1025                1030 
               
               
                   
               
               
                 tgc aag ctg tgc att gag cgg aga ctc tcg gcg ctg ctg act ggc atc     3412 
               
               
                 Cys Lys Leu Cys Ile Glu Arg Arg Leu Ser Ala Leu Leu Thr Gly Ile 
               
               
                         1035                1040                1045 
               
               
                   
               
               
                 tgt gcc tgacctttct ggcctggctg ggccccccgt cctgccgagc cctgcagagt      3468 
               
               
                 Cys Ala 
               
               
                     1050 
               
               
                   
               
               
                 gggctctgtg tgctggctgg actcctcggg acaagcccat ggcgctgatc gctggtgctg   3528 
               
               
                   
               
               
                 agccctgccc tgggccccac ggacagtcag cctgccggcc tccctgcagc tcacggggca   3588 
               
               
                   
               
               
                 gaaccagcac atctggagcc acacagcttg gggggtgtct cccatctttt acaggtgggg   3648 
               
               
                   
               
               
                 atcacagaat ttctgcccct ccagctgcct ggctcagcag gcgtgggtgc caccaccctc   3708 
               
               
                   
               
               
                 tagccccagg gcagccccgg aggacaggca agggcctgag accactgccg actcaaagcc   3768 
               
               
                   
               
               
                 aaagcgagct cctgcttagg gcaggtcagc aggcactgtg cccaggaaga gcctgcggcc   3828 
               
               
                   
               
               
                 tcggcgtccc ccagtctcca ggagcctctc cctccgagat acccacccag ctttgtcaat   3888 
               
               
                   
               
               
                 cacccaagca ctttatgcat atagagacag aacctggacc tcaccaggga ctgctgggca   3948 
               
               
                   
               
               
                 gcgattcctg gcagtggcct ggtgtttgta catacacata tgcagacaca tgccagggcc   4008 
               
               
                   
               
               
                 ccccaagccc gagcaccgga ccacgttgct gcccaggtct ggacctcagc gggagaactg   4068 
               
               
                   
               
               
                 gctccggggg gagtggggcc ctgcgctaga ggcagaggca gttctttgtt caagcgttcc   4128 
               
               
                   
               
               
                 tctggggacc ggcagcagag gcaccgtgtt ctctcagccc tggatacgtc ttgtaatctt   4188 
               
               
                   
               
               
                 tcacacttta ttcctaaaac gtgtcttatt tttatgcagc tcattttttc tttaaaggag   4248 
               
               
                   
               
               
                 aaaacttgta ggtgtttaag aattggtttt gggagggcga ggactgggcc aggttagagg   4308 
               
               
                   
               
               
                 cagatggcac aggggcgtgt ggcgggcggg tgaggctgct ttgcacacct gtgttggtgg   4368 
               
               
                   
               
               
                 ctgtcccctg ccgcccctcc ctgtggcagc agcaggacag gtgtgtgccc agcaccctcc   4428 
               
               
                   
               
               
                 ctacctgggc ctggaagcag atgaggggaa tacttcatgc aaagaaaaaa gtaacatgtg   4488 
               
               
                   
               
               
                 caaaagctcc ccgtccagct ttgacagtca gttttgatgt cagctcctcg gcagggtagg   4548 
               
               
                   
               
               
                 cctgatgaca gccctgtccc tccctgcctc cgccttgccc aaggccacgg agggcgtctg   4608 
               
               
                   
               
               
                 cagagaggcc tgccttccgg attccaggcg ggcatgccct gcaaaccccg cctgggcctc   4668 
               
               
                   
               
               
                 ccttggtctg cccagccctc ggttagccct gcctgaatca gtagatactt gaacgagtcc   4728 
               
               
                   
               
               
                 ccagtctgcg ggaggcagtg gtggggccat ggacccatgc ggggggttcc agggtcacac   4788 
               
               
                   
               
               
                 gccacataac agacaaaaat acacacacgt gtgtttttct ttgcaatact tgaaatattg   4848 
               
               
                   
               
               
                 ccactgtgct tggacttaga agaagaaaat ccccgtgact tcttcctcat caccttgatg   4908 
               
               
                   
               
               
                 gctttattct caccttgtgg ggcatgtttg aatttattgc ttcatggccg actggaatcc   4968 
               
               
                   
               
               
                 tgagtcctgg gaagctggca ctgcggggat cttgcccggt gtcctggtcc tcttgcttcc   5028 
               
               
                   
               
               
                 gtcgcggccg catgtgcgtg tgtccaagca ggtcctgggc gcctcaactg ctgcccctgg   5088 
               
               
                   
               
               
                 ttgaatgttc tcttgatagt gctggaccct ttgtctattt taaagcgaat tttgtgtgat   5148 
               
               
                   
               
               
                 ttcctgccct ttgcgttata ttgtataata ccaacgtaag gaaataaacc tttggaattg   5208 
               
               
                   
               
               
                 ttgaaaaaaa aaaaaaaaaa                                               5228 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 16 
               
               
                 &lt;211&gt; LENGTH: 1050 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Homo sapiens 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 16 
               
               
                   
               
               
                 Met Glu Pro Gly Arg Gly Gly Thr Glu Thr Val Gly Lys Phe Glu Phe 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 Ser Arg Lys Asp Leu Ile Gly His Gly Ala Phe Ala Val Val Phe Lys 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Gly Arg His Arg Glu Lys His Asp Leu Glu Val Ala Val Lys Cys Ile 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Asn Lys Lys Asn Leu Ala Lys Ser Gln Thr Leu Leu Gly Lys Glu Ile 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 Lys Ile Leu Lys Glu Leu Lys His Glu Asn Ile Val Ala Leu Tyr Asp 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Phe Gln Glu Met Ala Asn Ser Val Tyr Leu Val Met Glu Tyr Cys Asn 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Gly Gly Asp Leu Ala Asp Tyr Leu His Ala Met Arg Thr Leu Ser Glu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 Asp Thr Ile Arg Leu Phe Leu Gln Gln Ile Ala Gly Ala Met Arg Leu 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 Leu His Ser Lys Gly Ile Ile His Arg Asp Leu Lys Pro Gln Asn Ile 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Leu Leu Ser Asn Pro Ala Gly Arg Arg Ala Asn Pro Asn Ser Ile Arg 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Val Lys Ile Ala Asp Phe Gly Phe Ala Arg Tyr Leu Gln Ser Asn Met 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met Ala Pro Glu Val 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ile Met Ser Gln His Tyr Asp Gly Lys Ala Asp Leu Trp Ser Ile Gly 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Thr Ile Val Tyr Gln Cys Leu Thr Gly Lys Ala Pro Phe Gln Ala Ser 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Ser Pro Gln Asp Leu Arg Leu Phe Tyr Glu Lys Asn Lys Thr Leu Val 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Pro Thr Ile Pro Arg Glu Thr Ser Ala Pro Leu Arg Gln Leu Leu Leu 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Ala Leu Leu Gln Arg Asn His Lys Asp Arg Met Asp Phe Asp Glu Phe 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Phe His His Pro Phe Leu Asp Ala Ser Pro Ser Val Arg Lys Ser Pro 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Pro Val Pro Val Pro Ser Tyr Pro Ser Ser Gly Ser Gly Ser Ser Ser 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Ser Ser Ser Ser Thr Ser His Leu Ala Ser Pro Pro Ser Leu Gly Glu 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Met Gln Gln Leu Gln Lys Thr Leu Ala Ser Pro Ala Asp Thr Ala Gly 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Phe Leu His Ser Ser Arg Asp Ser Gly Gly Ser Lys Asp Ser Ser Cys 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Asp Thr Asp Asp Phe Val Met Val Pro Ala Gln Phe Pro Gly Asp Leu 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Val Ala Glu Ala Pro Ser Ala Lys Pro Pro Pro Asp Ser Leu Met Cys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Ser Gly Ser Ser Leu Val Ala Ser Ala Gly Leu Glu Ser His Gly Arg 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Thr Pro Ser Pro Ser Pro Pro Cys Ser Ser Ser Pro Ser Pro Ser Gly 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Arg Ala Gly Pro Phe Ser Ser Ser Arg Cys Gly Ala Ser Val Pro Ile 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Pro Val Pro Thr Gln Val Gln Asn Tyr Gln Arg Ile Glu Arg Asn Leu 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Gln Ser Pro Thr Gln Phe Gln Thr Pro Arg Ser Ser Ala Ile Arg Arg 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Ser Gly Ser Thr Ser Pro Leu Gly Phe Ala Arg Ala Ser Pro Ser Pro 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Pro Ala His Ala Glu His Gly Gly Val Leu Ala Arg Lys Met Ser Leu 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Gly Gly Gly Arg Pro Tyr Thr Pro Ser Pro Gln Val Gly Thr Ile Pro 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Glu Arg Pro Gly Trp Ser Gly Thr Pro Ser Pro Gln Gly Ala Glu Met 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Arg Gly Gly Arg Ser Pro Arg Pro Gly Ser Ser Ala Pro Glu His Ser 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 Pro Arg Thr Ser Gly Leu Gly Cys Arg Leu His Ser Ala Pro Asn Leu 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 Ser Asp Leu His Val Val Arg Pro Lys Leu Pro Lys Pro Pro Thr Asp 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 Pro Leu Gly Ala Val Phe Ser Pro Pro Gln Ala Ser Pro Pro Gln Pro 
               
               
                             580                 585                 590 
               
               
                   
               
               
                 Ser His Gly Leu Gln Ser Cys Arg Asn Leu Arg Gly Ser Pro Lys Leu 
               
               
                         595                 600                 605 
               
               
                   
               
               
                 Pro Asp Phe Leu Gln Arg Asn Pro Leu Pro Pro Ile Leu Gly Ser Pro 
               
               
                     610                 615                 620 
               
               
                   
               
               
                 Thr Lys Ala Val Pro Ser Phe Asp Phe Pro Lys Thr Pro Ser Ser Gln 
               
               
                 625                 630                 635                 640 
               
               
                   
               
               
                 Asn Leu Leu Ala Leu Leu Ala Arg Gln Gly Val Val Met Thr Pro Pro 
               
               
                                 645                 650                 655 
               
               
                   
               
               
                 Arg Asn Arg Thr Leu Pro Asp Leu Ser Glu Val Gly Pro Phe His Gly 
               
               
                             660                 665                 670 
               
               
                   
               
               
                 Gln Pro Leu Gly Pro Gly Leu Arg Pro Gly Glu Asp Pro Lys Gly Pro 
               
               
                         675                 680                 685 
               
               
                   
               
               
                 Phe Gly Arg Ser Phe Ser Thr Ser Arg Leu Thr Asp Leu Leu Leu Lys 
               
               
                     690                 695                 700 
               
               
                   
               
               
                 Ala Ala Phe Gly Thr Gln Ala Pro Asp Pro Gly Ser Thr Glu Ser Leu 
               
               
                 705                 710                 715                 720 
               
               
                   
               
               
                 Gln Glu Lys Pro Met Glu Ile Ala Pro Ser Ala Gly Phe Gly Gly Ser 
               
               
                                 725                 730                 735 
               
               
                   
               
               
                 Leu His Pro Gly Ala Arg Ala Gly Gly Thr Ser Ser Pro Ser Pro Val 
               
               
                             740                 745                 750 
               
               
                   
               
               
                 Val Phe Thr Val Gly Ser Pro Pro Ser Gly Ser Thr Pro Pro Gln Gly 
               
               
                         755                 760                 765 
               
               
                   
               
               
                 Pro Arg Thr Arg Met Phe Ser Ala Gly Pro Thr Gly Ser Ala Ser Ser 
               
               
                     770                 775                 780 
               
               
                   
               
               
                 Ser Ala Arg His Leu Val Pro Gly Pro Cys Ser Glu Ala Pro Ala Pro 
               
               
                 785                 790                 795                 800 
               
               
                   
               
               
                 Glu Leu Pro Ala Pro Gly His Gly Cys Ser Phe Ala Asp Pro Ile Ala 
               
               
                                 805                 810                 815 
               
               
                   
               
               
                 Ala Asn Leu Glu Gly Ala Val Thr Phe Glu Ala Pro Asp Leu Pro Glu 
               
               
                             820                 825                 830 
               
               
                   
               
               
                 Glu Thr Leu Met Glu Gln Glu His Thr Glu Ile Leu Arg Gly Leu Arg 
               
               
                         835                 840                 845 
               
               
                   
               
               
                 Phe Thr Leu Leu Phe Val Gln His Val Leu Glu Ile Ala Ala Leu Lys 
               
               
                     850                 855                 860 
               
               
                   
               
               
                 Gly Ser Ala Ser Glu Ala Ala Gly Gly Pro Glu Tyr Gln Leu Gln Glu 
               
               
                 865                 870                 875                 880 
               
               
                   
               
               
                 Ser Val Val Ala Asp Gln Ile Ser Leu Leu Ser Arg Glu Trp Gly Phe 
               
               
                                 885                 890                 895 
               
               
                   
               
               
                 Ala Glu Gln Leu Val Leu Tyr Leu Lys Val Ala Glu Leu Leu Ser Ser 
               
               
                             900                 905                 910 
               
               
                   
               
               
                 Gly Leu Gln Ser Ala Ile Asp Gln Ile Arg Ala Gly Lys Leu Cys Leu 
               
               
                         915                 920                 925 
               
               
                   
               
               
                 Ser Ser Thr Val Lys Gln Val Val Arg Arg Leu Asn Glu Leu Tyr Lys 
               
               
                     930                 935                 940 
               
               
                   
               
               
                 Ala Ser Val Val Ser Cys Gln Gly Leu Ser Leu Arg Leu Gln Arg Phe 
               
               
                 945                 950                 955                 960 
               
               
                   
               
               
                 Phe Leu Asp Lys Gln Arg Leu Leu Asp Arg Ile His Ser Ile Thr Ala 
               
               
                                 965                 970                 975 
               
               
                   
               
               
                 Glu Arg Leu Ile Phe Ser His Ala Val Gln Met Val Gln Ser Ala Ala 
               
               
                             980                 985                 990 
               
               
                   
               
               
                 Leu Asp Glu Met Phe Gln His Arg Glu Gly Cys Val Pro Arg Tyr His 
               
               
                         995                 1000                1005 
               
               
                   
               
               
                 Lys Ala Leu Leu Leu Leu Glu Gly Leu Gln His Met Leu Ser Asp Gln 
               
               
                     1010                1015                1020 
               
               
                   
               
               
                 Ala Asp Ile Glu Asn Val Thr Lys Cys Lys Leu Cys Ile Glu Arg Arg 
               
               
                 1025                1030                1035                1040 
               
               
                   
               
               
                 Leu Ser Ala Leu Leu Thr Gly Ile Cys Ala 
               
               
                                 1045                1050 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 17 
               
               
                 &lt;211&gt; LENGTH: 21 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated primer 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 17 
               
               
                   
               
               
                 tgcccaccct agcgctctat g                                               21 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 18 
               
               
                 &lt;211&gt; LENGTH: 21 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Artificial Sequence 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;223&gt; OTHER INFORMATION: Synthetically generated primer 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 18 
               
               
                   
               
               
                 attcgcatgg ctgccgcaat c                                               21 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 19 
               
               
                 &lt;211&gt; LENGTH: 445 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;221&gt; NAME/KEY: misc_feature 
               
               
                 &lt;222&gt; LOCATION: (1)...(445) 
               
               
                 &lt;223&gt; OTHER INFORMATION: n = A,T,C or G 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 19 
               
               
                   
               
               
                 tgcatgcctg cacgtcgact ctagaggatc tactantcat atggatttgc ccaccctacg     60 
               
               
                   
               
               
                 ctctatgtcc cgggggcgcg gccatggaag tggtgggcga cttcgagtac tgcaagcggg    120 
               
               
                   
               
               
                 acctcgtggg acacggggcc ttcgctgtgg tcttccgggg gcggcaccgc cagaaaactg    180 
               
               
                   
               
               
                 attgggaggt ggctattaaa agtattaata aaaagaactt gtcaaaatca caaattttgc    240 
               
               
                   
               
               
                 ttggaaagga aataaaaatc ttaaaggagc ttcagcatga aaacatcgta gcgctctatg    300 
               
               
                   
               
               
                 atgttcagga attgcccaac tctgtctttc tggtgatgga gtattgcaat ggtggagacc    360 
               
               
                   
               
               
                 tggcagatta tttgcaagct aaaggaactc tgagtgaaga tactatcaga gtgtttctcc    420 
               
               
                   
               
               
                 atcagattgc ggcagccatg cgaat                                          445 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 20 
               
               
                 &lt;211&gt; LENGTH: 3455 
               
               
                 &lt;212&gt; TYPE: DNA 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                 &lt;220&gt; FEATURE: 
               
               
                 &lt;221&gt; NAME/KEY: CDS 
               
               
                 &lt;222&gt; LOCATION: (42)...(3152) 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 20 
               
               
                   
               
               
                 cgcctgccca ccctagcgtt ctatgtcccg ggggcgcggc c atg gag gtg gtg ggc     56 
               
               
                                                               Met Glu Val Val Gly 
               
               
                                                                 1               5 
               
               
                   
               
               
                 gac ttc gag tac tgc aag cgg gac ctc gtg gga cac ggg gcc ttc gct      104 
               
               
                 Asp Phe Glu Tyr Cys Lys Arg Asp Leu Val Gly His Gly Ala Phe Ala 
               
               
                                  10                  15                  20 
               
               
                   
               
               
                 gtg gtc ttc cgg ggg cgg cac cgc cag aaa act gat tgg gag gtg gct      152 
               
               
                 Val Val Phe Arg Gly Arg His Arg Gln Lys Thr Asp Trp Glu Val Ala 
               
               
                              25                  30                  35 
               
               
                   
               
               
                 att aaa agt att aat aaa aag aac ttg tca aaa tca caa att ctg ctt      200 
               
               
                 Ile Lys Ser Ile Asn Lys Lys Asn Leu Ser Lys Ser Gln Ile Leu Leu 
               
               
                          40                  45                  50 
               
               
                   
               
               
                 gga aag gaa ata aaa atc tta aag gag ctt cag cat gaa aac atc gta      248 
               
               
                 Gly Lys Glu Ile Lys Ile Leu Lys Glu Leu Gln His Glu Asn Ile Val 
               
               
                      55                  60                  65 
               
               
                   
               
               
                 gcg ctc tat gat gtt cag gaa ttg ccc aac tct gtc ttt ctg gtg atg      296 
               
               
                 Ala Leu Tyr Asp Val Gln Glu Leu Pro Asn Ser Val Phe Leu Val Met 
               
               
                  70                  75                  80                  85 
               
               
                   
               
               
                 gag tat tgc aat ggt gga gac ctg gca gat tat ttg caa gct aaa gga      344 
               
               
                 Glu Tyr Cys Asn Gly Gly Asp Leu Ala Asp Tyr Leu Gln Ala Lys Gly 
               
               
                                  90                  95                 100 
               
               
                   
               
               
                 act ctg agt gaa gat act atc aga gtg ttt ctc cat cag att gcg gca      392 
               
               
                 Thr Leu Ser Glu Asp Thr Ile Arg Val Phe Leu His Gln Ile Ala Ala 
               
               
                             105                 110                 115 
               
               
                   
               
               
                 gcc atg cga atc ctg cac agc aaa ggg ata atc cac agg gat ctc aaa      440 
               
               
                 Ala Met Arg Ile Leu His Ser Lys Gly Ile Ile His Arg Asp Leu Lys 
               
               
                         120                 125                 130 
               
               
                   
               
               
                 cca cag aat atc ctg ttg tct tat gcc aat cga agg aag tcg aat gtc      488 
               
               
                 Pro Gln Asn Ile Leu Leu Ser Tyr Ala Asn Arg Arg Lys Ser Asn Val 
               
               
                     135                 140                 145 
               
               
                   
               
               
                 agt ggt att cgt att aaa ata gct gat ttt ggt ttc gca cgg tac cta      536 
               
               
                 Ser Gly Ile Arg Ile Lys Ile Ala Asp Phe Gly Phe Ala Arg Tyr Leu 
               
               
                 150                 155                 160                 165 
               
               
                   
               
               
                 cat agt aac aca atg gca gcg aca ctg tgt gga tcc cca atg tac atg      584 
               
               
                 His Ser Asn Thr Met Ala Ala Thr Leu Cys Gly Ser Pro Met Tyr Met 
               
               
                                 170                 175                 180 
               
               
                   
               
               
                 gct ccc gag gtt att atg tct caa cat tat gat gct aag gca gat tta      632 
               
               
                 Ala Pro Glu Val Ile Met Ser Gln His Tyr Asp Ala Lys Ala Asp Leu 
               
               
                             185                 190                 195 
               
               
                   
               
               
                 tgg agc ata gga aca gtg atc tat caa tgc cta gtt gga aaa cca cct      680 
               
               
                 Trp Ser Ile Gly Thr Val Ile Tyr Gln Cys Leu Val Gly Lys Pro Pro 
               
               
                         200                 205                 210 
               
               
                   
               
               
                 ttt cag gct aat agt cct cag gac cta agg atg ttt tat gaa aaa aac      728 
               
               
                 Phe Gln Ala Asn Ser Pro Gln Asp Leu Arg Met Phe Tyr Glu Lys Asn 
               
               
                     215                 220                 225 
               
               
                   
               
               
                 agg agc tta atg cct agt att ccc aga gaa aca tca cct tac ttg gct      776 
               
               
                 Arg Ser Leu Met Pro Ser Ile Pro Arg Glu Thr Ser Pro Tyr Leu Ala 
               
               
                 230                 235                 240                 245 
               
               
                   
               
               
                 aat ctc ctt ttg ggt ttg ctt cag aga aat caa aag gat aga atg gac      824 
               
               
                 Asn Leu Leu Leu Gly Leu Leu Gln Arg Asn Gln Lys Asp Arg Met Asp 
               
               
                                 250                 255                 260 
               
               
                   
               
               
                 ttt gaa gca ttt ttc agc cat cct ttc ctt gag caa gtt cca gtt aaa      872 
               
               
                 Phe Glu Ala Phe Phe Ser His Pro Phe Leu Glu Gln Val Pro Val Lys 
               
               
                             265                 270                 275 
               
               
                   
               
               
                 aaa tct tgc cca gtc cca gtg cct gtg tat tct ggc cct gtc cct gga      920 
               
               
                 Lys Ser Cys Pro Val Pro Val Pro Val Tyr Ser Gly Pro Val Pro Gly 
               
               
                         280                 285                 290 
               
               
                   
               
               
                 agc tcc tgc agc agc tca cca tct tgt cgc ttt gct tct cca cca tcc      968 
               
               
                 Ser Ser Cys Ser Ser Ser Pro Ser Cys Arg Phe Ala Ser Pro Pro Ser 
               
               
                     295                 300                 305 
               
               
                   
               
               
                 ctt cca gat atg cag cat att cag gaa gaa aac tta tcc tcc cca ccg     1016 
               
               
                 Leu Pro Asp Met Gln His Ile Gln Glu Glu Asn Leu Ser Ser Pro Pro 
               
               
                 310                 315                 320                 325 
               
               
                   
               
               
                 ttg ggt cct ccc aac tat cta cag gtg tcc aaa gac tct gcg agt aat     1064 
               
               
                 Leu Gly Pro Pro Asn Tyr Leu Gln Val Ser Lys Asp Ser Ala Ser Asn 
               
               
                                 330                 335                 340 
               
               
                   
               
               
                 agt agc aag aac tct tct tgt gac acg gat gac ttt gtt ttg gtt cca     1112 
               
               
                 Ser Ser Lys Asn Ser Ser Cys Asp Thr Asp Asp Phe Val Leu Val Pro 
               
               
                             345                 350                 355 
               
               
                   
               
               
                 cac aac atc tcg tca gac cac tca tat gac atg cca atg ggg act acg     1160 
               
               
                 His Asn Ile Ser Ser Asp His Ser Tyr Asp Met Pro Met Gly Thr Thr 
               
               
                         360                 365                 370 
               
               
                   
               
               
                 gcc aga cgc gct tca aat gaa ttc ttt atg tgt gga ggg cag tgt caa     1208 
               
               
                 Ala Arg Arg Ala Ser Asn Glu Phe Phe Met Cys Gly Gly Gln Cys Gln 
               
               
                     375                 380                 385 
               
               
                   
               
               
                 cct act gtg tca cct cac agc gaa aca gcc cca att cca gtt cct act     1256 
               
               
                 Pro Thr Val Ser Pro His Ser Glu Thr Ala Pro Ile Pro Val Pro Thr 
               
               
                 390                 395                 400                 405 
               
               
                   
               
               
                 caa gta agg aat tat cag cgc ata gaa cag aat ctt ata tcc act gcc     1304 
               
               
                 Gln Val Arg Asn Tyr Gln Arg Ile Glu Gln Asn Leu Ile Ser Thr Ala 
               
               
                                 410                 415                 420 
               
               
                   
               
               
                 agc tct ggc aca aac cca cat ggt tct cca aga tct gca gta gta cga     1352 
               
               
                 Ser Ser Gly Thr Asn Pro His Gly Ser Pro Arg Ser Ala Val Val Arg 
               
               
                             425                 430                 435 
               
               
                   
               
               
                 agg tct aat acc agc ccc atg ggc ttc ctc cgg gtt ggg tcc tgc tcc     1400 
               
               
                 Arg Ser Asn Thr Ser Pro Met Gly Phe Leu Arg Val Gly Ser Cys Ser 
               
               
                         440                 445                 450 
               
               
                   
               
               
                 cct gta cca gga gac aca gtg cag aca gga gga cga aga ctc tct act     1448 
               
               
                 Pro Val Pro Gly Asp Thr Val Gln Thr Gly Gly Arg Arg Leu Ser Thr 
               
               
                     455                 460                 465 
               
               
                   
               
               
                 ggc tct tcc agg cct tac tca cca tcc ccc ttg gtt ggt acc att cct     1496 
               
               
                 Gly Ser Ser Arg Pro Tyr Ser Pro Ser Pro Leu Val Gly Thr Ile Pro 
               
               
                 470                 475                 480                 485 
               
               
                   
               
               
                 gaa cag ttt agt cag tgc tgc tgt gga cat cct cag ggc cat gaa gcc     1544 
               
               
                 Glu Gln Phe Ser Gln Cys Cys Cys Gly His Pro Gln Gly His Glu Ala 
               
               
                                 490                 495                 500 
               
               
                   
               
               
                 agg agt agg cac tcc tca ggt tct cca gtg cca cag acc cag gca cca     1592 
               
               
                 Arg Ser Arg His Ser Ser Gly Ser Pro Val Pro Gln Thr Gln Ala Pro 
               
               
                             505                 510                 515 
               
               
                   
               
               
                 cag tca ctc tta ctg ggt gct aga ctg cag agt gca ccc acc ctc acc     1640 
               
               
                 Gln Ser Leu Leu Leu Gly Ala Arg Leu Gln Ser Ala Pro Thr Leu Thr 
               
               
                         520                 525                 530 
               
               
                   
               
               
                 gat atc tat cag aac aag cag aag ctc aga aag cag cac tct gac cct     1688 
               
               
                 Asp Ile Tyr Gln Asn Lys Gln Lys Leu Arg Lys Gln His Ser Asp Pro 
               
               
                     535                 540                 545 
               
               
                   
               
               
                 gtg tgt ccg tcc cat gct gga gct ggg tat agt tac tca cct cag cct     1736 
               
               
                 Val Cys Pro Ser His Ala Gly Ala Gly Tyr Ser Tyr Ser Pro Gln Pro 
               
               
                 550                 555                 560                 565 
               
               
                   
               
               
                 agt cgg cct ggc agc ctt ggg acc tct ccc acc aag cac acg ggg tcc     1784 
               
               
                 Ser Arg Pro Gly Ser Leu Gly Thr Ser Pro Thr Lys His Thr Gly Ser 
               
               
                                 570                 575                 580 
               
               
                   
               
               
                 tct cca cgg aat tct gac tgg ttc ttt aaa act cct tta cca aca atc     1832 
               
               
                 Ser Pro Arg Asn Ser Asp Trp Phe Phe Lys Thr Pro Leu Pro Thr Ile 
               
               
                             585                 590                 595 
               
               
                   
               
               
                 att ggc tct cct act aag act aca gct cct ttc aaa atc cct aaa aca     1880 
               
               
                 Ile Gly Ser Pro Thr Lys Thr Thr Ala Pro Phe Lys Ile Pro Lys Thr 
               
               
                         600                 605                 610 
               
               
                   
               
               
                 caa gca tct tct aac ctg tta gcc ttg gtt act cgt cat ggg cct gct     1928 
               
               
                 Gln Ala Ser Ser Asn Leu Leu Ala Leu Val Thr Arg His Gly Pro Ala 
               
               
                     615                 620                 625 
               
               
                   
               
               
                 gaa agc cag tcc aaa gat ggg aat gac cct cgt gag tgt tcc cac tgc     1976 
               
               
                 Glu Ser Gln Ser Lys Asp Gly Asn Asp Pro Arg Glu Cys Ser His Cys 
               
               
                 630                 635                 640                 645 
               
               
                   
               
               
                 ctc tca gta caa gga agc gag agg cat cga tct gag cag cag cag agc     2024 
               
               
                 Leu Ser Val Gln Gly Ser Glu Arg His Arg Ser Glu Gln Gln Gln Ser 
               
               
                                 650                 655                 660 
               
               
                   
               
               
                 aag gca gtg ttt ggc aga tct gtc agt act ggg aag tta tca gaa caa     2072 
               
               
                 Lys Ala Val Phe Gly Arg Ser Val Ser Thr Gly Lys Leu Ser Glu Gln 
               
               
                             665                 670                 675 
               
               
                   
               
               
                 caa gta aag gca cct tta ggt gga cac cag ggc agc acg gat agt tta     2120 
               
               
                 Gln Val Lys Ala Pro Leu Gly Gly His Gln Gly Ser Thr Asp Ser Leu 
               
               
                         680                 685                 690 
               
               
                   
               
               
                 aac aca gaa cga cca atg gat gta gct cct gca gga gcc tgt ggt gtt     2168 
               
               
                 Asn Thr Glu Arg Pro Met Asp Val Ala Pro Ala Gly Ala Cys Gly Val 
               
               
                     695                 700                 705 
               
               
                   
               
               
                 atg ctg gca ttg cca gca gga aca gca gca agc gcc aga gct gtc ctc     2216 
               
               
                 Met Leu Ala Leu Pro Ala Gly Thr Ala Ala Ser Ala Arg Ala Val Leu 
               
               
                 710                 715                 720                 725 
               
               
                   
               
               
                 ttc acc gtg ggg tct cct cca cac agt gcc aca gcc ccc act tgt act     2264 
               
               
                 Phe Thr Val Gly Ser Pro Pro His Ser Ala Thr Ala Pro Thr Cys Thr 
               
               
                                 730                 735                 740 
               
               
                   
               
               
                 cat atg gtc ctt cga aca aga acc acc tca gtg ggg tcc agc agc tca     2312 
               
               
                 His Met Val Leu Arg Thr Arg Thr Thr Ser Val Gly Ser Ser Ser Ser 
               
               
                             745                 750                 755 
               
               
                   
               
               
                 gga ggt tcc ttg tgt tct gca agt ggc cga gta tgt gtg ggc tcc cct     2360 
               
               
                 Gly Gly Ser Leu Cys Ser Ala Ser Gly Arg Val Cys Val Gly Ser Pro 
               
               
                         760                 765                 770 
               
               
                   
               
               
                 cct gga cca ggg ttg ggc tct tcc cca cca gga gca gag gga gct ccc     2408 
               
               
                 Pro Gly Pro Gly Leu Gly Ser Ser Pro Pro Gly Ala Glu Gly Ala Pro 
               
               
                     775                 780                 785 
               
               
                   
               
               
                 agc cta aga tac gtg cct tat ggt gct tca cca ccc agc cta gag ggt     2456 
               
               
                 Ser Leu Arg Tyr Val Pro Tyr Gly Ala Ser Pro Pro Ser Leu Glu Gly 
               
               
                 790                 795                 800                 805 
               
               
                   
               
               
                 ctc atc acc ttt gaa gcc cct gaa cta cca gag gag aca ctg atg gag     2504 
               
               
                 Leu Ile Thr Phe Glu Ala Pro Glu Leu Pro Glu Glu Thr Leu Met Glu 
               
               
                                 810                 815                 820 
               
               
                   
               
               
                 cga gag cac aca gac acc tta cgc cat ctg aac atg atg tta atg ttt     2552 
               
               
                 Arg Glu His Thr Asp Thr Leu Arg His Leu Asn Met Met Leu Met Phe 
               
               
                             825                 830                 835 
               
               
                   
               
               
                 act gag tgt gtg ctg gac ctg acg gca gtg agg ggt ggg aac cct gag     2600 
               
               
                 Thr Glu Cys Val Leu Asp Leu Thr Ala Val Arg Gly Gly Asn Pro Glu 
               
               
                         840                 845                 850 
               
               
                   
               
               
                 ctg tgc aca tct gct gtg tcc ttg tac cag att cag gag agt gta gtt     2648 
               
               
                 Leu Cys Thr Ser Ala Val Ser Leu Tyr Gln Ile Gln Glu Ser Val Val 
               
               
                     855                 860                 865 
               
               
                   
               
               
                 gtg gac cag atc agc cag cta agc aaa gat tgg ggg cgg gtg gag cag     2696 
               
               
                 Val Asp Gln Ile Ser Gln Leu Ser Lys Asp Trp Gly Arg Val Glu Gln 
               
               
                 870                 875                 880                 885 
               
               
                   
               
               
                 ctg gtg ttg tac atg aag gca gca cag ctg ctg gcg gct tcc ctg cat     2744 
               
               
                 Leu Val Leu Tyr Met Lys Ala Ala Gln Leu Leu Ala Ala Ser Leu His 
               
               
                                 890                 895                 900 
               
               
                   
               
               
                 ctc gcc aaa gct cag gtc aag tct ggg aag ctg agc cca tcc atg gct     2792 
               
               
                 Leu Ala Lys Ala Gln Val Lys Ser Gly Lys Leu Ser Pro Ser Met Ala 
               
               
                             905                 910                 915 
               
               
                   
               
               
                 gtg aaa caa gtt gtt aaa aat ctg aat gaa aga tac aaa ttc tgc atc     2840 
               
               
                 Val Lys Gln Val Val Lys Asn Leu Asn Glu Arg Tyr Lys Phe Cys Ile 
               
               
                         920                 925                 930 
               
               
                   
               
               
                 acc atg tgc aag aaa ctt aca gaa aag ctg aat cgc ttc ttc tcc gat     2888 
               
               
                 Thr Met Cys Lys Lys Leu Thr Glu Lys Leu Asn Arg Phe Phe Ser Asp 
               
               
                     935                 940                 945 
               
               
                   
               
               
                 aaa cag aga ttt att gat gaa atc aac agt gtg act gca gag aaa ctc     2936 
               
               
                 Lys Gln Arg Phe Ile Asp Glu Ile Asn Ser Val Thr Ala Glu Lys Leu 
               
               
                 950                 955                 960                 965 
               
               
                   
               
               
                 atc tat aat tgt gct gtg gaa atg gtt caa tct gca gcc ctg gat gag     2984 
               
               
                 Ile Tyr Asn Cys Ala Val Glu Met Val Gln Ser Ala Ala Leu Asp Glu 
               
               
                                 970                 975                 980 
               
               
                   
               
               
                 atg ttt cag cag act gaa gac atc gtt tat cgc tac cac aag gca gcc     3032 
               
               
                 Met Phe Gln Gln Thr Glu Asp Ile Val Tyr Arg Tyr His Lys Ala Ala 
               
               
                              985                 990                 995 
               
               
                   
               
               
                 gtt ctt ttg gaa ggc tta agt aag atc ctg cag gac cct aca gat gtt     3080 
               
               
                 Val Leu Leu Glu Gly Leu Ser Lys Ile Leu Gln Asp Pro Thr Asp Val 
               
               
                         1000                1005                1010 
               
               
                   
               
               
                 gaa aat gtg cat aag tat aaa tgt agt att gaa aga aga ttg tca gca     3128 
               
               
                 Glu Asn Val His Lys Tyr Lys Cys Ser Ile Glu Arg Arg Leu Ser Ala 
               
               
                     1015                1020                1025 
               
               
                   
               
               
                 ctc tgc tgt agc act gca act gtg tgagtagcag gcttgtccgt ggactggcat    3182 
               
               
                 Leu Cys Cys Ser Thr Ala Thr Val 
               
               
                 1030                1035 
               
               
                   
               
               
                 ggaacaggag gtgatacatt tgggattacg tcttggttct gtcacccatc ccaggacagt   3242 
               
               
                   
               
               
                 gtggtgacta ccaaagaaca agcagcagct taagaaggaa gaacaataca aaaccactac   3302 
               
               
                   
               
               
                 atattgtaga aaacctgcct tattggagaa gtcactcccc ctttcctttc tcttcataaa   3362 
               
               
                   
               
               
                 agcagaacaa aaagttttcc acatggctca agttatttga acctggcaaa taataaatgt   3422 
               
               
                   
               
               
                 accttagaac tagaaaaaaa aaaaaaaaaa aaa                                3455 
               
               
                   
               
               
                   
               
               
                 &lt;210&gt; SEQ ID NO 21 
               
               
                 &lt;211&gt; LENGTH: 1037 
               
               
                 &lt;212&gt; TYPE: PRT 
               
               
                 &lt;213&gt; ORGANISM: Mus musculus 
               
               
                   
               
               
                 &lt;400&gt; SEQUENCE: 21 
               
               
                   
               
               
                 Met Glu Val Val Gly Asp Phe Glu Tyr Cys Lys Arg Asp Leu Val Gly 
               
               
                   1               5                  10                  15 
               
               
                   
               
               
                 His Gly Ala Phe Ala Val Val Phe Arg Gly Arg His Arg Gln Lys Thr 
               
               
                              20                  25                  30 
               
               
                   
               
               
                 Asp Trp Glu Val Ala Ile Lys Ser Ile Asn Lys Lys Asn Leu Ser Lys 
               
               
                          35                  40                  45 
               
               
                   
               
               
                 Ser Gln Ile Leu Leu Gly Lys Glu Ile Lys Ile Leu Lys Glu Leu Gln 
               
               
                      50                  55                  60 
               
               
                   
               
               
                 His Glu Asn Ile Val Ala Leu Tyr Asp Val Gln Glu Leu Pro Asn Ser 
               
               
                  65                  70                  75                  80 
               
               
                   
               
               
                 Val Phe Leu Val Met Glu Tyr Cys Asn Gly Gly Asp Leu Ala Asp Tyr 
               
               
                                  85                  90                  95 
               
               
                   
               
               
                 Leu Gln Ala Lys Gly Thr Leu Ser Glu Asp Thr Ile Arg Val Phe Leu 
               
               
                             100                 105                 110 
               
               
                   
               
               
                 His Gln Ile Ala Ala Ala Met Arg Ile Leu His Ser Lys Gly Ile Ile 
               
               
                         115                 120                 125 
               
               
                   
               
               
                 His Arg Asp Leu Lys Pro Gln Asn Ile Leu Leu Ser Tyr Ala Asn Arg 
               
               
                     130                 135                 140 
               
               
                   
               
               
                 Arg Lys Ser Asn Val Ser Gly Ile Arg Ile Lys Ile Ala Asp Phe Gly 
               
               
                 145                 150                 155                 160 
               
               
                   
               
               
                 Phe Ala Arg Tyr Leu His Ser Asn Thr Met Ala Ala Thr Leu Cys Gly 
               
               
                                 165                 170                 175 
               
               
                   
               
               
                 Ser Pro Met Tyr Met Ala Pro Glu Val Ile Met Ser Gln His Tyr Asp 
               
               
                             180                 185                 190 
               
               
                   
               
               
                 Ala Lys Ala Asp Leu Trp Ser Ile Gly Thr Val Ile Tyr Gln Cys Leu 
               
               
                         195                 200                 205 
               
               
                   
               
               
                 Val Gly Lys Pro Pro Phe Gln Ala Asn Ser Pro Gln Asp Leu Arg Met 
               
               
                     210                 215                 220 
               
               
                   
               
               
                 Phe Tyr Glu Lys Asn Arg Ser Leu Met Pro Ser Ile Pro Arg Glu Thr 
               
               
                 225                 230                 235                 240 
               
               
                   
               
               
                 Ser Pro Tyr Leu Ala Asn Leu Leu Leu Gly Leu Leu Gln Arg Asn Gln 
               
               
                                 245                 250                 255 
               
               
                   
               
               
                 Lys Asp Arg Met Asp Phe Glu Ala Phe Phe Ser His Pro Phe Leu Glu 
               
               
                             260                 265                 270 
               
               
                   
               
               
                 Gln Val Pro Val Lys Lys Ser Cys Pro Val Pro Val Pro Val Tyr Ser 
               
               
                         275                 280                 285 
               
               
                   
               
               
                 Gly Pro Val Pro Gly Ser Ser Cys Ser Ser Ser Pro Ser Cys Arg Phe 
               
               
                     290                 295                 300 
               
               
                   
               
               
                 Ala Ser Pro Pro Ser Leu Pro Asp Met Gln His Ile Gln Glu Glu Asn 
               
               
                 305                 310                 315                 320 
               
               
                   
               
               
                 Leu Ser Ser Pro Pro Leu Gly Pro Pro Asn Tyr Leu Gln Val Ser Lys 
               
               
                                 325                 330                 335 
               
               
                   
               
               
                 Asp Ser Ala Ser Asn Ser Ser Lys Asn Ser Ser Cys Asp Thr Asp Asp 
               
               
                             340                 345                 350 
               
               
                   
               
               
                 Phe Val Leu Val Pro His Asn Ile Ser Ser Asp His Ser Tyr Asp Met 
               
               
                         355                 360                 365 
               
               
                   
               
               
                 Pro Met Gly Thr Thr Ala Arg Arg Ala Ser Asn Glu Phe Phe Met Cys 
               
               
                     370                 375                 380 
               
               
                   
               
               
                 Gly Gly Gln Cys Gln Pro Thr Val Ser Pro His Ser Glu Thr Ala Pro 
               
               
                 385                 390                 395                 400 
               
               
                   
               
               
                 Ile Pro Val Pro Thr Gln Val Arg Asn Tyr Gln Arg Ile Glu Gln Asn 
               
               
                                 405                 410                 415 
               
               
                   
               
               
                 Leu Ile Ser Thr Ala Ser Ser Gly Thr Asn Pro His Gly Ser Pro Arg 
               
               
                             420                 425                 430 
               
               
                   
               
               
                 Ser Ala Val Val Arg Arg Ser Asn Thr Ser Pro Met Gly Phe Leu Arg 
               
               
                         435                 440                 445 
               
               
                   
               
               
                 Val Gly Ser Cys Ser Pro Val Pro Gly Asp Thr Val Gln Thr Gly Gly 
               
               
                     450                 455                 460 
               
               
                   
               
               
                 Arg Arg Leu Ser Thr Gly Ser Ser Arg Pro Tyr Ser Pro Ser Pro Leu 
               
               
                 465                 470                 475                 480 
               
               
                   
               
               
                 Val Gly Thr Ile Pro Glu Gln Phe Ser Gln Cys Cys Cys Gly His Pro 
               
               
                                 485                 490                 495 
               
               
                   
               
               
                 Gln Gly His Glu Ala Arg Ser Arg His Ser Ser Gly Ser Pro Val Pro 
               
               
                             500                 505                 510 
               
               
                   
               
               
                 Gln Thr Gln Ala Pro Gln Ser Leu Leu Leu Gly Ala Arg Leu Gln Ser 
               
               
                         515                 520                 525 
               
               
                   
               
               
                 Ala Pro Thr Leu Thr Asp Ile Tyr Gln Asn Lys Gln Lys Leu Arg Lys 
               
               
                     530                 535                 540 
               
               
                   
               
               
                 Gln His Ser Asp Pro Val Cys Pro Ser His Ala Gly Ala Gly Tyr Ser 
               
               
                 545                 550                 555                 560 
               
               
                   
               
               
                 Tyr Ser Pro Gln Pro Ser Arg Pro Gly Ser Leu Gly Thr Ser Pro Thr 
               
               
                                 565                 570                 575 
               
               
                   
               
               
                 Lys His Thr Gly Ser Ser Pro Arg Asn Ser Asp Trp Phe Phe Lys Thr 
               
               
                             580                 585                 590 
               
               
                   
               
               
                 Pro Leu Pro Thr Ile Ile Gly Ser Pro Thr Lys Thr Thr Ala Pro Phe 
               
               
                         595                 600                 605 
               
               
                   
               
               
                 Lys Ile Pro Lys Thr Gln Ala Ser Ser Asn Leu Leu Ala Leu Val Thr 
               
               
                     610                 615                 620 
               
               
                   
               
               
                 Arg His Gly Pro Ala Glu Ser Gln Ser Lys Asp Gly Asn Asp Pro Arg 
               
               
                 625                 630                 635                 640 
               
               
                   
               
               
                 Glu Cys Ser His Cys Leu Ser Val Gln Gly Ser Glu Arg His Arg Ser 
               
               
                                 645                 650                 655 
               
               
                   
               
               
                 Glu Gln Gln Gln Ser Lys Ala Val Phe Gly Arg Ser Val Ser Thr Gly 
               
               
                             660                 665                 670 
               
               
                   
               
               
                 Lys Leu Ser Glu Gln Gln Val Lys Ala Pro Leu Gly Gly His Gln Gly 
               
               
                         675                 680                 685 
               
               
                   
               
               
                 Ser Thr Asp Ser Leu Asn Thr Glu Arg Pro Met Asp Val Ala Pro Ala 
               
               
                     690                 695                 700 
               
               
                   
               
               
                 Gly Ala Cys Gly Val Met Leu Ala Leu Pro Ala Gly Thr Ala Ala Ser 
               
               
                 705                 710                 715                 720 
               
               
                   
               
               
                 Ala Arg Ala Val Leu Phe Thr Val Gly Ser Pro Pro His Ser Ala Thr 
               
               
                                 725                 730                 735 
               
               
                   
               
               
                 Ala Pro Thr Cys Thr His Met Val Leu Arg Thr Arg Thr Thr Ser Val 
               
               
                             740                 745                 750 
               
               
                   
               
               
                 Gly Ser Ser Ser Ser Gly Gly Ser Leu Cys Ser Ala Ser Gly Arg Val 
               
               
                         755                 760                 765 
               
               
                   
               
               
                 Cys Val Gly Ser Pro Pro Gly Pro Gly Leu Gly Ser Ser Pro Pro Gly 
               
               
                     770                 775                 780 
               
               
                   
               
               
                 Ala Glu Gly Ala Pro Ser Leu Arg Tyr Val Pro Tyr Gly Ala Ser Pro 
               
               
                 785                 790                 795                 800 
               
               
                   
               
               
                 Pro Ser Leu Glu Gly Leu Ile Thr Phe Glu Ala Pro Glu Leu Pro Glu 
               
               
                                 805                 810                 815 
               
               
                   
               
               
                 Glu Thr Leu Met Glu Arg Glu His Thr Asp Thr Leu Arg His Leu Asn 
               
               
                             820                 825                 830 
               
               
                   
               
               
                 Met Met Leu Met Phe Thr Glu Cys Val Leu Asp Leu Thr Ala Val Arg 
               
               
                         835                 840                 845 
               
               
                   
               
               
                 Gly Gly Asn Pro Glu Leu Cys Thr Ser Ala Val Ser Leu Tyr Gln Ile 
               
               
                     850                 855                 860 
               
               
                   
               
               
                 Gln Glu Ser Val Val Val Asp Gln Ile Ser Gln Leu Ser Lys Asp Trp 
               
               
                 865                 870                 875                 880 
               
               
                   
               
               
                 Gly Arg Val Glu Gln Leu Val Leu Tyr Met Lys Ala Ala Gln Leu Leu 
               
               
                                 885                 890                 895 
               
               
                   
               
               
                 Ala Ala Ser Leu His Leu Ala Lys Ala Gln Val Lys Ser Gly Lys Leu 
               
               
                             900                 905                 910 
               
               
                   
               
               
                 Ser Pro Ser Met Ala Val Lys Gln Val Val Lys Asn Leu Asn Glu Arg 
               
               
                         915                 920                 925 
               
               
                   
               
               
                 Tyr Lys Phe Cys Ile Thr Met Cys Lys Lys Leu Thr Glu Lys Leu Asn 
               
               
                     930                 935                 940 
               
               
                   
               
               
                 Arg Phe Phe Ser Asp Lys Gln Arg Phe Ile Asp Glu Ile Asn Ser Val 
               
               
                 945                 950                 955                 960 
               
               
                   
               
               
                 Thr Ala Glu Lys Leu Ile Tyr Asn Cys Ala Val Glu Met Val Gln Ser 
               
               
                                 965                 970                 975 
               
               
                   
               
               
                 Ala Ala Leu Asp Glu Met Phe Gln Gln Thr Glu Asp Ile Val Tyr Arg 
               
               
                             980                 985                 990 
               
               
                   
               
               
                 Tyr His Lys Ala Ala Val Leu Leu Glu Gly Leu Ser Lys Ile Leu Gln 
               
               
                         995                 1000                1005 
               
               
                   
               
               
                 Asp Pro Thr Asp Val Glu Asn Val His Lys Tyr Lys Cys Ser Ile Glu 
               
               
                     1010                1015                1020 
               
               
                   
               
               
                 Arg Arg Leu Ser Ala Leu Cys Cys Ser Thr Ala Thr Val 
               
               
                 1025                1030                1035