Abstract:
The present invention relates to a probe for selecting ES cells, which characteristically contains one of DNAs having base sequences depicted in SEQ ID Nos; 1, 2, 3, 4, 5, 6, 7 and 8, or DNAs having base sequences depicted in SEQ ID Nos; 9, 11, 13, 15, 17, 19, 21, 23 and 41 and a screening method of ES cell using this probe. Preparation of a probe for selecting ES cells becomes feasible by identifying plural gene with ES cell-specific expressions (ECAT genes) and using the information of the base sequences of these gene groups. Efficient selection of ES cell enables supply of a large amount of ES cell expected to be applicable to regenerative medicine.

Description:
TECHNICAL FIELD  
         [0001]    The present invention relates to an ECAT gene (ES cell associated transcript gene) specifically expressed in ES cells (embryonic stem cells) and use thereof.  
         BACKGROUND ART  
         [0002]    Embryonic stem (ES) cell is a cell isolated from early embryo of mammal, which semipermanently continues to proliferate, while maintaining an ability to differentiate into any cell-in the body, i.e., pluripotency. ES cell was first established in mouse in 1981, and brought an epoch-making technique of gene function analysis using knock out mice. Ever since the establishment of human ES cell was reported in 1998, application thereof to regenerative medicine has been highly expected. It is an attempt to achieve functional recovery by transplanting heart muscle cells or nerve cells differentiated from ES cells into patients with heart infarction and neurodegenerative diseases.  
           [0003]    While the cell transplant therapy has been already employed, as typically seen in marrow graft in leukemia, it is associated with two problems of securing sufficient supply of cells to be transplanted and suppression of rejection reaction. Use of the ES cell that divides semipermanently altogether solves the problem of secured supply of sufficient amount of cell. When combined with the somatic cell clone technology, moreover, the rejection reaction can be also overcome. When an ES cell is established from a clone embryo prepared from the somatic cell of a patient and used for transplantation, rejection cannot occur since it has the same gene as does the patient. Therefore, ES cell has the potential to simultaneously solve the two problems in the cell transplant therapy.  
           [0004]    While ES cell has the high potential as described above, human ES cell is difficult to establish and maintain as compared to mouse ES cell. Therefore, the development of a reliable establishment technique and a culture technique is necessary. For a human ES cell to be established, moreover, an embryo needs to be sacrificed. When it is combined with the somatic cell clone technology, it easily leads to human cloning. To solve such ethical issues, therefore, the development of a technique to directly produce an ES-like cell having pluripotency from a somatic cell is desired, which does not go through an embryo.  
           [0005]    What plays a key role in the development of these techniques is a gene (ES cell associated transcript gene, hereinafter ECAT gene), which is specifically expressed in pluripotent cells such as ES cell and the like. The ECAT gene becomes a marker to determine if the cell is an ES cell. In addition, ES cell can be efficiently selected from a mixed culture of various kinds of cells by combining a control region of ECAT gene that induces ES cell specific expression and a drug resistance gene (JP-T-9-500004; corresponding U.S. Pat. No. 6,146,888). Furthermore, it may be possible to promote conversion of somatic cell to ES-like cell by inducing expression of ECAT gene.  
           [0006]    The only one gene reported heretofore as an ECAT gene is transcription factor Oct3 (also called Oct4, POU5f1, hereinafter to be referred to as Oct-3/4) gene. While a similar gene has been reported with regard to human (hereinafter to be referred to as hOct-3/4 gene: Takeda et al., Nucleic Acids Res. 20: 4613-4620, 1992, SEQ ID No; 39), no report has been so far found on verified ES cell specific expression of hOct-3/4 gene. Oct-3/4 is a transcription factor that is specifically expressed in an ES cell and EG cell (embryonic germ cells), whose expression disappears along with the cell differentiation. Therefore, it is used as a marker of ES cell, and efficient establishment of ES cell has been attempted by knocking-in a neomycin resistance gene into its gene locus (JP-T-9-500004; corresponding to U.S. Pat. No. 6,146,888). However, a report has also documented that Oct-3/4 is expressed in trophectoderm cell as well, besides pluripotent cells (Biol Reprod 63: 1698-1705, 2000). Thus, use of Oct-3/4 gene alone as an index results in the selection of cells other than ES cells. To avoid this risk, it is desirable to identify plural ECAT genes and use them in combination.  
           [0007]    Even if expression of Oct-3/4 alone in somatic cell is induced, conversion to ES-like cell is not observed. Even if Oct-3/4 is constantly expressed, differentiation of ES cell (differentiation into primitive-endoderm, primitive ectoderm) associated with withdrawal of LIF (leukemia inhibitor factor) cannot be suppressed. To the contrary, an interesting report has been made that, by increasing the expression amount of Oct-3/4 by only about 1.5 times the general level, differentiation similar to that associated with the withdrawal of LIF is induced (Experimental Medicine, 19, 330-338, 2001). As described above, the action of Oct-3/4 is not simple and induction thereof into ES cell by the expression of Oct-3/4 alone in somatic cell is difficult. From this aspect, too, it is considered necessary to combine plural ECAT genes and analyze ES cell.  
           [0008]    Nevertheless, ECAT gene other than Oct-3/4 gene has not been found and there is a strong demand for the provision of a new ECAT gene, from the aspects of regenerative medicine and application of ES cells to cell transplantation.  
         DISCLOSURE OF THE INVENTION  
         [0009]    The present invention aims at provision of a novel ECAT gene. More particularly, the present invention aims at provision of a screening method of ES cell using the new ECAT gene and a gene product peptide encoded thereby, as well as a probe for selecting an ES cell.  
           [0010]    To identify ECAT candidate genes, the present inventors used the EST (Expressed Sequence Tag) data base (detail to be described later) for computer analysis and identified candidate genes to reach 10 genes. Of the 10 genes, 8 genes were subjected to Northern blotting, whereby expression in ES cell and 12 kinds of organs (mouse) was analyzed. As a result, the expression of all the 8 genes was found to be specific to ES cells. It was also found that the expression of these genes quickly disappeared after stimulation of ES cell with retinoic acid, namely, by induction of differentiation. From the above results, the present inventors have found that these 8 genes are ECAT genes, which resulted in the completion of the present invention. Of the remaining two genes, one gene was analyzed by Northern blotting and the like to find the gene to be an ECAT gene.  
           [0011]    Further, they have identified a human gene homologous to the ECAT gene (hereinafter hECAT) and analyzed expression in the ES cell and 13 kinds of organs (human).  
           [0012]    Accordingly, the present invention provides the following.  
           [0013]    (1) A probe for selecting ES cells, comprising a DNA which has a base sequence depicted in any one of SEQ ID Nos; 1, 3, 4, 5, 6, 7 and 8.  
           [0014]    (2) A probe for selecting ES cells, comprising a DNA which hybridizes to a DNA having a base sequence depicted in any one of SEQ ID Nos; 1, 3, 4, 5, 6, 7 and 8 under stringent conditions, and which encodes a protein specifically expressed in an ES cell.  
           [0015]    (3) A probe for selecting ES cells, comprising a DNA which has a base sequence depicted in SEQ ID No; 1, 3, 4, 5, 6, 7 or 8, wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0016]    (4) A probe for selecting ES cells, comprising a DNA which has 5 a base sequence depicted in any one of SEQ ID Nos; 9, 13, 15, 17, 19, 21, 23 and 41.  
           [0017]    (5) The probe of the above-mentioned (4), comprising a DNA which has a base sequence depicted in any one of SEQ ID Nos; 9, 13, 15, 17, 19, 21 and 23.  
           [0018]    (6) A probe for selecting ES cells, comprising a DNA which hybridizes to a DNA having a base sequence depicted in any one of SEQ ID Nos; 9, 13, 15, 17, 19, 21, 23 and 41 under stringent conditions, and which encodes a protein specifically expressed in an ES cell.  
           [0019]    (7) The probe of the above-mentioned (6), comprising a DNA which hybridizes to a DNA which has a base sequence depicted in any one of SEQ ID Nos; 9, 13, 15, 17, 19, 21 and 23 under stringent conditions, and which encodes a protein specifically expressed in an ES cell.  
           [0020]    (8) A probe for selecting ES cells, comprising a DNA which has a base sequence depicted in SEQ ID No; 9, 13, 15, 17, 19, 21, 23 or 41, wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0021]    (9) The probe of the above-mentioned (8), comprising a DNA which has a base sequence depicted in SEQ ID No; 9, 13, 15, 17, 19, 21 or 23, wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0022]    (10) The probe of any of the above-mentioned (1) to (9), which is used for selecting a mouse ES cell.  
           [0023]    (11) A probe for selecting ES cells, comprising a DNA which has a base sequence depicted in any one of SEQ ID Nos; 27, 29, 31, 33, 35, 37 and 43.  
           [0024]    (12) The probe of the above-mentioned (11), which comprises a DNA which has a base sequence depicted in any one of SEQ ID Nos; 27, 29, 31, 33, 35 and 37.  
           [0025]    (13) A probe for selecting ES cells, comprising a DNA which hybridizes to a DNA which has a base sequence depicted in any one of SEQ ID Nos; 27, 29, 31, 33, 35, 37 and 43 under stringent conditions, and which encodes a protein specifically expressed in an ES cell.  
           [0026]    (14) The probe of the above-mentioned (13), which comprises a DNA which hybridizes to a DNA which has a base sequence depicted in any one of SEQ ID Nos; 27, 29, 31, 33, 35 and 37 under stringent conditions, and which encodes a protein specifically expressed in an ES cell.  
           [0027]    (15) A probe for selecting ES cells, comprising a DNA which has a base sequence depicted in SEQ ID No; 27, 29, 31, 33, 35, 37 or 43, wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0028]    (16) The probe of the above-mentioned (15), comprising a DNA which has a base sequence depicted in SEQ ID No; 27, 29, 31, 25 33, 35 or 37, wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0029]    (17) The probe of any of the above-mentioned (11) to (16), which is used for selecting a human ES cell.  
           [0030]    (18) A gene comprising a DNA of any of the following (a)-(c):  
           [0031]    (a) a DNA comprising a base sequence depicted in SEQ ID No; 17  
           [0032]    (b) a DNA which hybridizes to a DNA having a base sequence of  
           [0033]    (a) under stringent conditions, which encodes a protein specifically expressed in an ES cell  
           [0034]    (c) a DNA which has a base sequence of (a), wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0035]    (19) A protein of the following (a) or (b):  
           [0036]    (a) a protein having an amino acid sequence depicted in SEQ ID No; 18  
           [0037]    (b) a protein which has an amino acid sequence of (a), wherein one to several bases are deleted, substituted or added, and which is specifically expressed in an ES cell.  
           [0038]    (20) A gene comprising a DNA of any of the following (a)-(c):  
           [0039]    (a) a DNA comprising a base sequence depicted in SEQ ID No; 29  
           [0040]    (b) a DNA which hybridizes to a DNA having a base sequence of  
           [0041]    (a) under stringent conditions, and which encodes a protein specifically expressed in an ES cell  
           [0042]    (c) a DNA which has a base sequence of (a), wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0043]    (21) A protein of the following (a) or (b):  
           [0044]    (a) a protein having an amino acid sequence depicted in SEQ ID No; 30  
           [0045]    (b) a protein which has an amino acid sequence of (a), wherein one to several bases are deleted, substituted or added, and which is specifically expressed in an ES cell.  
           [0046]    (22) A gene comprising a DNA of any of the following (a)-(c):  
           [0047]    (a) a DNA comprising a base sequence depicted in SEQ ID No; 33  
           [0048]    (b) a DNA which hybridizes to a DNA having a base sequence of  
           [0049]    (a) under stringent conditions, and which encodes a protein specifically expressed in an ES cell  
           [0050]    (c) a DNA which has a base sequence of (a), wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0051]    (23) A protein of the following (a) or (b):  
           [0052]    (a) a protein having an amino acid sequence depicted in SEQ ID No; 34  
           [0053]    (b) a protein which has an amino acid sequence of (a), wherein one to several bases are deleted, substituted or added, and which is specifically expressed in an ES cell.  
           [0054]    (24) A gene comprising a DNA of any of the following (a)-(c):  
           [0055]    (a) a DNA comprising a base sequence depicted in SEQ ID No; 37  
           [0056]    (b) a DNA which hybridizes to a DNA having a base sequence of  
           [0057]    (a) under stringent conditions, and which encodes a protein specifically expressed in an ES cell  
           [0058]    (c) a DNA which has a base sequence of (a), wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell.  
           [0059]    (25) A protein of the following (a) or (b):  
           [0060]    (a) a protein having an amino acid sequence depicted in SEQ ID No; 38  
           [0061]    (b) a protein which has an amino acid sequence of (a), wherein one to several bases are deleted, substituted or added, and which is specifically expressed in an ES cell.  
           [0062]    (26) A method of screening an ES cell, which comprises analyzing an intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 9, 13, 15, 17, 19, 21, 23 or 41, or a protein having an amino acid sequence depicted in SEQ ID No; 10, 14, 16, 18, 20, 22, 24 or 42.  
           [0063]    (27) The method of the above-mentioned (26), wherein the intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 9, 13, 15, 17, 19, 21 or 23, or a protein having an amino acid sequence depicted in SEQ ID No; 10, 14, 16, 18, 20, 22 or 24 is analyzed.  
           [0064]    (28) The method of the above-mentioned (26) or (27), which further comprises analyzing an intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 11, or a protein having an amino acid sequence depicted in SEQ ID No; 12.  
           [0065]    (29) The method of any of the above-mentioned (26) to (28), which further comprises analyzing an intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 25, or a protein having an amino acid sequence depicted in SEQ ID No; 26.  
           [0066]    (30) A method of screening an ES cell, which comprises analyzing an intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 27, 29, 31, 33, 35, 37 or 43, or a protein having an amino acid sequence depicted in SEQ ID No; 28, 30, 32, 34, 36, 38 or 44.  
           [0067]    (31) The method of the above-mentioned (30), wherein the intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 27, 29, 31, 33, 35 or 37, or a protein having an amino acid sequence depicted in SEQ ID No; 28, 30, 32, 34, 36 or 38 is analyzed.  
           [0068]    (32) The method of the above-mentioned (30) or (31), which further comprises analyzing an intracellular expression state of a DNA having a base sequence depicted in SEQ ID No; 39, or a protein having an amino acid sequence depicted in SEQ ID No; 40.  
           [0069]    (33) A probe for selecting ES cells, comprising a DNA which has a non-repetitive sequence comprising not less than 20 continuous bases from a base sequence depicted in SEQ ID No; 9, 11, 13, 15, 17, 19, 21, 23 or 41, or SEQ ID No; 27, 29, 31, 33, 35, 37 or 43, and which has a sequence specific to a gene specifically expressed in an ES cell.  
           [0070]    (34) A method of screening an ES cell, which comprises analyzing an expression state of a gene specifically expressed in an ES cell, using a probe of any of the above-mentioned (1)-(17) and (33).  
           [0071]    (35) The method of the above-mentioned (34), which further comprises using a probe for selecting ES cells comprising a DNA having a base sequence depicted in SEQ ID No; 2 or 11.  
           [0072]    (36) The method of the above-mentioned (34) or (35), which further comprises using an ES cell selection probe comprising a DNA having a base sequence depicted in SEQ ID No; 25.  
           [0073]    (37) The method of the above-mentioned (34), which further comprises using an ES cell selection probe comprising a DNA having a base sequence depicted in SEQ ID No; 27.  
           [0074]    (38) The method of the above-mentioned (34) or (35), which further comprises using an ES cell selection probe comprising a DNA having a base sequence depicted in SEQ ID No; 39.  
           [0075]    The present invention further relates to a recombinant vector having a DNA encoding a gene specifically expressed in an ES cell or a protein specifically expressed in an ES cell, particularly, a vector for forced expression of a differentiation inhibiting gene, and a transformant cell transformed with said vector.  
           [0076]    The present invention moreover relates to a recombinant vector comprising a selection gene such as a drug resistance gene or the like, which is incorporated into a genomic DNA fragment containing a DNA encoding a gene specifically expressed in an ES cell or a protein specifically expressed in an ES cell, particularly a vector for selecting ES cell, and a transformant cell transformed with said vector. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0077]    [0077]FIG. 1 shows an analysis of the expression of each ECAT gene in an ES cell and 12 kinds of organs in adult mouse by Northern blotting.  
         [0078]    [0078]FIG. 2 shows an analysis of the expression of each ECAT gene in an ES cell, a mesenchymal stem cell and 13 kinds of organs in adult human by Northern blotting. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0079]    The present invention relates to a gene specifically expressed in an ES cell (hereinafter to be also referred to as gene with ES cell-specific expression), namely, ECAT gene. It is possible to determine if a cell is an ES cell with the presence of expression of ECAT gene as an index. The present invention provides an ES cell selection probe preferable for deciding on the ES cell as described. As this probe, a polynucleotide containing a DNA comprising a base sequence depicted in any one of SEQ ID Nos; 1-8, a DNA comprising a base sequence depicted in SEQ ID No; 9 (hereinafter ECAT1 gene), a DNA comprising a base sequence depicted in SEQ ID No; 11 (hereinafter ECAT2 gene), a DNA comprising a base sequence depicted in SEQ ID No; 13 (hereinafter ECAT3 gene), a DNA comprising a base sequence depicted in SEQ ID No; 15 (hereinafter ECAT4 gene), a DNA comprising a base sequence depicted in SEQ ID No; 17 (hereinafter ECAT5 gene), a DNA comprising a base sequence depicted in SEQ ID No; 19 (hereinafter ECAT6 gene), a DNA comprising a base sequence depicted in SEQ ID No; 21 (hereinafter ECAT7 gene), a DNA comprising a base sequence depicted in SEQ ID No; 23 (hereinafter ECAT8 gene) or a DNA comprising a base sequence depicted in SEQ ID No; 41 (hereinafter ECAT9 gene) can be specifically mentioned. In the present invention, moreover, the ES cell selection probe may be any as long as it can achieve the object of confirmation of the presence or otherwise of the expression of ECAT gene, and may be the above-mentioned base sequence which underwent modification by substitution, deletion, addition and the like. Specifically, a polynucleotide comprising a DNA that hybridizes to an ECAT gene under stringent conditions and encodes a protein specifically expressed in an ES cell, and a polynucleotide comprising a DNA which has a base sequence of an ECAT gene, wherein one to several bases are deleted, substituted or added, and which is capable of hybridizing, under stringent conditions, to a DNA encoding a protein specifically expressed in an ES cell, can be preferably used as a probe for selecting ES cells in the present invention. Specific examples include a polynucleotide containing a DNA comprising a base sequence depicted in SEQ ID No; 27 (hereinafter hECAT2 gene), a DNA comprising a base sequence depicted in SEQ ID No; 29 (hereinafter hECAT3 gene), a DNA comprising a base sequence depicted in SEQ ID No; 31 (hereinafter hECAT4 gene), a DNA comprising a base sequence depicted in SEQ ID No; 33 (hereinafter hECAT5 gene), a DNA comprising a base sequence depicted in SEQ ID No; 35 (hereinafter hECAT7 gene), a DNA comprising a base sequence depicted in SEQ ID No; 37 (hereinafter hECAT8 gene) or a DNA comprising a base sequence depicted in SEQ ID No; 43 (hereinafter hECAT9 gene).  
         [0080]    In addition, a polynucleotide containing a DNA comprising a base sequence depicted in SEQ ID No; 25, i.e., a DNA encoding Oct-3/4, or a DNA comprising a base sequence depicted in SEQ ID No; 39, i.e., a DNA encoding hOct-3/4 can be also used as an ES cell selection probe. Because a report has documented that the Oct-3/4 gene is expressed even in trophectoderm cells as mentioned above, concurrent use of a polynucleotide preferably containing an ECAT gene other than Oct-3/4 gene or hOct-3/4 gene and the like, such as the novel ES cell selection probe of the present invention is preferable. Even in the case of a novel ES cell selection probe containing the above-mentioned ECAT gene, concurrent use of several kinds of probes is preferable to more accurately determine if it is an ES cell.  
         [0081]    In the present specification, the term “stringent conditions” means the conditions under which a DNA having about 70% or more, preferably about 80% or more, particularly preferably about 90% or more, homology in a base sequence can hybridize, wherein stringency can be controlled by appropriately changing the temperature, salt concentration and the like during hybridizing reaction and washing. More preferable conditions are those under which a DNA having about not less than 95% homology can hybridize.  
         [0082]    ECAT2 gene is reported as a gene pH34 that shows a decreased expression when EC cell is stimulated with retinoic acid (Differentiation 46: 61-67, 1991), and according to the database of RIKEN, it is described as ESG (ES cell specific gene) 1. Furthermore, ECAT3 gene is a gene encoding a mouse protein having an F-box, whose expression in orchis and ovary is reported (Current Biology 9: 1180-1182, 1999). ECAT7 gene is reported as protein DNMT3L that is similar to DNMT3 that causes DNA methylation (Genomics 65: 293-298, 2000). ECAT9 gene is reported as a growth factor called GDF3, in Jones C M et al., Mol Endocrinol. 6: 1961-1968, 1992 for mouse and in Caricasole et al., Oncogene 16: 95-103, 1998 for human. There is no report on an ES cell specific expression. With regard to ECAT4 gene, ECAT5 gene and ECAT6 gene, no report is found in published literatures, but by a protein database search has revealed that ECAT4 gene has a homeo box, ECAT5 gene has homology with oncogene H-Ras, and that ECAT6 gene is similar to keratin. For ECAT5 gene, even though its partial sequence is known, a cDNA sequence per se and the amino acid sequence of a protein that the DNA sequence codes for have not been determined. Accordingly, the present invention provides an ECAT5 gene, an ECAT5 protein, a gene having extremely high homology with these and a protein showing similar behavior with these.  
         [0083]    As used herein, the “gene having extremely high homology” specifically means a gene that hybridizes to ECAT5 gene under stringent conditions, and as long as this requirement is satisfied, one to several bases may be deleted, substituted or added in the base sequence (SEQ ID No; 17) of ECAT5 gene. Specifically, it is a gene having about 70% or more, preferably about 80% or more, more preferably about 90% or more, particularly preferably 95% or more, homology with the ECAT5 gene. The “protein showing similar behavior” means a protein having the characteristics that the ECAT5 protein shows, namely, being specifically expressed in an ES cell. As long as this requirement is satisfied, one to several amino acids may be deleted, substituted or added in the amino acid sequence (SEQ ID No; 18) of ECAT5 protein.  
         [0084]    Moreover, the ES cell selection probe of the present invention encompasses a DNA fragment consisting of a partial sequence comprising 20 or more continuous bases without a repeated sequence, from the base sequence described in SEQ ID No; 9, 11, 13, 15, 17, 19, 21, 23 or 41, or SEQ ID No; 27, 29, 31, 33, 35, 37 or 43, which are constructed based on the sequences of various ECAT genes and hECAT genes. The DNA fragment is not particularly limited as long as it can hybridize to ECAT gene or hECAT gene. Specifically, it is a DNA containing a continuous partial sequence generally comprising 20 bases or more, preferably about 100 bases or more, and more preferably about 200 bases or more, of the base sequence of each SEQ ID No, which contains at least a sequence specific to various ECAT genes or hECAT genes intended for detection, and which does not consist of a repeated sequence alone. Preferable examples thereof include a DNA fragment depicted in SEQ ID Nos; 1-8.  
         [0085]    Of the aforementioned 9 kinds of mouse ECAT genes, 7 kinds of ECAT2 gene, ECAT3 gene, ECAT4 gene, ECAT5 gene, ECAT7 gene, ECAT8 gene and ECAT9 gene have been found to have the corresponding human ECAT genes (mentioned below: hECAT2 gene, hECAT3 gene, hECAT4 gene, hECAT5 gene, hECAT7 gene, hECAT8 gene and hECAT9 gene, respectively). Of these, the base sequences of hECAT3, hECAT5 and hECAT8 genes and the amino acid sequences of the proteins encoded by the base sequences have not been determined. Accordingly, the present invention provides the genes and proteins of hECAT3, hECAT5 and hECAT8, as well as genes having extremely high homology therewith and proteins showing similar behaviors.  
         [0086]    Here, the “genes having extremely high homology” and the “proteins showing similar behaviors” specifically mean genes that hybridize to the genes of hECAT3, hECAT5 or hECAT8 under stringent conditions. As long as this requirement is satisfied, one to several bases may be deleted, substituted or added in the base sequences of hECAT3, hECAT5 and hECAT8 genes (SEQ ID No; 29, SEQ ID No; 33 and SEQ ID No; 37, respectively). To be precise, it is a gene having about 70% or more, preferably about 80% or more, more preferably about 90% or more, particularly preferably 95% or more, homology with those genes. The “proteins showing similar behaviors” mean proteins having the characteristics of the hECAT3 protein, hECAT5 protein or hECAT8 protein. As long as this requirement is satisfied, one to several amino acids may be deleted, substituted or added in the amino acid sequences of hECAT3 protein, hECAT5 protein and hECAT8 protein (SEQ ID No; 30, SEQ ID No; 34 and SEQ ID No; 38, respectively).  
         [0087]    The probe of the present invention can be prepared according to the methods known in this field. For example, this probe can be prepared as a DNA isolated by cleaving EST of the corresponding ECAT gene with a restriction enzyme, a DNA obtained by amplification of PCR using, as a template, genomic DNA, complementary DNA (cDNA) prepared from ES cell-derived mRNA, chemically synthesized DNA, and a DNA constructed by a suitable combination of these methods.  
         [0088]    The present invention provides a screening method of ES cell, which is characterized by analyzing the expression state of a gene specifically expressed in an ES cell. As used herein, the tgene specifically expressed in an ES cell“is the same as the aforementioned ECAT gene or hECAT gene, and is specifically exemplified by ECAT1 gene, ECAT2 gene, ECAT3 gene, ECAT4 gene, ECAT5 gene, ECAT6 gene, ECAT7 gene, ECAT8 gene, ECAT9 gene, hECAT2 gene, hECAT3 gene, hECAT4 gene, hECAT5 gene, hECAT7 gene, hECAT8 gene and hECAT9 gene, as well as Oct-3/4gene, hOct-3/4 gene and the like.  
         [0089]    In the present invention, ES cell is screened by analyzing the expression state of a gene specifically expressed in ES cells or a protein specifically expressed in ES cells and encoded by said gene. For the analysis of expression state at the gene level, the aforementioned probe for selecting ES cells can be used. It is also preferable to concurrently use a probe comprising a polynucleotide having a DNA encoding Oct-3/4, as mentioned above. Such probe may be labeled with a fluorescent substance, an enzyme, a radioisotope or the like. For the analysis of the expression state at the protein level, a substance having specific affinity for the above-mentioned protein specifically expressed in ES cells, such as an antibody, is used to examine intracellular expression of the protein. More specifically, methods utilizing an antigen-antibody reaction generally practiced in the pertinent field, such as immunoblot, immunoprecipitation and the like, are used. The antibody here is not particularly limited as long as it can specifically bind to the protein, and may be any of a polyclonal antibody, a monoclonal antibody and a functional fragment thereof. These antibodies and fragments thereof may be labeled with a fluorescent substance, an enzyme, a radioisotope or the like.  
         [0090]    Moreover, they may be commercially available ones or may be prepared appropriately according to a conventional method.  
         [0091]    The present invention relates to an expression vector comprising any of the above-mentioned gene specifically expressed in ES cells and a gene encoding a protein specifically expressed in ES cells. As used herein, the gene specifically expressed in ES cells is as defined above, and the gene encoding a protein specifically expressed in ES cells is specifically a gene encoding ECAT1 (SEQ ID No; 10), a gene encoding ECAT2 (SEQ ID No; 12) or hECAT2 (SEQ ID No; 28), a gene encoding ECAT3 (SEQ ID No; 14) or hECAT3 (SEQ ID No; 30), a gene encoding ECAT4 (SEQ ID No; 16) or hECAT4 (SEQ ID No; 32), a gene encoding ECAT5 (SEQ ID No; 18) or hECAT5 (SEQ ID No; 34), a gene encoding ECAT6 (SEQ ID No; 20), a gene encoding ECAT7 (SEQ ID No; 22) or hECAT7 (SEQ ID No; 36), a gene encoding ECAT8 (SEQ ID No; 24) or hECAT8 (SEQ ID No; 38) and a gene encoding ECAT9 (SEQ ID No; 42) or hECAT9 (SEQ ID No; 44) can be mentioned. The expression vector preferably has a function of suppressing the differentiation by expression of the vector in the cell, particularly ES cells, in light of the nature of the gene contained in the vector. In other words, it is a vector that forcibly expresses a differentiation inhibiting gene (hereinafter to be also referred to as vector for forced expression of the differentiation inhibiting gene). The expression vector of the present invention is not particularly limited as long as it is capable of maintaining replicability or autonomous growth in various animal cells and expressing the gene specifically expressed in ES cells, and encompasses virus vector, plasmid vector and the like. This expression vector can be prepared based on conventional genetic engineering, for example, according to basic textbooks such as Molecular cloning 2nd Ed., Cold Spring Harbor Laboratory Press (1989) and the like. The vector is preferably a virus vector, which is prepared by incorporating gene specifically expressed in ES cells or the like into DNA virus or RNA virus such as retrovirus, adenovirus, adeno-associated virus, herpesvirus, vaccinia virus, poxvirus, poliovirus, sindbis virus or the like. Where necessary, a desired promoter region, a drug resistance gene region or an expression regulatory region can be also introduced.  
         [0092]    The expression vector of the present invention is 1o introduced into a cell according to conventionally known methods such as transfection, lipofection, microinjection, ballistic missile, electroporation or the like.  
         [0093]    Whether or not the expression vector of the present invention thus prepared is incorporated into a host cell and expressed can be confirmed by, for example, determining the amount of protein (polypeptide) that the introduced ECAT gene expressed and produced by, for example, ELISA and the like.  
         [0094]    In addition to the use of the ECAT gene as a probe to determine if a cell is an ES cell, the ECAT gene can be also used for selective separation of ES cells from a mixture of ES cells and other kinds of cells. The present inventors have prepared a targeting vector to knock-in a drug selection gene into a protein translation region of each ECAT gene and, using this vector, established ES cells that caused homologous recombination. Specifically, the technique described in JP-T-9-500004 (corresponding to U.S. Pat. No. 6,146,888) was applied. For example, a cell wherein a neomycin resistance gene had been knocked-in into an ECAT3 gene, ECAT4 gene or ECAT5 gene was cultured in the presence of G418, but cell differentiation was not observed in a selected cell. Such results suggest a possible use of the ECAT gene for the selective separation of ES cells. For an ensured selection of ES cells alone, it is preferable to perform homologous recombination using plural kinds of vectors incorporating different ECAT genes.  
       EXAMPLES  
       [0095]    The present invention is explained in detail by referring to Examples, which are not to be construed as limitative.  
       Example 1  
     Identification of Mouse ECAT Gene  
       [0096]    (1) Identification of Candidate Gene by Computer Analysis  
         [0097]    (Procedure)  
         [0098]    The EST database was used to identify the candidate genes of ECAT. EST is obtained by randomly extracting a number of cDNA clones from cDNA libraries derived from various cells and organs, analyzing only one reaction of the 5′ or 3′ end sequence thereof and registering same in a public database. ESTs can be said to be a catalog of genes expressed in each cell and each organ. More than one million clones derived from mouse and more than 30000 clones derived from mouse ES cell have been registered.  
         [0099]    As the EST database, Unigene was used. Unigene is prepared by clustering clones of EST, which are considered to be derived from the same gene, and as of Mar. 5, 2001, 79917 sets have been reported for the mouse EST database, where each set consists of at least one EST or known gene.  
         [0100]    As a method of analysis, Digital differential display method was used. This method is used to examine the frequency of presence of each set in the libraries of designated cells and organs, namely, the number of EST clones contained in each set is divided by the number of entire EST registrations derived from the library thereof, thereby to examine the frequency of expression between different cells and between different organs.  
         [0101]    The frequency of gene expression in the libraries derived from the following 5 kinds of cells and an organ was analyzed by the Digital differential display method. The number in the parenthesis for each group is the number of analyzed clones. For Group 1 to Group 5, all the corresponding libraries were analyzed. Since the data of Group 6 contained enormous quantity, 23 libraries extracted while including organs and cells of the entire body as many kinds as possible were analyzed.  
         [0102]    Group 1 fertilized eggs from 1-cell stage to blastocyst (49050 clones)  
         [0103]    Group 2 ES cell or Embryonic carcinoma cells (32277 clones)  
         [0104]    Group 3 fetus up to 8.5 days after fertilization (46728 clones)  
         [0105]    Group 4 fetus after 9 days from fertilization (128882 clones)  
         [0106]    Group 5 orchis (65685 clones)  
         [0107]    Group 6 other cells, tissues (272460 clones)  
         [0108]    As regards the set expected to specifically express in fertilized eggs and pluripotent cells, such as ES cell and the like, by the Digital differential display method, the mouse-derived EST database was searched using BlastN to examine if EST was present only in the pluripotent cell-derived libraries.  
         [0109]    The database and analysis program had the following URLs.  
         [0110]    Unigene Mouse Sequence Collection  
         [0111]    http://www.ncbi.nlm.nih.gov/Unigene/Mm.Home.html  
         [0112]    Digital Differential Display  
         [0113]    http://www.ncbi.nlm.nih.gov/Unigene/ddd.cgi?ORG=Mm  
         [0114]    Blast Search  
         [0115]    http://www.ncbi.nlm.nih.gov/BLAST/  
         [0116]    (Results)  
         [0117]    As a result of the analysis by the Digital differential display method and EST database search using BlastN, 10 genes were identified. ESTs of these genes were highly frequently present in fertilized eggs and ES cells but were not found in other cells and tissues of Group 6. While EST was included in the fetus- and orchis-derived libraries for some genes, since this was highly likely derived from primordial germ cell or sperm mother cell, which is a pluripotent cell, they were included in the candidates for ECAT gene. While Oct-3/4 gene was present at high frequency in the fertilized eggs and ES cell, it was also contained in other cells and organs, though small in number. Of the candidates, mouse-derived EST database was searched for 8 genes using BlastN, the results of which are shown in Table 1 (ECAT1-8).  
         [0118]    Of the remaining two genes, one gene (ECAT9) was analyzed in the same manner. The results are shown in Table 1.  
                                                                                   TABLE 1                                       EST                eggs   ES (EC)   -E8.5   E9-   testis   others       ECATs   Group 1   Group 2   Group 3   Group 4   Group 5   Group 6                    Oct3/4   10   13   4   1   0   2       1   7   24   0   0   0   0       2   32   18   0   0   0   0       3   37   13   0   0   0   0       4   2   14   1   1   3   0       5   0   11   0   0   0   0       6   0   7   0   0   0   0       7   4   9   0   0   1   2       8   0   7   0   0   2   0       9   4   11   0   0   0   2                  
 
         [0119]    (2) Northern Blotting Analysis  
         [0120]    (Procedure)  
         [0121]    The candidate genes identified by computer analysis were analyzed for actual ES cell specific expression by Northern blotting. Using Trizol (manufactured by Lifetech Oriental Co. Ltd.), total RNA was extracted from undifferentiated ES cells and ES cells differentiation-induced with retinoic acids for 5 days. RNAs derived from various organs of adult mice were purchased from Sawady Technology Co., Ltd. The total RNA (5 μg) was separated by formalin agarose gel, transferred to a nylon membrane and fixed with UV closslink. When EST of an object gene was available for purchase, this DNA was used as a probe. When EST was not available, a DNA fragment specific for each ECAT was amplified by PCR and used as a probe. To be specific, using the following probes, the expression of Oct-3/4, ECAT1, ECAT2, ECAT3, ECAT4, ECAT5, ECAT6, ECAT7 and ECAT8 was examined. In addition, the expression of ECAT9 was also examined.  
         [0122]    Oct-3/4: a DNA fragment containing a sequence depicted in SEQ ID No; 25, which was prepared by cleaving plasmid C1 in BS KS (Cell 60: 461-472, 1990) with EcoRI.  
         [0123]    ECAT1: a DNA fragment containing a sequence depicted in SEQ ID No; 1, which was prepared by cleaving Mm.31054EST (#AI467128) with SalI/NotI.  
         [0124]    ECAT2: a DNA fragment containing a sequence depicted in SEQ ID No; 2, which was prepared by cleaving pH34EST (#AA473366) with SalI/NotI.  
         [0125]    ECAT3: a DNA fragment containing a sequence depicted in SEQ ID No; 3, which was prepared by cleaving FBX15EST(#AA571680) with SalI/NotI.  
         [0126]    ECAT4: a DNA fragment containing a sequence depicted in SEQ ID No; 4, which was prepared by cleaving the fragment with EcoRI from a plasmid obtained by amplifying a homeobox coding region for gateway by PCR and TA cloning the same.  
         [0127]    ECAT5: a DNA fragment containing a sequence depicted in SEQ ID No; 5, which was prepared by cleaving the fragment with EcoRI from a plasmid obtained by RT-PCR of E-RasS118/RACE11 and TA cloning.  
         [0128]    ECAT6: a DNA fragment containing a sequence depicted in SEQ ID No; 6, which is a keratin-E PCR product (48927S/48927AS).  
         [0129]    ECAT7: a DNA fragment containing a sequence depicted in SEQ ID No; 7, which was prepared by cleaving out from DNMT3LEST clone (AA895770, pBSSK-dnmt31) with EcoRI/XhoI.  
         [0130]    ECAT8: a DNA fragment containing a sequence depicted in SEQ ID No; 8, which was prepared by cleaving Mm.77010RACE product from TA cloned plasmid with EcoRI.  
         [0131]    ECAT9: a DNA fragment containing a sequence depicted in SEQ ID No; 41, which was prepared by reference to GDF3 (Jones C M. et al., mentioned above).  
         [0132]    Probes were labeled with  32 P-dCTP using a Mega labeling kit manufactured by Amersham Pharmacia. Hybridization was performed using Quickhyb of Funakoshi Co., Ltd. Signals after washing were analyzed using BAS5000 of Fuji Photo Film Co., Ltd.  
         [0133]    (Results)  
         [0134]    Of the 10 genes identified by the computer search, 9 genes were so far subjected to Northern blotting, and the expression in ES cell and 12 kinds of organs was analyzed. To be precise, the expression of each ECAT gene in ES cell and 12 kinds of organs of adult mouse was each analyzed by Northern blotting, the results of which are shown in FIG. 1.  
         [0135]    It was found that every expression relating to 9 genes was specific to ES cell. While expression was somewhat observed in orchis, it was considered to have been derived from sperm mother cell. It was also found that the expression of these genes disappear quickly when ES cell was induced with retinoic acid stimulation. From these results, the 9 genes were considered to be ECAT genes.  
         [0136]    (3) Analysis of ECAT Gene  
         [0137]    when ECAT gene is an unknown gene, the full length cDNA was identified according to RACE (Rapid Amplification of cDNA Ends) method using 5′RACE system, version 2 of Lifetech Oriental Co. Ltd. The RIKEN database of mouse full length cDNA was searched at URL (http://genome.gsc.riken.go.jp/).  
       Example 2  
     Analysis of Known Information of the Obtained ECAT Gene  
       [0138]    (1) Blast Search  
         [0139]    EST sequence of 8 genes confirmed to be ECAT genes as a result of Northern blotting was searched using Blast. As a result, the sequences of 3 genes were already reported in papers. ECAT2 gene was reported as gene pH34 that shows a decrease in expression when EC cell is stimulated with retinoic acid. ECAT4 gene was reported as a mouse protein having F box, whose expression is observed only in orchis and ovary. ECAT7 gene was reported as protein DNMT3L similar to DNMT3 that performs DNA methylation. Identification of full length cDNA was tried by the RACE method and translation region was identified for ECAT4 gene, ECAT5 gene and ECAT6 gene. Deducible amino acid sequence was searched using BlastP and it was found that ECAT4 gene has homeobox, ECAT5 gene has homology with cancer gene H-Ras, and ECAT6 gene is similar to keratin. In addition, ECAT9 gene, which was newly confirmed to be ECAT gene, was found to be a growth factor called GDF3.  
         [0140]    (2) Search Through RIKEN Mouse cDNA Database  
         [0141]    The mouse full length cDNA database published from in February 2001 by RIKEN was searched. As a result, full length cDNAs of 8 genes except ECAT5 gene were found to have been published. ECAT5 gene was not included in the database. In addition, ECAT2 gene is described as an ES cell specific gene (ESG) 1 in the RIKEN database, but no information was available as regards the expression of other 8 genes in ES cell.  
       Example 3  
     Identification of Human ECAT Gene  
       [0142]    (1) Blast Search of Human Genomic DNA Database and Human Protein Database  
         [0143]    As a result of Blast search, ECAT2-5, 7, 8 genes were found to have ortholog having an amino acid sequence identical in not less than 50%. For ECAT9 gene, too, hECAT9 gene exists as hGDF3 (Caricasole et al., mentioned above). As regards ECAT1 gene and ECAT6 gene, human ortholog could not be identified.  
         [0144]    As a result of BlastP search, there was no publication of base sequence or amino acid sequence including hypothetical protein, for 3 genes of hECAT3 gene, hECAT5 gene and hECAT8 gene.  
       Example 4  
     Confirmation of Expression of Human Homologous Gene  
       [0145]    The ES cell specific expression of ECAT gene in primates was confirmed.  
         [0146]    Respective total RNAs derived from 13 kinds of organs of adult human (purchased from Sawady Technology Co., Ltd. or Funakoshi Co., Ltd.), total RNA derived from human mesenchymal stem cell (purchased from Takara), and total RNA derived from simian ES cell (undifferentiated and differentiation induced with retinoic acid, provided by Professor Nakatsuji of the Institute For Frontier Medical Sciences) were analyzed by the Northern blotting method. The full length cDNA of EST clone corresponding to hECAT2,4,7,8,9 and hOct3/4 was used as a probe. While hybridization was performed in the same manner as in the analysis of mouse ECAT in the above-mentioned Example 1, the temperature of reaction and washing was set lower (50° C.) so that simian RNA could be detected using the human probe. As a result, every gene showed a strong signal in undifferentiated ES cell (FIG. 2). Along with the differentiation of the ES cell, signal was dramatically attenuated. While a smear thin signal was observed in other organs (cells), this is considered to be a nonspecific one caused by the lowered temperature of reaction and washing. From the foregoing results, it has been confirmed that ECAT genes selectively express in ES cells of not only mouse but of primates, as marker genes thereof.  
       Industrial Applicability  
       [0147]    According to the present invention, 9 kinds of ECAT genes specifically expressed in mouse ES cell can be newly provided. In addition, human ECAT genes corresponding to 7 kinds out of these 9 kinds can be provided. Moreover, selective cell markers of ES cell can be obtained by combining these ECAT genes or fragments thereof. Furthermore, the present invention is more effective for a method for selecting ES cell based on a combination with drug resistance gene, in an attempt to introduce somatic cell into ES cell-like cell and the like than the single use of Oct-3/4 gene or a fragment thereof, and is considered to be useful in the actual application of a regenerative therapy and the like.  
         [0148]    This application is based on a patent application Ser. No. 2001-165927 filed in Japan, the contents of which are hereby incorporated by reference.  
     
       
       
         1 
         
           
             44  
           
           
             1  
             836  
             DNA  
             Mus musculus  
           
            1 

gcgaggctgc cacccggccg gctcccggga aggtccgcaa ggcggccacc cagccggctc     60 

cggtgcaggt ttgccaggag gccacccagt tggctcccgt gaaggtccgc gaggcggcca    120 

cccagccggc ttccgggaag gtccgcgagg cggccaccca gttggctcct gtgaaggtcc    180 

gcaaggcagc cacccagttg gctcctgtga aggtccacga ggcggccacc cagccggctc    240 

cggggaaggt cagcgatgct gccacgcagt cggcttcggt gcaggttcgt gaggctgcca    300 

cgcagctgtc tcccgtggag gccactgata ctagccagtt ggctcaggtg aaggctgatg    360 

aagcctttgc ccagcacact tcaggggagg cccaccaggt tgccaatggg cagtctccca    420 

ttgaagtctg tgagactgcc accgggcagc attctctaga tgtctctagg gccttgtccc    480 

agaagtgtcc tgaggttttt gagtgggaga cccagagttg tttggatggc agctatgtca    540 

tagttcagcc tccaagggat gcctgggaat catttatcat attataaatg catctctggt    600 

gtgagccagg atagatggta cacgtctgca aatccagaac ctaaaggcag gggttagctt    660 

gggctgagta aggcaatgat cttaaacctc agcctgccta agactccctt catctttctt    720 

tctggttttt gccctaggaa tcgggaagaa cagagtagag ctgtttttgt ttccccattg    780 

tgttaaatgt ttgcagacac aatttaaagt attctaataa aaaaaaaatt gcattc        836 

 
           
             2  
             591  
             DNA  
             Mus musculus  
           
            2 

gccgtgcgtg gtggataagc ttgatctcgt cttccctgaa gtctggttcc ttggcaggat     60 

gatggtgacc ctcgtgaccc gtaaagatat ccccccgtgg gtgaaagttc ctgaagacct    120 

gaaagatcca gaagtattcc aggtccagtc gctggtgctg aaatatctgt ttggcccaca    180 

gggatctcga atgtctcaca tcgagcaggt gagccaggcc atgtttgagc tgaagaacct    240 

ggaatctccc gaagaactta tcgaggtctt catttacggc tctcaaaaca acaagattcg    300 

ggctaaatgg atgcttcagt ccatggctga gaggtaccac ctgcgccagc aaaaaggagt    360 

gctgaagctg gaggaatcca tgaagaccct ggagctaggc cagtgtatcg agtgaagcca    420 

gtttccagtc cttgtgtctc cgacctggat gcaggttaag ctgtggccag tgtttggttc    480 

tggcgggatt tttagctttg ttacatccta gcaagatatt ctggatccct gctgcgcatt    540 

ctgatgtgaa tcccaaggtt accactctaa ataaaaaata aaattgaagt g             591 

 
           
             3  
             1667  
             DNA  
             Mus musculus  
           
            3 

acttgcctgt ccaagatctg ttggaatctg cttctacaga agaccagctg aaacaaatag     60 

cttcgtggga ctgagcacaa ctactagatt cttggacttc cgttcacagc tgccaattgt    120 

tgggagtaca ataatggagg agtcggaatt ggagattttt agaagtaagt ttgttagagg    180 

ctcatctgtc acgaagcagc atgcctggcg aaaccagcac agcgagaagc gttgctcttc    240 

ctccatcagt tctatatccc tggacagaat gccatcggaa atcttggtga agatactttc    300 

ttacttggat gcggtgacct tggtgtgcat tggatgtgtg agcagacgct tttatcattt    360 

ggctgatgac aatcttattt gggtcaggaa gtacgcagct gcatttagat caaaaagatc    420 

acgttggaaa gctacttcag tggaggaaac agccacaagt ctgagcttgc tgtcagtttg    480 

ggataaagaa gatggatact ggaagaaaga atatattaca aagcagatct catctgtgag    540 

agcagccctc accaacagcc tcagtcctgt caaacgccgc acaagccttc cttcgaaaac    600 

caaagagtcc ctcagaatat ctggcttagg ttggacaatc atcttaagag aagccagtgg    660 

caaagaacac atcatgcagc attcgaatct ttccgtaaat gacaactctg tcactgtttt    720 

ttggcatgac aaaaattggc cacatgtaga cacgttgtcc accctggatt tgtatggtgc    780 

cacaccaatt tttatggagc agtataaagg ccctaacaca agttgtccac gatggctgtc    840 

tttaattgaa aagtacgatc tgagtaattt acgcaagtct gctatgattg gctgcgacag    900 

acatgttcgg gtattctgtg taaatcctgg cctcctggtg gggctgtggc aggagaatgg    960 

tggactagct tttgtcatgg caaatattca ttcccatggc cttttcgaga gaagcataat   1020 

gggctcagac actattccct atacattgcc tcccgacact acatttgtgg ataactaccc   1080 

agactcaatg accttttatg gagataaagg ctttcagctg catatcgaca ttcatggcag   1140 

taagacttac ttcctgtgta gcaccttcca caatctcttc tgcaggagag cgggcattaa   1200 

caatggatat gtgaagttct tgatgataaa cttaaaaaat aacagagaac acctacctct   1260 

tgttggaaaa gttggccttg aatggagaac tgactgttta aatggccgta ttgagagttg   1320 

cattgtagtg gatatgacct tgctggatga ggacaagaag cccatctggt atgtgagttc   1380 

tccagtgtgc ttgagatctg cctgccttcc tgatttcccg cagccggctt actctttcga   1440 

gtacatggac agcgtaggag gagtgtgcgc agacctaggg tggtttgaaa ataccgatga   1500 

atacttcatt gtcagactgg acatttacct cagtgtagca aaattacaac aatggtttgg   1560 

gaggcaataa atgctgagtt agcagtaggg agtcttgtta ttagtaagct gtttgttttt   1620 

tacaactttg tttttattga aagttaaaat aaagcatatt tgtggta                 1667 

 
           
             4  
             930  
             DNA  
             Mus musculus  
           
            4 

ctgacatgag tgtgggtctt cctggtcccc acagtttgcc tagttctgag gaagcatcga     60 

attctgggaa cgcctcatca atgcctgcag tttttcatcc cgagaactat tcttgcttac    120 

aagggtctgc tactgagatg ctctgcacag aggctgcctc tcctcgccct tcctctgaag    180 

acctgcctct tcaaggcagc cctgattctt ctaccagtcc caaacaaaag ctctcaagtc    240 

ctgaggctga caagggccct gaggaggagg agaacaaggt ccttgccagg aagcagaaga    300 

tgcggactgt gttctctcag gcccagctgt gtgcactcaa ggacaggttt cagaagcaga    360 

agtacctcag cctccagcag atgcaagaac tctcctccat tctgaacctg agctataagc    420 

aggttaagac ctggtttcaa aaccaaaggg tgaagtgcaa gcggtggcag aaaaaccagt    480 

ggttgaagac tagcaatggt ctgattcaga agggctcagc accagtggag tatcccagca    540 

tccattgcag ctatccccag ggctatctgg tgaacgcatc tggaagcctt tccatgtggg    600 

gcagccagac ttggaccaac ccaacttgga gcagccagac ctggaccaac ccaacttgga    660 

acaaccagac ctggaccaac ccaacttgga gcagccaggc ctggaccgct cagtcctgga    720 

acggccagcc ttggaatgct gctccgctcc ataacttcgg ggaggacttt ctgcagcctt    780 

acgtacagtt gcagcaaaac ttctctgcca gtgatttgga ggtgaatttg gaagccacta    840 

gggaaagcca tgcgcatttt agcaccccac aagccttgga attattcctg aactactctg    900 

tgactccacc aggtgaaata tgagacttac                                     930 

 
           
             5  
             845  
             DNA  
             Mus musculus  
           
            5 

actgcccctc atcagactgc tactcctggg agcacagcac ctgctcttta cacctcttcc     60 

ttgagctgct ggggaatggc tttgcctaca aagtctagca tcttggacct gagctccggc    120 

accccatgca ccagatctcc agaggaaagt cacgaggctt gggcacagtg caaagatgct    180 

ggcaggcagc tacccgagta caaggcagtg gtggtgggtg caagtggtgt tggtaaaagt    240 

gctctcacca tccagatgac tcaccaatgc ttcgtgaaag accatgaccc cactatccaa    300 

gattcctact ggaaggaagt ggccagggac aacggaggct acattctaaa tgttctggat    360 

acatctgggc aggatattca ccgggctctg cgtgaccagt gcttggcatc tggtgatggt    420 

gtgctgggcg tctttgctct tgacgacccc tcgtctctgg accagttgca gcagatatgg    480 

tccacctgga cccctcacca caagcagcct ctggtactag tgggcaacaa gtgtgacctg    540 

gtgaccactg ctggagatgc tcatgctgcc gcagccctcc ttgctcacaa gttgggggcc    600 

cccttggtga agacctcagc caagacgcgg caaggtgtgg aggaagcctt tgccctgctt    660 

gtccatgaga ttcagagggc ccaggaggct gtggccgaat caagcaagaa gacccgacac    720 

cagaaagccg tgtgtagctg tggctgctct gtagcctgaa gatctttgtc tagcaaattg    780 

acccttgtct catgtcaagg tgacaattct cttgtaataa gatctccctc tccgaccaag    840 

ttacc                                                                845 

 
           
             6  
             166  
             DNA  
             Mus musculus  
           
            6 

actgaggccc ctgtctgcgt atgatagccc aggcccagga ccttaggctg cagctccctg     60 

catctactgc caagcctgaa ctcctatgag ctagctgttg ccttctgtgt ttgctttgtg    120 

ctgcccctta cagagaggcc ccttgggttg accccagaaa ttgcta                   166 

 
           
             7  
             1521  
             DNA  
             Mus musculus  
           
            7 

ggagacacct tcttcttgct ctaagaccct tgaaaccttg gacctggaga cttccgacag     60 

ctctagccct gatgctgaca gtcctctgga agagcaatgg ctgaaatcct ccccagccct    120 

gaaggaggac agtgtggatg tggtactgga agactgcaaa gagcctctgt ccccctcctc    180 

gcctccgaca ggcagagaga tgatcaggta cgaagtcaaa gtgaaccgac ggagcattga    240 

agacatctgc ctctgctgtg gaactctcca ggtgtacact cggcacccct tgtttgaggg    300 

agggttatgt gccccatgta aggataagtt cctggagtcc ctcttcctgt atgatgatga    360 

tggacaccag agttactgca ccatctgctg ttccgggggt accctgttca tctgtgagag    420 

ccccgactgt accagatgct actgtttcga gtgtgtggac atcctggtgg gccccgggac    480 

ctcagagagg atcaatgcca tggcctgctg ggtttgcttc ctgtgcctgc ccttctcacg    540 

gagtggactg ctgcagaggc gcaagaggtg gcggcaccag ctgaaggcct tccatgatca    600 

agagggagcg ggccctatgg agatatacaa gacagtgtct gcatggaaga gacagccagt    660 

gcgggtactg agccttttta gaaatattga taaagtacta aagagtttgg gctttttgga    720 

aagcggttct ggttctgggg gaggaacgct gaagtacgtg gaagatgtca caaatgtcgt    780 

gaggagagac gtggagaaat ggggcccctt tgacctggtg tacggctcga cgcagcccct    840 

aggcagctct tgtgatcgct gtcccggctg gtacatgttc cagttccacc ggatcctgca    900 

gtatgcgctg cctcgccagg agagtcagcg gcccttcttc tggatattca tggacaatct    960 

gctgctgact gaggatgacc aagagacaac tacccgcttc cttcagacag aggctgtgac   1020 

cctccaggat gtccgtggca gagactacca gaatgctatg cgggtgtgga gcaacattcc   1080 

agggctgaag agcaagcatg cgcccctgac cccaaaggaa gaagagtatc tgcaagccca   1140 

agtcagaagc aggagcaagc tggacgcccc gaaagttgac ctcctggtga agaactgcct   1200 

tctcccgctg agagagtact tcaagtattt ttctcaaaac tcacttcctc tttagaaatg   1260 

aatcaccata agatgaaagt ctttcctaga accagggcag atttcttcct aaggtctctt   1320 

ccctccacag ttttctctgg tttgctttca ggccttcggg tttctctcct gtttgattgc   1380 

caggatgcct ctgtgcagct cactttgcgg ggtgggaggt gcctacggct ctgcacaagt   1440 

tcccggtggg ataacctgcc atgtttctct gaaactgtgt gtacctgttg tgaagttttt   1500 

caaatatatc ataggattgt t                                             1521 

 
           
             8  
             489  
             DNA  
             Mus musculus  
           
            8 

atatatgctg atccagatgt tccatcagta agtgggtcta gccagaggcc gaatgagaag     60 

ccactgcggt tgactgaaaa gaaagactgt gacgagaaga acggctgtgt aaaattactg    120 

cagtttctaa atcctgatcc tttgagagct gatgggacct cagacctgca ccagttgcag    180 

aaggtgaagc tgggcacact gcagcctggg gtggtgctcc ggaacaggat cgagccctgc    240 

ctaaccctgg agaaatcacc tctgtcggca gacctgaaga aggtgaacat gttcttaaag    300 

ccagactcct gacgacatgc cagccctttc caacacagag tgttgctttg ttttgctttg    360 

tctgttctgt tctaagagtg acggggatga aatacagggc tttgcgcgtc ctgggcatgc    420 

attcatcact gaaccatacc ccaattccat aggaggattt taaataaaca cttctaaggc    480 

tacattgca                                                            489 

 
           
             9  
             1623  
             DNA  
             Mus musculus  
             
               CDS  
               (50)..(1369)  
             
           
            9 

tgactgatct tgagtttgca taggcttcct gcggtgaaac gggtacact atg gcc tct     58 
                                                      Met Ala Ser 
                                                      1 

ctg aag agg ttt cag acg ctc gtg ccc ctg gat cac aaa caa ggt acc      106 
Leu Lys Arg Phe Gln Thr Leu Val Pro Leu Asp His Lys Gln Gly Thr 
    5                   10                  15 

tta ttt gaa att att gga gag ccc aag ttg ccc aag tgg ttc cat gtc      154 
Leu Phe Glu Ile Ile Gly Glu Pro Lys Leu Pro Lys Trp Phe His Val 
20                  25                  30                  35 

gaa tgc ctg gaa gat cca aaa aga ctg tac gtg gaa cct cgg cta ctg      202 
Glu Cys Leu Glu Asp Pro Lys Arg Leu Tyr Val Glu Pro Arg Leu Leu 
                40                  45                  50 

gaa atc atg ttt ggt aag gat gga gag cac atc cca cat ctt gaa tct      250 
Glu Ile Met Phe Gly Lys Asp Gly Glu His Ile Pro His Leu Glu Ser 
            55                  60                  65 

atg ttg cac acc ctg ata cat gtg aac gtg tgg ggc cct gaa agg cga      298 
Met Leu His Thr Leu Ile His Val Asn Val Trp Gly Pro Glu Arg Arg 
        70                  75                  80 

gct gag att tgg ata ttc gga ccg ccg cct ttc cga agg gac gtt gac      346 
Ala Glu Ile Trp Ile Phe Gly Pro Pro Pro Phe Arg Arg Asp Val Asp 
    85                  90                  95 

cgg atg ctc act gat ctg gct cac tat tgc cgc atg aaa ctg atg gaa      394 
Arg Met Leu Thr Asp Leu Ala His Tyr Cys Arg Met Lys Leu Met Glu 
100                 105                 110                 115 

ata gag gct ctg gag gct gga gtt gag cgt cgt cgt atg gcg gcc cat      442 
Ile Glu Ala Leu Glu Ala Gly Val Glu Arg Arg Arg Met Ala Ala His 
                120                 125                 130 

aag gct gcc acc cag cct gct ccc gtg aag gtc cgc gag gct gcc cct      490 
Lys Ala Ala Thr Gln Pro Ala Pro Val Lys Val Arg Glu Ala Ala Pro 
            135                 140                 145 

cgg ccc gct tcc gtg aag gtc cct gag acg gcc acc cag cct gct ccc      538 
Arg Pro Ala Ser Val Lys Val Pro Glu Thr Ala Thr Gln Pro Ala Pro 
        150                 155                 160 

gtg aag gtc cgc gag gct gcc cct cag ccc gct ccg gtg cag gag gtc      586 
Val Lys Val Arg Glu Ala Ala Pro Gln Pro Ala Pro Val Gln Glu Val 
    165                 170                 175 

cgc gag gct gcc cct cag cag gct tcc gtg cag gag gag gtc cgc gag      634 
Arg Glu Ala Ala Pro Gln Gln Ala Ser Val Gln Glu Glu Val Arg Glu 
180                 185                 190                 195 

gct gcc acc gag cag gct ccc gtg cag gag gtc cgc gag gct gcc acc      682 
Ala Ala Thr Glu Gln Ala Pro Val Gln Glu Val Arg Glu Ala Ala Thr 
                200                 205                 210 

gag cag gct ccc gtg cag gag gtc agc gag gct gcc acc gag cag gct      730 
Glu Gln Ala Pro Val Gln Glu Val Ser Glu Ala Ala Thr Glu Gln Ala 
            215                 220                 225 

ccc gtg cag gag gtc aac gag gct gcc acc gag cag gct tcc gtg cag      778 
Pro Val Gln Glu Val Asn Glu Ala Ala Thr Glu Gln Ala Ser Val Gln 
        230                 235                 240 

gcg gtc cgc gag gct gcc acc cgg ccg gct ccc ggg aag gtc cgc aag      826 
Ala Val Arg Glu Ala Ala Thr Arg Pro Ala Pro Gly Lys Val Arg Lys 
    245                 250                 255 

gcg gcc acc cag ccg gct ccg gtg cag gtt tgc cag gag gcc acc cag      874 
Ala Ala Thr Gln Pro Ala Pro Val Gln Val Cys Gln Glu Ala Thr Gln 
260                 265                 270                 275 

ttg gct ccc gtg aag gtc cgc gag gcg gcc acc cag ccg gct tcc ggg      922 
Leu Ala Pro Val Lys Val Arg Glu Ala Ala Thr Gln Pro Ala Ser Gly 
                280                 285                 290 

aag gtc cgc gag gcg gcc acc cag ttg gct cct gtg aag gtc cgc aag      970 
Lys Val Arg Glu Ala Ala Thr Gln Leu Ala Pro Val Lys Val Arg Lys 
            295                 300                 305 

gca gcc acc cag ttg gct cct gtg aag gtc cac gag gcg gcc acc cag     1018 
Ala Ala Thr Gln Leu Ala Pro Val Lys Val His Glu Ala Ala Thr Gln 
        310                 315                 320 

ccg gct ccg ggg aag gtc agc gat gct gcc acg cag tcg gct tcg gtg     1066 
Pro Ala Pro Gly Lys Val Ser Asp Ala Ala Thr Gln Ser Ala Ser Val 
    325                 330                 335 

cag gtt cgt gag gct gcc acg cag ctg tct ccc gtg gag gcc act gat     1114 
Gln Val Arg Glu Ala Ala Thr Gln Leu Ser Pro Val Glu Ala Thr Asp 
340                 345                 350                 355 

act agc cag ttg gct cag gtg aag gct gat gaa gcc ttt gcc cag cac     1162 
Thr Ser Gln Leu Ala Gln Val Lys Ala Asp Glu Ala Phe Ala Gln His 
                360                 365                 370 

act tca ggg gag gcc cac cag gtt gcc aat ggg cag tct ccc att gaa     1210 
Thr Ser Gly Glu Ala His Gln Val Ala Asn Gly Gln Ser Pro Ile Glu 
            375                 380                 385 

gtc tgt gag act gcc acc ggg cag cat tct cta gat gtc tct agg gcc     1258 
Val Cys Glu Thr Ala Thr Gly Gln His Ser Leu Asp Val Ser Arg Ala 
        390                 395                 400 

ttg tcc cag aag tgt cct gag gtt ttt gag tgg gag acc cag agt tgt     1306 
Leu Ser Gln Lys Cys Pro Glu Val Phe Glu Trp Glu Thr Gln Ser Cys 
    405                 410                 415 

ttg gat ggc agc tat gtc ata gtt cag cct cca agg gat gcc tgg gaa     1354 
Leu Asp Gly Ser Tyr Val Ile Val Gln Pro Pro Arg Asp Ala Trp Glu 
420                 425                 430                 435 

tca ttt atc ata tta taaatgcatc tctggtgtga gccaggatag atggtacacg     1409 
Ser Phe Ile Ile Leu 
                440 

tctgcaaatc cagaacctaa aggcaggggt tagcttgggc tgagtaaggc aatgatctta   1469 

aacctcagcc tgcctaagac tcccttcatc tttctttctg gtttttgccc taggaatcgg   1529 

gaagaacaga gtagagctgt ttttgtttcc ccattgtgtt aaatgtttgc agacacaatt   1589 

taaagtattc taataaaaaa aaaattgcat tccc                               1623 

 
           
             10  
             440  
             PRT  
             Mus musculus  
           
            10 

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

Gln Gly Thr Leu Phe Glu Ile Ile Gly Glu Pro Lys Leu Pro Lys Trp 
            20                  25                  30 

Phe His Val Glu Cys Leu Glu Asp Pro Lys Arg Leu Tyr Val Glu Pro 
        35                  40                  45 

Arg Leu Leu Glu Ile Met Phe Gly Lys Asp Gly Glu His Ile Pro His 
    50                  55                  60 

Leu Glu Ser Met Leu His Thr Leu Ile His Val Asn Val Trp Gly Pro 
65                  70                  75                  80 

Glu Arg Arg Ala Glu Ile Trp Ile Phe Gly Pro Pro Pro Phe Arg Arg 
                85                  90                  95 

Asp Val Asp Arg Met Leu Thr Asp Leu Ala His Tyr Cys Arg Met Lys 
            100                 105                 110 

Leu Met Glu Ile Glu Ala Leu Glu Ala Gly Val Glu Arg Arg Arg Met 
        115                 120                 125 

Ala Ala His Lys Ala Ala Thr Gln Pro Ala Pro Val Lys Val Arg Glu 
    130                 135                 140 

Ala Ala Pro Arg Pro Ala Ser Val Lys Val Pro Glu Thr Ala Thr Gln 
145                 150                 155                 160 

Pro Ala Pro Val Lys Val Arg Glu Ala Ala Pro Gln Pro Ala Pro Val 
                165                 170                 175 

Gln Glu Val Arg Glu Ala Ala Pro Gln Gln Ala Ser Val Gln Glu Glu 
            180                 185                 190 

Val Arg Glu Ala Ala Thr Glu Gln Ala Pro Val Gln Glu Val Arg Glu 
        195                 200                 205 

Ala Ala Thr Glu Gln Ala Pro Val Gln Glu Val Ser Glu Ala Ala Thr 
    210                 215                 220 

Glu Gln Ala Pro Val Gln Glu Val Asn Glu Ala Ala Thr Glu Gln Ala 
225                 230                 235                 240 

Ser Val Gln Ala Val Arg Glu Ala Ala Thr Arg Pro Ala Pro Gly Lys 
                245                 250                 255 

Val Arg Lys Ala Ala Thr Gln Pro Ala Pro Val Gln Val Cys Gln Glu 
            260                 265                 270 

Ala Thr Gln Leu Ala Pro Val Lys Val Arg Glu Ala Ala Thr Gln Pro 
        275                 280                 285 

Ala Ser Gly Lys Val Arg Glu Ala Ala Thr Gln Leu Ala Pro Val Lys 
    290                 295                 300 

Val Arg Lys Ala Ala Thr Gln Leu Ala Pro Val Lys Val His Glu Ala 
305                 310                 315                 320 

Ala Thr Gln Pro Ala Pro Gly Lys Val Ser Asp Ala Ala Thr Gln Ser 
                325                 330                 335 

Ala Ser Val Gln Val Arg Glu Ala Ala Thr Gln Leu Ser Pro Val Glu 
            340                 345                 350 

Ala Thr Asp Thr Ser Gln Leu Ala Gln Val Lys Ala Asp Glu Ala Phe 
        355                 360                 365 

Ala Gln His Thr Ser Gly Glu Ala His Gln Val Ala Asn Gly Gln Ser 
    370                 375                 380 

Pro Ile Glu Val Cys Glu Thr Ala Thr Gly Gln His Ser Leu Asp Val 
385                 390                 395                 400 

Ser Arg Ala Leu Ser Gln Lys Cys Pro Glu Val Phe Glu Trp Glu Thr 
                405                 410                 415 

Gln Ser Cys Leu Asp Gly Ser Tyr Val Ile Val Gln Pro Pro Arg Asp 
            420                 425                 430 

Ala Trp Glu Ser Phe Ile Ile Leu 
        435                 440 

 
           
             11  
             591  
             DNA  
             Mus musculus  
             
               CDS  
               (59)..(412)  
             
           
            11 

gccgtgcgtg gtggataagc ttgatctcgt cttccctgaa gtctggttcc ttggcagg       58 

atg atg gtg acc ctc gtg acc cgt aaa gat atc ccc ccg tgg gtg aaa      106 
Met Met Val Thr Leu Val Thr Arg Lys Asp Ile Pro Pro Trp Val Lys 
1               5                   10                  15 

gtt cct gaa gac ctg aaa gat cca gaa gta ttc cag gtc cag tcg ctg      154 
Val Pro Glu Asp Leu Lys Asp Pro Glu Val Phe Gln Val Gln Ser Leu 
            20                  25                  30 

gtg ctg aaa tat ctg ttt ggc cca cag gga tct cga atg tct cac atc      202 
Val Leu Lys Tyr Leu Phe Gly Pro Gln Gly Ser Arg Met Ser His Ile 
        35                  40                  45 

gag cag gtg agc cag gcc atg ttt gag ctg aag aac ctg gaa tct ccc      250 
Glu Gln Val Ser Gln Ala Met Phe Glu Leu Lys Asn Leu Glu Ser Pro 
    50                  55                  60 

gaa gaa ctt atc gag gtc ttc att tac ggc tct caa aac aac aag att      298 
Glu Glu Leu Ile Glu Val Phe Ile Tyr Gly Ser Gln Asn Asn Lys Ile 
65                  70                  75                  80 

cgg gct aaa tgg atg ctt cag tcc atg gct gag agg tac cac ctg cgc      346 
Arg Ala Lys Trp Met Leu Gln Ser Met Ala Glu Arg Tyr His Leu Arg 
                85                  90                  95 

cag caa aaa gga gtg ctg aag ctg gag gaa tcc atg aag acc ctg gag      394 
Gln Gln Lys Gly Val Leu Lys Leu Glu Glu Ser Met Lys Thr Leu Glu 
            100                 105                 110 

cta ggc cag tgt atc gag tgaagccagt ttccagtcct tgtgtctccg             442 
Leu Gly Gln Cys Ile Glu 
        115 

acctggatgc aggttaagct gtggccagtg tttggttctg gcgggatttt tagctttgtt    502 

acatcctagc aagatattct ggatccctgc tgcgcattct gatgtgaatc ccaaggttac    562 

cactctaaat aaaaaataaa attgaagtg                                      591 

 
           
             12  
             118  
             PRT  
             Mus musculus  
           
            12 

Met Met Val Thr Leu Val Thr Arg Lys Asp Ile Pro Pro Trp Val Lys 
1               5                   10                  15 

Val Pro Glu Asp Leu Lys Asp Pro Glu Val Phe Gln Val Gln Ser Leu 
            20                  25                  30 

Val Leu Lys Tyr Leu Phe Gly Pro Gln Gly Ser Arg Met Ser His Ile 
        35                  40                  45 

Glu Gln Val Ser Gln Ala Met Phe Glu Leu Lys Asn Leu Glu Ser Pro 
    50                  55                  60 

Glu Glu Leu Ile Glu Val Phe Ile Tyr Gly Ser Gln Asn Asn Lys Ile 
65                  70                  75                  80 

Arg Ala Lys Trp Met Leu Gln Ser Met Ala Glu Arg Tyr His Leu Arg 
                85                  90                  95 

Gln Gln Lys Gly Val Leu Lys Leu Glu Glu Ser Met Lys Thr Leu Glu 
            100                 105                 110 

Leu Gly Gln Cys Ile Glu 
        115 

 
           
             13  
             1670  
             DNA  
             Mus musculus  
             
               CDS  
               (134)..(1567)  
             
           
            13 

acttgcctgt ccaagatctg ttggaatctg cttctacaga agaccagctg aaacaaatag     60 

cttcgtggga ctgagcacaa ctactagatt cttggacttc cgttcacagc tgccaattgt    120 
tgggagtaca ata atg gag gag tcg gaa ttg gag att ttt aga agt aag       169 
               Met Glu Glu Ser Glu Leu Glu Ile Phe Arg Ser Lys 
               1               5                   10 

ttt gtt aga ggc tca tct gtc acg aag cag cat gcc tgg cga aac cag      217 
Phe Val Arg Gly Ser Ser Val Thr Lys Gln His Ala Trp Arg Asn Gln 
        15                  20                  25 

cac agc gag aag cgt tgc tct tcc tcc atc agt tct ata tcc ctg gac      265 
His Ser Glu Lys Arg Cys Ser Ser Ser Ile Ser Ser Ile Ser Leu Asp 
    30                  35                  40 

aga atg cca tcg gaa atc ttg gtg aag ata ctt tct tac ttg gat gcg      313 
Arg Met Pro Ser Glu Ile Leu Val Lys Ile Leu Ser Tyr Leu Asp Ala 
45                  50                  55                  60 

gtg acc ttg gtg tgc att gga tgt gtg agc aga cgc ttt tat cat ttg      361 
Val Thr Leu Val Cys Ile Gly Cys Val Ser Arg Arg Phe Tyr His Leu 
                65                  70                  75 

gct gat gac aat ctt att tgg gtc agg aag tac gca gct gca ttt aga      409 
Ala Asp Asp Asn Leu Ile Trp Val Arg Lys Tyr Ala Ala Ala Phe Arg 
            80                  85                  90 

tca aaa aga tca cgt tgg aaa gct act tca gtg gag gaa aca gcc aca      457 
Ser Lys Arg Ser Arg Trp Lys Ala Thr Ser Val Glu Glu Thr Ala Thr 
        95                  100                 105 

agt ctg agc ttg ctg tca gtt tgg gat aaa gaa gat gga tac tgg aag      505 
Ser Leu Ser Leu Leu Ser Val Trp Asp Lys Glu Asp Gly Tyr Trp Lys 
    110                 115                 120 

aaa gaa tat att aca aag cag atc tca tct gtg aga gca gcc ctc acc      553 
Lys Glu Tyr Ile Thr Lys Gln Ile Ser Ser Val Arg Ala Ala Leu Thr 
125                 130                 135                 140 

aac agc ctc agt cct gtc aaa cgc cgc aca agc ctt cct tcg aaa acc      601 
Asn Ser Leu Ser Pro Val Lys Arg Arg Thr Ser Leu Pro Ser Lys Thr 
                145                 150                 155 

aaa gag tcc ctc aga ata tct ggc tta ggt tgg aca atc atc tta aga      649 
Lys Glu Ser Leu Arg Ile Ser Gly Leu Gly Trp Thr Ile Ile Leu Arg 
            160                 165                 170 

gaa gcc agt ggc aaa gaa cac atc atg cag cat tcg aat ctt tcc gta      697 
Glu Ala Ser Gly Lys Glu His Ile Met Gln His Ser Asn Leu Ser Val 
        175                 180                 185 

aat gac aac tct gtc act gtt ttt tgg cat gac aaa aat tgg cca cat      745 
Asn Asp Asn Ser Val Thr Val Phe Trp His Asp Lys Asn Trp Pro His 
    190                 195                 200 

gta gac acg ttg tcc acc ctg gat ttg tat ggt gcc aca cca att ttt      793 
Val Asp Thr Leu Ser Thr Leu Asp Leu Tyr Gly Ala Thr Pro Ile Phe 
205                 210                 215                 220 

atg gag cag tat aaa ggc cct aac aca agt tgt cca cga tgg ctg tct      841 
Met Glu Gln Tyr Lys Gly Pro Asn Thr Ser Cys Pro Arg Trp Leu Ser 
                225                 230                 235 

tta att gaa aag tac gat ctg agt aat tta cgc aag tct gct atg att      889 
Leu Ile Glu Lys Tyr Asp Leu Ser Asn Leu Arg Lys Ser Ala Met Ile 
            240                 245                 250 

ggc tgc gac aga cat gtt cgg gta ttc tgt gta aat cct ggc ctc ctg      937 
Gly Cys Asp Arg His Val Arg Val Phe Cys Val Asn Pro Gly Leu Leu 
        255                 260                 265 

gtg ggg ctg tgg cag gag aat ggt gga cta gct ttt gtc atg gca aat      985 
Val Gly Leu Trp Gln Glu Asn Gly Gly Leu Ala Phe Val Met Ala Asn 
    270                 275                 280 

att cat tcc cat ggc ctt ttc gag aga agc ata atg ggc tca gac act     1033 
Ile His Ser His Gly Leu Phe Glu Arg Ser Ile Met Gly Ser Asp Thr 
285                 290                 295                 300 

att ccc tat aca ttg cct ccc gac act aca ttt gtg gat aac tac cca     1081 
Ile Pro Tyr Thr Leu Pro Pro Asp Thr Thr Phe Val Asp Asn Tyr Pro 
                305                 310                 315 

gac tca atg acc ttt tat gga gat aaa ggc ttt cag ctg cat atc gac     1129 
Asp Ser Met Thr Phe Tyr Gly Asp Lys Gly Phe Gln Leu His Ile Asp 
            320                 325                 330 

att cat ggc agt aag act tac ttc ctg tgt agc acc ttc cac aat ctc     1177 
Ile His Gly Ser Lys Thr Tyr Phe Leu Cys Ser Thr Phe His Asn Leu 
        335                 340                 345 

ttc tgc agg aga gcg ggc att aac aat gga tat gtg aag ttc ttg atg     1225 
Phe Cys Arg Arg Ala Gly Ile Asn Asn Gly Tyr Val Lys Phe Leu Met 
    350                 355                 360 

ata aac tta aaa aat aac aga gaa cac cta cct ctt gtt gga aaa gtt     1273 
Ile Asn Leu Lys Asn Asn Arg Glu His Leu Pro Leu Val Gly Lys Val 
365                 370                 375                 380 

ggc ctt gaa tgg aga act gac tgt tta aat ggc cgt att gag agt tgc     1321 
Gly Leu Glu Trp Arg Thr Asp Cys Leu Asn Gly Arg Ile Glu Ser Cys 
                385                 390                 395 

att gta gtg gat atg acc ttg ctg gat gag gac aag aag ccc atc tgg     1369 
Ile Val Val Asp Met Thr Leu Leu Asp Glu Asp Lys Lys Pro Ile Trp 
            400                 405                 410 

tat gtg agt tct cca gtg tgc ttg aga tct gcc tgc ctt cct gat ttc     1417 
Tyr Val Ser Ser Pro Val Cys Leu Arg Ser Ala Cys Leu Pro Asp Phe 
        415                 420                 425 

ccg cag ccg gct tac tct ttc gag tac atg gac agc gta gga gga gtg     1465 
Pro Gln Pro Ala Tyr Ser Phe Glu Tyr Met Asp Ser Val Gly Gly Val 
    430                 435                 440 

tgc gca gac cta ggg tgg ttt gaa aat acc gat gaa tac ttc att gtc     1513 
Cys Ala Asp Leu Gly Trp Phe Glu Asn Thr Asp Glu Tyr Phe Ile Val 
445                 450                 455                 460 

aga ctg gac att tac ctc agt gta gca aaa tta caa caa tgg ttt ggg     1561 
Arg Leu Asp Ile Tyr Leu Ser Val Ala Lys Leu Gln Gln Trp Phe Gly 
                465                 470                 475 

agg caa taaatgctga gttagcagta gggagtcttg ttattagtaa gctgtttgtt      1617 
Arg Gln 

ttttacaact ttgtttttat tgaaagttaa aataaagcat atttgtggta ttc          1670 

 
           
             14  
             478  
             PRT  
             Mus musculus  
           
            14 

Met Glu Glu Ser Glu Leu Glu Ile Phe Arg Ser Lys Phe Val Arg Gly 
1               5                   10                  15 

Ser Ser Val Thr Lys Gln His Ala Trp Arg Asn Gln His Ser Glu Lys 
            20                  25                  30 

Arg Cys Ser Ser Ser Ile Ser Ser Ile Ser Leu Asp Arg Met Pro Ser 
        35                  40                  45 

Glu Ile Leu Val Lys Ile Leu Ser Tyr Leu Asp Ala Val Thr Leu Val 
    50                  55                  60 

Cys Ile Gly Cys Val Ser Arg Arg Phe Tyr His Leu Ala Asp Asp Asn 
65                  70                  75                  80 

Leu Ile Trp Val Arg Lys Tyr Ala Ala Ala Phe Arg Ser Lys Arg Ser 
                85                  90                  95 

Arg Trp Lys Ala Thr Ser Val Glu Glu Thr Ala Thr Ser Leu Ser Leu 
            100                 105                 110 

Leu Ser Val Trp Asp Lys Glu Asp Gly Tyr Trp Lys Lys Glu Tyr Ile 
        115                 120                 125 

Thr Lys Gln Ile Ser Ser Val Arg Ala Ala Leu Thr Asn Ser Leu Ser 
    130                 135                 140 

Pro Val Lys Arg Arg Thr Ser Leu Pro Ser Lys Thr Lys Glu Ser Leu 
145                 150                 155                 160 

Arg Ile Ser Gly Leu Gly Trp Thr Ile Ile Leu Arg Glu Ala Ser Gly 
                165                 170                 175 

Lys Glu His Ile Met Gln His Ser Asn Leu Ser Val Asn Asp Asn Ser 
            180                 185                 190 

Val Thr Val Phe Trp His Asp Lys Asn Trp Pro His Val Asp Thr Leu 
        195                 200                 205 

Ser Thr Leu Asp Leu Tyr Gly Ala Thr Pro Ile Phe Met Glu Gln Tyr 
    210                 215                 220 

Lys Gly Pro Asn Thr Ser Cys Pro Arg Trp Leu Ser Leu Ile Glu Lys 
225                 230                 235                 240 

Tyr Asp Leu Ser Asn Leu Arg Lys Ser Ala Met Ile Gly Cys Asp Arg 
                245                 250                 255 

His Val Arg Val Phe Cys Val Asn Pro Gly Leu Leu Val Gly Leu Trp 
            260                 265                 270 

Gln Glu Asn Gly Gly Leu Ala Phe Val Met Ala Asn Ile His Ser His 
        275                 280                 285 

Gly Leu Phe Glu Arg Ser Ile Met Gly Ser Asp Thr Ile Pro Tyr Thr 
    290                 295                 300 

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

Phe Tyr Gly Asp Lys Gly Phe Gln Leu His Ile Asp Ile His Gly Ser 
                325                 330                 335 

Lys Thr Tyr Phe Leu Cys Ser Thr Phe His Asn Leu Phe Cys Arg Arg 
            340                 345                 350 

Ala Gly Ile Asn Asn Gly Tyr Val Lys Phe Leu Met Ile Asn Leu Lys 
        355                 360                 365 

Asn Asn Arg Glu His Leu Pro Leu Val Gly Lys Val Gly Leu Glu Trp 
    370                 375                 380 

Arg Thr Asp Cys Leu Asn Gly Arg Ile Glu Ser Cys Ile Val Val Asp 
385                 390                 395                 400 

Met Thr Leu Leu Asp Glu Asp Lys Lys Pro Ile Trp Tyr Val Ser Ser 
                405                 410                 415 

Pro Val Cys Leu Arg Ser Ala Cys Leu Pro Asp Phe Pro Gln Pro Ala 
            420                 425                 430 

Tyr Ser Phe Glu Tyr Met Asp Ser Val Gly Gly Val Cys Ala Asp Leu 
        435                 440                 445 

Gly Trp Phe Glu Asn Thr Asp Glu Tyr Phe Ile Val Arg Leu Asp Ile 
    450                 455                 460 

Tyr Leu Ser Val Ala Lys Leu Gln Gln Trp Phe Gly Arg Gln 
465                 470                 475 

 
           
             15  
             2184  
             DNA  
             Mus musculus  
             
               CDS  
               (190)..(1104)  
             
           
            15 

agaaaggctg atttggttgg tgtcttgctc tttctgtggg aaggctgcgg ctcacttcct     60 

tccgacttct tgataatttt gcattagaca tttaactctt ctttctatga tctttccttc    120 

tagacactga gttttttggt tgttgcctaa aaccttttca gaaatccctt ccctcgccat    180 

cacactgac atg agt gtg ggt ctt cct ggt ccc cac agt ttg cct agt tct    231 
          Met Ser Val Gly Leu Pro Gly Pro His Ser Leu Pro Ser Ser 
          1               5                   10 

gag gaa gca tcg aat tct ggg aac gcc tca tca atg cct gca gtt ttt      279 
Glu Glu Ala Ser Asn Ser Gly Asn Ala Ser Ser Met Pro Ala Val Phe 
15                  20                  25                  30 

cat ccc gag aac tat tct tgc tta caa ggg tct gct act gag atg ctc      327 
His Pro Glu Asn Tyr Ser Cys Leu Gln Gly Ser Ala Thr Glu Met Leu 
                35                  40                  45 

tgc aca gag gct gcc tct cct cgc cct tcc tct gaa gac ctg cct ctt      375 
Cys Thr Glu Ala Ala Ser Pro Arg Pro Ser Ser Glu Asp Leu Pro Leu 
            50                  55                  60 

caa ggc agc cct gat tct tct acc agt ccc aaa caa aag ctc tca agt      423 
Gln Gly Ser Pro Asp Ser Ser Thr Ser Pro Lys Gln Lys Leu Ser Ser 
        65                  70                  75 

cct gag gct gac aag ggc cct gag gag gag gag aac aag gtc ctt gcc      471 
Pro Glu Ala Asp Lys Gly Pro Glu Glu Glu Glu Asn Lys Val Leu Ala 
    80                  85                  90 

agg aag cag aag atg cgg act gtg ttc tct cag gcc cag ctg tgt gca      519 
Arg Lys Gln Lys Met Arg Thr Val Phe Ser Gln Ala Gln Leu Cys Ala 
95                  100                 105                 110 

ctc aag gac agg ttt cag aag cag aag tac ctc agc ctc cag cag atg      567 
Leu Lys Asp Arg Phe Gln Lys Gln Lys Tyr Leu Ser Leu Gln Gln Met 
                115                 120                 125 

caa gaa ctc tcc tcc att ctg aac ctg agc tat aag cag gtt aag acc      615 
Gln Glu Leu Ser Ser Ile Leu Asn Leu Ser Tyr Lys Gln Val Lys Thr 
            130                 135                 140 

tgg ttt caa aac caa agg gtg aag tgc aag cgg tgg cag aaa aac cag      663 
Trp Phe Gln Asn Gln Arg Val Lys Cys Lys Arg Trp Gln Lys Asn Gln 
        145                 150                 155 

tgg ttg aag act agc aat ggt ctg att cag aag ggc tca gca cca gtg      711 
Trp Leu Lys Thr Ser Asn Gly Leu Ile Gln Lys Gly Ser Ala Pro Val 
    160                 165                 170 

gag tat ccc agc atc cat tgc agc tat ccc cag ggc tat ctg gtg aac      759 
Glu Tyr Pro Ser Ile His Cys Ser Tyr Pro Gln Gly Tyr Leu Val Asn 
175                 180                 185                 190 

gca tct gga agc ctt tcc atg tgg ggc agc cag act tgg acc aac cca      807 
Ala Ser Gly Ser Leu Ser Met Trp Gly Ser Gln Thr Trp Thr Asn Pro 
                195                 200                 205 

act tgg agc agc cag acc tgg acc aac cca act tgg aac aac cag acc      855 
Thr Trp Ser Ser Gln Thr Trp Thr Asn Pro Thr Trp Asn Asn Gln Thr 
            210                 215                 220 

tgg acc aac cca act tgg agc agc cag gcc tgg acc gct cag tcc tgg      903 
Trp Thr Asn Pro Thr Trp Ser Ser Gln Ala Trp Thr Ala Gln Ser Trp 
        225                 230                 235 

aac ggc cag cct tgg aat gct gct ccg ctc cat aac ttc ggg gag gac      951 
Asn Gly Gln Pro Trp Asn Ala Ala Pro Leu His Asn Phe Gly Glu Asp 
    240                 245                 250 

ttt ctg cag cct tac gta cag ttg cag caa aac ttc tct gcc agt gat      999 
Phe Leu Gln Pro Tyr Val Gln Leu Gln Gln Asn Phe Ser Ala Ser Asp 
255                 260                 265                 270 

ttg gag gtg aat ttg gaa gcc act agg gaa agc cat gcg cat ttt agc     1047 
Leu Glu Val Asn Leu Glu Ala Thr Arg Glu Ser His Ala His Phe Ser 
                275                 280                 285 

acc cca caa gcc ttg gaa tta ttc ctg aac tac tct gtg act cca cca     1095 
Thr Pro Gln Ala Leu Glu Leu Phe Leu Asn Tyr Ser Val Thr Pro Pro 
            290                 295                 300 

ggt gaa ata tgagacttac gcaacatctg ggcttaaagt cagggcaaag cca         1147 
Gly Glu Ile 
        305 

ggttccttcc ttcttccaaa tattttcata ttttttttaa agatttattt attcattata   1207 

tgtaagtaca ctgtagctgt cttcagacac tccagaagag ggcgtcagat cttgttacgt   1267 

atggttgtga gccaccatgt ggttgctggg atttgaactc ctgaccttcg gaagagcagt   1327 

cgggtgctct tatccactga gccatctcac cagcccctgg tttatttttt taattattat   1387 

ttgctttttg tttatcaaga cagggtttct ctgcatagct ctaattgtct ttgaactagc   1447 

tctgcagacc agcctggcct tgaactcaga gatctgccca cttatctttg cctcctgaat   1507 

gctgggacca aaggtggcat accaccacac ctggcatata tattgtttat ttctatttct   1567 

atttttattg gtgccagagc aaacctagga cttagaacat gctgggcacc aactcaactt   1627 

ctgagctcta tttacaactt ggtgtgttag tgtatttgtc ttagttctga atttgtcctt   1687 

tttttagtgt taactctagg ctttggagac agtgaggtgc atatactctc tccttcccaa   1747 

gaataagtgc ttgaacaccc ttacccacgc ccacccaccc atgctagtct tttttcttag   1807 

aagcgtgggt cttggtatac actgtgtcat tttgaggggt gaggtttaaa agtatataca   1867 

aagtataacg atatggtggc tactctcgag gatgagacag aaggaccagg agtttgaggg   1927 

tagctcagat atgcaataag ttcaaggcca acctgtacta tgtttaaata gtaagacagc   1987 

atctcgataa aataataaaa ctaaagtctc aacaaaataa aagctttcac ctattaaggt   2047 

gcttgcttgt ccttggagtc ccccaagagt aactgctatg ttaatatctg tagaaagatg   2107 

tttatatttg actgtaccat gatgaaccga tgccagctgg actagtttaa acaaaataaa   2167 

acactaattt taccttt                                                  2184 

 
           
             16  
             305  
             PRT  
             Mus musculus  
           
            16 

Met Ser Val Gly Leu Pro Gly Pro His Ser Leu Pro Ser Ser Glu Glu 
1               5                   10                  15 

Ala Ser Asn Ser Gly Asn Ala Ser Ser Met Pro Ala Val Phe His Pro 
            20                  25                  30 

Glu Asn Tyr Ser Cys Leu Gln Gly Ser Ala Thr Glu Met Leu Cys Thr 
        35                  40                  45 

Glu Ala Ala Ser Pro Arg Pro Ser Ser Glu Asp Leu Pro Leu Gln Gly 
    50                  55                  60 

Ser Pro Asp Ser Ser Thr Ser Pro Lys Gln Lys Leu Ser Ser Pro Glu 
65                  70                  75                  80 

Ala Asp Lys Gly Pro Glu Glu Glu Glu Asn Lys Val Leu Ala Arg Lys 
                85                  90                  95 

Gln Lys Met Arg Thr Val Phe Ser Gln Ala Gln Leu Cys Ala Leu Lys 
            100                 105                 110 

Asp Arg Phe Gln Lys Gln Lys Tyr Leu Ser Leu Gln Gln Met Gln Glu 
        115                 120                 125 

Leu Ser Ser Ile Leu Asn Leu Ser Tyr Lys Gln Val Lys Thr Trp Phe 
    130                 135                 140 

Gln Asn Gln Arg Val Lys Cys Lys Arg Trp Gln Lys Asn Gln Trp Leu 
145                 150                 155                 160 

Lys Thr Ser Asn Gly Leu Ile Gln Lys Gly Ser Ala Pro Val Glu Tyr 
                165                 170                 175 

Pro Ser Ile His Cys Ser Tyr Pro Gln Gly Tyr Leu Val Asn Ala Ser 
            180                 185                 190 

Gly Ser Leu Ser Met Trp Gly Ser Gln Thr Trp Thr Asn Pro Thr Trp 
        195                 200                 205 

Ser Ser Gln Thr Trp Thr Asn Pro Thr Trp Asn Asn Gln Thr Trp Thr 
    210                 215                 220 

Asn Pro Thr Trp Ser Ser Gln Ala Trp Thr Ala Gln Ser Trp Asn Gly 
225                 230                 235                 240 

Gln Pro Trp Asn Ala Ala Pro Leu His Asn Phe Gly Glu Asp Phe Leu 
                245                 250                 255 

Gln Pro Tyr Val Gln Leu Gln Gln Asn Phe Ser Ala Ser Asp Leu Glu 
            260                 265                 270 

Val Asn Leu Glu Ala Thr Arg Glu Ser His Ala His Phe Ser Thr Pro 
        275                 280                 285 

Gln Ala Leu Glu Leu Phe Leu Asn Tyr Ser Val Thr Pro Pro Gly Glu 
    290                 295                 300 

Ile 
305 

 
           
             17  
             1078  
             DNA  
             Mus musculus  
             
               CDS  
               (178)..(858)  
             
           
            17 

caggggtcgg gcaggtggga gggggaagct cacatctccg ccctctgctg cctctggggg     60 

tagggagcat cctaaccccc aactgtccgg tcagatccgc ctactgcccc tcatcagact    120 

gctactcctg ggagcacagc acctgctctt tacacctctt ccttgagctg ctgggga       177 

atg gct ttg cct aca aag tct agc atc ttg gac ctg agc tcc ggc acc      225 
Met Ala Leu Pro Thr Lys Ser Ser Ile Leu Asp Leu Ser Ser Gly Thr 
1               5                   10                  15 

cca tgc acc aga tct cca gag gaa agt cac gag gct tgg gca cag tgc      273 
Pro Cys Thr Arg Ser Pro Glu Glu Ser His Glu Ala Trp Ala Gln Cys 
            20                  25                  30 

aaa gat gct ggc agg cag cta ccc gag tac aag gca gtg gtg gtg ggt      321 
Lys Asp Ala Gly Arg Gln Leu Pro Glu Tyr Lys Ala Val Val Val Gly 
        35                  40                  45 

gca agt ggt gtt ggt aaa agt gct ctc acc atc cag atg act cac caa      369 
Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Met Thr His Gln 
    50                  55                  60 

tgc ttc gtg aaa gac cat gac ccc act atc caa gat tcc tac tgg aag      417 
Cys Phe Val Lys Asp His Asp Pro Thr Ile Gln Asp Ser Tyr Trp Lys 
65                  70                  75                  80 

gaa gtg gcc agg gac aac gga ggc tac att cta aat gtt ctg gat aca      465 
Glu Val Ala Arg Asp Asn Gly Gly Tyr Ile Leu Asn Val Leu Asp Thr 
                85                  90                  95 

tct ggg cag gat att cac cgg gct ctg cgt gac cag tgc ttg gca tct      513 
Ser Gly Gln Asp Ile His Arg Ala Leu Arg Asp Gln Cys Leu Ala Ser 
            100                 105                 110 

ggt gat ggt gtg ctg ggc gtc ttt gct ctt gac gac ccc tcg tct ctg      561 
Gly Asp Gly Val Leu Gly Val Phe Ala Leu Asp Asp Pro Ser Ser Leu 
        115                 120                 125 

gac cag ttg cag cag ata tgg tcc acc tgg acc cct cac cac aag cag      609 
Asp Gln Leu Gln Gln Ile Trp Ser Thr Trp Thr Pro His His Lys Gln 
    130                 135                 140 

cct ctg gta cta gtg ggc aac aag tgt gac ctg gtg acc act gct gga      657 
Pro Leu Val Leu Val Gly Asn Lys Cys Asp Leu Val Thr Thr Ala Gly 
145                 150                 155                 160 

gat gct cat gct gcc gca gcc ctc ctt gct cac aag ttg ggg gcc ccc      705 
Asp Ala His Ala Ala Ala Ala Leu Leu Ala His Lys Leu Gly Ala Pro 
                165                 170                 175 

ttg gtg aag acc tca gcc aag acg cgg caa ggt gtg gag gaa gcc ttt      753 
Leu Val Lys Thr Ser Ala Lys Thr Arg Gln Gly Val Glu Glu Ala Phe 
            180                 185                 190 

gcc ctg ctt gtc cat gag att cag agg gcc cag gag gct gtg gcc gaa      801 
Ala Leu Leu Val His Glu Ile Gln Arg Ala Gln Glu Ala Val Ala Glu 
        195                 200                 205 

tca agc aag aag acc cga cac cag aaa gcc gtg tgt agc tgt ggc tgc      849 
Ser Ser Lys Lys Thr Arg His Gln Lys Ala Val Cys Ser Cys Gly Cys 
    210                 215                 220 

tct gta gcc tgaagatctt tgtctagcaa attgaccctt gtctcatgtc              898 
Ser Val Ala 
225 

aaggtgacaa ttctcttgta ataagatctc cctctccgac caagttacca cagacatctt    958 

tttattgtca tttggtgaga agttacgtgg taacatggga catccctcat tgactgtgtt   1018 

ttatgaaact ctatgcaaaa ttaaataaat gttttcagga ttcaaagctt cctttatacc   1078 

 
           
             18  
             227  
             PRT  
             Mus musculus  
           
            18 

Met Ala Leu Pro Thr Lys Ser Ser Ile Leu Asp Leu Ser Ser Gly Thr 
1               5                   10                  15 

Pro Cys Thr Arg Ser Pro Glu Glu Ser His Glu Ala Trp Ala Gln Cys 
            20                  25                  30 

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

Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Met Thr His Gln 
    50                  55                  60 

Cys Phe Val Lys Asp His Asp Pro Thr Ile Gln Asp Ser Tyr Trp Lys 
65                  70                  75                  80 

Glu Val Ala Arg Asp Asn Gly Gly Tyr Ile Leu Asn Val Leu Asp Thr 
                85                  90                  95 

Ser Gly Gln Asp Ile His Arg Ala Leu Arg Asp Gln Cys Leu Ala Ser 
            100                 105                 110 

Gly Asp Gly Val Leu Gly Val Phe Ala Leu Asp Asp Pro Ser Ser Leu 
        115                 120                 125 

Asp Gln Leu Gln Gln Ile Trp Ser Thr Trp Thr Pro His His Lys Gln 
    130                 135                 140 

Pro Leu Val Leu Val Gly Asn Lys Cys Asp Leu Val Thr Thr Ala Gly 
145                 150                 155                 160 

Asp Ala His Ala Ala Ala Ala Leu Leu Ala His Lys Leu Gly Ala Pro 
                165                 170                 175 

Leu Val Lys Thr Ser Ala Lys Thr Arg Gln Gly Val Glu Glu Ala Phe 
            180                 185                 190 

Ala Leu Leu Val His Glu Ile Gln Arg Ala Gln Glu Ala Val Ala Glu 
        195                 200                 205 

Ser Ser Lys Lys Thr Arg His Gln Lys Ala Val Cys Ser Cys Gly Cys 
    210                 215                 220 

Ser Val Ala 
225 

 
           
             19  
             1063  
             DNA  
             Mus musculus  
             
               CDS  
               (177)..(872)  
             
           
            19 

gatacaaatt cgaatgtagg tgctaggcgc gcttgtgtta gagtgtttgt taggggagac     60 

tgatggaatc cacagtccaa tgagtacagg gcctgtcctc cgtgtggcag cttcacccgg    120 

gagttgctgg cctggctgcc tacctgcttt cctgagatcc agggactttt cccaga atg    179 
                                                              Met 
                                                              1 

gct ttg ggt gac ctc ctg ctg tct gtc ctc tct gcc cag gaa atg aat      227 
Ala Leu Gly Asp Leu Leu Leu Ser Val Leu Ser Ala Gln Glu Met Asn 
            5                   10                  15 

gcc ctt cgt ggc cag gtg ggc ggg gac gtc aat gtg gag atg gac gcc      275 
Ala Leu Arg Gly Gln Val Gly Gly Asp Val Asn Val Glu Met Asp Ala 
        20                  25                  30 

gcc ccc ggt gtg gac ctg agc cgc atc ctg aac gag atg cgg gat cag      323 
Ala Pro Gly Val Asp Leu Ser Arg Ile Leu Asn Glu Met Arg Asp Gln 
    35                  40                  45 

tat gag aag atg gcg gag aag aac cgc aag gat gct gag gaa tgg ttc      371 
Tyr Glu Lys Met Ala Glu Lys Asn Arg Lys Asp Ala Glu Glu Trp Phe 
50                  55                  60                  65 

ttc acc aag aca gag gag ctg aac cga gaa gtg gcc acc aac acg gag      419 
Phe Thr Lys Thr Glu Glu Leu Asn Arg Glu Val Ala Thr Asn Thr Glu 
                70                  75                  80 

gcc ctg cag agc agc cgg aca gag atc acg gag ctc cgc cgc tct gtg      467 
Ala Leu Gln Ser Ser Arg Thr Glu Ile Thr Glu Leu Arg Arg Ser Val 
            85                  90                  95 

cag aac ctg gag att gag ctg cag tcc cag ctc agc atg aaa gca tca      515 
Gln Asn Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys Ala Ser 
        100                 105                 110 

ctg gag aac agc ctg gca gag aca gag gcg cgc tat ggg gcc cag ctg      563 
Leu Glu Asn Ser Leu Ala Glu Thr Glu Ala Arg Tyr Gly Ala Gln Leu 
    115                 120                 125 

gcg cag ctg cag ggc ctc att agc agt gtg gaa cag cag ctg tgt gag      611 
Ala Gln Leu Gln Gly Leu Ile Ser Ser Val Glu Gln Gln Leu Cys Glu 
130                 135                 140                 145 

ctg cgt tgt gac atg gaa agg cag aat cat gag tac cag gtg ctg ctg      659 
Leu Arg Cys Asp Met Glu Arg Gln Asn His Glu Tyr Gln Val Leu Leu 
                150                 155                 160 

gat gtg aag acc cga ctg gag cag gag atc gcc acc tac cgc cgt ctg      707 
Asp Val Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg Arg Leu 
            165                 170                 175 

ctg gag ggc gag gac gcc cac ctg gct act caa tac tcc tca tcc ctg      755 
Leu Glu Gly Glu Asp Ala His Leu Ala Thr Gln Tyr Ser Ser Ser Leu 
        180                 185                 190 

gct tcg cag ccc tcc cga gaa ggc atg gtg acc agc cgc cag gtg cgc      803 
Ala Ser Gln Pro Ser Arg Glu Gly Met Val Thr Ser Arg Gln Val Arg 
    195                 200                 205 

acc att gtg gag gaa gtc cag gat ggt aag gtg ttt tcc tcc aga gag      851 
Thr Ile Val Glu Glu Val Gln Asp Gly Lys Val Phe Ser Ser Arg Glu 
210                 215                 220                 225 

cag gag cac cgc tcc acc cac tgaggcccct gtctgcgtat gatagcccag         902 
Gln Glu His Arg Ser Thr His 
                230 

gcccaggacc ttaggctgca gctccctgca tctactgcca agcctgaact cctatgagct    962 

agctgttgcc ttctgtgttt gctttgtgct gccccttaca gagaggcccc ttgggttgac   1022 

cccagaaatt gctaataaag ctttgaagaa gtctgatcct t                       1063 

 
           
             20  
             232  
             PRT  
             Mus musculus  
           
            20 

Met Ala Leu Gly Asp Leu Leu Leu Ser Val Leu Ser Ala Gln Glu Met 
1               5                   10                  15 

Asn Ala Leu Arg Gly Gln Val Gly Gly Asp Val Asn Val Glu Met Asp 
            20                  25                  30 

Ala Ala Pro Gly Val Asp Leu Ser Arg Ile Leu Asn Glu Met Arg Asp 
        35                  40                  45 

Gln Tyr Glu Lys Met Ala Glu Lys Asn Arg Lys Asp Ala Glu Glu Trp 
    50                  55                  60 

Phe Phe Thr Lys Thr Glu Glu Leu Asn Arg Glu Val Ala Thr Asn Thr 
65                  70                  75                  80 

Glu Ala Leu Gln Ser Ser Arg Thr Glu Ile Thr Glu Leu Arg Arg Ser 
                85                  90                  95 

Val Gln Asn Leu Glu Ile Glu Leu Gln Ser Gln Leu Ser Met Lys Ala 
            100                 105                 110 

Ser Leu Glu Asn Ser Leu Ala Glu Thr Glu Ala Arg Tyr Gly Ala Gln 
        115                 120                 125 

Leu Ala Gln Leu Gln Gly Leu Ile Ser Ser Val Glu Gln Gln Leu Cys 
    130                 135                 140 

Glu Leu Arg Cys Asp Met Glu Arg Gln Asn His Glu Tyr Gln Val Leu 
145                 150                 155                 160 

Leu Asp Val Lys Thr Arg Leu Glu Gln Glu Ile Ala Thr Tyr Arg Arg 
                165                 170                 175 

Leu Leu Glu Gly Glu Asp Ala His Leu Ala Thr Gln Tyr Ser Ser Ser 
            180                 185                 190 

Leu Ala Ser Gln Pro Ser Arg Glu Gly Met Val Thr Ser Arg Gln Val 
        195                 200                 205 

Arg Thr Ile Val Glu Glu Val Gln Asp Gly Lys Val Phe Ser Ser Arg 
    210                 215                 220 

Glu Gln Glu His Arg Ser Thr His 
225                 230 

 
           
             21  
             1670  
             DNA  
             Mus musculus  
             
               CDS  
               (139)..(1401)  
             
           
            21 

gacaccctca accccatcat cccaggccct cataggctcc atccagcatt acgtcctcat     60 

ccctacctac gggttctgac gaccctgctg tcacacccgc catcccttgg acgcagaccc    120 

ttctagccga ttacatca atg ggt tcc cgg gag aca cct tct tct tgc tct      171 
                    Met Gly Ser Arg Glu Thr Pro Ser Ser Cys Ser 
                    1               5                   10 

aag acc ctt gaa acc ttg gac ctg gag act tcc gac agc tct agc cct      219 
Lys Thr Leu Glu Thr Leu Asp Leu Glu Thr Ser Asp Ser Ser Ser Pro 
            15                  20                  25 

gat gct gac agt cct ctg gaa gag caa tgg ctg aaa tcc tcc cca gcc      267 
Asp Ala Asp Ser Pro Leu Glu Glu Gln Trp Leu Lys Ser Ser Pro Ala 
        30                  35                  40 

ctg aag gag gac agt gtg gat gtg gta ctg gaa gac tgc aaa gag cct      315 
Leu Lys Glu Asp Ser Val Asp Val Val Leu Glu Asp Cys Lys Glu Pro 
    45                  50                  55 

ctg tcc ccc tcc tcg cct ccg aca ggc aga gag atg atc agg tac gaa      363 
Leu Ser Pro Ser Ser Pro Pro Thr Gly Arg Glu Met Ile Arg Tyr Glu 
60                  65                  70                  75 

gtc aaa gtg aac cga cgg agc att gaa gac atc tgc ctc tgc tgt gga      411 
Val Lys Val Asn Arg Arg Ser Ile Glu Asp Ile Cys Leu Cys Cys Gly 
                80                  85                  90 

act ctc cag gtg tac act cgg cac ccc ttg ttt gag gga ggg tta tgt      459 
Thr Leu Gln Val Tyr Thr Arg His Pro Leu Phe Glu Gly Gly Leu Cys 
            95                  100                 105 

gcc cca tgt aag gat aag ttc ctg gag tcc ctc ttc ctg tat gat gat      507 
Ala Pro Cys Lys Asp Lys Phe Leu Glu Ser Leu Phe Leu Tyr Asp Asp 
        110                 115                 120 

gat gga cac cag agt tac tgc acc atc tgc tgt tcc ggg ggt acc ctg      555 
Asp Gly His Gln Ser Tyr Cys Thr Ile Cys Cys Ser Gly Gly Thr Leu 
    125                 130                 135 

ttc atc tgt gag agc ccc gac tgt acc aga tgc tac tgt ttc gag tgt      603 
Phe Ile Cys Glu Ser Pro Asp Cys Thr Arg Cys Tyr Cys Phe Glu Cys 
140                 145                 150                 155 

gtg gac atc ctg gtg ggc ccc ggg acc tca gag agg atc aat gcc atg      651 
Val Asp Ile Leu Val Gly Pro Gly Thr Ser Glu Arg Ile Asn Ala Met 
                160                 165                 170 

gcc tgc tgg gtt tgc ttc ctg tgc ctg ccc ttc tca cgg agt gga ctg      699 
Ala Cys Trp Val Cys Phe Leu Cys Leu Pro Phe Ser Arg Ser Gly Leu 
            175                 180                 185 

ctg cag agg cgc aag agg tgg cgg cac cag ctg aag gcc ttc cat gat      747 
Leu Gln Arg Arg Lys Arg Trp Arg His Gln Leu Lys Ala Phe His Asp 
        190                 195                 200 

caa gag gga gcg ggc cct atg gag ata tac aag aca gtg tct gca tgg      795 
Gln Glu Gly Ala Gly Pro Met Glu Ile Tyr Lys Thr Val Ser Ala Trp 
    205                 210                 215 

aag aga cag cca gtg cgg gta ctg agc ctt ttt aga aat att gat aaa      843 
Lys Arg Gln Pro Val Arg Val Leu Ser Leu Phe Arg Asn Ile Asp Lys 
220                 225                 230                 235 

gta cta aag agt ttg ggc ttt ttg gaa agc ggt tct ggt tct ggg gga      891 
Val Leu Lys Ser Leu Gly Phe Leu Glu Ser Gly Ser Gly Ser Gly Gly 
                240                 245                 250 

gga acg ctg aag tac gtg gaa gat gtc aca aat gtc gtg agg aga gac      939 
Gly Thr Leu Lys Tyr Val Glu Asp Val Thr Asn Val Val Arg Arg Asp 
            255                 260                 265 

gtg gag aaa tgg ggc ccc ttt gac ctg gtg tac ggc tcg acg cag ccc      987 
Val Glu Lys Trp Gly Pro Phe Asp Leu Val Tyr Gly Ser Thr Gln Pro 
        270                 275                 280 

cta ggc agc tct tgt gat cgc tgt ccc ggc tgg tac atg ttc cag ttc     1035 
Leu Gly Ser Ser Cys Asp Arg Cys Pro Gly Trp Tyr Met Phe Gln Phe 
    285                 290                 295 

cac cgg atc ctg cag tat gcg ctg cct cgc cag gag agt cag cgg ccc     1083 
His Arg Ile Leu Gln Tyr Ala Leu Pro Arg Gln Glu Ser Gln Arg Pro 
300                 305                 310                 315 

ttc ttc tgg ata ttc atg gac aat ctg ctg ctg act gag gat gac caa     1131 
Phe Phe Trp Ile Phe Met Asp Asn Leu Leu Leu Thr Glu Asp Asp Gln 
                320                 325                 330 

gag aca act acc cgc ttc ctt cag aca gag gct gtg acc ctc cag gat     1179 
Glu Thr Thr Thr Arg Phe Leu Gln Thr Glu Ala Val Thr Leu Gln Asp 
            335                 340                 345 

gtc cgt ggc aga gac tac cag aat gct atg cgg gtg tgg agc aac att     1227 
Val Arg Gly Arg Asp Tyr Gln Asn Ala Met Arg Val Trp Ser Asn Ile 
        350                 355                 360 

cca ggg ctg aag agc aag cat gcg ccc ctg acc cca aag gaa gaa gag     1275 
Pro Gly Leu Lys Ser Lys His Ala Pro Leu Thr Pro Lys Glu Glu Glu 
    365                 370                 375 

tat ctg caa gcc caa gtc aga agc agg agc aag ctg gac gcc ccg aaa     1323 
Tyr Leu Gln Ala Gln Val Arg Ser Arg Ser Lys Leu Asp Ala Pro Lys 
380                 385                 390                 395 

gtt gac ctc ctg gtg aag aac tgc ctt ctc ccg ctg aga gag tac ttc     1371 
Val Asp Leu Leu Val Lys Asn Cys Leu Leu Pro Leu Arg Glu Tyr Phe 
                400                 405                 410 

aag tat ttt tct caa aac tca ctt cct ctt tagaaatgaa tcaccataag       1421 
Lys Tyr Phe Ser Gln Asn Ser Leu Pro Leu 
            415                 420 

atgaaagtct ttcctagaac cagggcagat ttcttcctaa ggtctcttcc ctccacagtt   1481 

ttctctggtt tgctttcagg ccttcgggtt tctctcctgt ttgattgcca ggatgcctct   1541 

gtgcagctca ctttgcgggg tgggaggtgc ctacggctct gcacaagttc ccggtgggat   1601 

aacctgccat gtttctctga aactgtgtgt acctgttgtg aagtttttca aatatatcat   1661 

aggattgtt                                                           1670 

 
           
             22  
             421  
             PRT  
             Mus musculus  
           
            22 

Met Gly Ser Arg Glu Thr Pro Ser Ser Cys Ser Lys Thr Leu Glu Thr 
1               5                   10                  15 

Leu Asp Leu Glu Thr Ser Asp Ser Ser Ser Pro Asp Ala Asp Ser Pro 
            20                  25                  30 

Leu Glu Glu Gln Trp Leu Lys Ser Ser Pro Ala Leu Lys Glu Asp Ser 
        35                  40                  45 

Val Asp Val Val Leu Glu Asp Cys Lys Glu Pro Leu Ser Pro Ser Ser 
    50                  55                  60 

Pro Pro Thr Gly Arg Glu Met Ile Arg Tyr Glu Val Lys Val Asn Arg 
65                  70                  75                  80 

Arg Ser Ile Glu Asp Ile Cys Leu Cys Cys Gly Thr Leu Gln Val Tyr 
                85                  90                  95 

Thr Arg His Pro Leu Phe Glu Gly Gly Leu Cys Ala Pro Cys Lys Asp 
            100                 105                 110 

Lys Phe Leu Glu Ser Leu Phe Leu Tyr Asp Asp Asp Gly His Gln Ser 
        115                 120                 125 

Tyr Cys Thr Ile Cys Cys Ser Gly Gly Thr Leu Phe Ile Cys Glu Ser 
    130                 135                 140 

Pro Asp Cys Thr Arg Cys Tyr Cys Phe Glu Cys Val Asp Ile Leu Val 
145                 150                 155                 160 

Gly Pro Gly Thr Ser Glu Arg Ile Asn Ala Met Ala Cys Trp Val Cys 
                165                 170                 175 

Phe Leu Cys Leu Pro Phe Ser Arg Ser Gly Leu Leu Gln Arg Arg Lys 
            180                 185                 190 

Arg Trp Arg His Gln Leu Lys Ala Phe His Asp Gln Glu Gly Ala Gly 
        195                 200                 205 

Pro Met Glu Ile Tyr Lys Thr Val Ser Ala Trp Lys Arg Gln Pro Val 
    210                 215                 220 

Arg Val Leu Ser Leu Phe Arg Asn Ile Asp Lys Val Leu Lys Ser Leu 
225                 230                 235                 240 

Gly Phe Leu Glu Ser Gly Ser Gly Ser Gly Gly Gly Thr Leu Lys Tyr 
                245                 250                 255 

Val Glu Asp Val Thr Asn Val Val Arg Arg Asp Val Glu Lys Trp Gly 
            260                 265                 270 

Pro Phe Asp Leu Val Tyr Gly Ser Thr Gln Pro Leu Gly Ser Ser Cys 
        275                 280                 285 

Asp Arg Cys Pro Gly Trp Tyr Met Phe Gln Phe His Arg Ile Leu Gln 
    290                 295                 300 

Tyr Ala Leu Pro Arg Gln Glu Ser Gln Arg Pro Phe Phe Trp Ile Phe 
305                 310                 315                 320 

Met Asp Asn Leu Leu Leu Thr Glu Asp Asp Gln Glu Thr Thr Thr Arg 
                325                 330                 335 

Phe Leu Gln Thr Glu Ala Val Thr Leu Gln Asp Val Arg Gly Arg Asp 
            340                 345                 350 

Tyr Gln Asn Ala Met Arg Val Trp Ser Asn Ile Pro Gly Leu Lys Ser 
        355                 360                 365 

Lys His Ala Pro Leu Thr Pro Lys Glu Glu Glu Tyr Leu Gln Ala Gln 
    370                 375                 380 

Val Arg Ser Arg Ser Lys Leu Asp Ala Pro Lys Val Asp Leu Leu Val 
385                 390                 395                 400 

Lys Asn Cys Leu Leu Pro Leu Arg Glu Tyr Phe Lys Tyr Phe Ser Gln 
                405                 410                 415 

Asn Ser Leu Pro Leu 
            420 

 
           
             23  
             1560  
             DNA  
             Mus musculus  
             
               CDS  
               (147)..(1367)  
             
           
            23 

ggtgcatgct aggggcttac gaaggctggt ggtgcagagg ctcccaggcc aggtcttttt     60 

gtcggtggtg agggacgctc actctcactc cgcgtgctgt ctccccgtct gtgtgctgtg    120 

atctcctctg tgagagaagg gccagg atg ttc gag gtc ctg gtg ctg aag att     173 
                             Met Phe Glu Val Leu Val Leu Lys Ile 
                             1               5 

gaa gat cca ggt tgc ttc tgg gta att ata aaa gga tgt agt cat ttt      221 
Glu Asp Pro Gly Cys Phe Trp Val Ile Ile Lys Gly Cys Ser His Phe 
10                  15                  20                  25 

tta gaa caa gaa gtt gac tac caa aaa cta aac act gcc atg aat gac      269 
Leu Glu Gln Glu Val Asp Tyr Gln Lys Leu Asn Thr Ala Met Asn Asp 
                30                  35                  40 

ttc tat aac agc atg tgt cag gac gta gaa atg aaa cca tta atg ctg      317 
Phe Tyr Asn Ser Met Cys Gln Asp Val Glu Met Lys Pro Leu Met Leu 
            45                  50                  55 

gaa gaa ggg cag gtg tgt gtg gtg tac tgc cag gag ctg aag tgc tgg      365 
Glu Glu Gly Gln Val Cys Val Val Tyr Cys Gln Glu Leu Lys Cys Trp 
        60                  65                  70 

tgc agg gct ctg att aag tcc atc atc tct tct gca gac cat tac ctg      413 
Cys Arg Ala Leu Ile Lys Ser Ile Ile Ser Ser Ala Asp His Tyr Leu 
    75                  80                  85 

gca gag tgt ttc ctg gtc gat ttt gcc aag tat att cca gta aaa tct      461 
Ala Glu Cys Phe Leu Val Asp Phe Ala Lys Tyr Ile Pro Val Lys Ser 
90                  95                  100                 105 

aaa aac atc cga gtt gca gta gag tct ttt atg cag ctt cct tac aga      509 
Lys Asn Ile Arg Val Ala Val Glu Ser Phe Met Gln Leu Pro Tyr Arg 
                110                 115                 120 

gca aaa aaa ttc aga ctt tac ggt aca aag cct gtg aca ttg cac att      557 
Ala Lys Lys Phe Arg Leu Tyr Gly Thr Lys Pro Val Thr Leu His Ile 
            125                 130                 135 

gac ttc tgt gaa gac aat gct gag att gta cct gcc aca aaa tgg gac      605 
Asp Phe Cys Glu Asp Asn Ala Glu Ile Val Pro Ala Thr Lys Trp Asp 
        140                 145                 150 

agt gca gcc atc cag tac ttt cag aac ctt cta aga gca act acc caa      653 
Ser Ala Ala Ile Gln Tyr Phe Gln Asn Leu Leu Arg Ala Thr Thr Gln 
    155                 160                 165 

gtg gaa gca aaa cta tgt gcg gtg gaa gaa gat act ttt gag gtt tac      701 
Val Glu Ala Lys Leu Cys Ala Val Glu Glu Asp Thr Phe Glu Val Tyr 
170                 175                 180                 185 

ctt tat gca aca ata aaa aat gaa aaa gtt tgt gtt aat gat gac cta      749 
Leu Tyr Ala Thr Ile Lys Asn Glu Lys Val Cys Val Asn Asp Asp Leu 
                190                 195                 200 

gtt gca aag aat ttt gct tat tat gtg tca cca atg ggg aat aaa aac      797 
Val Ala Lys Asn Phe Ala Tyr Tyr Val Ser Pro Met Gly Asn Lys Asn 
            205                 210                 215 

ctc aat cct ttg gag aaa ccc agg cag agt ctc aat tcg gtg acc tgc      845 
Leu Asn Pro Leu Glu Lys Pro Arg Gln Ser Leu Asn Ser Val Thr Cys 
        220                 225                 230 

tcc agt aag ctc agc cca tca ctt act ctg tgg cca atg ctt cta caa      893 
Ser Ser Lys Leu Ser Pro Ser Leu Thr Leu Trp Pro Met Leu Leu Gln 
    235                 240                 245 

gga aaa gac tat cac aga atg gaa aat aaa gct cta aac tat aag gat      941 
Gly Lys Asp Tyr His Arg Met Glu Asn Lys Ala Leu Asn Tyr Lys Asp 
250                 255                 260                 265 

tcc ttg aca gac tcg cct aaa atg atg ctt gag aag cag cag cag agc      989 
Ser Leu Thr Asp Ser Pro Lys Met Met Leu Glu Lys Gln Gln Gln Ser 
                270                 275                 280 

ctc cct tta aag cac acg gag aag tgt act gaa tct tct gtg tac tgg     1037 
Leu Pro Leu Lys His Thr Glu Lys Cys Thr Glu Ser Ser Val Tyr Trp 
            285                 290                 295 

cca acc aaa aga ggc ata acc ata tat gct gat cca gat gtt cca tca     1085 
Pro Thr Lys Arg Gly Ile Thr Ile Tyr Ala Asp Pro Asp Val Pro Ser 
        300                 305                 310 

gta agt ggg tct agc cag agg ccg aat gag aag cca ctg cgg ttg act     1133 
Val Ser Gly Ser Ser Gln Arg Pro Asn Glu Lys Pro Leu Arg Leu Thr 
    315                 320                 325 

gaa aag aaa gac tgt gac gag aag aac ggc tgt gta aaa tta ctg cag     1181 
Glu Lys Lys Asp Cys Asp Glu Lys Asn Gly Cys Val Lys Leu Leu Gln 
330                 335                 340                 345 

ttt cta aat cct gat cct ttg aga gct gat ggg acc tca gac ctg cac     1229 
Phe Leu Asn Pro Asp Pro Leu Arg Ala Asp Gly Thr Ser Asp Leu His 
                350                 355                 360 

cag ttg cag aag gtg aag ctg ggc aca ctg cag cct ggg gtg gtg ctc     1277 
Gln Leu Gln Lys Val Lys Leu Gly Thr Leu Gln Pro Gly Val Val Leu 
            365                 370                 375 

cgg aac agg atc gag ccc tgc cta acc ctg gag aaa tca cct ctg tcg     1325 
Arg Asn Arg Ile Glu Pro Cys Leu Thr Leu Glu Lys Ser Pro Leu Ser 
        380                 385                 390 

gca gac ctg aag aag gtg aac atg ttc tta aag cca gac tcc             1367 
Ala Asp Leu Lys Lys Val Asn Met Phe Leu Lys Pro Asp Ser 
    395                 400                 405 

tgacgacatg ccagcccttt ccaacacaga gtgttgcttt gttttgcttt gtctgttctg   1427 

ttctaagagt gacggggatg aaatacaggg ctttgcgcgt cctgggcatg cattcatcac   1487 

tgaaccatac cccaattcca taggaggatt ttaaataaac acttctaagg ctacattgca   1547 

gaattcttgc tcc                                                      1560 

 
           
             24  
             407  
             PRT  
             Mus musculus  
           
            24 

Met Phe Glu Val Leu Val Leu Lys Ile Glu Asp Pro Gly Cys Phe Trp 
1               5                   10                  15 

Val Ile Ile Lys Gly Cys Ser His Phe Leu Glu Gln Glu Val Asp Tyr 
            20                  25                  30 

Gln Lys Leu Asn Thr Ala Met Asn Asp Phe Tyr Asn Ser Met Cys Gln 
        35                  40                  45 

Asp Val Glu Met Lys Pro Leu Met Leu Glu Glu Gly Gln Val Cys Val 
    50                  55                  60 

Val Tyr Cys Gln Glu Leu Lys Cys Trp Cys Arg Ala Leu Ile Lys Ser 
65                  70                  75                  80 

Ile Ile Ser Ser Ala Asp His Tyr Leu Ala Glu Cys Phe Leu Val Asp 
                85                  90                  95 

Phe Ala Lys Tyr Ile Pro Val Lys Ser Lys Asn Ile Arg Val Ala Val 
            100                 105                 110 

Glu Ser Phe Met Gln Leu Pro Tyr Arg Ala Lys Lys Phe Arg Leu Tyr 
        115                 120                 125 

Gly Thr Lys Pro Val Thr Leu His Ile Asp Phe Cys Glu Asp Asn Ala 
    130                 135                 140 

Glu Ile Val Pro Ala Thr Lys Trp Asp Ser Ala Ala Ile Gln Tyr Phe 
145                 150                 155                 160 

Gln Asn Leu Leu Arg Ala Thr Thr Gln Val Glu Ala Lys Leu Cys Ala 
                165                 170                 175 

Val Glu Glu Asp Thr Phe Glu Val Tyr Leu Tyr Ala Thr Ile Lys Asn 
            180                 185                 190 

Glu Lys Val Cys Val Asn Asp Asp Leu Val Ala Lys Asn Phe Ala Tyr 
        195                 200                 205 

Tyr Val Ser Pro Met Gly Asn Lys Asn Leu Asn Pro Leu Glu Lys Pro 
    210                 215                 220 

Arg Gln Ser Leu Asn Ser Val Thr Cys Ser Ser Lys Leu Ser Pro Ser 
225                 230                 235                 240 

Leu Thr Leu Trp Pro Met Leu Leu Gln Gly Lys Asp Tyr His Arg Met 
                245                 250                 255 

Glu Asn Lys Ala Leu Asn Tyr Lys Asp Ser Leu Thr Asp Ser Pro Lys 
            260                 265                 270 

Met Met Leu Glu Lys Gln Gln Gln Ser Leu Pro Leu Lys His Thr Glu 
        275                 280                 285 

Lys Cys Thr Glu Ser Ser Val Tyr Trp Pro Thr Lys Arg Gly Ile Thr 
    290                 295                 300 

Ile Tyr Ala Asp Pro Asp Val Pro Ser Val Ser Gly Ser Ser Gln Arg 
305                 310                 315                 320 

Pro Asn Glu Lys Pro Leu Arg Leu Thr Glu Lys Lys Asp Cys Asp Glu 
                325                 330                 335 

Lys Asn Gly Cys Val Lys Leu Leu Gln Phe Leu Asn Pro Asp Pro Leu 
            340                 345                 350 

Arg Ala Asp Gly Thr Ser Asp Leu His Gln Leu Gln Lys Val Lys Leu 
        355                 360                 365 

Gly Thr Leu Gln Pro Gly Val Val Leu Arg Asn Arg Ile Glu Pro Cys 
    370                 375                 380 

Leu Thr Leu Glu Lys Ser Pro Leu Ser Ala Asp Leu Lys Lys Val Asn 
385                 390                 395                 400 

Met Phe Leu Lys Pro Asp Ser 
                405 

 
           
             25  
             1248  
             DNA  
             Mus musculus  
             
               CDS  
               (32)..(1003)  
             
           
            25 

agtggatccc ccgggctgca ggaattccgg g atg gat cct cga acc tgg cta        52 
                                   Met Asp Pro Arg Thr Trp Leu 
                                   1               5 

agc ttc caa ggg cct cca ggt ggg cct gga atc gga cca ggc tca gag      100 
Ser Phe Gln Gly Pro Pro Gly Gly Pro Gly Ile Gly Pro Gly Ser Glu 
        10                  15                  20 

gta ttg ggg atc tcc cca tgt ccg ccc gca tac gag ttc tgc gga ggg      148 
Val Leu Gly Ile Ser Pro Cys Pro Pro Ala Tyr Glu Phe Cys Gly Gly 
    25                  30                  35 

atg gca tac tgt gga cct cag gtt ggt ctg ggc cta gtc ccc caa gtt      196 
Met Ala Tyr Cys Gly Pro Gln Val Gly Leu Gly Leu Val Pro Gln Val 
40                  45                  50                  55 

ggc gtg gag act ttg cag cct gag ggc cag gca gga gca cga gtg gaa      244 
Gly Val Glu Thr Leu Gln Pro Glu Gly Gln Ala Gly Ala Arg Val Glu 
                60                  65                  70 

agc aac tca gag gga acc tcc tct gag ccc tgt gcc gac cgc ccc aat      292 
Ser Asn Ser Glu Gly Thr Ser Ser Glu Pro Cys Ala Asp Arg Pro Asn 
            75                  80                  85 

gcc gtg aag ttg gag aag gtg gaa cca act ccc gag gag tcc cag gac      340 
Ala Val Lys Leu Glu Lys Val Glu Pro Thr Pro Glu Glu Ser Gln Asp 
        90                  95                  100 

atg aaa gcc ctg cag aag gag cta gaa cag ttt gcc aag ctg ctg aag      388 
Met Lys Ala Leu Gln Lys Glu Leu Glu Gln Phe Ala Lys Leu Leu Lys 
    105                 110                 115 

cag aag agg atc acc ttg ggg tac acc cag gcc gac gtg ggg ctc acc      436 
Gln Lys Arg Ile Thr Leu Gly Tyr Thr Gln Ala Asp Val Gly Leu Thr 
120                 125                 130                 135 

ctg ggc gtt ctc ttt gga aag gtg ttc agc cag acc acc atc tgt cgc      484 
Leu Gly Val Leu Phe Gly Lys Val Phe Ser Gln Thr Thr Ile Cys Arg 
                140                 145                 150 

ttc gag gcc ttg cag ctc agc ctt aag aac atg tgt aag ctg cgg ccc      532 
Phe Glu Ala Leu Gln Leu Ser Leu Lys Asn Met Cys Lys Leu Arg Pro 
            155                 160                 165 

ctg ctg gag aag tgg gtg gag gaa gcc gac aac aat gag aac ctt cag      580 
Leu Leu Glu Lys Trp Val Glu Glu Ala Asp Asn Asn Glu Asn Leu Gln 
        170                 175                 180 

gag ata tgc aaa tcg gag acc ctg gtg cag gcc cgg aag aga aag cga      628 
Glu Ile Cys Lys Ser Glu Thr Leu Val Gln Ala Arg Lys Arg Lys Arg 
    185                 190                 195 

act agc att gag aac cgt gtg agg tgg agt ctg gag acc atg ttt ctg      676 
Thr Ser Ile Glu Asn Arg Val Arg Trp Ser Leu Glu Thr Met Phe Leu 
200                 205                 210                 215 

aag tgc ccg aag ccc tcc cta cag cag atc act cac atc gcc aat cag      724 
Lys Cys Pro Lys Pro Ser Leu Gln Gln Ile Thr His Ile Ala Asn Gln 
                220                 225                 230 

ctt ggg cta gag aag gat gtg gtt cga gta tgg ttc tgt aac cgg cgc      772 
Leu Gly Leu Glu Lys Asp Val Val Arg Val Trp Phe Cys Asn Arg Arg 
            235                 240                 245 

cag aag ggc aaa aga tca agt att gag tat tcc caa cga gaa gag tat      820 
Gln Lys Gly Lys Arg Ser Ser Ile Glu Tyr Ser Gln Arg Glu Glu Tyr 
        250                 255                 260 

gag gct aca ggg aca cct ttc cca ggg ggg gct gta tcc ttt cct ctg      868 
Glu Ala Thr Gly Thr Pro Phe Pro Gly Gly Ala Val Ser Phe Pro Leu 
    265                 270                 275 

ccc cca ggt ccc cac ttt ggc acc cca ggc tat gga agc ccc cac ttc      916 
Pro Pro Gly Pro His Phe Gly Thr Pro Gly Tyr Gly Ser Pro His Phe 
280                 285                 290                 295 

acc aca ctc tac tca gtc cct ttt cct gag ggc gag gcc ttt ccc tct      964 
Thr Thr Leu Tyr Ser Val Pro Phe Pro Glu Gly Glu Ala Phe Pro Ser 
                300                 305                 310 

gtt ccc gtc act gct ctg ggc tct ccc atg cat tca aac tgaggcacca      1013 
Val Pro Val Thr Ala Leu Gly Ser Pro Met His Ser Asn 
            315                 320 

gccctccctg gggatgctgt gagccaaggc aagggaggta gacaagagaa cctggagctt   1073 

tggggttaaa ttcttttact gaggagggat taaaagcaca acaggggtgg ggggtgggat   1133 

ggggaaagaa gctcagtgat gctgttgatc aggagcctgg cctgtctgtc actcatcatt   1193 

ttgttcttaa ataaagactg ggacacacag taaaaaaaaa aaaaaaaaac tcgag        1248 

 
           
             26  
             324  
             PRT  
             Mus musculus  
           
            26 

Met Asp Pro Arg Thr Trp Leu Ser Phe Gln Gly Pro Pro Gly Gly Pro 
1               5                   10                  15 

Gly Ile Gly Pro Gly Ser Glu Val Leu Gly Ile Ser Pro Cys Pro Pro 
            20                  25                  30 

Ala Tyr Glu Phe Cys Gly Gly Met Ala Tyr Cys Gly Pro Gln Val Gly 
        35                  40                  45 

Leu Gly Leu Val Pro Gln Val Gly Val Glu Thr Leu Gln Pro Glu Gly 
    50                  55                  60 

Gln Ala Gly Ala Arg Val Glu Ser Asn Ser Glu Gly Thr Ser Ser Glu 
65                  70                  75                  80 

Pro Cys Ala Asp Arg Pro Asn Ala Val Lys Leu Glu Lys Val Glu Pro 
                85                  90                  95 

Thr Pro Glu Glu Ser Gln Asp Met Lys Ala Leu Gln Lys Glu Leu Glu 
            100                 105                 110 

Gln Phe Ala Lys Leu Leu Lys Gln Lys Arg Ile Thr Leu Gly Tyr Thr 
        115                 120                 125 

Gln Ala Asp Val Gly Leu Thr Leu Gly Val Leu Phe Gly Lys Val Phe 
    130                 135                 140 

Ser Gln Thr Thr Ile Cys Arg Phe Glu Ala Leu Gln Leu Ser Leu Lys 
145                 150                 155                 160 

Asn Met Cys Lys Leu Arg Pro Leu Leu Glu Lys Trp Val Glu Glu Ala 
                165                 170                 175 

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

Gln Ala Arg Lys Arg Lys Arg Thr Ser Ile Glu Asn Arg Val Arg Trp 
        195                 200                 205 

Ser Leu Glu Thr Met Phe Leu Lys Cys Pro Lys Pro Ser Leu Gln Gln 
    210                 215                 220 

Ile Thr His Ile Ala Asn Gln Leu Gly Leu Glu Lys Asp Val Val Arg 
225                 230                 235                 240 

Val Trp Phe Cys Asn Arg Arg Gln Lys Gly Lys Arg Ser Ser Ile Glu 
                245                 250                 255 

Tyr Ser Gln Arg Glu Glu Tyr Glu Ala Thr Gly Thr Pro Phe Pro Gly 
            260                 265                 270 

Gly Ala Val Ser Phe Pro Leu Pro Pro Gly Pro His Phe Gly Thr Pro 
        275                 280                 285 

Gly Tyr Gly Ser Pro His Phe Thr Thr Leu Tyr Ser Val Pro Phe Pro 
    290                 295                 300 

Glu Gly Glu Ala Phe Pro Ser Val Pro Val Thr Ala Leu Gly Ser Pro 
305                 310                 315                 320 

Met His Ser Asn 

 
           
             27  
             640  
             DNA  
             Homo sapiens  
             
               CDS  
               (15)..(362)  
             
           
            27 

ggcacgagga taag atg gga act ctc ccg gca cgt aga cat atc ccg ccg       50 
                Met Gly Thr Leu Pro Ala Arg Arg His Ile Pro Pro 
                1               5                   10 

tgg gtg aaa gtt ccc gaa gac ctg aaa gat cca gag gtg ttc cag gtc       98 
Trp Val Lys Val Pro Glu Asp Leu Lys Asp Pro Glu Val Phe Gln Val 
        15                  20                  25 

cag acg cgg ctg ctg aaa gcc att ttc ggc ccg gac gga tct cga atc      146 
Gln Thr Arg Leu Leu Lys Ala Ile Phe Gly Pro Asp Gly Ser Arg Ile 
    30                  35                  40 

cct tac atc gag cag gtg agc aag gcc atg ctc gag ctg aag gct ctg      194 
Pro Tyr Ile Glu Gln Val Ser Lys Ala Met Leu Glu Leu Lys Ala Leu 
45                  50                  55                  60 

gag tct tca gac ctc acc gag gtc gtg gtt tac ggc tcc tat ttg tac      242 
Glu Ser Ser Asp Leu Thr Glu Val Val Val Tyr Gly Ser Tyr Leu Tyr 
                65                  70                  75 

aag ctc cgg acc aag tgg atg ctc cag tcc atg gct gag tgg cac cgc      290 
Lys Leu Arg Thr Lys Trp Met Leu Gln Ser Met Ala Glu Trp His Arg 
            80                  85                  90 

cag cgc cag gag cga ggg atg ctc aaa ctt gcc gaa gcc atg aat gcc      338 
Gln Arg Gln Glu Arg Gly Met Leu Lys Leu Ala Glu Ala Met Asn Ala 
        95                  100                 105 

ctc gaa cta ggc cct tgg atg aag tgaaccagtt tccagccaat gcaatgaagc     392 
Leu Glu Leu Gly Pro Trp Met Lys 
    110                 115 

cgggttgcag agattaggtt gtggccagag ctagagtgat tccttaagct tgttttaaaa    452 

tctgctccag cctaaagagt taagggaaaa ccatttgttc ccttaaagag ttaagggaaa    512 

acccttggct ctgagtcttg ttgtgaatat ttctttgatg attgttaata aaaagtgttt    572 

tttctttttt cccattttta aaaataacaa taaagtttta aataagttga taaaaaaaaa    632 

aaaaaaaa                                                             640 

 
           
             28  
             116  
             PRT  
             Homo sapiens  
           
            28 

Met Gly Thr Leu Pro Ala Arg Arg His Ile Pro Pro Trp Val Lys Val 
1               5                   10                  15 

Pro Glu Asp Leu Lys Asp Pro Glu Val Phe Gln Val Gln Thr Arg Leu 
            20                  25                  30 

Leu Lys Ala Ile Phe Gly Pro Asp Gly Ser Arg Ile Pro Tyr Ile Glu 
        35                  40                  45 

Gln Val Ser Lys Ala Met Leu Glu Leu Lys Ala Leu Glu Ser Ser Asp 
    50                  55                  60 

Leu Thr Glu Val Val Val Tyr Gly Ser Tyr Leu Tyr Lys Leu Arg Thr 
65                  70                  75                  80 

Lys Trp Met Leu Gln Ser Met Ala Glu Trp His Arg Gln Arg Gln Glu 
                85                  90                  95 

Arg Gly Met Leu Lys Leu Ala Glu Ala Met Asn Ala Leu Glu Leu Gly 
            100                 105                 110 

Pro Trp Met Lys 
        115 

 
           
             29  
             1665  
             DNA  
             Homo sapiens  
             
               CDS  
               (21)..(1550)  
             
           
            29 

agggtgaact ccttgtctct atg gcg act gga cgc ggt cgg atc ttg cag cag     53 
                      Met Ala Thr Gly Arg Gly Arg Ile Leu Gln Gln 
                      1               5                   10 

cac tgg ctc ggc ctc cag acg ctg cgc ggg ccc agc agg ggc ggt ggc      101 
His Trp Leu Gly Leu Gln Thr Leu Arg Gly Pro Ser Arg Gly Gly Gly 
            15                  20                  25 

gcg gcc cgg ggg cgc gcc agg gcc ttt ggg tgc aga aag ggg cca ggg      149 
Ala Ala Arg Gly Arg Ala Arg Ala Phe Gly Cys Arg Lys Gly Pro Gly 
        30                  35                  40 

gtc aag ctt tct gca ggc tct gct gcc ctg agg tgc cat gcc gga ggt      197 
Val Lys Leu Ser Ala Gly Ser Ala Ala Leu Arg Cys His Ala Gly Gly 
    45                  50                  55 

gga cag cac tgg gag agc tct ttc tcc tgc tgt tct ggg ttc ctg gat      245 
Gly Gln His Trp Glu Ser Ser Phe Ser Cys Cys Ser Gly Phe Leu Asp 
60                  65                  70                  75 

gga atg cct tca gaa atc ttg ctg aag ata ttt tcc tac ttg gat gct      293 
Gly Met Pro Ser Glu Ile Leu Leu Lys Ile Phe Ser Tyr Leu Asp Ala 
                80                  85                  90 

gtg agc ctt ctg tgt act gga tgt gtg agc agg cgc ttt tat cat cta      341 
Val Ser Leu Leu Cys Thr Gly Cys Val Ser Arg Arg Phe Tyr His Leu 
            95                  100                 105 

gcc aat gac aat ttt att tgg atc gga atc tac tca act gct ttt tca      389 
Ala Asn Asp Asn Phe Ile Trp Ile Gly Ile Tyr Ser Thr Ala Phe Ser 
        110                 115                 120 

cct gca aga tca aat tgg aaa ttt aat tca gta gag aag ata gct atg      437 
Pro Ala Arg Ser Asn Trp Lys Phe Asn Ser Val Glu Lys Ile Ala Met 
    125                 130                 135 

tct atg agc ttt ctg tca gtt cag gat aaa gaa gct ggt tat tgg aag      485 
Ser Met Ser Phe Leu Ser Val Gln Asp Lys Glu Ala Gly Tyr Trp Lys 
140                 145                 150                 155 

aaa gaa tat atc aca aaa caa ata gca tct gta aaa gcc gca cta gct      533 
Lys Glu Tyr Ile Thr Lys Gln Ile Ala Ser Val Lys Ala Ala Leu Ala 
                160                 165                 170 

gac att ctc aaa cct gtc aac cct tac aca ggc ctt cca gtt aag acc      581 
Asp Ile Leu Lys Pro Val Asn Pro Tyr Thr Gly Leu Pro Val Lys Thr 
            175                 180                 185 

aaa gag gcc ctc aga ata ttt ggt tta ggt tgg gca att ata ctg aaa      629 
Lys Glu Ala Leu Arg Ile Phe Gly Leu Gly Trp Ala Ile Ile Leu Lys 
        190                 195                 200 

gaa aaa ggt gga aaa gaa tat atc atg gag cat gtt gat ctt tcc ata      677 
Glu Lys Gly Gly Lys Glu Tyr Ile Met Glu His Val Asp Leu Ser Ile 
    205                 210                 215 

aat gac aca tca gtt act gtt ata tgg tat ggc aaa aaa tgg cca tgc      725 
Asn Asp Thr Ser Val Thr Val Ile Trp Tyr Gly Lys Lys Trp Pro Cys 
220                 225                 230                 235 

cta gca tca ttg tca acc tta gat tta tgt ggc atg aca cca gtt ttt      773 
Leu Ala Ser Leu Ser Thr Leu Asp Leu Cys Gly Met Thr Pro Val Phe 
                240                 245                 250 

acc gac tgg tat aaa act ccc acc aaa cat aga ctc cga tgg cat tct      821 
Thr Asp Trp Tyr Lys Thr Pro Thr Lys His Arg Leu Arg Trp His Ser 
            255                 260                 265 

tta att gca aag tac aat ctg agt cat ttg acc ata tct acc atg att      869 
Leu Ile Ala Lys Tyr Asn Leu Ser His Leu Thr Ile Ser Thr Met Ile 
        270                 275                 280 

ggc tgt gac aga ctc att cgg atc ttc tgc ctg cac cct ggc ctc ctg      917 
Gly Cys Asp Arg Leu Ile Arg Ile Phe Cys Leu His Pro Gly Leu Leu 
    285                 290                 295 

gtg gga gtg tgg aag aag gag gaa gaa ctg gct ttt gtt atg gca aat      965 
Val Gly Val Trp Lys Lys Glu Glu Glu Leu Ala Phe Val Met Ala Asn 
300                 305                 310                 315 

ctt cat ttt cat cac ctt gtg gag agg agc aca tta ggc tcg gct act     1013 
Leu His Phe His His Leu Val Glu Arg Ser Thr Leu Gly Ser Ala Thr 
                320                 325                 330 

atc ccc tat gaa ctg cct cca cat agc ccc ttt ttg gat gat agc ccc     1061 
Ile Pro Tyr Glu Leu Pro Pro His Ser Pro Phe Leu Asp Asp Ser Pro 
            335                 340                 345 

gag tat gga ctg cac ggc tac caa ctc cat gtt gat ctg cac agc ggt     1109 
Glu Tyr Gly Leu His Gly Tyr Gln Leu His Val Asp Leu His Ser Gly 
        350                 355                 360 

ggg gtt ttc tac cta tgt ggt aca ttt cgc aat ctc ttc acc aag aga     1157 
Gly Val Phe Tyr Leu Cys Gly Thr Phe Arg Asn Leu Phe Thr Lys Arg 
    365                 370                 375 

gga aat att gaa aat gga cat gtg aag ctc att gtt ata cat tta aaa     1205 
Gly Asn Ile Glu Asn Gly His Val Lys Leu Ile Val Ile His Leu Lys 
380                 385                 390                 395 

aat aac aga gaa cac cta cct ctt att gga aaa gtt ggc ctc tcg tgg     1253 
Asn Asn Arg Glu His Leu Pro Leu Ile Gly Lys Val Gly Leu Ser Trp 
                400                 405                 410 

aaa act gat att ttt gat ggc tgt ata aag agt tgt tcc atg atg gac     1301 
Lys Thr Asp Ile Phe Asp Gly Cys Ile Lys Ser Cys Ser Met Met Asp 
            415                 420                 425 

gta act ctt ttg gat gaa cat ggg aaa ccc ttt tgg tgt ttc agt tcc     1349 
Val Thr Leu Leu Asp Glu His Gly Lys Pro Phe Trp Cys Phe Ser Ser 
        430                 435                 440 

ccg gtg tgc ctg aga tcg cct gcc aca ccc tct gac agc tct agc ttc     1397 
Pro Val Cys Leu Arg Ser Pro Ala Thr Pro Ser Asp Ser Ser Ser Phe 
    445                 450                 455 

ttg gga cag aca tac aac gtg gac tac gtt gat gcg gaa gga aga gtg     1445 
Leu Gly Gln Thr Tyr Asn Val Asp Tyr Val Asp Ala Glu Gly Arg Val 
460                 465                 470                 475 

cac gtg gag ctg gtg tgg atc aga gag acc gaa gaa tac ctt att gtc     1493 
His Val Glu Leu Val Trp Ile Arg Glu Thr Glu Glu Tyr Leu Ile Val 
                480                 485                 490 

aac ctg gtc ctt tat ctt agt atc gca aaa atc aac cat tgg ttt ggg     1541 
Asn Leu Val Leu Tyr Leu Ser Ile Ala Lys Ile Asn His Trp Phe Gly 
            495                 500                 505 

act gaa tat tagcagtagg tggcaaatta ttgttgttat ttagttgttt             1590 
Thr Glu Tyr 
        510 

atttttgact ggctttgttc ttggtgttga aaattaaaat aaagcaaatc tgcaaaaaaa   1650 

aaaaaaaaaa aaaaa                                                    1665 

 
           
             30  
             510  
             PRT  
             Homo sapiens  
           
            30 

Met Ala Thr Gly Arg Gly Arg Ile Leu Gln Gln His Trp Leu Gly Leu 
1               5                   10                  15 

Gln Thr Leu Arg Gly Pro Ser Arg Gly Gly Gly Ala Ala Arg Gly Arg 
            20                  25                  30 

Ala Arg Ala Phe Gly Cys Arg Lys Gly Pro Gly Val Lys Leu Ser Ala 
        35                  40                  45 

Gly Ser Ala Ala Leu Arg Cys His Ala Gly Gly Gly Gln His Trp Glu 
    50                  55                  60 

Ser Ser Phe Ser Cys Cys Ser Gly Phe Leu Asp Gly Met Pro Ser Glu 
65                  70                  75                  80 

Ile Leu Leu Lys Ile Phe Ser Tyr Leu Asp Ala Val Ser Leu Leu Cys 
                85                  90                  95 

Thr Gly Cys Val Ser Arg Arg Phe Tyr His Leu Ala Asn Asp Asn Phe 
            100                 105                 110 

Ile Trp Ile Gly Ile Tyr Ser Thr Ala Phe Ser Pro Ala Arg Ser Asn 
        115                 120                 125 

Trp Lys Phe Asn Ser Val Glu Lys Ile Ala Met Ser Met Ser Phe Leu 
    130                 135                 140 

Ser Val Gln Asp Lys Glu Ala Gly Tyr Trp Lys Lys Glu Tyr Ile Thr 
145                 150                 155                 160 

Lys Gln Ile Ala Ser Val Lys Ala Ala Leu Ala Asp Ile Leu Lys Pro 
                165                 170                 175 

Val Asn Pro Tyr Thr Gly Leu Pro Val Lys Thr Lys Glu Ala Leu Arg 
            180                 185                 190 

Ile Phe Gly Leu Gly Trp Ala Ile Ile Leu Lys Glu Lys Gly Gly Lys 
        195                 200                 205 

Glu Tyr Ile Met Glu His Val Asp Leu Ser Ile Asn Asp Thr Ser Val 
    210                 215                 220 

Thr Val Ile Trp Tyr Gly Lys Lys Trp Pro Cys Leu Ala Ser Leu Ser 
225                 230                 235                 240 

Thr Leu Asp Leu Cys Gly Met Thr Pro Val Phe Thr Asp Trp Tyr Lys 
                245                 250                 255 

Thr Pro Thr Lys His Arg Leu Arg Trp His Ser Leu Ile Ala Lys Tyr 
            260                 265                 270 

Asn Leu Ser His Leu Thr Ile Ser Thr Met Ile Gly Cys Asp Arg Leu 
        275                 280                 285 

Ile Arg Ile Phe Cys Leu His Pro Gly Leu Leu Val Gly Val Trp Lys 
    290                 295                 300 

Lys Glu Glu Glu Leu Ala Phe Val Met Ala Asn Leu His Phe His His 
305                 310                 315                 320 

Leu Val Glu Arg Ser Thr Leu Gly Ser Ala Thr Ile Pro Tyr Glu Leu 
                325                 330                 335 

Pro Pro His Ser Pro Phe Leu Asp Asp Ser Pro Glu Tyr Gly Leu His 
            340                 345                 350 

Gly Tyr Gln Leu His Val Asp Leu His Ser Gly Gly Val Phe Tyr Leu 
        355                 360                 365 

Cys Gly Thr Phe Arg Asn Leu Phe Thr Lys Arg Gly Asn Ile Glu Asn 
    370                 375                 380 

Gly His Val Lys Leu Ile Val Ile His Leu Lys Asn Asn Arg Glu His 
385                 390                 395                 400 

Leu Pro Leu Ile Gly Lys Val Gly Leu Ser Trp Lys Thr Asp Ile Phe 
                405                 410                 415 

Asp Gly Cys Ile Lys Ser Cys Ser Met Met Asp Val Thr Leu Leu Asp 
            420                 425                 430 

Glu His Gly Lys Pro Phe Trp Cys Phe Ser Ser Pro Val Cys Leu Arg 
        435                 440                 445 

Ser Pro Ala Thr Pro Ser Asp Ser Ser Ser Phe Leu Gly Gln Thr Tyr 
    450                 455                 460 

Asn Val Asp Tyr Val Asp Ala Glu Gly Arg Val His Val Glu Leu Val 
465                 470                 475                 480 

Trp Ile Arg Glu Thr Glu Glu Tyr Leu Ile Val Asn Leu Val Leu Tyr 
                485                 490                 495 

Leu Ser Ile Ala Lys Ile Asn His Trp Phe Gly Thr Glu Tyr 
            500                 505                 510 

 
           
             31  
             2114  
             DNA  
             Homo sapiens  
             
               CDS  
               (217)..(1131)  
             
           
            31 

attataaatc tagagactcc aggattttaa cgttctgctg gactgagctg gttgcctcat     60 

gttattatgc aggcaactca ctttatccca atttcttgat acttttcctt ctggaggtcc    120 

tatttctcta acatcttcca gaaaagtctt aaagctgcct taaccttttt tccagtccac    180 

ctcttaaatt ttttcctcct cttcctctat actaac atg agt gtg gat cca gct      234 
                                        Met Ser Val Asp Pro Ala 
                                        1               5 

tgt ccc caa agc ttg cct tgc ttt gaa gca tcc gac tgt aaa gaa tct      282 
Cys Pro Gln Ser Leu Pro Cys Phe Glu Ala Ser Asp Cys Lys Glu Ser 
            10                  15                  20 

tca cct atg cct gtg att tgt ggg cct gaa gaa aac tat cca tcc ttg      330 
Ser Pro Met Pro Val Ile Cys Gly Pro Glu Glu Asn Tyr Pro Ser Leu 
        25                  30                  35 

caa atg tct tct gct gag atg cct cac acg gag act gtc tct cct ctt      378 
Gln Met Ser Ser Ala Glu Met Pro His Thr Glu Thr Val Ser Pro Leu 
    40                  45                  50 

ccc tcc tcc atg gat ctg ctt att cag gac agc cct gat tct tcc acc      426 
Pro Ser Ser Met Asp Leu Leu Ile Gln Asp Ser Pro Asp Ser Ser Thr 
55                  60                  65                  70 

agt ccc aaa ggc aaa caa ccc act tct gca gag aat agt gtc gca aaa      474 
Ser Pro Lys Gly Lys Gln Pro Thr Ser Ala Glu Asn Ser Val Ala Lys 
                75                  80                  85 

aag gaa gac aag gtc cca gtc aag aaa cag aag acc aga act gtg ttc      522 
Lys Glu Asp Lys Val Pro Val Lys Lys Gln Lys Thr Arg Thr Val Phe 
            90                  95                  100 

tct tcc acc cag ctg tgt gta ctc aat gat aga ttt cag aga cag aaa      570 
Ser Ser Thr Gln Leu Cys Val Leu Asn Asp Arg Phe Gln Arg Gln Lys 
        105                 110                 115 

tac ctc agc ctc cag cag atg caa gaa ctc tcc aac atc ctg aac ctc      618 
Tyr Leu Ser Leu Gln Gln Met Gln Glu Leu Ser Asn Ile Leu Asn Leu 
    120                 125                 130 

agc tac aaa cag gtg aag acc tgg ttc cag aac cag aga atg aaa tct      666 
Ser Tyr Lys Gln Val Lys Thr Trp Phe Gln Asn Gln Arg Met Lys Ser 
135                 140                 145                 150 

aag agg tgg cag aaa aac aac tgg ccg aag aat agc aat ggt gtg acg      714 
Lys Arg Trp Gln Lys Asn Asn Trp Pro Lys Asn Ser Asn Gly Val Thr 
                155                 160                 165 

cag aag gcc tca gca cct acc tac ccc agc ctc tac tct tcc tac cac      762 
Gln Lys Ala Ser Ala Pro Thr Tyr Pro Ser Leu Tyr Ser Ser Tyr His 
            170                 175                 180 

cag gga tgc ctg gtg aac ccg act ggg aac ctt cca atg tgg agc aac      810 
Gln Gly Cys Leu Val Asn Pro Thr Gly Asn Leu Pro Met Trp Ser Asn 
        185                 190                 195 

cag acc tgg aac aat tca acc tgg agc aac cag acc cag aac atc cag      858 
Gln Thr Trp Asn Asn Ser Thr Trp Ser Asn Gln Thr Gln Asn Ile Gln 
    200                 205                 210 

tcc tgg agc aac cac tcc tgg aac act cag acc tgg tgc acc caa tcc      906 
Ser Trp Ser Asn His Ser Trp Asn Thr Gln Thr Trp Cys Thr Gln Ser 
215                 220                 225                 230 

tgg aac aat cag gcc tgg aac agt ccc ttc tat aac tgt gga gag gaa      954 
Trp Asn Asn Gln Ala Trp Asn Ser Pro Phe Tyr Asn Cys Gly Glu Glu 
                235                 240                 245 

tct ctg cag tcc tgc atg cag ttc cag cca aat tct cct gcc agt gac     1002 
Ser Leu Gln Ser Cys Met Gln Phe Gln Pro Asn Ser Pro Ala Ser Asp 
            250                 255                 260 

ttg gag gct gct ttg gaa gct gct ggg gaa ggc ctt aat gta ata cag     1050 
Leu Glu Ala Ala Leu Glu Ala Ala Gly Glu Gly Leu Asn Val Ile Gln 
        265                 270                 275 

cag acc act agg tat ttt agt act cca caa acc atg gat tta ttc cta     1098 
Gln Thr Thr Arg Tyr Phe Ser Thr Pro Gln Thr Met Asp Leu Phe Leu 
    280                 285                 290 

aac tac tcc atg aac atg caa cct gaa gac gtg tgaagatgag tgaaactgat   1151 
Asn Tyr Ser Met Asn Met Gln Pro Glu Asp Val 
295                 300                 305 

attactcaat ttcagtctgg acactggctg aatccttcct ctcccctcct cccatccctc   1211 

ataggatttt tcttgtttgg aaaccacgtg ttctggtttc catgatgcct atccagtcaa   1271 

tctcatggag ggtggagtat ggttggagcc taatcagcga ggtttctttt tttttttttc   1331 

ctattggatc ttcctggaga aaatactttt tttttttttt ttgagacgga gtcttgctct   1391 

gtcgcccagg ctggagtgca gtggcgcggt cttggctcac tgcaagctcc gcctcccggg   1451 

ttcacgccat tctcctgcct cagcctcccg agcagctggg actacaggcg cccgccacct   1511 

cgcccggcta atattttgta tttttagtag agacagggtt tcactgtgtt agccaggatg   1571 

gtctcgatct cctgaccttg tgatccgccc gcctcggcct ccctaacagc tgggattaca   1631 

ggcgtgagcc accgcgccct gcctagaaaa gacattttaa taaccttggc tgctaaggac   1691 

aacattgata gaagccgtct ctggctatag ataagtagat ctaatactag tttggatatc   1751 

tttagggttt agaatctaac ctcaagaata agaaatacaa gtacgaattg gtgatgaaga   1811 

tgtattcgta ttgtttggga ttgggaggct ttgcttattt ttttaaaact attgaggtaa   1871 

agggttaagc tgtaacatac ttaattgatt tcttaccgtt tttggctctg ttttgctata   1931 

tcccctaatt tgttggttgt gctaatcttt gtagaaagag gtcttgtatt tgctgcatcg   1991 

taatgacatg agtactactt tagttggttt aagttcaaat gaatgaaaca aatatttttc   2051 

ctttagttga ttttaccctg atttcaccga gtgtttcgat gagtaaatat acagcttaaa   2111 

cat                                                                 2114 

 
           
             32  
             305  
             PRT  
             Homo sapiens  
           
            32 

Met Ser Val Asp Pro Ala Cys Pro Gln Ser Leu Pro Cys Phe Glu Ala 
1               5                   10                  15 

Ser Asp Cys Lys Glu Ser Ser Pro Met Pro Val Ile Cys Gly Pro Glu 
            20                  25                  30 

Glu Asn Tyr Pro Ser Leu Gln Met Ser Ser Ala Glu Met Pro His Thr 
        35                  40                  45 

Glu Thr Val Ser Pro Leu Pro Ser Ser Met Asp Leu Leu Ile Gln Asp 
    50                  55                  60 

Ser Pro Asp Ser Ser Thr Ser Pro Lys Gly Lys Gln Pro Thr Ser Ala 
65                  70                  75                  80 

Glu Asn Ser Val Ala Lys Lys Glu Asp Lys Val Pro Val Lys Lys Gln 
                85                  90                  95 

Lys Thr Arg Thr Val Phe Ser Ser Thr Gln Leu Cys Val Leu Asn Asp 
            100                 105                 110 

Arg Phe Gln Arg Gln Lys Tyr Leu Ser Leu Gln Gln Met Gln Glu Leu 
        115                 120                 125 

Ser Asn Ile Leu Asn Leu Ser Tyr Lys Gln Val Lys Thr Trp Phe Gln 
    130                 135                 140 

Asn Gln Arg Met Lys Ser Lys Arg Trp Gln Lys Asn Asn Trp Pro Lys 
145                 150                 155                 160 

Asn Ser Asn Gly Val Thr Gln Lys Ala Ser Ala Pro Thr Tyr Pro Ser 
                165                 170                 175 

Leu Tyr Ser Ser Tyr His Gln Gly Cys Leu Val Asn Pro Thr Gly Asn 
            180                 185                 190 

Leu Pro Met Trp Ser Asn Gln Thr Trp Asn Asn Ser Thr Trp Ser Asn 
        195                 200                 205 

Gln Thr Gln Asn Ile Gln Ser Trp Ser Asn His Ser Trp Asn Thr Gln 
    210                 215                 220 

Thr Trp Cys Thr Gln Ser Trp Asn Asn Gln Ala Trp Asn Ser Pro Phe 
225                 230                 235                 240 

Tyr Asn Cys Gly Glu Glu Ser Leu Gln Ser Cys Met Gln Phe Gln Pro 
                245                 250                 255 

Asn Ser Pro Ala Ser Asp Leu Glu Ala Ala Leu Glu Ala Ala Gly Glu 
            260                 265                 270 

Gly Leu Asn Val Ile Gln Gln Thr Thr Arg Tyr Phe Ser Thr Pro Gln 
        275                 280                 285 

Thr Met Asp Leu Phe Leu Asn Tyr Ser Met Asn Met Gln Pro Glu Asp 
    290                 295                 300 

Val 
305 

 
           
             33  
             1266  
             DNA  
             Homo sapiens  
             
               CDS  
               (252)..(950)  
             
           
            33 

cgtgaggagg gaaggagaga tggggggacg tgggacaggg agaaaacaac ataaatcata     60 

tatatatagc atgcaaattg gaaggtgatc agcacacaat aggcattcaa taaatgttga    120 

aataatgaca ccccactgtc tccttgccct caaatggtct cccctaacgt atcccctgtt    180 

gtcttgcttc ttctcttccc acttgcagag cctgctgccc acgtctcttc cctgagctgc    240 

ctgctggggt c atg gag ctg cca aca aag cct ggc acc ttc gac ctg ggc     290 
             Met Glu Leu Pro Thr Lys Pro Gly Thr Phe Asp Leu Gly 
             1               5                   10 

ctg gcc aca tgg agc cct tcc ttc cag ggg gaa acc cac cgg gct cag      338 
Leu Ala Thr Trp Ser Pro Ser Phe Gln Gly Glu Thr His Arg Ala Gln 
    15                  20                  25 

gca cgc cgc agg gat gtt ggc agg cag ctg cct gag tac aag gct gtg      386 
Ala Arg Arg Arg Asp Val Gly Arg Gln Leu Pro Glu Tyr Lys Ala Val 
30                  35                  40                  45 

gtg gtg ggc gcc agt ggc gtg ggc aag agt gcg ctg acc atc cag ctg      434 
Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu 
                50                  55                  60 

aac cac cag tgc ttc gtg gag gac cac gac ccc acc atc cag gat tcc      482 
Asn His Gln Cys Phe Val Glu Asp His Asp Pro Thr Ile Gln Asp Ser 
            65                  70                  75 

tac tgg aag gag ttg acc ctg gac agt ggg gac tgc att ctg aat gtg      530 
Tyr Trp Lys Glu Leu Thr Leu Asp Ser Gly Asp Cys Ile Leu Asn Val 
        80                  85                  90 

ctg gac aca gca ggg cag gcc atc cat agg gcc ctg cgt gac cag tgc      578 
Leu Asp Thr Ala Gly Gln Ala Ile His Arg Ala Leu Arg Asp Gln Cys 
    95                  100                 105 

ctg gct gtc tgt gat ggt gtg ctg ggc gtc ttc gct ctc gat gac ccc      626 
Leu Ala Val Cys Asp Gly Val Leu Gly Val Phe Ala Leu Asp Asp Pro 
110                 115                 120                 125 

tcg tct ctg atc cag ctg cag cag ata tgg gcc acc tgg ggc cct cac      674 
Ser Ser Leu Ile Gln Leu Gln Gln Ile Trp Ala Thr Trp Gly Pro His 
                130                 135                 140 

ccc gcc cag ccc ctt gtc ctc gtg ggc aac aag tgt gac ctt gtg acc      722 
Pro Ala Gln Pro Leu Val Leu Val Gly Asn Lys Cys Asp Leu Val Thr 
            145                 150                 155 

act gct gga gat gct cat gcc gct gct gca gcc ctc gca cac agc tgg      770 
Thr Ala Gly Asp Ala His Ala Ala Ala Ala Ala Leu Ala His Ser Trp 
        160                 165                 170 

ggg gcc cac ttc gtg gag acc tcg gcc aaa aca cgg caa ggc gtg gag      818 
Gly Ala His Phe Val Glu Thr Ser Ala Lys Thr Arg Gln Gly Val Glu 
    175                 180                 185 

gag gcc ttt tcc ctg ctg gtc cat gag atc cag agg gtc cag gag gcc      866 
Glu Ala Phe Ser Leu Leu Val His Glu Ile Gln Arg Val Gln Glu Ala 
190                 195                 200                 205 

atg gcg aag gag ccc atg gca agg tcc tgt agg gag aag acc cgg cac      914 
Met Ala Lys Glu Pro Met Ala Arg Ser Cys Arg Glu Lys Thr Arg His 
                210                 215                 220 

cag aag gcc acc tgc cac tgt ggc tgc tct gtg gcc tgaaggtctt           960 
Gln Lys Ala Thr Cys His Cys Gly Cys Ser Val Ala 
            225                 230 

ggccaagaaa tgtagacctt tccccaggcc agggtgattg ttcatttgac atgagacccc   1020 

tgaggcaact agctttgagg gacacatcag gtatactagg gaaagatgga catctctctt   1080 

gttttcactt ggtgaggggc tttttggtaa catgggagtg cctaatgttg cttttgttat   1140 

gtcaagttga aagattttgt gcaaaattaa ataaatggtg ttttgggttt caaagctgcc   1200 

tccatgccga gtgttgtgtg ggtgggagtg agactgggta gaatgttact tgagttgtga   1260 

gaattc                                                              1266 

 
           
             34  
             233  
             PRT  
             Homo sapiens  
           
            34 

Met Glu Leu Pro Thr Lys Pro Gly Thr Phe Asp Leu Gly Leu Ala Thr 
1               5                   10                  15 

Trp Ser Pro Ser Phe Gln Gly Glu Thr His Arg Ala Gln Ala Arg Arg 
            20                  25                  30 

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

Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Asn His Gln 
    50                  55                  60 

Cys Phe Val Glu Asp His Asp Pro Thr Ile Gln Asp Ser Tyr Trp Lys 
65                  70                  75                  80 

Glu Leu Thr Leu Asp Ser Gly Asp Cys Ile Leu Asn Val Leu Asp Thr 
                85                  90                  95 

Ala Gly Gln Ala Ile His Arg Ala Leu Arg Asp Gln Cys Leu Ala Val 
            100                 105                 110 

Cys Asp Gly Val Leu Gly Val Phe Ala Leu Asp Asp Pro Ser Ser Leu 
        115                 120                 125 

Ile Gln Leu Gln Gln Ile Trp Ala Thr Trp Gly Pro His Pro Ala Gln 
    130                 135                 140 

Pro Leu Val Leu Val Gly Asn Lys Cys Asp Leu Val Thr Thr Ala Gly 
145                 150                 155                 160 

Asp Ala His Ala Ala Ala Ala Ala Leu Ala His Ser Trp Gly Ala His 
                165                 170                 175 

Phe Val Glu Thr Ser Ala Lys Thr Arg Gln Gly Val Glu Glu Ala Phe 
            180                 185                 190 

Ser Leu Leu Val His Glu Ile Gln Arg Val Gln Glu Ala Met Ala Lys 
        195                 200                 205 

Glu Pro Met Ala Arg Ser Cys Arg Glu Lys Thr Arg His Gln Lys Ala 
    210                 215                 220 

Thr Cys His Cys Gly Cys Ser Val Ala 
225                 230 

 
           
             35  
             1705  
             DNA  
             Homo sapiens  
             
               CDS  
               (485)..(1645)  
             
           
            35 

cccatctcca cccctcccct gaaccccact ccccactgag gtccccaaac cccacccctc     60 

actccaccct gagggcccca tcctctgaac cccaatcccc cagccccact gagctcttaa    120 

ccctccccac ctgagggttc cctttccctg cccgtccccc agcttcctag ctccccaccc    180 

caagtgaccc cccgcagctc ctcgcccctc ccactgcaaa ccggcactga agggctgccc    240 

cgcccccgcc cctccccgcc cccgcgggac acgcccagat tctttgcccc catagcctgg    300 

tgacctctgg ccacccgctg tcccaggtgg gcctggatcc ttccagctca ttctttgcct    360 

gcgccgtccc tcgttccatg gcccagtcct ccccggggac cctgagcctg gaagccccgg    420 

accactggaa ccttgaaccc accagctggc tgtacccgga gccgtggcag cagccctcat    480 

cccc atg gcg gcc atc cca gcc ctg gac cca gag gcc gag ccc agc atg     529 
     Met Ala Ala Ile Pro Ala Leu Asp Pro Glu Ala Glu Pro Ser Met 
     1               5                   10                  15 

gac gtg att ttg gtg gga tcc agt gag ctc tca agc tcc gtt tca ccc      577 
Asp Val Ile Leu Val Gly Ser Ser Glu Leu Ser Ser Ser Val Ser Pro 
                20                  25                  30 

ggg aca ggc aga gat ctt att gca tat gaa gtc aag gct aac cag cga      625 
Gly Thr Gly Arg Asp Leu Ile Ala Tyr Glu Val Lys Ala Asn Gln Arg 
            35                  40                  45 

aat ata gaa gac atc tgc atc tgc tgc gga agt ctc cag gtt cac aca      673 
Asn Ile Glu Asp Ile Cys Ile Cys Cys Gly Ser Leu Gln Val His Thr 
        50                  55                  60 

cag cac cct ctg ttt gag gga ggg atc tgc gcc cca tgt aag gac aag      721 
Gln His Pro Leu Phe Glu Gly Gly Ile Cys Ala Pro Cys Lys Asp Lys 
    65                  70                  75 

ttc ctg gat gcc ctc ttc ctg tac gac gat gac ggg tac caa tcc tac      769 
Phe Leu Asp Ala Leu Phe Leu Tyr Asp Asp Asp Gly Tyr Gln Ser Tyr 
80                  85                  90                  95 

tgc tcc atc tgc tgc tcc gga gag acg ctg ctc atc tgc gga aac cct      817 
Cys Ser Ile Cys Cys Ser Gly Glu Thr Leu Leu Ile Cys Gly Asn Pro 
                100                 105                 110 

gat tgc acc cga tgc tac tgc ttc gag tgt gtg gat agc ctg gtc ggc      865 
Asp Cys Thr Arg Cys Tyr Cys Phe Glu Cys Val Asp Ser Leu Val Gly 
            115                 120                 125 

ccc ggg acc tcg ggg aag gtg cac gcc atg agc aac tgg gtg tgc tac      913 
Pro Gly Thr Ser Gly Lys Val His Ala Met Ser Asn Trp Val Cys Tyr 
        130                 135                 140 

ctg tgc ctg ccg tcc tcc cga agc ggg ctg ctg cag cgt cgg agg aag      961 
Leu Cys Leu Pro Ser Ser Arg Ser Gly Leu Leu Gln Arg Arg Arg Lys 
    145                 150                 155 

tgg cgc agc cag ctc aag gcc ttc tac gac cga gag tcg gag aat ccc     1009 
Trp Arg Ser Gln Leu Lys Ala Phe Tyr Asp Arg Glu Ser Glu Asn Pro 
160                 165                 170                 175 

ctt gag atg ttc gaa acc gtg cct gtg tgg agg aga cag cca gtc cgg     1057 
Leu Glu Met Phe Glu Thr Val Pro Val Trp Arg Arg Gln Pro Val Arg 
                180                 185                 190 

gtg ctg tcc ctt ttt gaa gac atc aag aaa gag ctg acg agt ttg ggc     1105 
Val Leu Ser Leu Phe Glu Asp Ile Lys Lys Glu Leu Thr Ser Leu Gly 
            195                 200                 205 

ttt ttg gaa agt ggt tct gac ccg gga caa ctg aag cat gtg gtt gat     1153 
Phe Leu Glu Ser Gly Ser Asp Pro Gly Gln Leu Lys His Val Val Asp 
        210                 215                 220 

gtc aca gac aca gtg agg aag gat gtg gag gag tgg gga ccc ttc gat     1201 
Val Thr Asp Thr Val Arg Lys Asp Val Glu Glu Trp Gly Pro Phe Asp 
    225                 230                 235 

ctt gtg tac ggc gcc aca gct ccc ctg ggc cac acc tgt gac cgt cct     1249 
Leu Val Tyr Gly Ala Thr Ala Pro Leu Gly His Thr Cys Asp Arg Pro 
240                 245                 250                 255 

ccc agc tgg tac ctg ttc cag ttc cac cgg ttc ctg cag tac gca cgg     1297 
Pro Ser Trp Tyr Leu Phe Gln Phe His Arg Phe Leu Gln Tyr Ala Arg 
                260                 265                 270 

ccc aag cca ggc agc ccc agg ccc ttc ttc tgg atg ttc gtg gac aat     1345 
Pro Lys Pro Gly Ser Pro Arg Pro Phe Phe Trp Met Phe Val Asp Asn 
            275                 280                 285 

ctg gtg ctg aac aag gaa gac ctg gac gtc gca tct cgc ttc ctg gag     1393 
Leu Val Leu Asn Lys Glu Asp Leu Asp Val Ala Ser Arg Phe Leu Glu 
        290                 295                 300 

atg gag cca gtc acc atc cca gat gtc cac ggc gga tcc ttg cag aat     1441 
Met Glu Pro Val Thr Ile Pro Asp Val His Gly Gly Ser Leu Gln Asn 
    305                 310                 315 

gct gtc cgc gtg tgg agc aac atc cca gcc ata agg agc agc agg cac     1489 
Ala Val Arg Val Trp Ser Asn Ile Pro Ala Ile Arg Ser Ser Arg His 
320                 325                 330                 335 

tgg gct ctg gtt tcg gaa gaa gaa ttg tcc ctg ctg gcc cag aac aag     1537 
Trp Ala Leu Val Ser Glu Glu Glu Leu Ser Leu Leu Ala Gln Asn Lys 
                340                 345                 350 

cag agc tcg aag ctc gcg gcc aag tgg ccc acc aag ctg gtg aag aac     1585 
Gln Ser Ser Lys Leu Ala Ala Lys Trp Pro Thr Lys Leu Val Lys Asn 
            355                 360                 365 

tgc ttt ctc ccc cta aga gaa tat ttc aag tat ttt tca aca gaa ctc     1633 
Cys Phe Leu Pro Leu Arg Glu Tyr Phe Lys Tyr Phe Ser Thr Glu Leu 
        370                 375                 380 

act tcc tct tta taaatgagtc actatactgt gaagaaaaag acttttccta         1685 
Thr Ser Ser Leu 
    385 

gaacaaaggc aactttcctc                                               1705 

 
           
             36  
             387  
             PRT  
             Homo sapiens  
           
            36 

Met Ala Ala Ile Pro Ala Leu Asp Pro Glu Ala Glu Pro Ser Met Asp 
1               5                   10                  15 

Val Ile Leu Val Gly Ser Ser Glu Leu Ser Ser Ser Val Ser Pro Gly 
            20                  25                  30 

Thr Gly Arg Asp Leu Ile Ala Tyr Glu Val Lys Ala Asn Gln Arg Asn 
        35                  40                  45 

Ile Glu Asp Ile Cys Ile Cys Cys Gly Ser Leu Gln Val His Thr Gln 
    50                  55                  60 

His Pro Leu Phe Glu Gly Gly Ile Cys Ala Pro Cys Lys Asp Lys Phe 
65                  70                  75                  80 

Leu Asp Ala Leu Phe Leu Tyr Asp Asp Asp Gly Tyr Gln Ser Tyr Cys 
                85                  90                  95 

Ser Ile Cys Cys Ser Gly Glu Thr Leu Leu Ile Cys Gly Asn Pro Asp 
            100                 105                 110 

Cys Thr Arg Cys Tyr Cys Phe Glu Cys Val Asp Ser Leu Val Gly Pro 
        115                 120                 125 

Gly Thr Ser Gly Lys Val His Ala Met Ser Asn Trp Val Cys Tyr Leu 
    130                 135                 140 

Cys Leu Pro Ser Ser Arg Ser Gly Leu Leu Gln Arg Arg Arg Lys Trp 
145                 150                 155                 160 

Arg Ser Gln Leu Lys Ala Phe Tyr Asp Arg Glu Ser Glu Asn Pro Leu 
                165                 170                 175 

Glu Met Phe Glu Thr Val Pro Val Trp Arg Arg Gln Pro Val Arg Val 
            180                 185                 190 

Leu Ser Leu Phe Glu Asp Ile Lys Lys Glu Leu Thr Ser Leu Gly Phe 
        195                 200                 205 

Leu Glu Ser Gly Ser Asp Pro Gly Gln Leu Lys His Val Val Asp Val 
    210                 215                 220 

Thr Asp Thr Val Arg Lys Asp Val Glu Glu Trp Gly Pro Phe Asp Leu 
225                 230                 235                 240 

Val Tyr Gly Ala Thr Ala Pro Leu Gly His Thr Cys Asp Arg Pro Pro 
                245                 250                 255 

Ser Trp Tyr Leu Phe Gln Phe His Arg Phe Leu Gln Tyr Ala Arg Pro 
            260                 265                 270 

Lys Pro Gly Ser Pro Arg Pro Phe Phe Trp Met Phe Val Asp Asn Leu 
        275                 280                 285 

Val Leu Asn Lys Glu Asp Leu Asp Val Ala Ser Arg Phe Leu Glu Met 
    290                 295                 300 

Glu Pro Val Thr Ile Pro Asp Val His Gly Gly Ser Leu Gln Asn Ala 
305                 310                 315                 320 

Val Arg Val Trp Ser Asn Ile Pro Ala Ile Arg Ser Ser Arg His Trp 
                325                 330                 335 

Ala Leu Val Ser Glu Glu Glu Leu Ser Leu Leu Ala Gln Asn Lys Gln 
            340                 345                 350 

Ser Ser Lys Leu Ala Ala Lys Trp Pro Thr Lys Leu Val Lys Asn Cys 
        355                 360                 365 

Phe Leu Pro Leu Arg Glu Tyr Phe Lys Tyr Phe Ser Thr Glu Leu Thr 
    370                 375                 380 

Ser Ser Leu 
385 

 
           
             37  
             1301  
             DNA  
             Homo sapiens  
             
               CDS  
               (97)..(1167)  
             
           
            37 

ttacagattg aagatccagg ttgcttctgg gttattataa aagggtgtag tcccttttta     60 

gatcatgatg tcgattatca aaaattaaat agtgcc atg aat gac ttc tac aac      114 
                                        Met Asn Asp Phe Tyr Asn 
                                        1               5 

agc acg tgt caa gat ata gaa ata aaa ccc tta aca ttg gaa gaa gga      162 
Ser Thr Cys Gln Asp Ile Glu Ile Lys Pro Leu Thr Leu Glu Glu Gly 
            10                  15                  20 

cag gtg tgt gtg gtc tat tgt gag gag cta aag tgc tgg tgc agg gcc      210 
Gln Val Cys Val Val Tyr Cys Glu Glu Leu Lys Cys Trp Cys Arg Ala 
        25                  30                  35 

att gtc aaa tca att acg tct tcc gca gac cag tac ctg gca gaa tgt      258 
Ile Val Lys Ser Ile Thr Ser Ser Ala Asp Gln Tyr Leu Ala Glu Cys 
    40                  45                  50 

ttc ctt gtg gac ttt gcc aag aac att cca gtc aaa tct aaa agc atc      306 
Phe Leu Val Asp Phe Ala Lys Asn Ile Pro Val Lys Ser Lys Ser Ile 
55                  60                  65                  70 

cga gtt gta gta gaa tcg ttt atg cag ctt ccc tat aga gca aaa aaa      354 
Arg Val Val Val Glu Ser Phe Met Gln Leu Pro Tyr Arg Ala Lys Lys 
                75                  80                  85 

ttc agc ctg tac tgc aca aag cct gtc aca tta cac att gac ttc tgc      402 
Phe Ser Leu Tyr Cys Thr Lys Pro Val Thr Leu His Ile Asp Phe Cys 
            90                  95                  100 

cga gac agt act gac att gtg cct gcc aag aag tgg gac aat gca gct      450 
Arg Asp Ser Thr Asp Ile Val Pro Ala Lys Lys Trp Asp Asn Ala Ala 
        105                 110                 115 

att cag tac ttt cag aac ctt ctg aaa gca act acc cag gtg gaa gcc      498 
Ile Gln Tyr Phe Gln Asn Leu Leu Lys Ala Thr Thr Gln Val Glu Ala 
    120                 125                 130 

aga tta tgt gct gtg gaa gaa gat aca ttt gag gtt tac ctt tat gta      546 
Arg Leu Cys Ala Val Glu Glu Asp Thr Phe Glu Val Tyr Leu Tyr Val 
135                 140                 145                 150 

act ata aaa gat gaa aaa gtt tgt gtt aat gat gat ctt gtt gca aag      594 
Thr Ile Lys Asp Glu Lys Val Cys Val Asn Asp Asp Leu Val Ala Lys 
                155                 160                 165 

aac tat gct tgt tat atg tca cct aca aag aat aaa aac ctt gat tat      642 
Asn Tyr Ala Cys Tyr Met Ser Pro Thr Lys Asn Lys Asn Leu Asp Tyr 
            170                 175                 180 

tta gaa aaa cca aga ttg aat ata aaa tca gca ccc tcc ttc aat aaa      690 
Leu Glu Lys Pro Arg Leu Asn Ile Lys Ser Ala Pro Ser Phe Asn Lys 
        185                 190                 195 

ctc aat cca gca ctt aca ctc tgg cca atg ttt ttg caa gga aaa gat      738 
Leu Asn Pro Ala Leu Thr Leu Trp Pro Met Phe Leu Gln Gly Lys Asp 
    200                 205                 210 

gtt caa gga atg gaa gat tca cat ggt gta aat ttt ccg gca caa tct      786 
Val Gln Gly Met Glu Asp Ser His Gly Val Asn Phe Pro Ala Gln Ser 
215                 220                 225                 230 

ctg caa cat aca tgg tgc aag ggt att gtc ggt gac ctc agg cca aca      834 
Leu Gln His Thr Trp Cys Lys Gly Ile Val Gly Asp Leu Arg Pro Thr 
                235                 240                 245 

gcc aca gca cag gac aaa gct gta aaa tgt aat atg gat tca ttg aga      882 
Ala Thr Ala Gln Asp Lys Ala Val Lys Cys Asn Met Asp Ser Leu Arg 
            250                 255                 260 

gat tca cct aaa gac aaa tct gaa aag aaa cac cat tgc atc tct tta      930 
Asp Ser Pro Lys Asp Lys Ser Glu Lys Lys His His Cys Ile Ser Leu 
        265                 270                 275 

aaa gat aca aat aag cgt gtt gaa tcc tca gtg tac tgg cca gca aaa      978 
Lys Asp Thr Asn Lys Arg Val Glu Ser Ser Val Tyr Trp Pro Ala Lys 
    280                 285                 290 

aga ggc ata acc ata tat gct gat cca gat gta cca gaa gca agt gct     1026 
Arg Gly Ile Thr Ile Tyr Ala Asp Pro Asp Val Pro Glu Ala Ser Ala 
295                 300                 305                 310 

tta agt cag aag tca aat gag aaa cct ctt aga ttg act gag aag aaa     1074 
Leu Ser Gln Lys Ser Asn Glu Lys Pro Leu Arg Leu Thr Glu Lys Lys 
                315                 320                 325 

gaa tat gat gag aag aat agc tgt gtg aaa tta ctg cag ttt tta aat     1122 
Glu Tyr Asp Glu Lys Asn Ser Cys Val Lys Leu Leu Gln Phe Leu Asn 
            330                 335                 340 

cct gat cct ttg aga gct gac gga atc tct gat ctc cag cag act         1167 
Pro Asp Pro Leu Arg Ala Asp Gly Ile Ser Asp Leu Gln Gln Thr 
        345                 350                 355 

tgagattaga agagaaactc cttagatggg ggacttaacc tgaagacatc cttttagaaa   1227 

cgatcgaatg gattgttgct tctgagaaat tgttccttgt tttttggata ataaacgatc   1287 

ttccttttgg taaa                                                     1301 

 
           
             38  
             357  
             PRT  
             Homo sapiens  
           
            38 

Met Asn Asp Phe Tyr Asn Ser Thr Cys Gln Asp Ile Glu Ile Lys Pro 
1               5                   10                  15 

Leu Thr Leu Glu Glu Gly Gln Val Cys Val Val Tyr Cys Glu Glu Leu 
            20                  25                  30 

Lys Cys Trp Cys Arg Ala Ile Val Lys Ser Ile Thr Ser Ser Ala Asp 
        35                  40                  45 

Gln Tyr Leu Ala Glu Cys Phe Leu Val Asp Phe Ala Lys Asn Ile Pro 
    50                  55                  60 

Val Lys Ser Lys Ser Ile Arg Val Val Val Glu Ser Phe Met Gln Leu 
65                  70                  75                  80 

Pro Tyr Arg Ala Lys Lys Phe Ser Leu Tyr Cys Thr Lys Pro Val Thr 
                85                  90                  95 

Leu His Ile Asp Phe Cys Arg Asp Ser Thr Asp Ile Val Pro Ala Lys 
            100                 105                 110 

Lys Trp Asp Asn Ala Ala Ile Gln Tyr Phe Gln Asn Leu Leu Lys Ala 
        115                 120                 125 

Thr Thr Gln Val Glu Ala Arg Leu Cys Ala Val Glu Glu Asp Thr Phe 
    130                 135                 140 

Glu Val Tyr Leu Tyr Val Thr Ile Lys Asp Glu Lys Val Cys Val Asn 
145                 150                 155                 160 

Asp Asp Leu Val Ala Lys Asn Tyr Ala Cys Tyr Met Ser Pro Thr Lys 
                165                 170                 175 

Asn Lys Asn Leu Asp Tyr Leu Glu Lys Pro Arg Leu Asn Ile Lys Ser 
            180                 185                 190 

Ala Pro Ser Phe Asn Lys Leu Asn Pro Ala Leu Thr Leu Trp Pro Met 
        195                 200                 205 

Phe Leu Gln Gly Lys Asp Val Gln Gly Met Glu Asp Ser His Gly Val 
    210                 215                 220 

Asn Phe Pro Ala Gln Ser Leu Gln His Thr Trp Cys Lys Gly Ile Val 
225                 230                 235                 240 

Gly Asp Leu Arg Pro Thr Ala Thr Ala Gln Asp Lys Ala Val Lys Cys 
                245                 250                 255 

Asn Met Asp Ser Leu Arg Asp Ser Pro Lys Asp Lys Ser Glu Lys Lys 
            260                 265                 270 

His His Cys Ile Ser Leu Lys Asp Thr Asn Lys Arg Val Glu Ser Ser 
        275                 280                 285 

Val Tyr Trp Pro Ala Lys Arg Gly Ile Thr Ile Tyr Ala Asp Pro Asp 
    290                 295                 300 

Val Pro Glu Ala Ser Ala Leu Ser Gln Lys Ser Asn Glu Lys Pro Leu 
305                 310                 315                 320 

Arg Leu Thr Glu Lys Lys Glu Tyr Asp Glu Lys Asn Ser Cys Val Lys 
                325                 330                 335 

Leu Leu Gln Phe Leu Asn Pro Asp Pro Leu Arg Ala Asp Gly Ile Ser 
            340                 345                 350 

Asp Leu Gln Gln Thr 
        355 

 
           
             39  
             1371  
             DNA  
             Homo sapiens  
             
               CDS  
               (43)..(1122)  
             
           
            39 

ctcatttcac caggcccccg gcttggggcg ccttccttcc cc atg gcg gga cac        54 
                                               Met Ala Gly His 
                                               1 

ctg gct tcg gat ttc gcc ttc tcg ccc cct cca ggt ggt gga ggt gat      102 
Leu Ala Ser Asp Phe Ala Phe Ser Pro Pro Pro Gly Gly Gly Gly Asp 
5                   10                  15                  20 

ggg cca ggg ggg ccg gag ccg ggc tgg gtt gat cct cgg acc tgg cta      150 
Gly Pro Gly Gly Pro Glu Pro Gly Trp Val Asp Pro Arg Thr Trp Leu 
                25                  30                  35 

agc ttc caa ggc cct cct gga ggg cca gga atc ggg ccg ggg gtt ggg      198 
Ser Phe Gln Gly Pro Pro Gly Gly Pro Gly Ile Gly Pro Gly Val Gly 
            40                  45                  50 

cca ggc tct gag gtg tgg ggg att ccc cca tgc ccc ccg ccg tat gag      246 
Pro Gly Ser Glu Val Trp Gly Ile Pro Pro Cys Pro Pro Pro Tyr Glu 
        55                  60                  65 

ttc tgt ggg ggg atg gcg tac tgt ggg ccc cag gtt gga gtg ggg cta      294 
Phe Cys Gly Gly Met Ala Tyr Cys Gly Pro Gln Val Gly Val Gly Leu 
    70                  75                  80 

gtg ccc caa ggc ggc ttg gag acc tct cag cct gag ggc gaa gca gga      342 
Val Pro Gln Gly Gly Leu Glu Thr Ser Gln Pro Glu Gly Glu Ala Gly 
85                  90                  95                  100 

gtc ggg gtg gag agc aac tcc gat ggg gcc tcc ccg gag ccc tgc acc      390 
Val Gly Val Glu Ser Asn Ser Asp Gly Ala Ser Pro Glu Pro Cys Thr 
                105                 110                 115 

gtc acc cct ggt gcc gtg aag ctg gag aag gag aag ctg gag caa aac      438 
Val Thr Pro Gly Ala Val Lys Leu Glu Lys Glu Lys Leu Glu Gln Asn 
            120                 125                 130 

ccg gag gag tcc cag gac atc aaa gct ctg cag aaa gaa ctc gag caa      486 
Pro Glu Glu Ser Gln Asp Ile Lys Ala Leu Gln Lys Glu Leu Glu Gln 
        135                 140                 145 

ttt gcc aag ctc ctg aag cag aag agg atc acc ctg gga tat aca cag      534 
Phe Ala Lys Leu Leu Lys Gln Lys Arg Ile Thr Leu Gly Tyr Thr Gln 
    150                 155                 160 

gcc gat gtg ggg ctc acc ctg ggg gtt cta ttt ggg aag gta ttc agc      582 
Ala Asp Val Gly Leu Thr Leu Gly Val Leu Phe Gly Lys Val Phe Ser 
165                 170                 175                 180 

caa acg acc atc tgc cgc ttt gag gct ctg cag ctt agc ttc aag aac      630 
Gln Thr Thr Ile Cys Arg Phe Glu Ala Leu Gln Leu Ser Phe Lys Asn 
                185                 190                 195 

atg tgt aag ctg cgg ccc ttg ctg cag aag tgg gtg gag gaa gct gac      678 
Met Cys Lys Leu Arg Pro Leu Leu Gln Lys Trp Val Glu Glu Ala Asp 
            200                 205                 210 

aac aat gaa aat ctt cag gag ata tgc aaa gca gaa acc ctc gtg cag      726 
Asn Asn Glu Asn Leu Gln Glu Ile Cys Lys Ala Glu Thr Leu Val Gln 
        215                 220                 225 

gcc cga aag aga aag cga acc agt atc gag aac cga gtg aga ggc aac      774 
Ala Arg Lys Arg Lys Arg Thr Ser Ile Glu Asn Arg Val Arg Gly Asn 
    230                 235                 240 

ctg gag aat ttg ttc ctg cag tgc ccg aaa ccc aca ctg cag cag atc      822 
Leu Glu Asn Leu Phe Leu Gln Cys Pro Lys Pro Thr Leu Gln Gln Ile 
245                 250                 255                 260 

agc cac atc gcc cag cag ctt ggg ctc gag aag gat gtg gtc cga gtg      870 
Ser His Ile Ala Gln Gln Leu Gly Leu Glu Lys Asp Val Val Arg Val 
                265                 270                 275 

tgg ttc tgt aac cgg cgc cag aag ggc aag cga tca agc agc gac tat      918 
Trp Phe Cys Asn Arg Arg Gln Lys Gly Lys Arg Ser Ser Ser Asp Tyr 
            280                 285                 290 

gca caa cga gag gat ttt gag gct gct ggg tct cct ttc tca ggg gga      966 
Ala Gln Arg Glu Asp Phe Glu Ala Ala Gly Ser Pro Phe Ser Gly Gly 
        295                 300                 305 

cca gtg tcc ttt cct ctg gcc cca ggg ccc cat ttt ggt acc cca ggc     1014 
Pro Val Ser Phe Pro Leu Ala Pro Gly Pro His Phe Gly Thr Pro Gly 
    310                 315                 320 

tat ggg agc cct cac ttc act gca ctg tac tcc tcg gtc cct ttc cct     1062 
Tyr Gly Ser Pro His Phe Thr Ala Leu Tyr Ser Ser Val Pro Phe Pro 
325                 330                 335                 340 

gag ggg gaa gcc ttt ccc cct gtc tct gtc acc act ctg ggc tct ccc     1110 
Glu Gly Glu Ala Phe Pro Pro Val Ser Val Thr Thr Leu Gly Ser Pro 
                345                 350                 355 

atg cat tca aac tgaggtgcct gcccttctag gaatggggga cagggggagg         1162 
Met His Ser Asn 
            360 

ggaggagcta gggaaagaaa acctggagtt tgtgccaggg tttttggatt aagttcttca   1222 

ttcactaagg aaggaattgg gaacacaaag ggtgggggca ggggagtttg gggcaactgg   1282 

ttggagggaa ggtgaagttc aatgatgctc ttgattttaa tcccacatca tgtatcactt   1342 

ttttcttaaa taaagaagct tgggacaca                                     1371 

 
           
             40  
             360  
             PRT  
             Homo sapiens  
           
            40 

Met Ala Gly His Leu Ala Ser Asp Phe Ala Phe Ser Pro Pro Pro Gly 
1               5                   10                  15 

Gly Gly Gly Asp Gly Pro Gly Gly Pro Glu Pro Gly Trp Val Asp Pro 
            20                  25                  30 

Arg Thr Trp Leu Ser Phe Gln Gly Pro Pro Gly Gly Pro Gly Ile Gly 
        35                  40                  45 

Pro Gly Val Gly Pro Gly Ser Glu Val Trp Gly Ile Pro Pro Cys Pro 
    50                  55                  60 

Pro Pro Tyr Glu Phe Cys Gly Gly Met Ala Tyr Cys Gly Pro Gln Val 
65                  70                  75                  80 

Gly Val Gly Leu Val Pro Gln Gly Gly Leu Glu Thr Ser Gln Pro Glu 
                85                  90                  95 

Gly Glu Ala Gly Val Gly Val Glu Ser Asn Ser Asp Gly Ala Ser Pro 
            100                 105                 110 

Glu Pro Cys Thr Val Thr Pro Gly Ala Val Lys Leu Glu Lys Glu Lys 
        115                 120                 125 

Leu Glu Gln Asn Pro Glu Glu Ser Gln Asp Ile Lys Ala Leu Gln Lys 
    130                 135                 140 

Glu Leu Glu Gln Phe Ala Lys Leu Leu Lys Gln Lys Arg Ile Thr Leu 
145                 150                 155                 160 

Gly Tyr Thr Gln Ala Asp Val Gly Leu Thr Leu Gly Val Leu Phe Gly 
                165                 170                 175 

Lys Val Phe Ser Gln Thr Thr Ile Cys Arg Phe Glu Ala Leu Gln Leu 
            180                 185                 190 

Ser Phe Lys Asn Met Cys Lys Leu Arg Pro Leu Leu Gln Lys Trp Val 
        195                 200                 205 

Glu Glu Ala Asp Asn Asn Glu Asn Leu Gln Glu Ile Cys Lys Ala Glu 
    210                 215                 220 

Thr Leu Val Gln Ala Arg Lys Arg Lys Arg Thr Ser Ile Glu Asn Arg 
225                 230                 235                 240 

Val Arg Gly Asn Leu Glu Asn Leu Phe Leu Gln Cys Pro Lys Pro Thr 
                245                 250                 255 

Leu Gln Gln Ile Ser His Ile Ala Gln Gln Leu Gly Leu Glu Lys Asp 
            260                 265                 270 

Val Val Arg Val Trp Phe Cys Asn Arg Arg Gln Lys Gly Lys Arg Ser 
        275                 280                 285 

Ser Ser Asp Tyr Ala Gln Arg Glu Asp Phe Glu Ala Ala Gly Ser Pro 
    290                 295                 300 

Phe Ser Gly Gly Pro Val Ser Phe Pro Leu Ala Pro Gly Pro His Phe 
305                 310                 315                 320 

Gly Thr Pro Gly Tyr Gly Ser Pro His Phe Thr Ala Leu Tyr Ser Ser 
                325                 330                 335 

Val Pro Phe Pro Glu Gly Glu Ala Phe Pro Pro Val Ser Val Thr Thr 
            340                 345                 350 

Leu Gly Ser Pro Met His Ser Asn 
        355                 360 

 
           
             41  
             1280  
             DNA  
             Mus musculus  
             
               CDS  
               (122)..(1219)  
             
           
            41 

tgaggggctg agaagagagc aattcacact tgattagctc ccaggctcct gaattgagca     60 

gaggaggcta gaccgctgag ctgcgcaccc cagaggctgc tctaccctgg ctcagacgac    120 

c atg cag cct tat caa cgg ctt ctg gcg ctt ggc ttc ctt ctg tta acc    169 
  Met Gln Pro Tyr Gln Arg Leu Leu Ala Leu Gly Phe Leu Leu Leu Thr 
  1               5                   10                  15 

ctg ccc tgg ggc cag aca tcc gag ttt caa gac tct gac ctt ttg cag      217 
Leu Pro Trp Gly Gln Thr Ser Glu Phe Gln Asp Ser Asp Leu Leu Gln 
            20                  25                  30 

ttt ctg gga tta gag aaa gcg cct tca cct cac agg ttc caa cct gtg      265 
Phe Leu Gly Leu Glu Lys Ala Pro Ser Pro His Arg Phe Gln Pro Val 
        35                  40                  45 

cct cgc gtc tta agg aaa atc atc cgg gct cga gaa gcc gct gca gcc      313 
Pro Arg Val Leu Arg Lys Ile Ile Arg Ala Arg Glu Ala Ala Ala Ala 
    50                  55                  60 

agt ggg gcc tcg cag gac tta tgc tac gtg aag gag ctg ggt gtt cgt      361 
Ser Gly Ala Ser Gln Asp Leu Cys Tyr Val Lys Glu Leu Gly Val Arg 
65                  70                  75                  80 

ggg aac ctg ctt cag ctt ctc cca gac cag ggt ttt ttc ctt aat aca      409 
Gly Asn Leu Leu Gln Leu Leu Pro Asp Gln Gly Phe Phe Leu Asn Thr 
                85                  90                  95 

cag aaa cct ttc caa gat ggc tcc tgt ctc cag aag gtc ctc tat ttt      457 
Gln Lys Pro Phe Gln Asp Gly Ser Cys Leu Gln Lys Val Leu Tyr Phe 
            100                 105                 110 

aac ttg tct gcc atc aaa gaa aag gca aag ttg acc atg gcc cag ctg      505 
Asn Leu Ser Ala Ile Lys Glu Lys Ala Lys Leu Thr Met Ala Gln Leu 
        115                 120                 125 

act cta gac ttg ggg ccc agg tcc tac tat aac ctg cga cca gag ctg      553 
Thr Leu Asp Leu Gly Pro Arg Ser Tyr Tyr Asn Leu Arg Pro Glu Leu 
    130                 135                 140 

gtg gtt gct ctg tct gtg gtt cag gac cgg ggc gtg tgg ggg cga tcc      601 
Val Val Ala Leu Ser Val Val Gln Asp Arg Gly Val Trp Gly Arg Ser 
145                 150                 155                 160 

cac cct aag gtg ggc aga ttg ctt ttt ctg cgg tct gtc cct ggg cct      649 
His Pro Lys Val Gly Arg Leu Leu Phe Leu Arg Ser Val Pro Gly Pro 
                165                 170                 175 

caa ggt cag ctc cag ttc aac ctg cag ggt gcg ctt aag gat tgg agc      697 
Gln Gly Gln Leu Gln Phe Asn Leu Gln Gly Ala Leu Lys Asp Trp Ser 
            180                 185                 190 

agc aac cga ctg aag aat ttg gac tta cac tta gag att ttg gtc aaa      745 
Ser Asn Arg Leu Lys Asn Leu Asp Leu His Leu Glu Ile Leu Val Lys 
        195                 200                 205 

gag gac aga tac tcc agg gta act gtc cag ccc gag aac ccc tgt gac      793 
Glu Asp Arg Tyr Ser Arg Val Thr Val Gln Pro Glu Asn Pro Cys Asp 
    210                 215                 220 

ccg ctg ctc cgc tct cta cat gcc tcg ctg ctg gtg gta acc ctc aat      841 
Pro Leu Leu Arg Ser Leu His Ala Ser Leu Leu Val Val Thr Leu Asn 
225                 230                 235                 240 

cct aaa cac tgt cat cct tct tcc aga aaa agg agg gcg gcc atc tct      889 
Pro Lys His Cys His Pro Ser Ser Arg Lys Arg Arg Ala Ala Ile Ser 
                245                 250                 255 

gtc ccc aag ggt ttc tgt agg aac ttc tgc cac cgt cat cag ctg ttc      937 
Val Pro Lys Gly Phe Cys Arg Asn Phe Cys His Arg His Gln Leu Phe 
            260                 265                 270 

atc aac ttc cag gac ctg ggt tgg cac aag tgg gtc atc gcc cct aag      985 
Ile Asn Phe Gln Asp Leu Gly Trp His Lys Trp Val Ile Ala Pro Lys 
        275                 280                 285 

ggg ttc atg gca aat tac tgt cat gga gag tgc ccc ttc tca atg acc     1033 
Gly Phe Met Ala Asn Tyr Cys His Gly Glu Cys Pro Phe Ser Met Thr 
    290                 295                 300 

acg tat tta aat agt tcc aat tat gct ttc atg cag gct ctg atg cat     1081 
Thr Tyr Leu Asn Ser Ser Asn Tyr Ala Phe Met Gln Ala Leu Met His 
305                 310                 315                 320 

atg gct gac ccc aag gtc ccc aag gct gtc tgt gtc ccc acc aag ctc     1129 
Met Ala Asp Pro Lys Val Pro Lys Ala Val Cys Val Pro Thr Lys Leu 
                325                 330                 335 

tcg ccc atc tcc atg ctc tat cag gat agt gat aag aac gtc att ctc     1177 
Ser Pro Ile Ser Met Leu Tyr Gln Asp Ser Asp Lys Asn Val Ile Leu 
            340                 345                 350 

cga cat tat gaa gac atg gta gtc gat gag tgt ggg tgt ggg             1219 
Arg His Tyr Glu Asp Met Val Val Asp Glu Cys Gly Cys Gly 
        355                 360                 365 

tagtctcggg actaggctag gagtgtgctt agggtaaatc ctttaataaa actaccaccc   1279 

c                                                                   1280 

 
           
             42  
             366  
             PRT  
             Mus musculus  
           
            42 

Met Gln Pro Tyr Gln Arg Leu Leu Ala Leu Gly Phe Leu Leu Leu Thr 
1               5                   10                  15 

Leu Pro Trp Gly Gln Thr Ser Glu Phe Gln Asp Ser Asp Leu Leu Gln 
            20                  25                  30 

Phe Leu Gly Leu Glu Lys Ala Pro Ser Pro His Arg Phe Gln Pro Val 
        35                  40                  45 

Pro Arg Val Leu Arg Lys Ile Ile Arg Ala Arg Glu Ala Ala Ala Ala 
    50                  55                  60 

Ser Gly Ala Ser Gln Asp Leu Cys Tyr Val Lys Glu Leu Gly Val Arg 
65                  70                  75                  80 

Gly Asn Leu Leu Gln Leu Leu Pro Asp Gln Gly Phe Phe Leu Asn Thr 
                85                  90                  95 

Gln Lys Pro Phe Gln Asp Gly Ser Cys Leu Gln Lys Val Leu Tyr Phe 
            100                 105                 110 

Asn Leu Ser Ala Ile Lys Glu Lys Ala Lys Leu Thr Met Ala Gln Leu 
        115                 120                 125 

Thr Leu Asp Leu Gly Pro Arg Ser Tyr Tyr Asn Leu Arg Pro Glu Leu 
    130                 135                 140 

Val Val Ala Leu Ser Val Val Gln Asp Arg Gly Val Trp Gly Arg Ser 
145                 150                 155                 160 

His Pro Lys Val Gly Arg Leu Leu Phe Leu Arg Ser Val Pro Gly Pro 
                165                 170                 175 

Gln Gly Gln Leu Gln Phe Asn Leu Gln Gly Ala Leu Lys Asp Trp Ser 
            180                 185                 190 

Ser Asn Arg Leu Lys Asn Leu Asp Leu His Leu Glu Ile Leu Val Lys 
        195                 200                 205 

Glu Asp Arg Tyr Ser Arg Val Thr Val Gln Pro Glu Asn Pro Cys Asp 
    210                 215                 220 

Pro Leu Leu Arg Ser Leu His Ala Ser Leu Leu Val Val Thr Leu Asn 
225                 230                 235                 240 

Pro Lys His Cys His Pro Ser Ser Arg Lys Arg Arg Ala Ala Ile Ser 
                245                 250                 255 

Val Pro Lys Gly Phe Cys Arg Asn Phe Cys His Arg His Gln Leu Phe 
            260                 265                 270 

Ile Asn Phe Gln Asp Leu Gly Trp His Lys Trp Val Ile Ala Pro Lys 
        275                 280                 285 

Gly Phe Met Ala Asn Tyr Cys His Gly Glu Cys Pro Phe Ser Met Thr 
    290                 295                 300 

Thr Tyr Leu Asn Ser Ser Asn Tyr Ala Phe Met Gln Ala Leu Met His 
305                 310                 315                 320 

Met Ala Asp Pro Lys Val Pro Lys Ala Val Cys Val Pro Thr Lys Leu 
                325                 330                 335 

Ser Pro Ile Ser Met Leu Tyr Gln Asp Ser Asp Lys Asn Val Ile Leu 
            340                 345                 350 

Arg His Tyr Glu Asp Met Val Val Asp Glu Cys Gly Cys Gly 
        355                 360                 365 

 
           
             43  
             1224  
             DNA  
             Homo sapiens  
             
               CDS  
               (37)..(1128)  
             
           
            43 

ggagctctcc ccggtctgac agccactcca gaggcc atg ctt cgt ttc ttg cca       54 
                                        Met Leu Arg Phe Leu Pro 
                                        1               5 

gat ttg gct ttc agc ttc ctg tta att ctg gct ttg ggc cag gca gtc      102 
Asp Leu Ala Phe Ser Phe Leu Leu Ile Leu Ala Leu Gly Gln Ala Val 
            10                  15                  20 

caa ttt caa gaa tat gtc ttt ctc caa ttt ctg ggc tta gat aag gcg      150 
Gln Phe Gln Glu Tyr Val Phe Leu Gln Phe Leu Gly Leu Asp Lys Ala 
        25                  30                  35 

cct tca ccc cag aag ttc caa cct gtg cct tat atc ttg aag aaa att      198 
Pro Ser Pro Gln Lys Phe Gln Pro Val Pro Tyr Ile Leu Lys Lys Ile 
    40                  45                  50 

ttc cag gat cgc gag gca gca gcg acc act ggg gtc tcc cga gac tta      246 
Phe Gln Asp Arg Glu Ala Ala Ala Thr Thr Gly Val Ser Arg Asp Leu 
55                  60                  65                  70 

tgc tac gta aag gag ctg ggc gtc cgc ggg aat gta ctt cgc ttt ctc      294 
Cys Tyr Val Lys Glu Leu Gly Val Arg Gly Asn Val Leu Arg Phe Leu 
                75                  80                  85 

cca gac caa ggt ttc ttt ctt tac cca aag aaa att tcc caa gct tcc      342 
Pro Asp Gln Gly Phe Phe Leu Tyr Pro Lys Lys Ile Ser Gln Ala Ser 
            90                  95                  100 

tcc tgc ctg cag aag ctc ctc tac ttt aac ctg tct gcc atc aaa gaa      390 
Ser Cys Leu Gln Lys Leu Leu Tyr Phe Asn Leu Ser Ala Ile Lys Glu 
        105                 110                 115 

agg gaa cag ttg aca ttg gcc cag ctg ggc ctg gac ttg ggg ccc aat      438 
Arg Glu Gln Leu Thr Leu Ala Gln Leu Gly Leu Asp Leu Gly Pro Asn 
    120                 125                 130 

tct tac tat aac ctg gga cca gag ctg gaa ctg gct ctg ttc ctg gtt      486 
Ser Tyr Tyr Asn Leu Gly Pro Glu Leu Glu Leu Ala Leu Phe Leu Val 
135                 140                 145                 150 

cag gag cct cat gtg tgg ggc cag acc acc cct aag cca ggt aaa atg      534 
Gln Glu Pro His Val Trp Gly Gln Thr Thr Pro Lys Pro Gly Lys Met 
                155                 160                 165 

ttt gtg ttg cgg tca gtc cca tgg cca caa ggt gct gtt cac ttc aac      582 
Phe Val Leu Arg Ser Val Pro Trp Pro Gln Gly Ala Val His Phe Asn 
            170                 175                 180 

ctg ctg gat gta gct aag gat tgg aat gac aac ccc cgg aaa aat ttc      630 
Leu Leu Asp Val Ala Lys Asp Trp Asn Asp Asn Pro Arg Lys Asn Phe 
        185                 190                 195 

ggg tta ttc ctg gag ata ctg gtc aaa gaa gat aga gac tca ggg gtg      678 
Gly Leu Phe Leu Glu Ile Leu Val Lys Glu Asp Arg Asp Ser Gly Val 
    200                 205                 210 

aat ttt cag cct gaa gac acc tgt gcc aga cta aga tgc tcc ctt cat      726 
Asn Phe Gln Pro Glu Asp Thr Cys Ala Arg Leu Arg Cys Ser Leu His 
215                 220                 225                 230 

gct tcc ctg ctg gtg gtg act ctc aac cct gat cag tgc cac cct tct      774 
Ala Ser Leu Leu Val Val Thr Leu Asn Pro Asp Gln Cys His Pro Ser 
                235                 240                 245 

cgg aaa agg aga gca gcc atc cct gtc ccc aag ctt tct tgt aag aac      822 
Arg Lys Arg Arg Ala Ala Ile Pro Val Pro Lys Leu Ser Cys Lys Asn 
            250                 255                 260 

ctc tgc cac cgt cac cag cta ttc att aac ttc cgg gac ctg ggt tgg      870 
Leu Cys His Arg His Gln Leu Phe Ile Asn Phe Arg Asp Leu Gly Trp 
        265                 270                 275 

cac aag tgg atc att gcc ccc aag ggg ttc atg gca aat tac tgc cat      918 
His Lys Trp Ile Ile Ala Pro Lys Gly Phe Met Ala Asn Tyr Cys His 
    280                 285                 290 

gga gag tgt ccc ttc tca ctg acc atc tct ctc aac agc tcc aat tat      966 
Gly Glu Cys Pro Phe Ser Leu Thr Ile Ser Leu Asn Ser Ser Asn Tyr 
295                 300                 305                 310 

gct ttc atg caa gcc ctg atg cat gcc gtt gac cca gag atc ccc cag     1014 
Ala Phe Met Gln Ala Leu Met His Ala Val Asp Pro Glu Ile Pro Gln 
                315                 320                 325 

gct gtg tgt atc ccc acc aag ctg tct ccc att tcc atg ctc tac cag     1062 
Ala Val Cys Ile Pro Thr Lys Leu Ser Pro Ile Ser Met Leu Tyr Gln 
            330                 335                 340 

gac aat aat gac aat gtc att cta cga cat tat gaa gac atg gta gtc     1110 
Asp Asn Asn Asp Asn Val Ile Leu Arg His Tyr Glu Asp Met Val Val 
        345                 350                 355 

gat gaa tgt ggg tgt ggg taggatgtca gaaatgggaa tagaaggagt            1158 
Asp Glu Cys Gly Cys Gly 
    360 

gttcttaggg taaatctttt aataaaacta cctatctggt ttatgaccac ttagatcgaa   1218 

atgtca                                                              1224 

 
           
             44  
             364  
             PRT  
             Homo sapiens  
           
            44 

Met Leu Arg Phe Leu Pro Asp Leu Ala Phe Ser Phe Leu Leu Ile Leu 
1               5                   10                  15 

Ala Leu Gly Gln Ala Val Gln Phe Gln Glu Tyr Val Phe Leu Gln Phe 
            20                  25                  30 

Leu Gly Leu Asp Lys Ala Pro Ser Pro Gln Lys Phe Gln Pro Val Pro 
        35                  40                  45 

Tyr Ile Leu Lys Lys Ile Phe Gln Asp Arg Glu Ala Ala Ala Thr Thr 
    50                  55                  60 

Gly Val Ser Arg Asp Leu Cys Tyr Val Lys Glu Leu Gly Val Arg Gly 
65                  70                  75                  80 

Asn Val Leu Arg Phe Leu Pro Asp Gln Gly Phe Phe Leu Tyr Pro Lys 
                85                  90                  95 

Lys Ile Ser Gln Ala Ser Ser Cys Leu Gln Lys Leu Leu Tyr Phe Asn 
            100                 105                 110 

Leu Ser Ala Ile Lys Glu Arg Glu Gln Leu Thr Leu Ala Gln Leu Gly 
        115                 120                 125 

Leu Asp Leu Gly Pro Asn Ser Tyr Tyr Asn Leu Gly Pro Glu Leu Glu 
    130                 135                 140 

Leu Ala Leu Phe Leu Val Gln Glu Pro His Val Trp Gly Gln Thr Thr 
145                 150                 155                 160 

Pro Lys Pro Gly Lys Met Phe Val Leu Arg Ser Val Pro Trp Pro Gln 
                165                 170                 175 

Gly Ala Val His Phe Asn Leu Leu Asp Val Ala Lys Asp Trp Asn Asp 
            180                 185                 190 

Asn Pro Arg Lys Asn Phe Gly Leu Phe Leu Glu Ile Leu Val Lys Glu 
        195                 200                 205 

Asp Arg Asp Ser Gly Val Asn Phe Gln Pro Glu Asp Thr Cys Ala Arg 
    210                 215                 220 

Leu Arg Cys Ser Leu His Ala Ser Leu Leu Val Val Thr Leu Asn Pro 
225                 230                 235                 240 

Asp Gln Cys His Pro Ser Arg Lys Arg Arg Ala Ala Ile Pro Val Pro 
                245                 250                 255 

Lys Leu Ser Cys Lys Asn Leu Cys His Arg His Gln Leu Phe Ile Asn 
            260                 265                 270 

Phe Arg Asp Leu Gly Trp His Lys Trp Ile Ile Ala Pro Lys Gly Phe 
        275                 280                 285 

Met Ala Asn Tyr Cys His Gly Glu Cys Pro Phe Ser Leu Thr Ile Ser 
    290                 295                 300 

Leu Asn Ser Ser Asn Tyr Ala Phe Met Gln Ala Leu Met His Ala Val 
305                 310                 315                 320 

Asp Pro Glu Ile Pro Gln Ala Val Cys Ile Pro Thr Lys Leu Ser Pro 
                325                 330                 335 

Ile Ser Met Leu Tyr Gln Asp Asn Asn Asp Asn Val Ile Leu Arg His 
            340                 345                 350 

Tyr Glu Asp Met Val Val Asp Glu Cys Gly Cys Gly 
        355                 360