CA2336225A1 - Human proteins having hydrophobic domains and dnas encoding these proteins - Google Patents

Abstract

The present invention provides human proteins having hydrophobic domains, DN As coding for these proteins, and expression vectors for these DNAs as well as eucaryotic cells expressing these DNAs.

Description

DEMANDES OU BREVETS VOLUM(NEUX
t.A PRESENTS PART1E DE CETTE DE3VIANDE OU CE BREVET
COMPREND PLUS D'UN TOME.
CECI EST LE TOME ~ DE
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THAN ONE VOLUME
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s f t' WOTE:.For additional volumes please contact'the Canadian Patent Office DESCRIPTION
THCHNT . T. T .T.~
The present invention relates to human proteins having hydrophobic domains, DNAs coding for these proteins, and expression vectors for these DNAs as well as eucaryotic IO cells expressing these DNAs. The proteins of the present invention can be employed as pharmaceuticals or as antigens for preparing antibodies against these proteins. The human cDNAs of the present invention can be utilized as probes for the genetic diagnosis and gene sources for the gene therapy.
Furthermore, the cDNAs can be utilized as gene sources for large-scale production of the proteins encoded by these cDNAs. Cells into which these genes are introduced to express secretory proteins and membrane proteins in large amounts can be utilized for detection of the corresponding receptors and ligands, screening of novel low-molecular pharmaceuticals, and so on.
BOiIND ART
Cells secrete many proteins outside the cells. These secretory proteins play important roles for the proliferation control, the differentiation induction, the material transportation, the biological protection, etc. in the cells. Different from intracellular proteins, the secretory proteins exert their actions outside the cells, whereby they can be administered in the intracorporeal manner such as the injection or the drip, so that there are hidden potentialities as medicines. In fact, a number of human secretory proteins such as interferons, interleukins, erythropoietin, thrombolytic agents, etc. have been currently employed as medicines. In addition, secretory proteins other than those described above have been undergoing clinical trials to develop as pharmaceuticals.
Because it has been conceived that the human cells still produce many unknown secretory proteins, availability of these secretory proteins as well as genes coding for them is expected to lead to development of novel pharmaceuticals utilizing these proteins.
on the other hand, membrane proteins play important roles, as signal receptors, ion channels, transporters, etc.
in the material transportation and the information transmission through the cell membrane. Examples thereof include receptors for a variety of cytokines, ion channels for the sodium ion, the potassium ion, the chloride ion, etc., transporters for saccharides and amino acids, and so on, where the genes for many of them have been cloned already. It has been clarified that abnormalities of these membrane proteins are associated with a number of hitherto-cryptogenic diseases. Therefore, discovery of a new membrane protein is anticipated to lead to elucidation of the causes of many diseases, so that isolation of a new gene coding for the membrane protein has been desired.
Heretofore, owing to difficulty in the purification from human cells, these secretory proteins and membrane proteins have been isolated by an approach from the gene side. A general method is the so-called expression cloning which comprises introduction of a cDNA library into eucaryotic cells to express cDNAs and then screening of the cells secreting, or expressing on the surface of membrane, the objective active protein. However, this method is applicable only to cloning of a gene for a protein with a known function.
In general, secretory proteins and membrane proteins possess at least one hydrophobic domain inside the proteins, wherein, after synthesis thereof in the ribosome, this domain works as a secretory signal or remains in the phospholipid membrane to be trapped in the membrane.
Accordingly, the evidence of this cDNA for encoding a secretory protein and a membrane protein is provided by determination of the whole base sequence of a full-length cDNA followed by detection of highly hydrophobic domains) in the amino acid sequence of the protein encoded by this cDNA.
OB~ T O TH . TNVF'NTTnN
The main object of the present invention is to provide novel human proteins having hydrophobic domains, DNAs coding for these proteins, and expression vectors for these DNAs as well as transformed eucaryotic cells that are capable of expressing these DNAs. This object as well as other objects and advantages of the present invention will become apparent to those skilled in the art from the following description with reference to the accompanying drawings.
D .~, RT1~TTON O D AWTNCS
Fig. 1 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP01550.
Fig. 2 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP02593.
Fig. 3 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10195.

Fig. 4 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP10423.
protein encoded Fig. 5 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP10506.
protein encoded Fig. 6 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP10507.
protein encoded Fig. 7 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP10548.
protein encoded Fig. 8 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP10566.
protein encoded Fig. 9 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP10567.
protein encoded Fig. 10 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10568.

Fig. I1 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP01426.

Fig. 12 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP02515.

Fig. I3 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP02575.

Fig. 14 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10357.

Fig. 15 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10447.

Fig. 16 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10477.

Fig. 17 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10513.

Fig. 18 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10540.

Fig. 19 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10557.

Fig. 20 illustrates the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP10563.

Fig. 21 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP01467.
protein encoded 5 Fig. 22 illustrates the hydrophobicity/hydrophilicity profile of the by clone HPOI956.
protein encoded Fig. 23 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP02545.
protein encoded Fig. 24 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP02551.
protein encoded Fig. 25 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP02631.
protein encoded Fig. 26 illustrates the hydrophobicity/hydrophilicity profile of the by clone HP02632.
protein encoded Fig. 27 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10488.

Fig. 28 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10538.

Fig. 29 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10542.

Fig. 30 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10571.

Fig. 31 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP01470.

Fig. 32 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP02419.

Fig. 33 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP02631.

Fig. 34 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP02695.

Fig. 35 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10031.

Fig. 36 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10530.

Fig. 37 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10541.

Fig. 38 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10550.

Fig. 39 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10590.

Fig. 40 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10591.

Fig. 41 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP01462.

Fig. 42 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP02485.

Fig. 43 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP02798.

Fig. 44 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10041.

Fig. 45 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10246.

Fig. 46 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10392.

Fig. 47 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10489.

Fig. 48 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10519.

Fig. 49 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10531.

Fig. 50 illustrates the hydrophobicity/hydrophilicity profile of theprotein encoded by clone HP10574.

As the result of intensive studies, the present inventors have been successful in cloning of cDNAs coding for proteins having hydrophobic domains from the human full-length cDNA bank, thereby completing the present invention.
In other words, the present invention provides human proteins having hydrophobic domains, namely proteins comprising any of the amino acid sequences represented by SEQ ID Nos. 1 to 10, 31 to 40, 61 to 70, 91 to 100, and 121 to 130. Moreover, the present invention provides DNAs coding for the above-mentioned proteins, exemplified by cDNAs comprising any of the base sequences represented by SEQ ID
Nos. 11 to 20, 41 to 50, 71 to 80, 101 to 110, and 131 to 140, as well as expression vectors that are capable of expressing any of these DNAs by in vitro translation or in eucaryotic cells and transformed eucaryotic cells that are capable of expressing these DNAs and of producing the above-mentioned proteins.
nFmAILED DE~CRTPTTON OF H. I .NT ON
The proteins of the present invention can be obtained, for example, by a method for isolation from human organs, cell lines, etc., a method for preparation of peptides by the chemical synthesis, or a method for production with the recombinant DNA technology using the DNAs coding for the hydrophobic domains of the present invention, among which the method for production with the recombinant DNA
technology is employed preferably. For instance, in vitro expression of the proteins can be achieved by preparation of an RNA by in vitro transcription from a vector having one of the cDNAs of the present invention, followed by in vitro translation using this RNA as a template. Also, introduction of the translated region into a suitable expression vector by the method known in the art leads to expression of a large amount of the encoded protein in prokaryotic cells such as Escherichia coli, Bacillus subtilis, etc., and eucaryotic cells such as yeasts, insect cells, mammalian cells, etc.
In the case where one of the proteins of the present invention is produced by expressing the DNA by in vitro translation, the protein of the present invention can be produced in vitro, when the translated region of this cDNA
is introduced into a vector having an RNA polymerase promoter, followed by addition of the vector to an in vitro translation system such as a rabbit reticulocyte lysate or a wheat germ extract, containing an RNA polymerase corresponding to the promoter. RNA polymerase promoters are exemplified by T7, T3, SP6, and the like. The vectors containing these RNA polymerase promoters are exemplified by pKAl, pCDMB, pT3/T7 18, pT7/3 19, pHluescript II, and so on.
Furthermore, the protein of the present invention can be expressed as the secreted form or the form incorporated into the microsome membrane, when a canine pancreas microsome or the like is added to the reaction system.
In the case where one of the protein of the present invention is produced by expressing the DNA in a microorganism such as Escherichia coli etc., a recombinant expression vector bearing the translated region of the cDNA
of the present invention is constructed in an expression vector having an origin which can be replicated in the microorganism, a promoter, a ribosome-binding site, a cDNA-cloning site, a terminator etc. and, after transformation of the host cells with this expression vector, the resulting transformant is incubated, whereby the protein encoded by said cDNA can be produced on a large scale in the WO 00/0536? PCT/JP99/03929 microorganism. In this case, a protein fragment containing any region can be obtained by carrying out the expression with inserting an initiation codon and a termination codon in front of and behind the selected translated region.
Alternatively, a fusion protein with another protein can be expressed. Only the portion of the protein encoded by this cDNA can be obtained by cleavage of this fusion protein with a suitable protease. The expression vector for Escherichia coli is exemplified by the pUC series, pBluescript II, the pET expression system, the pGEX expression system, and so on.
In the case where one of the proteins of the present invention is produced by expressing the DNA in eucaryotic cells, the protein of the present invention can be produced as a secretory protein or as a membrane protein on the cell membrane surface, when the translated region of this cDNA is introduced into an expression vector for eucaryotic cells that has a promoter, a splicing region, a poly(A) addition site, etc., followed by introduction into the eucaryotic cells. The expression vector is exemplified by pKAl, pED6dpc2, pCDM8, pSVK3, pMSG, pSVL, pBK-CMV, pBK-RSV, EHV
vector, pRS, pYES2, and so on. Examples of eucaryotic cells to be used in general include mammalian cultured cells such as simian kidney cells COS7, Chinese hamster ovary cells CHO, etc., budding yeasts, fission yeasts, silkworm cells, Xenopus oocytes, and so on, but any eucaryotic cells may be used, provided that they are capable of expressing the proteins of the present invention. The expression vector can be introduced into the eucaryotic cells by methods known in the art such as the electroporation method, the calcium phosphate method, the liposome method, the DEAE-dextran method, and so on.
After one of the proteins of the present invention is expressed in prokaryotic cells or eucaryotic cells, the objective protein can be isolated from the culture and purif ied by a combination of separation procedures known in the art. Such examples include treatment with a denaturing 5 agent such as urea or a detergent, sonication, enzymatic digestion, salting-out or solvent precipitation, dialysis, centrifugation, ultrafiltration, gel filtration, SDS-PAGE, isoelectric focusing, ion-exchange chromatography, hydrophobic chromatography, affinity chromatography, reverse 10 phase chromatography, and so on.
The proteins of the present invention include peptide fragments (5 amino acid residues or more) containing any partial amino acid sequence in the amino acid sequences represented by SEQ ID Nos. 1. to 10, 31 to 40, 61 to 70, 91 to 100, and 121 to 130. These peptide fragments can be utilized as antigens for preparation of antibodies. Hereupon, among the proteins of the present invention, those having the signal sequences are secreted in the form of mature proteins, after the signal sequences are removed. Therefore, these mature proteins shall come within the scope of the present invention. The N-terminal amino acid sequences of the mature proteins can be easily determined by using the method for the determination of cleavage site of a signal sequence [JP 8-187100 A]. Furthermore, some membrane proteins undergo the processing on the cell surface to be converted to the secretory forms. Such proteins or peptides in the secretory forms shall come within the scope of the present invention. In the case where sugar chain-binding sites are present in the amino acid sequences, expression in appropriate eucaryotic cells affords proteins to which sugar chains are attached. Accordingly, such proteins or peptides to which sugar chains are attached shall come within the WO 00/05367 PC'T/JP99/03929 scope of the present invention.
The DNAs of the present invention include all the DNAs coding for the above-mentioned proteins. These DNAs can be obtained by using a method by chemical synthesis, a method by cDNA cloning, and so on.
The cDNAs of the present invention can be cloned, for example, from cDNA libraries derived from the human cells.
These cDNAs are synthesized by using as templates poly(A)+
RNAs extracted from human cells. The human cells may be cells delivered from the human body, for example, by the operation or may be the cultured cells. The cDNAs can be synthesized by using any method selected from the Okayama-Berg method [Okayama, H. and Herg, P., Mol. Cell. Biol. 2:
161-170 (1982)j, the Gubler-Hoffman method [Gubler, U. and Hoffman, J. Gene 25: 263-269 ( 1983 ) ] , and so on, but it is preferred to use the capping method [Kato, S. et al., Gene 150: 243-250 (1994)], as exemplified in Examples, in order to obtain a full-length clone in an effective manner. In addition, commercially available, human cDNA libraries can be utilized. Cloning of the cDNAs of the present invention from the cDNA libraries can be carried out by synthesis of an oligonucleotide on the basis of base sequences of any portion in the cDNA of the present invention, followed by screening using this oligonucleotide as the probe according to the colony or plaque hybridization by a method known in the art. In addition, the cDNA fragments of the present invention can be prepared by synthesis of oligonucleotides which hybridize with both termini of the objective cDNA
fragment, followed by the usage of these oligonucleotides as the primers for the RT-PCR method using an mRNA isolated from human cells.
The cDNAs of the present invention are characterized by comprising either of the base sequences represented by SEQ
ID Nos. 11 to 20, 41 to 50, 71 to 80, 101 to 110, and 131 to 140 or the base sequences represented by SEQ ID Nos. 21 to 30, 51 to 60, 81 to 90, 111 to 120, and 141 to 150. Table 1 summarizes the clone number (HP number), the cells from which the cDNA was obtained, the total base number of the cDNA, and the number of the amino acid residues of the encoded protein, for each of the cDNAs.

Table 1 Number SEQ ID No. HP Cells Base of amino number number acid residues l, 11,21 HP01550 Stomachcancer 510 125 2, 12,22 HP02593 Saos-2 697 131 3, 13,23 HP10195 HT-1080 1619 24.2 4, 14,24 HP10423 U-2 1066 264 OS

5, 15,25 HP10506 Stomachcancer 618 I12 6, 16,26 HP10507 Stomachcancer 1021 146 7, 17,27 HP10548 Stomachcancer 1432 344 8, 18,28 HP10566 Stomachcancer 601 97 9, 19,29 HP10567 Stomachcancer 585 124 10, 20,30 HP10568 Stomachcancer 1100 327 31, 41,51 HP01426 Stomachcancer 1065 313 32, 42,52 HP02515 Saos-2 937 229 33, 43,53 HP02575 Saos-2 1678 467 34, 44,54 HP10357 Stomachcancer 467 99 35, 45,55 HP10447 Liver 875 189 36, 46,56 HP10477 Liver 1256 363 37, 47,57 HP105I3 Stomachcancer 884 249 38, 48,58 HP10540 Saos-2 589 98 39, 49,59 HP10557 Stomachcancer 673 172 40, 50,60 HP10563 Saos-2 1425 120 61, 71,81 HP01467 HT-1080 1436 307 62, 72,82 HP01956 Liver 997 183 63, 73,83 HP02545 Saos-2 1753 327 64, 74,84 HP02551 Saos-2 1117 223 65, 75,85 HP02631 Saos-2 1380 48 66, 76,86 HP02632 HT-1080 1503 371 67, 77,87 HP10488 Liver 733 90 68, 78,88 HP10538 Saos-2 3768 499 69, 79,89 HP10542 Stomachcancer 770 106 70, 80,90 HP10571 Stomachcancer 1229 152 91, 101,111 HP01470 Stomachcancer 1619 358 92, 102,112 HP024I9 Stomachcancer 2054 226 93, 103,113 HP02631 Saos-2 1380 195 94, 104,114 HP02695 Stomachcancer 1292 339 95, 105,115 HP10031 Saos-2 2168 487 96, 106,116 HP10530 Saos-2 1357 393 97, 107,117 HP1054I Stomachcancer 711 196 98, 108,118 HP10550 Stomachcancer 651 107 99, 109,119 HP10590 HT-1080 1310 350 100, 110,120 HP10591 HT-1080 1400 107 121, 131,14I HP01462 HT-1080 2050 483 122, 132,142 HP02485 Stomachcancer 2746 334 123, 133,143 HP02798 HT-1080 1136 267 124, 134,144 HP10041 Saos-2 619 106 125, 135,145 HP10246 KB 864 224 126, 136,146 HP10392 U-2 1527 258 OS

127, 137,147 HP10489 Stomachcancer 659 110 128, 138,148 HP10519 Stomachcancer 710 91 129, 139,149 HP10531 Saos-2 2182 344 130, 140,150 HP10574 Stomachcancer 2773 428 Hereupon, the same clones as the cDNAs of the present invention can be easily obtained by screening of the cDNA
libraries constructed from the human cell lines or human tissues utilized in the present invention by the use of an oligonucleotide probe synthesized on the basis of the cDNA
base sequence described in any of SEQ ID Nos. 11 to 30, 41 to 60, 71 to 90, 101 to 120, and 131 to 150.
In general, the polymorphism due to the individual difference is frequently observed in human genes.
Accordingly, any cDNA in which one or plural nucleotides are inserted, deleted and/or substituted with other nucleotides in SEQ ID Nos. 11 to 30, 41 to 60, 71 to 90, 101 to 120, and 131 to 150 shall come within the scope of the present invention.
In a similar manner, any protein in which one or plural amino acids are inserted, deleted and/or substituted with 5 other amino acids shall come within the scope of the present invention, as far as the protein possesses the activity of any protein having the amino acid sequences represented by SEQ ID Nos. 1 to 10, 31 to 40, 61 to 70, 91 to 100, and 121 to 130.
10 The cDNAs of the present invention include cDNA
fragments (10 by or more) containing any partial base sequence in the base sequences represented by SEQ ID Nos. 11 to 20, 41 to 50, 71 to 80, 101 to 110, and 131 to 140 or in the base sequences represented by SEQ ID Nos. 21 to 30, 51 15 to 60, 81 to 90, 111 to 120, and 141 to 150. Also, DNA
fragments consisting of a sense strand and an anti-sense strand shall come within this scope. These DNA fragments can be utilized as the probes for the genetic diagnosis.
In addition to the activities and uses described above, the polynucleotides and proteins of the present invention may exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA).
Research Us and Llti 1 i i _s The polynucleotides provided by the present invention can be used by the research community for various purposes.
The polynucleotides can be used to express recombinant protein for analysis, characterization or therapeutic use;
as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to "subtract-out" known sequences in. the process of discovering other novel polynucleotides;
for selecting and making oligomers for attachment to a "gene chip" or other support, including for examination of expression patterns; to raise anti-protein antibodiesusing DNA immunization techniques; and as an antigen to raise anti-DNA antibodies or elicit another immune response.
Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the polynucleotide can also be used in interaction trap assays (such as, for example, that described in Gyuris et al., Cell 75:791-803 (1993)) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction.
The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction.
Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.
Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.
Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning:
A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E.F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S.L. and A.R. Kimmel eds., 1987.
Nut_r,'_t,'_onal_ UseR
Polynucleotides and proteins of the present invention can also be used as nutritional sources or supplements.
Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the protein or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured.
C~~toki_ne and C;11 Prol_iferatlQri/Di_ffrPntiatinn Activity A protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a protein of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2, DA1G, T10, H9, B9/11, BaF3, MC9/G, M+ (preH M+), 2E8, RB5, DA1, 123, T1165, HT2, CTLL2, TF-1, Mo7e and CMK.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by ,T. E. Coligan, A.M. Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol.
137:3494-3500, 1986; Hertagnolli et al., J. Immunol.
145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., J.
Immunol. 149:3778-3783, 1992; Bowman et al., J. Immunol.
152: 1756-1761, 1994.
Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp.
3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurement of mouse and human Interferon y, Schreiber, R.D.
In Current Protocols in Immunology. J.E.e.a. Coligan eds.
Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons, Toronto. 1994.
Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine Interleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In Current Protocols in Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988;
Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983; Measurement of mouse and human interleukin 6-Nordan, R. In Current Protocols in Immunology. J.E.e.a.
Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., Proc. Natl. Acad. Sci. U.S.A.
83:1857-1861, 1986; Measurement of human Interleukin 11 -Hennett, F., Giannotti, J., Clark, S.C. and Turner, K. J.
In Current Protocols in Immunology. J.E.e.a. Coligan eds.
Vol 1 pp. 6.15.1 John Wiley and Sons, Toronto. 1991;
Measurement of mouse and human Interleukin 9 - Ciarletta, A., Giannotti, J., Clark,S.C. and Turner, K.J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp.

6.13.1, John Wiley and Sons, Toronto. 1991.
Assays for T-cell clone responses to antigens (which will identify, among others,. proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring 5 proliferation and cytokine production) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro 10 assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA
77:6091-6095, 1980; Weinberger et al., Eur. J. Immun.
11:405-411, 1981; Takai et al., J. Immunol. 137:3494-3500, 15. 1986; Takai et al., J. Immunol. 140:508-512, 1988.
I~ne St i mu1_at,'_nr~r o_r Supyres s my Act i vi tv A protein of the present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are 20 described herein. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SLID)), e.g., in regulating (up or down) growth and proliferation of T and/or H lymphocytes, as well as effecting the cytolytic activity of NR cells and other cell populations. These immune deficiencies may be genetic or be caused by viral (e. g., HIV) as well as bacterial orfungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, herpesviruses, mycobacteria, Leishmania spp., malaria spp.

and various fungal infections such as candidiasis. Of course, in this regard, a protein of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer.
Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease. Such a protein of the present invention may also to be useful in the treatment of allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein of the present invention.
Using the proteins of the invention it may also be possible to immune responses, in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both. Immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent. Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence of the tolerizing agent.
Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as , for example, B7}), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD}.
For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation.
Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a soluble, monomeric form of a peptide having B7-2 activity alone or in conjunction with a monomeric form of a peptide having an activity of another B lymphocyte antigen (e.g., B7-1, B7-3) or blocking antibody } , prior to transplantation can lead to the binding of the molecule to the natural ligand(s) on the immune cells without transmitting the corresponding costimulatory signal. Blocking B lymphocyte antigen function in this matter prevents cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, the lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens.
The efficacy of particular blocking reagents in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. Natl. Acad. Sci USA, 89:11102-11105 (1992). In addition, murine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of blocking B lymphocyte antigen function in vivo on the development of that disease.
Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T
cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block costimulation of T cells by disrupting receptor:ligand interactions of B lymphocyte antigens can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen-specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythmatosis in l~tL/lpr/lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BH rats, and murine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York, /989, pp.
840-856).
Upregulation of an antigen function (preferably a B
lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy.
Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response through stimulating B lymphocyte antigen function may be useful in cases of viral infection. In addition, systemic viral diseases such as influenza, the commoncold, and encephalitis might be alleviated by the administration of stimulatory forms of B lymphocyte antigens systemically.
Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducing the in vitro activated T cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a costimulatory signal to, and thereby activate, T cells in vivo.
In another application, up regulation or enhancement of 5 antigen function (preferably B lymphocyte antigen function}
may be useful in the induction of tumor immunity. Tumor cells (e. g., sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, carcinoma) transfected with a nucleic acid encoding at least one peptide of the present invention can 10 be administered to a subject to overcome tumor-specific tolerance in the subject. If desired, the tumor cell can be transfected to express a combination of peptides. For example, tumor cells obtained from a patient can be transfected ex vivo with an expression vector directing the 15 expression of a peptide ~ having B7-2-like activity alone, or in conjunction with a peptide having B7-1-like activity and/or B7-3-like activity. The transfected tumor cells are returned to the patient to result in expression of the peptides on the surface of the transfected cell.
20 Alternatively, gene therapy techniques can be used to target a tumor cell for transfection in vivo.
The presence of the peptide of the present invention having the activity of a B lymphocyte antigens) on the surface of the tumor cell provides the necessary 25 costimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells. In addition, tumor cells which lack MHC class I or I~iC class II
molecules, or which fail to reexpress sufficient amounts of MHC class I or 1~IC class II molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytopiasmic-domain truncated portion) of an MHC class I a chain protein and Z microglobulin protein or an I~iC class II chain protein and an MHC class II chain protein to thereby express MHC class I or MHC class II proteins on the cell surface. Expression of the appropriate class I or class II MHC in conjunction with a peptide having the activity of a H lymphocyte antigen (e.g., B7-1, B7-2, B7-3) induces a T cell mediated immune response against the transfected tumor cell. optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub.
Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19;
Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J.
Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol.
137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet al., J.

Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Brown et al., J. Immunol. 153:3079-3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl/Th2 profiles) include, without limitation, those described in: Maliszewski, J. Immunol.
144:3028-3033, 1990; and Assays for B cell function: In vitro antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto. 1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E.
Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W
Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986;
Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. Immunol. 149:3778-3783, 1992.
Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995;
Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 1995; Porgador et al., Journal of Experimental Medicine 182:255-260, 1995; Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 172:631-640, 1990.
Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in: Darzynkiewicz et al., Cytometry 13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991; Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993; Gorczyca et al., International Journal of Oncology 1:639-648, 1992.
Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994;
Fine et al. , Cellular Immunology 155:111-122, 1994; Galy et al., Blood 85:2770-27?8, 1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.
Hematogo,'_esss Re~u a ~ n~ Act ~ vi tv A protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies. Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction with irradiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferation of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.
Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915, 1993.
Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate 5 lympho-hematopoiesis) include, without limitation, those described in: Methylcellulose colony fonaing assays, Freshney, M.G. In Culture of Hematopoietic Cells. R.I.
Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, NY. 1994; Hirayama et al., Proc. Natl. Acad. Sci.
10 USA 89:5907-5911, 1992; Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, I.K. and Briddell, R.A. In Culture of Hematopoietic Cells.
R.I. Freshney, et al. eds. Vol pp. 23-39, Wiley-Liss, Inc., New York, NY. 1994; Neben et al., Experimental Hematology 15 22:353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of Hematopoietic Cells. R.I.
Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc., New York, NY. 1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and 20 Allen, T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. I63-179, Wiley-Liss, Inc., New York, NY.
1994; Long term culture initiating cell assay, Sutherland, H.J. In Culture of Hematopoietic Cells. R.I. Freshney, et al.
eds. Vol pp. 139-162, Wiley-Liss, Inc., New York, NY. 1994.
25 Tissm Growth Activity A protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and 30 in the treatment of burns, incisions and ulcers.
A protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals. Such a preparation employing a protein of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery.
A protein of this invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone-forming cells, stimulate growth of bone-forming cells or induce differentiation of progenitors of bone-forming cells. A protein of the invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes.
Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon/ligament formation. A protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide an environment to attract tendon or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendinitis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art.
The protein of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which -involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, a protein may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer~s, Parkinson's disease, Huntington~s disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke.
Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a protein of the invention.
Proteins of the invention may also be useful to promote better or faster closure of non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.
It is expected that a protein of the present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring to allow normal tissue to regenerate. A protein of the invention may also exhibit angiogenic activity.
A protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.
A protein of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for tissue generation activity include, without limitation, those described in: International Patent Publication No. W095/16035 (bone, cartilage, tendon);

WO 00/05367 PC'T/JP99/03929 International Patent Publication No. W095/05846 (nerve, neuronal); International Patent Publication No. W091/07491 (skin, endothelium ).
Assays for wound healing activity include, without limitation, those described in: Winter, Epidern~al Wound Healing, pps. 71-112 (Maibach, HI and Rovee, DT, eds.), Year Hook Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J. Invest. Dermatol 71:382-84 (1978).
Acti_v,'_n/Tnh,'_b1n Act,'_v,'_tv A protein of the present invention may also exhibit activin- or inhibin-related activities. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a protein of the present invention, alone or in heterodimers with a member of the inhibin family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease sperznatagenesis in male mammals.
Administration of sufficient amounts of other inhibins can induce infertility in these mammals. Alternatively, the protein of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin- group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary. See, for example, United States Patent 4,798,885. A protein of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for activin/inhibin activity include, without limitation, those described in: Vale et al., Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986;
5 Vale et al. , Nature 321: 776-779, 1986; Mason et al. , Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad: Sci. USA
83:3091-3095, 1986.
Chemotactic/Chemokinetic stivit~
A protein of the present invention may have chemotactic 10 or chemokinetic activity (e.g., act as a chemokine) for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells. Chemotactic and chemokinetic proteins can be used to mobilize or attract a 15 desired cell population to a desired site of action.
Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections.
For example, attraction of lymphocytes, monocytes or 20 neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent.
A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or 25 indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells.
Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing 30 such protein or peptide in any known assay for cell chemotaxis.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis)consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in:
Current Protocols in Immunology, Ed by J.E. Coligan, A.M.
Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub.
Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995;
Lind et al. APMIS 103:140-146, 1995; Muller et al Eur. J.
Immunol. 25: 1744-1748; Gruber et al. J. of Immunol.
152:5860-5867, 1994; Johnston et al. J. of Immunol. 153:
1762-1768, 1994.
Hemostatic and Thrombolytic Actjvitw A protein of the invention may also exhibit hemostatic or thrombolytic activity. As a result,such a protein is expected to be useful in treatment of various coagulation disorders (includinghereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e. g., stroke).
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J.
Clin. Pharmacol. 26:131-140, 1986; Burdick et al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467 474, 1988.
y or/r. i sand Act i_v,'_tv A protein of the present invention may also demonstrate activity as receptors, receptor ligands or inhibitors or agonists of receptor/ligand interactions. Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selectins, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses). Receptors and ligands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A
protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for receptor-ligand activity include without limitation those described in:Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H.
Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987;
Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; Stitt et al., Cell 80:661-670, 1995.
Anti-Tnfl,mma or'~~ Activity Proteins of the present invention may also exhibit anti-inflammatory activity. The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell. interactions (such as, for example, cell adhesion}, by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Proteins exhibiting such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation inflammation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of ytokines such as TNF or IL-1. Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.
In addition to the activities described above for immunological treatment or prevention of tumors, a protein of the invention may exhibit other anti-tumor activities. A

protein may inhibit tumor growth directly or indirectly (such as, for example, via ADCC). A protein may exhibit its tumor inhibitory activity by acting on tumor tissue or tumor precursor tissue, by inhibiting formation of tissues necessary to support tumor growth ( such as, for example, by inhibiting angiogenesis), by causing production of other factors, agents or cell types which inhibit tumor growth, or by suppressing, eliminating or inhibiting factors, agents or cell types which promote tumor growth Ot-h-e_r Act sv~ t ~ es A protein of the invention may also exhibit one or more of the following additional activities or effects:
inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites; effecting (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape);
effecting biorhythms or caricadic cycles or rhythms;
effecting the fertility of male or female subjects;
effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, cofactors. or other nutritional factors or component(s); effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative 5 disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is 10 cross-reactive with such protein.
Examples The present invention is specifically illustrated in more detail by the following Examples, but Examples are not 15 intended to restrict the present invention. The basic operations with regard to the recombinant DNA and the enzymatic reactions were carried out according to the literature ("Molecular Cloning. A Laboratory Manual~~, Cold Spring Harbor Laboratory, 1989]. Unless otherwise stated, 20 restrictive enzymes and a variety of modification enzymes to be used were those available from Takara Shuzo. The buffer compositions and the reaction conditions for each of the enzyme reactions were as described in the manufacturer's instructions. The cDNA synthesis was carried out according 25 to the literature [Kato, S. et al., Gene 150: 243-250 (1994)].
(1) Selection of cDNAs Encoding Proteins Having Hydrophobic Domains The cDNA library of fibrosarcoma cell line HT-1080 30 (W098/11217), the cDNA library of osteosarcoma cell line Saos-2 (W097/33993), the cDNA library of osteosarcoma cell line U-2 OS (W098/21328), the cDNA library of epiderznoid carcinoma cell line KH (W098/1I217), the cDNA library of tissues of stomach cancer delivered by the operation (WO98/21328), the cDNA library of liver tissue delivered by the operation (WO98/2I328), and were used for the DNA
libraries. Full-length cDNA clones were selected from respective libraries and the whole base sequences thereof were determined to construct a homo-protein cDNA bank consisting of the full-length cDNA clones. The hydrophobicity/hydrophilicity profiles were determined for the proteins encoded by the full-length cDNA clones registered in the homo-protein cDNA bank by the Kyte-Doolittle method [Kyte, J. & Doolittle, R. F., J. Mol. Biol.
157: 105-132 (1982)] to examine the presence or absence of a hydrophobic region. Any clone that has a hydrophobic region being putative as a secretory signal or a transmembrane domain in the amino acid sequence of the encoded protein was selected as a clone candidate.
(2) Protein Synthesis by In Vitro Translation The plasmid vector bearing the cDNA of the present invention was used for in vitro transcription/translation with a TNT rabbit reticulocyte lysate kit (Promega). In this case, ['ss]methionine was added to label the expression product with a radioisotope. Each of the reactions was carried out according to the protocols attached to the kit.
Two micrograms of the plasmid was subjected to the reaction at 30°C for 90 minutes in the reaction solution of a total volume of 25 ul containing I2.5 ~1 N of TNT rabbit reticulocyte lysate, 0.5 N1 of a buffer solution (attached to the kit), 2 N1 of an amino acid mixture (without methionine), 2 N1 of ['SS]methionine (Amersham) (0.37 MHq/N1), 0.5 girl of T7 RNA polymerase, and 20 U of RNasin. Also, an experiment in the presence of a membrane system was carried out by adding to this reaction system 2.5 N1 of a canine pancreas microsome fraction (Promega). To 3 ul of the resulting reaction solution was added 2 N1 of the SDS
sampling buffer (125 mM Tris-hydrochloric acid buffer, pB
6.8, 120 mM 2-mercaptoethanol, 2% SDS solution, 0.025%
bromophenol blue, and 20% glycerol) and the resulting mixture was heated at 95°C for 3 minutes and then subjected to SDS-polyacrylamide gel electrophoresis. The molecular weight of the translation product was determined by carrying out the autoradiography.
(3) Expression by COS7 Escherichia coli cells bearing the expression vector for the protein of the present invention was incubated at 37°C for 2 hours in 2 ml of the 2xYT culture medium I5 containing 100 pg/ml of ampicillin, the helper phage M13R07 ( 50 a 1 ) was added, and the incubation was continued at 37 °C
overnight. A supernatant separated by centrifugation underwent precipitation with polyethylene glycol to obtain single-stranded phage particles. These particles were suspended in 100 N1 of 1 mM Tris-0.1 mM EDTA, pH 8 (TE}.
The cultured cells derived from simian kidney, COS7, were incubated at 37°C in the presence of 5% COz in the Dulbecco's modified Eagle's culture medium (DMEM) containing 10% fetal calf serum. Into a 6-well plate (Nunc, well diameter: 3 cm) were inoculated with 1 x lOs COS7 cells and incubation was carried out at 37°C for 22 hours in the presence of 5% COz. After the culture medium was removed, the cell surface was washed with a phosphate buffer solution and then washed again with DMEM containing 50 mM Tris-hydrochloric acid (pH 7.5) (TDMEM). To the resulting cells was added a suspension of 1 Nl of the single-stranded phage suspension, 0.6 ml of the DMEM culture medium, and 3 pl of TRANSFECTAM~'' (IBF) and the resulting mixture was incubated at 37°C for 3 hours in the presence of 5% COz. After the sample solution was removed, the cell surface was washed with TDMEM, 2 ml per well of DMEM containing 10% fetal calf serum was added, and the incubation was carried out at 37 °C
for 2 days in the presence of 5% COz. After the culture medium was replaced by a culture medium containing ['SS]cystine or ['SS]methionine, the incubation was carried out for one hour. After the culture medium and the cells were separated by centrifugation, proteins in the culture medium fraction and the cell-membrane fraction were subjected to SDS-PAGE.
(4) Clone Examples <HP01550> (SEQ ID Nos. 1, 11, and 21) Determination of the whole base sequence of the cDNA
insert of clone HP01550 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 65-by 5'-untranslated region, a 378-by ORF, and a 67-by 3'-untranslated region. The ORF codes for a protein consisting of 125 amino acid residues and there existed one putative transmembrane domain. Figure 1 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 15 kDa that was almost identical with the molecular weight of 13,825 predicted from the ORF.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein F45G2.c (GenBank Accession No. Z93382).
Table 2 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C.

elegans hypothetical protein F45G2.c (CE). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 44.5% in the entire region.
Table 2 HP MAKYLAQIIVMGVQWGRAFARALRQEF------AASRAAADARGRAGHRSAAASNLS-.. . . ..*..*..**.*.*. **..**..... .. *..*.** .
CE MPWRTALKVALAAGEAVAKALTRAVRDEIKQTQQAAARHAASTGQSASETRENANSNAKL
HP GLSLQEAQQILNV-SKLSPEEVQKNYEHLFKVNDKSVGGSFYLQSKWRAKERLDEEL-K
*,**,*, ***** , * " ***,*,***** " **** ** " ****** *****,***, .
CE GISLEESLQILNVKTPLNREEVEKHYEHLFNINDKSKGGTLYLQSKVFRAKERIDEEFGR
HP IQAQEDREKGQMPHT
*. .*...*.. ..*
CE IELKEEKKKEENAKTE
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA338859) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02593> (SEQ ID Nos. 2, 12, and 22) Determination of the whole base sequence of the cDNA
insert of clone HP02593 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 103-by 5'-untranslated region, a 396-by ORF, and a 198-by 3'-untranslated region. The ORF codes for a protein consisting of 131 amino acid residues and there existed four putative transmembrane domains at the C-terminus. Figure 2 depicts the hydrophobicity/hydrophilicity 5 profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of a high molecular weight.
The search of the protein data base using the amino acid sequence of the present protein revealed that the 10 protein was similar to a human OB-R gene-related protein (E1~L Accession No. Y12670). Table 3 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human OB-R gene-related protein (OB) . Therein, the marks of -, *, and . represent a 15 gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 67.9%
in the entire region.
Table 3 HP MAGIKALISLSFGGAIGLMFLMLGCALPIYNKYWPLFVLFFYILSPIPYCIARRLVDDTD
***_***__*** ***** ******** *_ *******_*_ _****_ **.*
OB MAGVKALVALSFSGAIGLTFLMLGCALEDYGVYWPLFVLIFHAISPIPHFIAKRVTYDSD
HP AMSNACKELAIFLTTGIWSAFGLPIVFARAHLIEWGACALVLTGNTVIFATILGFFLVF
* *,**,*** *,**********,*,..**. .*.****,***,**,*** ** ****,*
OB ATSSACRELAYFFTTGIWSAFGFPVILARVAVIKWGACGLVLAGNAVIFLTIQGFFLIF
HP GSNDDFSWQQW
*..*****.**
OB GRGDDFSWEQW

Furthermore, the search of the GenHank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA306490) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10195> (SEQ ID Nos. 3, 13, and 23) Determination of the whole base sequence of the cDNA
insert of clone HP10195 obtained from cDNA library of human fibrosarcoma HT-1080 revealed the structure consisting of a 286-by 5'-untranslated region, a 729-by ORF, and a 604-by 3'-untranslated region. The ORF codes for a protein consisting of 242 amino acid residues and there existed one putative transmembrane domain at the C-terminus. Figure 3 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 32 kDa that was somewhat larger than the molecular weight of 27,300 predicted from the ORF. When expressed in COS7 cells, an expression product of about 21 kDa was observed in the supernatant fraction and the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein has revealed the registration of sequences that were similar to the Aplysia VAP-33 (SWISS-PROT Accession No. P53173). Table 4 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the Aplysia VAP-33 (AP).
Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 46.5% in the entire region.
Table 4 HP MAKHEQILVLDPPTDLKFKGPFTDWTTNLKLRNPSDRKVCFKVKTTAPRRYCVRPNSGI
**,*** *,*,*,..*.********** " ***,**,**" *********,**********
AP MASHEQALILEPAGELRFKGPFTDVVTADLKLSNPTDRRICFKVRTTAPKRYCVRPNSGI
HP IDPGSTVTVSVMLQPFDYDPNEKSKHKFMVQTIFAPPNTSD-MEAVWKEAKPDELMDSKL
..* ....*.******,******,*******,..** .. . * .**.* *~~***~**
AP LEPKTSIAVAVMLQPFNYDPNEKNKHKFMVQSMYAPDHWESQELLWKDAPPESLMDTKL
HP RCVFEMPNENDKLNDMEPSK--------------AVPLNASKQDGPMPKP-HSVSLNDTE
*******..... . ..*. . .....* ... **. .*. ....
AP RCVFEMPDGSHQAPASDASRATDAGAHFSESALEDPTVASRKTETQSPKRVGAVGSAGED
HP TRKLMEECKRLQGEMMKLSEENRHLRDEGLRLRKVAHSD--KPGSTSTASFRDNVTSPLP
..** .* *. *.*. .*..**..*.***.****** .* .*.. .... ........*
AP VKKLQHELKKAQSEITSLKGENSQLKDEGIRLRKVAMTDTVSPTPLNPSPAPAAAVRAFP
HP SLLWIAAIFIGFFLGRFIL
... *,*** " *...***,*
AP PWYWAAIILGLIIGKFLL
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA447905) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10423> (SEQ ID Nos. 4, 14, and 24) WO 00/05367 PCT/,fP99/03929 Determination of the whole base sequence of the cDNA
insert of clone HP10423 obtained from cDNA library of human osteosarcoma cell line U-2 OS revealed the structure consisting of a 64-by 5~-untranslated region, a 795-by ORF, and a 207-by 3'-untranslated region. The ORF codes for a protein consisting of 264 amino acid residues and there existed a secretory signal at the N-terminus and one putative transmembrane domain at the N-terminus. Figure 4 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 30 kDa that was almost identical with the molecular weight of 29,377 predicted from the ORF. When expressed in COS7 cells, an expression product of about 3I
kDa was observed in the membrane fraction.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. D80116) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10506> (SEQ ID Nos. 5, 15, and 25) Determination of the whole base sequence of the cDNA
insert of clone HP10506 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 53-by 5'-untranslated region, a 339-by ORF, and a 226-by 3~-untranslated region. The ORF codes for a protein consisting of 112 amino acid residues and there existed one putative transmembrane domain. Figure 5 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 12 kDa that was almost identical with the molecular weight of 11,821 predicted from the ORF. When expressed in COS7 cells, an expression product of about 13 kDa was observed in the membrane fraction.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA282544) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10507> (SEQ ID Nos. 6, 16, and 26) Determination of the whole base sequence of the cDNA
insert of clone HP10507 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 412-by 5'-untranslated region, a 441-by ORF, and a 168-by 3~-untranslated region. The ORF codes for a protein consisting of 146 amino acid residues and there existed a secretory signal at the N-terminus and one putative transmembrane domain at the C-terminus. Figure 6 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 19 kDa that was somewhat larger than the molecular weight of 16,347 predicted from the oRF.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA424759) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
5 <HP10548> (SEQ ID Nos. 7, 17, and 27) Determination of the whole base sequence of the cDNA

insert of clone HP10548 obtained from cDNA~library of human stomach cancer revealed the structure consisting of a 330-by 5'-untranslated region, a 1035-by ORF, and a 67-by 3'-10 untranslated region. The ORF codes for a protein consisting of 344 amino acid residues and there existed four putative transmembrane domains. Figure 7 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro 15 translation resulted in formation of a translation product of a high molecular weight.

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for 20 example, Accession No. AA143152) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.

25 <HP10566> (SEQ ID Nos. 8, 18, and 28) Determination of the whole base sequence of the cDNA
insert of clone HP10566 obtained from cDNA library of the human stomach cancer revealed the structure consisting of a 61-by 5'-untranslated region, a 294-by ORF, and a 246-by 3'-30 untranslated region. The ORF codes for a protein consisting of 97 amino acid residues and there existed one putative transmembrane domain at the C-terminus. Figure 8 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 12 kDa that was almost identical with the molecular weight of 11,452 predicted from the ORF. When expressed in COS7 cells, an expression product of about 12 kDa was observed in the membrane fraction.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for ' example, Accession No. W79821) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10567> (SEQ ID Nos. 9, 19, and 29) Determination of the whole base sequence of the cDNA
insert of clone HP10567 obtained from cDNA library of the human stomach cancer revealed the structure consisting of a 77-by 5'-untranslated region, a 375-by ORF, and a 133-by 3~-untranslated region. The ORF codes for a protein consisting of 124 amino acid residues and there existed one putative transmembrane domain at the C-terminus. Figure 9 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 14 kDa that was almost identical with the molecular weight of 14,484 predicted from the ORF.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA428475) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10568> (SEQ ID Nos. 10, 20, and 30) Determination of the whole base sequence of the cDNA
insert of clone HP10568 obtained from cDNA library of the human stomach cancer revealed the structure consisting of a 56-by 5 ~-untranslated region, a 984-by ORF, and a 60-by 3 ~-untranslated region. The ORF codes for a protein consisting of 327 amino acid residues and there existed a secretory signal at the N-terminus and one putative transmembrane domain at the C-terminus. Figure 10 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 36.5 kDa that was almost identical with the molecular weight of 34,326 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 40 kDa which is considered to have a sugar chain being attached. In addition, there exist in the amino acid sequence of this protein two sites at which N-glycosylation may occur (Asn-Leu-Thr at position 138 and Asn-Leu-Ser at position 206). Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from valine at position 24. When expressed in COS7 cells, an expression product of about 31 kDa was observed in the supernatant fraction and the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein has revealed that the protein was similar to the human cell-surface A33 antigen (SWISS-PROT Accession No. Q99795). Table 5 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human cell-surface A33 antigen (A3). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 30.0%
in the N-terminal region of 243 residues.
Table 5 HP MAELPGPFLCGALLGFLCLSGLAVEVKVPTEPLSTPLGKTAELTCTYSTSVGDSFAL-EW
*..*..* . *... **...*.*** **,... .* .*

HP SFVQPGKPISESHPILYFTNGHLYPTGSKSKRVSLLQNPPTVGVATLKLTDVHPSDTGTY
. . . .*. * *,* . * *. *. , * .. . *....... ,*,***

HP LCQVNNPPDFYTNGLGLINLTVLVPPSNPLCSQSGQTSVGGSTALRCSSSEGAPKPVYNW
* *. .*. .*. . ..* ******,* *, .*.* ,*....* * *.**,*,* *,*

HP VRLGTFPTPSPGSMVQDEVSGQLILTNLSLTSSGTYRCVATNQMGSASCELTLSVTEPS
* ... * ..* . . .. *.*.* ..** * *,..*. *.. *..*..* ,**

HP -QGRVAGALIGVLLGVLLLSVAAFCLVRFQKERGKKPKETYGGSDLREDAIAPGISEHTC
.* .**. ....... .*

HP MRADSSKGFLERPSSASTVTTTKSKLPMW

Furthermore, the search of the GenHank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. T24595) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP01426> (SEQ ID Nos. 31, 41, and 51) Determination of the whole base sequence of the cDNA
insert of clone HP01426 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 1-by 5'-untranslated region, a 942-by ORF, and a 122-by 3~-untranslated region. The ORF codes for a protein consisting of 313 amino acid residues and there existed a putative secretory signal. Figure 11 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 36 kDa that was almost identical with the molecular weight of 34, 955 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 38 kDa which is considered to have a sugar chain being attached after secretion. In addition, there exists in the amino acid sequence of this protein one site at which N-glycosylation may occur (Asn-Ser-Ser at position 163).
Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from tryptophan at position 17. When expressed in COS7 cells, an expression product of about 39 kDa was observed in the supernatant fraction and the membrane traction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Xenopus laevis cortical granule lectin (EMBL Accession No. X82626}. Table 6 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the X. laevis cortical 5 granule lectin (XL). Therein, the marks of -, *, and represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology 10 of 67.9% in the region other than the N-terminal region.
Table 6 HP MNQLSFLLFLIATTRGWSTDEANTYFKEWTCSSSPSLPRSCKEIKDECPSAFDGLYFLRT
15 * ** * ********, ,* **,* * , XL MLVHILLLLVTGGLSQSCEPWIVASKNMVKQLDCDKFRSCKEIKDSNEEAQDGIYTLTS
HP ENGVIYQTFCDMTSGGGGWTLVASVHENDMRGKCTVGDRWSSQQGSKADYPEGDGNWANY
..*. ******** " *************,* ****,********* " *************
XL SDGISYQTFCDMTTNGGGWTLVASVHENNMAGKCTIGDRWSSQQGNRADYPEGDGNWANY

****** " **************,* ,**,******,*, ****** **** " *,* , XL NTFGSAGGATSDDYKNPGYYDIEAYNLGVWHVPNKTPLSVWRNSSLQRYRTTDGILFRHG
HP HNLFGIYQKYPVKYGEGKCWTDNGPVIPWYDFGDAQKTASYYSPYGQREFTAGFVQFRV
*** " *, ****** *,* ,*,** " *****,*,*, ***,*** ...**.*..***

HP FNNERAANALCAGMRVTGCNTEHHCIGGGGYFPEASPQQCGDFSGFDWSGYGTHVGYSSS
*,*,** ***,**,...**.** ***********,*,*****,..*..****, *..
XL INTEKA.ALALCPGMKMESCNVEHVCIGGGGYFPEADPRQCGDFAAYDFNGYGTKRFNSAG
HP REITEAAVLLFYR
30 ***********
XL IEITEAAVLLFYL

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. 806009 ) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02515> (SEQ ID Nos. 32, 42, and 52) Determination of the whole base sequence of the cDNA
insert of clone HP02515 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 176-by 5'-untranslated region, a 690-by ORF, and a 71-by 3'-untranslated region. The ORF codes for a protein consisting of 229 amino acid residues and there existed a putative secretory signal at N-terminus and one putative transmembrane domain at the C-tern~inus. Figure 12 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 27 kDa that was almost identical with the molecular weight of 26,000 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 25.5 kDa from which the secretory signal is considered to have been cleaved. Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from phenylalanine at position 28.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human T1/ST2 receptor binding protein (GenBank Accession No. U41804). Table 7 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human T1/ST2 receptor binding protein (T1). Therein, the marks of -, *, and represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 55.8% in the entire region.
Tabie 7 HP MGDKIWLPFPVLLLAALPPVLLPGAAGFTPSLDSDFTFTLPAGQKECFYQPMPLKASLE
*.... ** ,*** , *,** ,* *" *** ****,*,****, * ,****

HP IEYQVLDGAGLDIDFHLASPEGKTLVFEQRKSDGVHTVE-TEVGDYMFCFDNTFSTISEK
,****" *****,** *,**,* ** * **,******* **,***" ****,*******

HP VIFFELILDNMGEQAQEQEDWKKYITGTDILDMKLEDILESINSIKSRLSKSGHIQILLR
..*****.*.. ....* *.* . .. ...**.*.*** ***.....**..* .. .***

HP AFEARDRNIQESNFDRVNFWSMVNLVVMVWSAIQVYMLKSLFEDKRKSRT
********,**,*"****** **"*...*...**. **"*,*** ,*

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA381943) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.

<HP02575> (SEQ ID Nos. 33, 43, and 53) Determination of the whole base sequence of the cDNA
insert of clone HP02575 obtained from cDNA library of human osteosarcome cell line Saos-2 revealed the structure consisting of a 55-by 5'-untranslated region, a 1404-by ORF, and a 219-by 3'-untranslated region. The ORF codes for a protein consisting of 467 amino acid residues and there existed a putative secretory signal at the N-terminus.
Figure 13 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 52 kDa that was almost identical with the molecular weight of 54,065 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 57 kDa which is considered to have a sugar chain being attached afetr secretion. In addition, there exist in the amino acid sequence of this protein three sites at which N-glycosylation may occur (Asn-Arg-Thr at position 171, Asn-Ser-Thr at position 239 and Asn-Asp-Thr at position 377). Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from histidine at position 29. When expressed in COS7 cells, an expression product of about 55 kDa was observed in the supernatant fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human a -L-fucosidase (SWISS-PROT
Accession No. P04066). Table 8 shows the comparison between amino acid sequences of the human protein of the present invention ( HP ) and the human a -L-fucosidase ( FC ) . Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 54.8% in the entire region.
Table 8 HP MRPQELPRLAFPLLLLLLLLLPPPPC-PAHSATRFDPTWESLDARQLPAWFDQAKFGIFI
,******,* .. . .*... *..*.* ***,*,******,****,**
FC MRSRPAGPALLLLLLFLGAAESVRRAQPPRRYTPDWPSLDSRPLPAWFDEAKFGVFI
HP HWGVFSVPSFGSEWFWWYWQKEKIPKYVEFMKDNYPPSFKYEDFGPLFTAKFFNANQWAD
******** " *******,** * *,* **,*****,*,*,**** ***,**,...***
FC HWGVFSVPAWGSEWFWWHWQGEGRPQYQRFMRDNYPPGFSYADFGPQFTARFFHPEEWAD
HP IFQASGAKYIVLTSKHHEGFTLWGSEYSWNWNAIDEGPKRDIVKELEVAIRNRTDLRFGL
***,****,***,******* * * *****, * **,**,* ** " *,*,* ..*.**
FC LFQAAGAKYWLTTKHHEGFTNWPSPVSWNWNSKDVGPHRDLVGELGTALRRR-NIRYGL
HP YYSLFEWFHPLFLEDESSSFHKRQFPVSRTLPELYELVNNYQPEVLWSDGDGGAPDQYWN
*,**,******,* *,...*....* .**.****,***,*,*,..****, , ** ***
FC YHSLLEWFHPLYLLDKKNGFKTQHFVSAKTMPELYDLVNSYKPDLIWSDGEWECPDTYWN
HP STGFLAWLYNESPVRGTWTNDRWGAGSICKHGGFYTCSDRYNPGHLLPHKWENCMTIDK
**,**,****,***,..**,*****,.. *.***,*,*,*,..* * **** * ,***
FC STNFLSWLYNDSPVKDEVVVNDRWGQNCSCHHGGYYNCEDKFKPQSLPDHKWEMCTSIDK
HP LSWGYRREAGISDYLTIEELVKQLVETVSCGGNLLMNIGPTLDGTISWFEERLRQMGSW
,******, ..** . .*....**.*** *** *,***** ** * ,*,*** " *,*
FC FSWGYRRDMALSDVTEESEIISELVQTVSLGGNYLLNIGPTKDGLIVPIFQERLLAVGKW
HP LKVNGEAIYETHTWRSQNDTVTPDVWYTSKPKEKLVYAIFLKWPTSGQLFLGHPKAILGA
* " ****** ** * * ****** , ****** **
.... .. .. . . .. . .. ..
FC LSINGEAIYASKPWRVQWEKNTTSVWYTSKGSA--VYAIFLHWPENGVLNLESPITT-ST
HP TEVKLLGHGQPLNWISLEQNGIMVELPQLTIHQMPCKWGWALALTNVI
*....** *.* . ..*....****. ..* ...*.. **.*
FC TKITMLGIQGDLKWSTDPDKGLFISLPQLPPSAVPAEFAWTIKLTGVK

sa Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. N28668) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10357> (SEQ ID Nos. 34, 44, and 54) Determination of the whole base sequence of the cDNA
insert of clone HP10357 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 113 -by 5'-untranslated region, a 300-by ORF, and a 54-by 3'-untranslated region. The ORF codes for a protein consisting of 99 amino acid residues and there existed two putative transmembrare domains. Figure 14 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 11 kDa that was almost identical with the molecular weight of 10,923 predicted from the ORF.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA477156) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10447> (SEQ ID Nos. 35, 45, and 55) Determination of the whole base sequence of the cDNA

insert of clone HP10447 obtained from cDNA library of human liver revealed the structure consisting of a 271-by 5~-untranslated region, a 570-by ORF, and a 34-by 3~-untranslated region. The ORF codes for a protein consisting of 189 amino acid residues and there existed five putative transmembrare domains. Figure 15 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA296976) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10477> (SEQ ID Nos. 36, 46, and 56) Determination of the whole base sequence of the cDNA
insert of clone HP10477 obtained from cDNA library of human liver revealed the structure consisting of a 149-by 5~-untranslated region, a 1092-by ORF, and a 15-by 3~-untranslated region. The ORF codes for a protein consisting of 363 amino acid residues and there existed one putative transmembrane domain at the N-terminus. Figure 16 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 40 kDa that was almost identical with the molecular weight of 39,884 predicted from the ORF.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human peptidoglycan recognition protein (GenBank Accession No. AF076483). Table 9 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human peptidoglycan recognition protein (PG}. Therein, the marks of -, *, and .
represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 54.8% in the entire region.
Table 9 HP MVDSLLAVTLAGNLGLTFLRGSQTQSHPDLGTEGCWDQLSAPRTFTLLDPKASLLTKAFL
HP NGALDGVILGDYLSRTPEPRPSLSHLLSQYYGAGVARDPGFRSNFRRQNGAALTSASILA
HP QQVWGTLVLLQRLEPVHLQLQCMSQEQLAQVAANATKEFTEAFLGCPAIHPRCRWGAAPY
*" * ** * * , PG MSRRSMLLAWALPSLLRLGAAQETEDPACCSPIVPRNEWKALA-HP RGRPRLLQLPLGFLYVHHTYVPAPPCTDFTRCAANMRSMQRYHQDTQGWGDIGYSFWGS
.. .. * *** ., * ** ....*.. ..*... *..*.** ,* ** *,**,*" *.
PG SECAQHLSLPLRYVWSHT--AGSSCNTPASCQQQARNVQHYHMKTLGWCDVGYNFLIGE
HP DGYVYEGRGWHWVGAHTLGH-NSRGFGVAIVGNYTAALPTEAALRTVRDTLPSCAVRAGL
** *******...***, *....*....*** . .** .*.*.... * .*,* .*
PG DGLVYEGRGWNFTGAHSGHLWNPMSIGISFMGNYMDRVPTPQAIRAAQGLL-ACGVAQGA
HP LRPDYALLGHRQLVRTDCPGDALFDLLRTWPHFTATVKPRPARSVSKRSRREPPPRTLPA
**"*,* ***" ** ,**"*..*...***, PG LRSNYVLKGHRDVQRTLSPGNQLYHLIQNWPHYRSP
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA424759) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10513> (SEQ ID Nos. 37, 47, and 57) Determination of the whole base sequence of the cDNA
insert of clone HP10513 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 134-by 5'-untransiated region, a 750-by ORF, and a 0-by 3'-untranslated region. The ORF codes for a protein consisting of 249 amino acid residues and there existed one putative transmembrane domain at the N-terminus. Figure 17 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 29 kDa that was almost identical with the molecular weight of 27,373 predicted from the ORF.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human hypothetical protein KIAA0512 (GenHank Accession No. AB011084). Table 10 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human hypothetical protein KIAA0512 (KI). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 31.6% in the C-terminal region of 196 amino acid residues.

Table 10 HP MGGPRGAGWVAAGLLLGAGACYCIYRLTRGRRRG
KI RGRGRRPVAMQKRPFPYEIDEILGVRDLRKVLALLQKSDDPFIQQVALLTLSNNANYSCN
HP DRELGIRSSKSAEDLTDGSYDDVLNAEQLQKLLYLLESTEDPVIIERALITLGNNAAFSV
* .....* . * *. *.. .. . .. ..
KI QETIRKLGGLPIIANMINKTDPHIKEKALMAMNNLSENYENQGRLQVYMNRVMDDIMASN
HP NQAIIRELGGIPIVANKINHSNQSIKEKALNALNNLSVNVENQIKIKVQVLRLLLNLSEN
.. .. .* ... .*... * . ...... ... .. **** " **,* * " **
KI LNSAVQWGLKFLTNMTITNDYQHLLVNSIANF--FRLLSQGGGKIKVEILKILSNFAEN
HP PAMTEGLLRAQVDSSFLSLYDSHVAKEILLRVLTLFQNIKNCLKIEGHLAVQPTFTEGSL
*,* , ** " ** ,** ***,*,* " ***,..****, * , *, * , ..*..***
KI PDMLKRLLSTQVPASFSSLYNSYVESEILINALTLFEIIYDNLRAE--VFNYREFNKGSL
HP FFL-LHGEECAQKIRALVDHHDAEVKEKWTIIPKI
*.* .. *..*****,.*** ** **.... *.
KI FYLCTTSGVCVRKIRALANHHDLLVRVKVIKLVNRF
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession .No. N92228) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10540> (SEQ ID Nos. 38, 48, and 58) Determination of the whole base sequence of the cDNA
insert of clone HP10540 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 47-by 5'-untranslated region, a 297-by ORF, and a 245-by 3'-untranslated region. The ORF codes for a protein consisting of 98 amino acid residues and there existed two putative transmembrane domains. Figure 18 5 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
The search of the protein data base using the amino 10 acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein CEF49CI2.12 (GenHank Accession No.
Z68227). Table 11 shows the comparison between amino acid sequences of the human protein of the present invention (HP) 15 and the C. elegans hypothetical protein CEF49C12.12 (CE).
Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The 20 both proteins shared a homology of 36.1% in the entire region.
Table 11 * *** * * * **** * ** **
CE MGKICPLMGPKMSAFCMVMSVWGVIFLGLLGVFFYIQAVTLFPDLHF-EGHGKVPSSVID
HP NLYEQVSYNCFIAAGLYLLLGGFSFCQVRLNKRKEYMVR
* * ****** * * **

' 66 Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA420715) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10557> (SEQ ID Nos. 39, 49, and 59) Determination of the whole base sequence of the cDNA
insert of clone FiP10557 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 24-by 5'-untranslated region, a 519-by ORF, and a 130-by 3'-untranslated region. The ORF codes for a protein consisting of 172 amino acid residues and there existed a putative secretory signal at the N-terminus. Figure 19 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 32 kDa that was larger than the molecular weight of 18,844 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 39 kDa which is considered to have been subjected to some modification after secretion. In addition, there exist in the amino acid sequence of this protein no site at which N-glycosylation may occur. Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from glycine at position 32. When expressed in COS7 cells, an expression product of about 20 kDa was observed in the supernatant fraction and the membrane fraction.

The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human progesterone binding protein (EMBL Accession No. AJ002030). Table 12 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human progesterone binding protein (PG). Therein, the marks of -, *, and represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 30.5% in the C-terminal region of 151 amino acid residues.
Table 12 HP MVGPAP
PG MAAGDGDVKLGTLGSGSESSNDGGSESPGDAGAAAEGGGWAAAALALLTGGGEMLLNVAL
HP RRRLRPLA,ALALVLALAPGLPTARAGQTPRPAERGPPV--RLFTEEELARYGGEEEDQPI
** .. .. . .**.. *.. * *. *.* .*.* . ...*
PG VALVLLGAYRLWRWGRRGLGAGAGAGEESPATSLPRMKKRDFSLEQLRQYDG-SRNPRI
HP YLAVKGWFDVTSGKEFYGRGAPYNALTGKDSTRGVAKMSLDPADLTHDTTGLTAKELEA
***,* *****.*..***...**. ..*.*..**.*...** ..* .. ..*.. .
PG LLAVNGKVFDVTKGSKFYGPAGPYGIFAGRDASRGLATFCLDKDALRDEYDDLSDLNAVQ
HP LDEV--FTKVYKAKYPIVGYTARRILNEDGSPNLDFKPEDQPHFDIKDEF
...* ... .*.** .*.. *.*. ...*. ... *.... . *..
PG MESVREWEMQFKEKY---DYVG-RLLKPGEEPS-EYTDEEDTKDHNKQD
Furthermore, the search of the GenHank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (far example, Accession No. AA101709) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10563> (SEQ ID Nos. 40, 50, and 60) Determination of the whole base sequence of the cDNA
insert of clone HP10563 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 126-by 5'-untranslated region, a 363-by ORF, and a 936-by 3'-untranslated region. The ORF codes for a protein consisting of 120 amino acid residues and there existed two putative transmembrane domains. Figure 20 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 18.5 kDa that was larger than the molecular weight of 13,180 predicted from the ORF.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Arabidopsis thaliana hypothetical protein F27F23.15 (GenBank Accession No. AC003058). Table 13 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the A.
thaliana hypothetical protein F27F23.15 (AT). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 35.5% in the entire region.

WO 00/05367 PCT/,TP99/03929 Table 13 HP MMPSRTNLATGIPSSKVKYSRLSSTDDGYIDLQFKRTPPKIPYKAIALATVLFLIGAFLI
*..* ~*. . ... . * *.*_**_ *___*
AT MAYVDHAFSISDEDLMIGTSY-TVSNRPPVKEISLAVGLLVFGTLGI
HP IIGSLLLSGYISKGGADRAVPVLIIGILVFLPGFYHLRIAYYASKGYRGYSYDDIPDFDD
..* .. . .. *. .... ...* *.*.****, ****** ***,*,*,..**
AT VLGFFMAYNRVG-GDRGHGIFFIVLGCLLFIPGFYYTRIAYYAYRGYKGFSFSNIPSV
Furthermore, the search of the GenBank using the base seguences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA083574) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP01467> (SEQ ID Nos. 61, 71, and 81) Determination of the whole base sequence of the cDNA
insert of clone HP01467 obtained from cDNA library of human fibrosarcoma cell line HT-1080 revealed the structure consisting of a 65-by 5'-untranslated region, a 924-by ORF, and a 447-by 3'-untranslated region. The ORF codes for a protein consisting of 307 amino acid residues and there existed three putative transmembrane domains. Figure 21 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
The search of the protein data base using the amino ?0 acid sequence of the present protein revealed that the protein was similar to the rat Sec22 homologue (GenHank Accession No. U42209). Table 14 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the rat Sec22 homologue (RN). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 94.6% in the N-terminal region of 241 amino acid residues. The protein of the present invention was longer .by 53 amino acids at the C-terminus than the rat Sec22 homologue.
Table 14 HP MSMILSASVIRVRDGLPLSASTDYEQSTGMQECRKYFKMLSRKLAQLPDRCTLKTGHYNI
*********,*************,***,*.****************,********* " **
RN MSMILSASVVRVRDGLPLSASTDCEQSAGVQECRKYFKMLSRKLAQFPDRCTLKTGRHNI
HF NFISSLGVSYMMLCTENYPNVLAFSFLDELQKEFITTYNMMKTNTAVRPYCFIEFDNFIQ
************************************************************
RN NFISSLGVSYMMLCTENYPNVLAFSFLDELQKEFITTYNMMKTNTAVRPYCFIEFDNFIQ
HP RTKQRYNNPRSLSTKINLSDMQTEIKLRPPYQISMCELGSANGVTSAFSVDCKGAGKISS
********************** **********,**************************
RN RTKQRYNNPRSLSTKINLSDMQMEIKLRPPYQIPMCELGSANGVTSAFSVDCKGAGKISS
HP AHQRLEPATLSGIVGFILSLLCGALNLIRGFHAIESLLQSDGDDFNYIIAFFLGTAACLY
**************,***************************,**,*,************
RN AHQRLEPATLSGIVAFILSLLCGALNLIRGFHAIESLLQSDGEDFSYMIAFFLGTAACLY
HP QCYLLVYYTGWRNVKSFLTFGLICLCNMYLYELRNLWQLFFHVTVGAFVTLQIWLRQAQG
RN QMICLCLQGRKERT

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA421925) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP01956> (SEQ ID Nos. 62, 72, and 82) Determination of the whole base sequence of the cDNA
insert of clone HP01956 obtained from cDNA library of human liver revealed the structure consisting of a 86-by 5~-untranslated region, a 552-by ORF, and a 359-by 3~-untranslated region. The ORF codes for a protein consisting of 183 amino acid residues and there existed one putative transmembrane domain. Figure 22 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 20.5 kDa that was almost identical with the molecular weight of 20,073 predicted from the ORF.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the yeast hypothetical protein 21.5 kDa (SWISS-PROT Accession No. P53073). Table 15 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the yeast hypothetical protein 21.5 kDa (SC). Therein, the marks of -, *, and represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 34.3% in the C-terminal region of 108 amino acid residues.
Table 15 HP MTAQGGLVANRGRRFRWAIELSGPGGGSRGRSDRGSGQGDSLYPVGYLDKQVPDTS
SC MSEQEPYEWAKHLLDTKYIEKYNIQNSNTLPSPPGFEGNSSKGNVTRKQQDATSQTTSLA
HP VQETDRILVEKRCWDIALGPLKQIPMNLFIMYMAGNTISIFPTMMVCMMAWRpIQALMAI
.* .. *.*** * * ****,*. **,*... *.*.* . *. ** *,...
SC QKNQITVLQVQKAWQIALQPAKSIPMNIFMSYMSGTSLQIIPIMTALMLLSGPIKAIFST
HP SATFK--MLESSSQKFLQGLVYLIGNLMGLALAV-Y-KCQSMGLLPTHASDWLAFIEPPE
...** . ....*. .*. ... . *. . . * * ,****.*, ,***, SC RSAFKPVLGNKATQSQVQTAMFMYIVFQGVLMYIGYRKLNSMGLIPNAKGDWLPWERIAH
HP RMEFSGGGLLL
SC YNNGLQWFSD
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AAI59753) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02545> (SEQ ID Nos. 63, 73, and 83) Determination of the whole base sequence of the cDNA
insert of clone HP02545 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 133-by 5'-untranslated region, a 984-by ORF, and a 636-by 3'-untranslated region. The ORF codes for a protein consisting of 327 amino acid residues and there existed a putative secretory signal at the N-terminus and one putative transmembrane domain at the C-terminus. Figure 23 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the rat embigin (E1~L Accession No.
AJ009698). Table 16 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the rat embigin (RN). Therein, the marks of -, *, and .
represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 65.4% in the entire region.

Table 16 HP MRALPGLLEARARTPRLLLLQCLLAAARPSSADGSAPDSPFTSPPLREEIMAN--NFSLE
**, ,** , *,. ,**** ,****,**" * *,..**,*** *,***,**, *,***
RN MRSHTGLRALVAPGCSLLLL-YLLAATRPDRAVGDPADSAFTSLPVREEMMAKYANLSLE
HP SHNISLTEHSSMPVEKNITLERPSNVNLTCQFTTSGDLNAVNVTWKKDGEQLE--NNYLV
..******..... *.********,..*.* **...*. ..*******., ** ,.. .
RN TYNISLTEQTRVS-EQNITLERPSHLELECTFTATEDVMSMNVTWKKDDALLETTDGFNT
HP SATGSTLYTQYRFTIINSKQMGSYSCFFREEKEQRGTFNFKVPELHGKNRpLISYVGDST
. *,***,***** " ******,****, ** ***** " ** " ********,******
RN TKMGDTLYSQYRFTVFNSKQMGKYSCFLGEE--LRGTFNIRVPRVHGKNKPLITYVGDST
HP VLTCKCQNCFPLNWTWYSSNGSVKVPVGVQM-NKYVINGTYANETKLKITQLLEEDGESY
**,*,****,******* ***,..**..*.. .*. ***,********,..******,**
RN VLKCECQNCLPLNWTWYMSNGTAQVPIDVHVNDKFDINGSYANETKLKVKHLLEEDGGSY
HP WCRALFQLGESEEHIELWLSYLVPLKPFLVIVAEVILLVATILLCEKYTQKKKKHSDEG
**** *,********,***** " *******,*,********,***** ******,..*.*
RN WCRAAFPLGESEEHIKLWLSFMVPLKPFLAIIAEVILLVAIILLCEVYTQKKRNDPDDG
HP KEFEQIEQLKSDDSNGIENNVPRHRKNESLGQ
*********************** **
RN KEFEQIEQLRSDDSNGIENNVPRYRKTDSGDQ
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA312629) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02551> (SEQ ID Nos. 64, 74, and 84) Determination of the whole base sequence of the cDNA
insert of clone HP02551 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 61-by 5~-untranslated region, a 672-by ORF, and a 384-by 3'-untranslated region. The ORF codes for a protein consisting of 223 amino acid residues and there 5 existed a putative secretory signal at the N-terminus.
Figure 24 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 27 kDa that was somewhat larger than 10 the molecular weight of 24,555 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 26 kDa from which the secretory signal is considered to have been cleaved. Application of the (-3,-1) rule, a method for predicting the cleavage site of the 15 secretory signal sequence, allows to expect that the mature protein starts from glutamine at position 20.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the mouse FGF binding protein 20 (GenBank Accession No. U49641). Table 17 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the mouse FGF binding protein (lei) . Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the 25 protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 21.2%
in the entire region other than the N-terminal region. In particular, all the eight cysteine residues contained in the 30 both proteins were conserved.

Table 17 HP MKFVPCLLLVTLSCLGTLGQAPRQKQGST
..**. . .* . ...
MM MRLHSLILLSFLLLATQAFSEKVRKRAKNAPHSTAEEGVEGSAPSLGKAQNKQRSRTSKS
HP GEEFHFQTGGRDSCTMRPSSLGQGAGEVWLRVDCRNTDQTYWCEYRGQPSMCQAFAADPK
.. .* * ....* . ...... .. * *.* ..**.. * . *.*. * . * .
MM LTHGKFVTKDQATC---RWAVTEEEQGISLKVQCTQADQEFSCVFAGDPTDCLRHDKD-Q
HP SYWNQALQELRRLHHACQGA-PVLRPSVCREAGPQAHMQQVTSSLKGSPEPNQQPEAGTP
**.*. ..**. .. *..* .**...***, *..... *... .*...*... .. ..
MM IYWKQVARTLRKQKNICRDAKSVLKTRVCRKRFPESNLKLVNPNARGNTKPRKEKAEVSA
HP SLRPKATVKLTEATQLGKDSMEELGKAKPTTRPTAKPTQPGPRPGGNEEAKKKAWEHCWK
. . *. ...... *... .*. * . *. * . .. *. .. .*.* * * .
MM REHNKVQEAVSTEPNRIKEDI-TLNPAATQTM-TIRDPECLEDPDVLNQ-RKTALEFCGE
HP PFQALCAFLISFFRG
.. ..*.*.......
MM SWSSICTFFLNMLQATSC
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA317400} in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02631> (SEQ ID Nos. 65, 75, and 85) Determination of the whole base sequence of the cDNA
insert of clone HP02631 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 42-by 5'-untranslated region, a 147-by ORF, and a 1191-by 3'-untranslated region. The ORF codes for a protein consisting of 48 amino acid residues and there existed a putative secretory signal at the N-terminus.
Figure 25 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 10 kDa or less.
Furthermore, the search of the GenHank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA156969) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02632> (SEQ ID Nos. 66, 76, and 86) Determination of the whole base sequence of the cDNA
insert of clone HP02632 obtained from cDNA library of human fibrosarcoma cell line HT-1080 revealed the structure consisting of a 50-by 5'-untranslated region, a 1116-by ORF, and a 337-by 3'-untranslated region. The ORF codes for a protein consisting of 371 amino acid residues and there existed eight putative transmembrane domains. Figure 26 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein CELC2H12 (GenBank Accession No. U23169).
Table 18 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C.
elegans hypothetical protein CELC2H12 (CE). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 51.4% in the entire region.
Table 18 HP MAWTKYQLFLAGLMLVTGSINTLSAKWADNFMAEGCGGSKEHSFQHPFLQAVGMFLGEFS
...... .*.****,** " *****,..*. . .*,******, **,***
CE MVAFAVIISVMMWTGSLNTICAKWADSIKAD------GVPFNHPFLQATCMFFGEFL
HP CLAAFYL---------LRCRAAGQSDS-------SVDPQQPFNPLLFLPPALCDMTGTSL
**..*.* * ...*.*.* . . ,****,**,******, ***, CE CLWFFLIFGYKRYVWNRANVQGESGSVTEITSEEKPTLPPFNPFLFFPPALCDILGTSI
HP MYVALNMTSASSFQMLRGAVIIFTGLFSVAFLGRRLVLSQWLGILATIAGLVWGLADLL
** " **~*~*****************,** " *. .. .*.*.* .. ***,** " *.
CE MYIGLNLTTASSFQMLRGAVIIFTGLLSVGMLNAQIKPFKWFGMLFVMLGLVIVGVTDIY
HP SKHDSQHKLSEVITGDLLIIMAQIIVAIQMVLEEKFVYKHNVHPLRAVGTEGLFGFVILS
..*. .. ...***,***,*********** *,* " *..*..* *** *****,*,**
CE YDDDPLDDKNAIITGNLLIVMAQIIVAIQMVYEQKYLTKYDVPALFAVGLEGLFGMVTLS
HP LLLVPMYYIpAG-SFSGNPRGTLEDALDAFCQVGQQPLIAVALLGNISSIAFFNFAGISV
.*..*.***,. .**.** * *** " *. .....* **,** *~~ *********,**
CE ILMIPFYYIHVPRTFSTNPEGRLEDVFYAWKEITEEPTIALALSGTWSIAFFNFAGVSV
HP TKELSATTRMVLDSLRTWIWALSLALGWEAFHALQILGFLILLIGTALYNGLHRPLLGR
'**************,**,*** " *..* * * *,*, ** ,* " ** ,**,.
CE TKELSATTRMVLDSVRTLVIWWSIPLFHEKFIAIQLSGFAMLILGTLIYNDILIGPWFR
HP LSRGRPLAEESEQERLLGGTRTPINDAS
CE RNILPNLSSHANCARCWLCICGGDSELIEYEQEDQEHLMEA

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. N50907) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10488> (SEQ ID Nos. 67, 77, and 87) Determination of the whole base sequence of the cDNA
insert of clone HP10488 obtained from cDNA library of human liver revealed the structure consisting of a 39-by 5~-untranslated region, a 273-by ORF, and a 421-by 3~-untranslated region. The ORF codes for a protein consisting of 90 amino acid residues and there existed one putative transmembrane domain at the N-terminus. Figure 27 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 10 kDa that was almost identical with the molecular weight of 10,151 predicted from the ORF. When expressed in COS7 cells, an expression product of about 6 kDa was observed in the membrane fraction.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. H73534) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10538> (SEQ ID Nos. 68, 78, and 88) Determination of the whole base sequence of the cDNA
insert of clone HP10538 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 357-by 5'-untranslated region, a 1500-by ORF, 5 and a 1911-by 3'-untranslated region. The ORF codes for a protein consisting of 499 amino acid residues and there existed at least four putative transmembrane domains. Figure 28 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present 10 protein. In vitro translation resulted in formation of a translation product of high molecular weight.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the mouse pore-forming K+ channel 15 subunit (GenBank Accession No. AF056492). Table 19 shows the comparison between amino acid sequences of the human protein of the present invention ( HP ) and the mouse pore-forming K' channel subunit (MM). Therein, the marks of -, *, and represent a gap, an amino acid residue identical with that 20 of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 32.4% in the N-terminal region of 241 amino acid residues.

WO 00!05367 PCT/JP99/03929 Table 19 HP MVDRGPLLTSAIIFYLAIGAAIFEVLEEPHWKEAKKNYYTQKLHLLKEFPCLGQEGLDK
* . ...**. ** ,*" **,** .,*,*. . ..*.. **..*..*..
MM MRSTTLLALLALVLLYLVSGALVFQALEQPHEQQAQKKMDHGRDQFLRDHPCVSQKSLED
HP ILEWSDAAGQG-----VAITGNQTFNNWNWPNAMIFAATVITTIGYGNVAPKTPAGRLF
..... .* * * ..... ..** .*..*..*.********,. .* *****
MM FIKLLVEALGGGANPETSWTNSSNHSSAWNLGSAFFFSGTIITTIGYGNIVLHTDAGRLF
HP CVFYGLFGVPLCLTWISALGKFFGGRAKR----LGQFLTKRGVSLRKAQITCTVIFIVWG
*,**.* *.** ....*. .*.. .* ..... *. *. .. ..*.*..
MM CIFYALVGIPLFGMLLAGVGDRLGSSLRRGIGHIEAIFLKWHVPPGLVRSLSAVLFLLIG
HP VLVHLVIPPFVFMVTEGWNYIEGLYYSFITISTIGFGDFVAGVNPSANYHALYRYFVELW
*. ...*.*** *,*, ,*..*. ..*..*.****,*.* , ... . *. .* .*
MM CLLFVLTPTFVFSYMESWSKLEAIYFVIVTLTTVGFGDYVPG-DGTGQNSPAYQPLVWFW
HP IYLGLAWLSLFVNWKVSMFVEVHKAIKKRRRRRKESFESSPHSRKALQVKGSTASKDVNI
* ,***,..
MM ILFGLAYFASVLTTIGNWLRAVSRRTRAEMGGLTAQAASWTGTVTARVTQRTGPSAPPPE
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. 825184) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10542> (SEQ ID Nos. 69, 79, and 89) Determination of the whole base sequence of the cDNA
insert of clone HP10542 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 23-by 5'-untranslated region, a 321-by ORF, and a 426-by 3' untranslated region. The ORF codes for a protein consisting of 106 amino acid residues and there existed one putative transmembrane domain. Figure 29 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 12 kDa that was almost identical with the molecular weight of 11,724 predicted from the ORF. When expressed in COS7 cells, an expression product of about 13 kDa was observed in the membrane fraction.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA029683) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10571> (SEQ ID Nos. 70, 80, and 90) Determination of the whole base sequence of the cDNA
insert of clone HP10571 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 95-by 5'-untranslated region, a 459-by ORF, and a 675-by 3'-untranslated region. The ORF codes for a protein consisting of 152 amino acid residues and there existed one putative transmembrane domain. Figure 30 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 20 kDa that was larger than the molecular weight of 17,062 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 23 kDa which is considered to have a sugar chain being attached after secretion. In addition, there exists in the amino acid sequence of this protein one site at which N-glycosylation may occur (Asn-Ile-Thr at position 10).
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA105822) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP01470> (SEQ ID Nos. 91, 101, and 111) Determination of the whole base sequence of the cDNA
insert of clone HP01470 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 157-by 5'-untranslated region, a 1077-by ORF, and a 385-by 3' untranslated region. The ORF codes for a protein consisting of 358 amino acid residues and there existed one putative transmembrane domain. Figure 31 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 43 kDa that was somewhat larger than the molecular weight of 40,489 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 40 kDa from which the secretory signal is considered to have been cleaved and a product of 43.5 kDa which is considered to have been subjected to some modification. Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from glycine at position 23. When expressed in COS7 cells, an expression product of about 44 kDa was observed in the supernatant fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein 39.9 kDa (SWISS-PROT Accession No.
Q10005). Table 20 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C. elegans hypothetical protein 39.9 kDa (CE).
20 Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 58.9$ in the entire region .

Table 20 HP MAPQNLSTFCLLLLYLIGAVIAGRDFYKILGVPRSASIKDIKKAYRKLALQLHPDRNPDD
* " * **********,..*. ..********* _********

HP PQAQEKFQDLGAAYEVLSDSEKRKQYDTYGEEGL--KDGHQSSHGDIFSHFFGDFGFMFG
*,****** " *******,*** ** ,****, ..* .. * ** *****
CE EMANERFQDLSSAYEVLSDKEKRAMYDRHGEEGVAKMGGGGGGGHDPFSSFFGDF-FG-G
HP GTPRQQDRNIPRGSDIIVDLEVTLEEVYAGNFVEVVRNRPVARQAPGKRRCNCRQEMRTT
10 *. . . ..*.*.*...** *******,*,***, *,*,* ,* " *,*,****,****, CE GGGHGGEEGTPKGADVTIDLFVTLEEVYNGHFVEIKRKKAVYRQTSGTRQCNCRHEMRTE
HP QLGPGRFQMTQEWCDECFNVKLVNEERTLEVEIEPGVRDGMEYPFIGEGEPHVDGEPGD
*,*,***** * ***********,*,..****,* *, ,* , * ****** " *,***
CE QMGQGRFQMFQVKVCDECPNVKLVQENKVLEVEVEVGADNGHQQIFHGEGEPHIEGDPGD

*,*,* " *** ***,************ " * ****,* ***** * " ***,*,***, CE LRFKIRIQKHPRFERKGDDLYTNVTISLQDALNGFEMEIQHLDGHIVKVQRDKVTWPGAR
HP LWRKGEGLPNFDNNNIKGSLIITFDVDFPKEQLTEEAREGIKQLLKQGSVQ-KVYNGLQG
*,**,**,*,...** ** * " ****,*** " *..*... * ..*.*..*. *,****

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for 25 example, Accession No. AA282838) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
30 <HP002419> (SEQ ID Nos. 92, 102, and 112}
Determination of the whole base sequence of the cDNA
insert of clone HP02419 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 253-by 5'-untranslated region, a 681-by ORF, and a 1120-by 3'-untranslated region. The ORF codes for a protein consisting of 226 amino acid residues and there existed four putative transmembrane domains. Figure 32 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human hypothetical protein KIAA0108 (SWISS-PROT Accession No. Q15012). Table 21 shows the comparison between amino acid sequences of the human protein of the present invention (AP) and the human hypothetical protein KIAA0108 (KI). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 43.9% in the entire region.

Table 21 HP MKMVAPWTRFYSNSCCLCCHVRTGTILLGVWYLIINAWLLILLSALADPD---QY
**** " ** *********,**,**...* .. ..* ..
KI MVSMSFKRNRSDRFYSTRCCGCCHVRTGTIILGTWYMVVNLLMAILLTVEVTHFNSMPAV
HP NFSSSELGGDFEF-MDDANMCIAIAISLLMILICAMATYGAYKQRAAWIIPFFCYQIFDF
*. . .*. .. . ..* *. .*.*.**..*..* .*** . ...*.******..***
KI NIQYEVIGNYYSSERMADNACVLFAVSVLMFIISSMLVYGAISYQVGWLIPFFCYRLFDF
HP ALNMLVAITVLIYPNSIQEYIRQLPPNFPYRDDVMSVNPTCLVLIILLFISIILTFKGYL
.*. ****. *.* .*.**. ** *.***.**.......**..*.*.*......**.**
KI VLSCLVAISSLTYLPRIKEYLDQL-PDFPYKDDLLALDSSCLLFIVLVFFALFIIFKAYL
HP ISCVWNCYRYINGRNSSDVLVYVT-SNDTTVLLPPYDDATVNGAAKEPPPPYVSA
*.******.***.** ... ** . .. . .**.* . .*. ..*******.,*
KI INCVWNCYKYINNRNVPEIAVYPAFEAPPQYVLPTY-EMAVKMPEKEPPPPYLPA

Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA173214) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02631> (SEQ ID Nos. 93, 103, and 113) Determination of the whole base sequence of the cDNA
insert of clone HP02631 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 42-by 5 ~-untranslated region, a 588-by oRF, and a 750-by 3'-untranslated region. Although the 49th amino acid residue is encoded by a stop codon, it is likely that this codon encodes selenocysteine from the molecular weight of the translation product and the sequence comparison data with the Caenorhabditis elegans homologue. The ORF codes for a protein consisting of 195 amino acid residues and there existed a putative secretory signal at the N=terminus and one putative transmembrane domain in the intermediate region.
Figure 33 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 58 kDa. In this case, the addition of a microsome led to the formation of a product of 56. kDa from which the secretory signal is considered to have been cleaved. Since both of these products are larger than the molecular weight of 22 kDa predicted from the ORF, it is likely that the protein interacts with another protein.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein C35C5.3 (EMBL Accession No. 278417).
Table 22 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C.
elegans hypothetical protein C35C5.3 (CE). U at position 49 in the amino acid sequence of the protein of the present invention represents selenocysteine. Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 37.9% in the entire region other than the N-terminal region. Cystein was found in the sequence of the C.
elegans protein at the posistion corresponding to position 49 encoded by the stop codon (selenocysteine) of the protein of the present invention.

Table 22 HP MRLLLL
CE MRIHDELQKQDMSRFGVFIIGVLFFMSVCDVLRTEEHSHDENHVHERDDFEAEFGDETDS
HP LLVAASAMVRSEASANLGGVPSKRLKMQYATGPLLKFQIGVSUGYRRVFEEYMRVISQRY
* * " *** **,..*... ...*
CE QSFSQGTEEDHIEVREQSSFVKPTAVHHAKDLPTLRIFYCVSCGYKQAFDQFTTFAKERY
HP PDIRIEGENYLPQPIYRHIASFLSVFKLVLIGLIIVGKDPFAFFGMQAPSIWQWGQENKV
*...***,*, * .,* ** *,... *.. * ,.**, **. * * * ...**.
CE PNMPIEGANFAPVLWKAYVAQALSFVKMAVLVLVLGGINPFERFGLGYPQILQHAHGNKM
HP YACMMVFFLSNMIENQCMSTGAFEITLNDVPVWSKLESGHLPSMQQLVQILDNEMKLNVH
.**,**,*,* " *, ~.******, *.. ..***,*** " ** *,..*..*... .
CE SSCMLVFMLGNLVEQSLISTGAFEVYLGNEQIWSKIESGRVPSPQEFMQLIDAQLAVLGK
HP MDSIPHHRS
CE APVNTESFGEFQQTV
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA156969) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02695> (SEQ ID Nos. 94, 104, and 114) Determination of the whole base sequence of the cDNA
insert of clone HP02695 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 112-by 5'-untranslated region, a 1020-by ORF, and a 160-by 3' untranslated region. The ORF codes for a protein consisting of 339 amino acid residues and there existed three putative transmembrane domains. Figure 34 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-5 Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 38 kDa that was almost identical with the molecular weight of 38,274 kDa predicted from the ORF.
The search of the protein data base using the amino 10 acid sequence of the present protein revealed that the protein was similar to the rat hypertension-induced protein S-2 fragment (PIR Accession No. 539959). Table 23 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the rat hypertension 15 induced protein S-2 fragment (RN). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a 20 homology of 74.3% in the entire region.

Table 23 HP MNWELLLWLLVLCALLLLLVQLLRFLRADGDLTLLWAEWQGRRPEWELTDMWWVTGASS
HP GIGEELAYQLSKLGVSLVLSARRVHELERVKRRCLENGNLKEKDILVLPLDLTDTGSHEA
****,******************,**,**, RN VKRRSLENGNLKEKDILVLPLDLADTSSHDI
HP ATKAVLQEFGRIDILVNNGGMSQRSLCMDTSLDVYRKLIELNYLGTVSLTKCVLPHMIER
***,****************,.. ** .*..*... ***,*********** ****,**
RN ATKTVLQEFGRIDILVNNGGVAHASLVENTNMDIFKVLIEVNYLGTVSLTKCFLPHMMER
HP KQGKIVTVNSILGIISVPLSIGYCASKHALRGFFNGLRTELATYPGIIVSNICPGPVQSN
*****,..*
RN NQGKIVVMKS
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. T84331) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10031> (SEQ ID Nos. 95, 105, and 115) Determination of the whole base sequence of the cDNA
insert of clone HP10031 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 55-by 5'-untranslated region, a 1464-by ORF, and a 649-by 3'-untranslated region. The ORF codes for a protein consisting of 487 amino acid residues and there existed eleven putative transmembrane domains. Figure 35 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight. When expressed in COS7 cells, an expression product of about 55 kDa was observed in the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein CELK07H8 (GenBank Accession No.
AF047659). Table 24 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C. elegans hypothetical protein CELK07H8 (CE).
Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 44.2% in the entire region.

Table 24 HP MDGTETRQRRLDSCGKPGELGLPHPLSTGGLPVAS
CE MKGGGGIGDGKKDYQSAVHEGLTTFDQLGIALEDVGKSMDAETATPGGSLFSRVIFRFRN
HP EDGALRAPESQSVTPKPLETEPSRETAWSIGLQVTVPFMFAGLGLSWAGMLLDYFQHWPV
*...*.... . . . . *... . .** ** ****, ,**..*. **, CE ENSSLKSRTYDHSNDLVNMSVIPAESSYVLFFQVLFPFAVAGLGMVFAGLVLSIVVTWPL
HP FVEVKDLLTLVPPLVGLRGNLEMTLASRLSTAANTGQIDDPQEQHRVISSNLALIQVQAT
* *. ..*.***,*,**************** ** * " *...... *. ,****,*****
CE FEEIPEILILVPALLGLRGNLEMTLASRLSTLANLGHMDSSKQRKDWIANLALVQVQAT
HP WGLLAAVAALLLGWSREEVDVAKVELLCASSVLTAFLAAFALGVLMVCIVIGARKLGV
** " **.. * *, ..... * *. .*.****, ** *...*..*** .....** ..
CE WAFLASAFAAALAFIPSGDFDWAHGALMCASSLATACSASLVLSLLMVWIVTSRKYNI
HP NPDNIATPIAASLGDLITLSILALVSSFFYR-HKDSRYLTPLVCLSFAALTPVWVLIAKQ
****,***********,** " **, ,* * , *.....*. .* . * * * *, **,.
CE NPDNVATPIAASLGDLTTLTVLAFFGSVFLKAHNTESWLNVIVIVLFLLLLPFWIKIANE
HP SPPIVKILKFGWFPIILAMVISSFGGLILSKTVSKQQYKGMAIFTPVICGVGGNLVAIQT
. ..* ** *.*,.*,*** **.**...* ..*.......**. ******.*,*.
CE NEGTQETLYNGWTPVIMSMLISSAGGFILETAV--RRYHSLSTYGPVLNGVGGNLAAVQA
HP SRISTYLHMWSAPGVLPLQ--MKKFWPNPCSTFCTSEINSMSARVLLLLVVPGHLIF-FY
**.***.*, .. **** . ...* .. ..* ..* .*.*************, CE SRLSTYFHKAGTVGVLPNEWTVSRF-TSVQRAFFSKEWDSRSARVLLLLVVPGHICFNFL
HP I-IYLVEGQSVINSQ--TFWLYLLAGLIQVTILLYLAEVMVRLTWHQALDPDNHCIPYL
* .. ..... .... *. **..*..***.***,. ...* * *, .**** ****
CE IQLFTLTSKNNVTPHGPLFTSLYMIAAIIQWILLFVCQLLVALLWKWKIDPDNSVIPYL
HP TGLGDLLGTGLLALCFFTDWLLKSKAELGGISELASGPP
*,********** , *,*
CE TALGDLLGTGLLFIVFLTTDHFDPKELTSS
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA334000) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10530> (SEQ ID Nos. 96, 106, and 116) Determination of the whole base sequence of the cDNA
insert of clone HP10530 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 80-by 5'-untranslated region, a 1182-by ORF, and a 95-by 3'-untranslated region. The ORF codes for a protein consisting of 393 amino acid residues and there existed a putative secretory signal at the N-terminus.
Figure 36 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 46 kDa that was somewhat larger than the molecular weight of 44,912 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 45.5 kDa from which the secretory signal is considered to have been cleaved. Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from lysine at position 23. When expressed in COS7 cells, an expression product of about 43 kDa was observed in the supernatant fraction and the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Arabidopsis thaliana hypothetical protein IG002N01 (GenBank Accession No. AF007269). Table 25 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the A.
thaliana hypothetical protein IG002N01 (AT). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, 5 and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 27.0% in the N-terminal region of 355 amino acid residues.

Table 25 HP MRTLFNLLWL
AT MELTSFQKSPSSNDWSFSVSLVRNSMARRRRSSAAESLKRRNDGYESLCQWQQDSDRR
HP ALACSPVHTTLSKSDAKKAASKTLLEKSQFSDKPVQDRGLWTDLKAESVVLEHRSYCSA
........*.* **,. .... **.. ..
AT LITIFVIFFIVIPAVSIAVYKVKFADRVIQTESSIRQKGIVKTDINFQEILTEHSK--AS
HP KARDRHFAGDVLGYVTPWNSHGYDVTKVFGSKFTQISPVWLQ-LKRRGREMFEVTGLHDV
....**.. **.*,** " * .. *.... . . *.* *..**... . .**.
AT ENSTRHYDYPVLAYITP--CQGSGL--VLEGR-HNADKGWIQELRSRGNALSASKGLPRL
HP DQGWMRAVRKHAKGLHIVPRLLFEDWTYDDFRNVLDSEDEIEELSKTWQVAKNQHFDGF
. . . . * ... . * . ** .. .*.* *.* . .. .. . .. .
AT ---YNSCIFHALKRMNFFTLELVNFNTYLVIMFALNS-REMEYNGIVLESWSRWAAYGVL
HP WEVWNQLLSQKRVGLIHMLTHLAEALHQARLLALLVIPPAITPGTDQLGMFTHKEFEQL
... . * . * ... .... .... . . ... *. *......
AT HDPDLRKMALKFVKQLGDALHSTSSPRNNQQHMQFMYWGPPRSEKLQMYDFGPEDLQFL
HP APVLDGFSLMTYDYSTAHQPGPNAPLSWVRACVQ-VLDPKSK----WRSKILLGLNFYGM
*********,*,...****** " *. .. .*..... .*.***,****
AT KDSVDGFSLMTYDFSNPQNPGPNAPVKWIDLTLKLLLGSSNNIDSNIARKVLLGINFYGN
HP DYATSKDAREPWGARYIQTLKDHRPRMVWDSQASEHFFEYKKSRSGRHWFYPTLKSLQ
*...* .. ....* *.. *..*.* . **....**.* *..... .*.******.*, AT DFVISGGGGGAITGRDYLALLQKHKPTFRWDKESGEHLFMYRDDKNIKHAVFYPTLMSIL
HP VRLELARELGVGVSIWELGQGLDYFYDLL
,*** ** *,*,****,**, ..*
AT LRLENARLWGIGISIWEIGQDKGHFGKYAEASLEASSIFSGHTFDMQFRTNPRQLSRNGS
Furthermore, the search of the GenHank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA302913) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10541> (SEQ ID Nos. 97, 107, and 117) Determination of the whole base sequence of the cDNA
insert of clone HP10541 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 7-by 5'-untranslated region, a 591-by ORF, and a 113-by 3~
untranslated region. The ORF codes for a protein consisting of 196 amino acid residues and there existed a putative secretory signal at the N-terminus. Figure 37 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 23 kDa that was somewhat larger than the molecular weight of 21,553 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 20 kDa from which the secretory signal is considered to have been cleaved and a product of 23 kDa which is considered to have a sugar chain being attached. Application of the (-3,-1}
rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from glycine at position 41. In addition, there exists in the amino acid sequence of this protein one site at which N-glycosylation may occur (Asn-Leu-Thr at position 185).
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human zymogen membrane protein (GenHank Accession No. AF056492). Table 26 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human zymogen membrane protein (ZM). Therein, the marks of -, *, and . represent a 9$
gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 37.6%
in the C-terminal region of 133 amino acid residues.
Table 26 HP MWRVPGTTRRPVTGESPGMHRPEAMLLLLTLALLGGPTWAGKMYGPGGGKYFS-TTEDYD
**,**** ** ....
ZM MLTVALLALLCASASGNAIQARSSSYSGEYGSGGGKRFSHSGNQLD
HP HEITGLRVSVGLLLVKSVQVKLGDSWDVKLGALGGNTQEVTLQPGEYITKVFVAFQAFLR
**,***,*, . ..**. *. *. .*. .*. .*. *,*** ,..* .. .*.
ZM GPITALRVRVNTYYIVGLQVRYGKVWSDYVGGRNGDLEEIFLHPGESVIQVSGKYKWYLK
HP GMVMYTSKDRYFYFGKLDGQISSAYPSQEGQVLVGIYGQYQLLGIKSIGFEWN-YPLEEP
*, *,*,**, *** ,* ,* * . . ** * *, * * " ** " *, **
ZM KLVFVTDKGRYLSFGKDSGTSFNAVPLHPNTVLRFISGRSGSL-IDAIGLHWDVYPTSCS
HP TTEPPVNLTYSANSPVGR
ZM RC
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA340605) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10550> (SEQ ID Nos. 98, 108, and 118) Determination of the whole base sequence of the cDNA

insert of clone HP10550 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 241-by 5'-untranslated region, a 324-by ORF, and a 86-by 3'-untranslated region. The ORF codes for a protein consisting of 107 amino acid residues and there existed one putative transmembrane domain. Figure 38 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
Furthermore, the search of the GenHank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA348310) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10590> (SEQ ID Nos. 99, 109, and 119) Determination of the whole base sequence of the cDNA
insert of clone HP10590 obtained from cDNA library of human fibrosarcoma cell line HT-1080 revealed the structure consisting of a 77-by 5'-untranslated region, a 1053-by ORF, and a 180-by 3'-untranslated region. The ORF codes for a protein consisting of 350 amino acid residues and there existed one putative transmembrane domain. Figure 39 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 40 kDa that was almost identical with the molecular weight of 39, 285 predicted from the ORF. In this case, the addition of a microsome led to the formation of a product of 43 kDa which is considered to have a sugar chain being attached. In addition, there exist in the amino acid sequence of this protein two sites at which N-glycosylation may occur (Asn-Asn-Ser at position 144 and Asn-Leu-Thr at position 328).
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA461346) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10591> (SEQ ID Nos. 100, 1I0, and 120) Determination of the whole base sequence of the cDNA
insert of clone HP10591 obtained from cDNA library of human fibrosarcoma cell line HT-1080 revealed the structure consisting of a 232-by 5'-untranslated region, a 324-by ORF, and a 844-by 3'-untranslated region. The ORF codes for a protein consisting of 107 amino acid residues and there existed one putative transmembrane domain. Figure 40 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 12 kDa that was almost identical with the molecular weight of 11,328 predicted from the ORF.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. H09424) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP01462> (SEQ ID Nos. 121, 131, and 141) Determination of the whole base sequence of the cDNA
insert of clone HP01462 obtained from cDNA library of human fibrosarcoma cell line HT-1080 revealed the structure consisting of a 121-by 5'-untranslated region, a 1452-by ORF, and a 477-by 3'-untranslated region. The ORF codes for a protein consisting of 483 amino acid residues and there existed a putative secretory signal at the N-terminus.
Figure 41 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 72 kDa that was larger than the molecular weight of 55,838 predicted from the ORF.
Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from lysine at position 2l.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein ZR1058.4 (EMBL Accession No. Z35604).
Table 27 shows the comparison between amino acid sequences of the human protein of the present invention (HP} and the C.
elegans hypothetical protein ZK1058.4 (CE}. Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 35.6$ in the entire region.

Table 27 HP MKAFHTFCWLLVFGSVSEAKFDDFEDEEDIVEYDDNDFAEFEDVMEDSVTESPQRVIIT
CE MKIVWIFLIFFIGFAIST
HP EDDE-DETTVELEGQDENQEGDFEDADTQEGDTESEPYDDEEFEGYEDKP---------D
.*.* .* . *. * ...*. ... .... .... ...*.*. *..*
CE DDNEFAEFEDEFVGSSATQAPEIQREGEPPVLKQKDDFEEEDFGWEEEPEEAEKVREAD
HP TSSSRNKDPITIVDVPAHLQNSWESYYLEILMVTGLLAYIMNYIIGRNKNSRLAQAWFNT
.... .*....*****,...*.** .* ..* .* *. **,*** " *...**. *.
CE SDDAAPAQPLKFADVPAHFRSNWASYQVEGIWLIILIYMTNYLIGKTTNASIAQTIFDM
HP HRELLESNFTLVGDDGTNKEATSTGKLNQENEHIYNLWCSGRVCCEGMLIQLRFLKRQDL
* ** " *..******,. .. . .*..... ... **,*** .....*....****, CE CRPTLEEQFAWGDDGTTDLDKMIPSLKHDTDSTFSAWCTGRVNVNSLFLQMKMVKRQDV
HP LNVLARMMRPVSDQVQIKVTMN-DEDMDTYVFAVGTRKALVRLQKEMQDLSEFCSDKPKS
.. . *. * .*.. **.... ..* *. .****..* , *** ** " * *,. ..
CE VSRIMEMFTPSGDKMTIKASLETTNDTDPLIFAVGEKKIASKYFKEMLDLNSFASERRQA
HP GARYGLPDSLAILSEMGEVTDGMMDTKMVHFLTHYADKIESVHFSDQFSGPKIMQEEGQP
.....**.* .. .. .**. ...*. .* .*....* ** .*,****,*** .,*. .
CE AQQFNLPASWQVYADQNEWFSILDPGWSLLKKHEDAIEFIHISDQFTGPKPAEGESYT
HP LKLPDTKRTLLFTFNVPGSGNTYPKDMEALLPLMNMVIYSIDKAKKFRLNREGKQKADKN
.**...* .. ..*.. * .* *... ..*.*.* ****,*" *....* **,..
CE -RLPEAQRYMFVSLNLQYLG----QDEESVMEILNLVFYLIDKARKMKLSKDAKVKAERR
HP RARVEENFLKLTHVQRQEAAQSRREEKKRAEKERIMNEEDPEKQRRLEEAALRREQKKLE
* * " *** ** ******,*****,*, *,..*.*.***,*,***, ,*,**,*
CE RKEFEDAFLKQTHQFRQEAAQARREEKTRERKQKLMDESDPERQKRLEAKELKREAKA--HP KKQMKMKQIRVKAM
* **** ***
CE -KSPKMKQLKVK
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA307793) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02485> (SEQ ID Nos. 122, 132, and 142) Determination of the whole base sequence of the cDNA
insert of clone HP02485 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 69-by 5'-untranslated region, a 1005-by ORF, and a 1672-by 3~-untranslated region. The ORF codes for a protein consisting of 334 amino acid residues and there existed one putative transmembrane domain. Figure 42 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 36 kDa that was almost identical with the molecular weight of 38,1?1 predicted from the ORF. When expressed in COS7 cells, an expression product of about 23 kDa was observed in the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein WOlAll.2 (GenBank Accession No. U64852).
Table 28 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C.
elegans hypothetical protein WOlAll.2 (CE). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 45.5% in the entire region.

Table 28 HP MVEFAPLFMPWERRLQTLAVLQFVFSFLALAEICT-V
,*** " **,***,****, *,* " *. .
CE MRLRLSSISGKAKLPDKEICSSVSRILAPLLVPWKRRLETLAVMGFIFMWVILPIMDLWV
HP GFIALLFTRFWLLTVLYAAWWYLDRDKPRQGGRHIQAIRCWTIWKYMKDYFPISLVKTAE
* ,*, **,*,*, ***,*,* * *,*,...*. . * , ***, ,*** " *,***, CE PFHVLFNTRWWFLVPLYAVWFYYDFDTPKRASRRWNWARRHVAWKYFASYFPLRLIKTAD
HP LDPSRNYIAGFHPHGVLAVGAFANLCTESTGFSSIFPGIRPHLMMLTLWFRAPFFRDYIM
* " **** * ****,..**.*....*..***" **** " *,* *, * ** *,. .
CE LPADRNYIIGSHPHGMFSVGGFTAMSTNATGFEDKFPGIKSHIMTLNGQFYFPFRREFGI
HP SAGLVTSEKESAAHILNRKGGGNLLGIIVGGAQEALDARPGSFTLLLRNRKGFVRLALTH
* .. .*** ...*.. * *. .*..*** ***.*.*.. ** * **.** . **.
CE MLGGIEVSKESLEYTLTKCGKGRACAIVIGGASEALEAHPNKNTLTLINRRGFCKYALKF
HP GAPLVPIFSFGENDLFDQIPNSSGSWLRYIQNRLQKIMGISLPLFHGRGVF-QYSFGLIP
** ***,..****** " * * " **,** ,*,......*.. **..**..* ** ,**,*
CE GADLVPMYNFGENDLYEQYENPKGSRLREVQEKIKDMFGLCPPLLRGRSLFNQYLIGLLP
HP YRRPITTWGKPIEVQKTLHPSEEEVNQLHQRYIKELCNLFEAHKLKFNIPADQHLEFC
*,*,***,*,** * ,* ,*, *,...**..* ..*.**** " * ,**,* **
CE FRKPVTTVMGRPIRVTQTDEPTVEQIDELHAKYCDALYNLFEEYKHLHSIPPDTHLIFQ
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. D25664) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP02798> (SEQ ID Nos. 123, 133, and 143) Determination of the whole base sequence of the cDNA

insert of clone HP02798 obtained from cDNA library of human fibrosarcoma cell line HT-1080 revealed the structure consisting of a 31-by 5~-untranslated region, a 804-by ORF, and a 301-by 3'-untranslated region. The ORF codes for a protein consisting of 267 amino acid residues and there existed four putative transmembrane domains. Figure 43 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 29 kDa that was almost identical with the molecular weight of 30,778 predicted from the ORF. When expressed in COS7 cells, an expression product of about 26 kDa was observed in the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human DHHC-containing cysteine rich protein (GenBank Accession No. U90653). Table 29 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human DHHC
containing cysteine-rich protein (DH). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 35.0% in the intermediate region of 100 amino acid residues. The positions of seven cysteines were conserved between the two proteins. The protein of the present invention also had the DHHC (Asp-His-His-Cys) sequence.

Table 29 HP MAPWALLSPGVLVRTGHTVLTWGI
DH MYRMNICNKPSNKTAPEKSVWTAPAQPSGPSPELQGQRSRRNGWSWPPHPLQIVAWLLYL
HP TLVLFLHDTELRQWEEQGELLLPLTFLLLVLGSLLLYLAVSLMDPGYVNVQPQP-QEELR
* *...*.. .**. **, .. ..
DH FFAVIGFGILVPLLPHHWVPAGYACMGAIFAGHLWHLTAVSIDPADDNVRDKSYAGPLP
HP.EEQTAMVPPAIPLRRCRYCLVLQPLRARHCRECRRCVRRYDHHCPWMENCVGERNHPLFV
. . ...* .*. * * . *..**..*..** .**** *..******* " **, DH IFNRSQHAHVIEDLHCNLCNVDVSARSKHCSACNKCVCGFDHHCKWLNNCVGERNYRLFL
HP VYLALQLWLLWGLYLAWSGLRFFQPWGLWLRSSGLLFATFLLLSLFSLVASLLLVSHLY
.* .*. .*
DH HSVASALLGVLLLVLGGHICLRGVLCQPHASAHQPTL
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. D79050) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10041> (SEQ ID Nos. 124, 134, and 144) Determination of the whole base sequence of the cDNA
insert of clone HP10041 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 12-by 5'-untranslated region, a 321-by ORF, and a 286-by 3'-untranslated region. The ORF codes for a protein consisting of 106 amino acid residues and there existed one putative transmembrane domain. Figure 44 depicts the hydrophobicity/hydrophilicity profile, obtained by the Ryte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 12 kDa that was almost identical with the molecular weight of 12,060 predicted from the ORF. When expressed in COS7 cells, an expression product of about 13 kDa was observed in the membrane fraction.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Caenorhabditis elegans hypothetical protein K10B2.4 (GenBank Accession No. U28730).
Table 30 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the C.
elegans hypothetical protein K10B2.4 (CE). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The both proteins shared a homology of 62.1% in the entire region.
Table 30 HP MSTNNMSDPRRPNKVLRYKP---PPSECNPALDDPTPDYMNLLGMIFSMCGLMLKLRWCA
,****,*,..**** .... .. .** *,***,***********,..***, CE MQQNGDPRRTNRIVRYKPLDSTANQQQAISEDPLPEYMNVLGMIFSMCGLMIRMKWCS
HP WVAVYCSFISFANSRSSEDTKQMMSSFMLSISAVVMSYLQNPQPMTPPW
*,*, ** *****,*,*,*,** " ******,*********** * " ***
CE WLALVCSCISFANTRTSDDAKQIVSSFMLSVSAWMSYLQNPSPIIPPWVTLLQS
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. H20098) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10246> (SEQ ID Nos. I25, 135, and 145) Determination of the whole base sequence of the cDNA
insert of clone HP10246 obtained from cDNA library of human epidermoid carcinoma cell line KB revealed the structure consisting of a 110-by 5'-untranslated region, a 675-by ORF, and a 79-by 3'-untranslated region. The ORF codes for a protein consisting of 224 amino acid residues and there existed five putative transmembrane domains. Figure 45 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 23 kDa that was somewhat smaller than the molecular weight of 25,244 predicted from the ORF. When expressed in COS7 cells, an expression product of about 21 kDa was observed in the membrane fraction.
The search 'of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the human putative seven transmembrane domain protein (GenBank Accession No. Y18007}.
Table 31 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the human putative seven transmembrane domain protein (TM).
Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that WO 00/05367 PC'T/JP99I03929 of the protein of the present invention, respectively. The both proteins shared a homology of 93.3% in the entire region.
Table 31 HP MTLFHFGNCFALAYFPYFITYKCSGLSEYNAFWKCVQAGVTYLFVQLCKMLFLATFFPTW
***********************.,***********************************
TM MTLFHFGNCFALAYFPYFITYKCTDLSEYNAFWKCVQAGVTYLFVQLCKMLFLATFFPTW
HP EGGIYDFIGEFMKASVDVADLIGLNLVMSRNAGKGEYKIMVAALGWATAELIMSRCIPLW
************************************************************
TM EGGIYDFIGEFMKASVDVADLIGLNLVMSRNAGKGEYKIMVAALGWATAELIMSRCIPLW
HP VGARGIEFDWKYIQMSIDSNISLVHYIVASAQVWMITRYDLYHTFRPAVLLLMFLSVYKA
*********************** ,******************************,****
TM VGARGIEFDWKYIQMSIDSNISLGPYIVASAQVWMITRYDLYHTFRPAVLLLMFLRVYKA
HP FVMETFVHLCSLGSWAALLARAVVTGLLALSTLALYVAWNVHS
****************,*.* .**,***,...**,*********
TM FVMETFVHLCSLGSWAVLMAGVWKGLLVIRNLAMYVAVVNVHS
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA453931) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10392> (SEQ ID Nos. I26, 136, and 146) Determination of the whole base sequence of the cDNA
insert of clone HP10392 obtained from cDNA library of human osteosarcoma cell line U-2 OS revealed the structure consisting of a 24-by 5'-untranslated region, a ?77-by ORF, and a 726-by 3'-untranslated region. The ORF codes for a protein consisting of 258 amino acid residues and there existed a putative secretory signal at the N-terminus.
Figure 46 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 34 kDa that was somewhat larger than the molecular weight of 29,623 predicted from the ORF.
Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from leucine at position 49.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. H15999) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention. In addition, partial identity with the hypothetical protein KIAA0384 (Accession No. AB002382) was observed, although the hypothetical protein had a different ORF.
<HP10489> (SEQ ID Nos. 127, 137, and 147) Determination of the whole base sequence of the cDNA
insert of clone HP10489 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 137-by 5'-untranslated region, a 333-by ORF, and a 189-by 3'-untranslated region. The ORF codes for a protein consisting of 110 amino acid residues and there existed two putative transmembrane domains. Figure 47 depicts the hydrophobicity/hydrophilicity profile, obtained by the Ryte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 19 kDa that was somewhat larger than the molecular weight of 12,010 predicted from the ORF.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA262162) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10519> (SEQ ID Nos. 128, 138, and 148) Determination of the whole base sequence of the cDNA
insert of clone HP10519 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 67-by 5'-untranslated region, a 276-by ORF, and a 367-by 3~-untranslated region. The ORF codes for a protein consisting of 91 amino acid residues and there existed one putative transmembrane domain. Figure 48 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 10 kDa that was almost identical with the molecular weight of 10,275 predicted from the ORF.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. W16639) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10531> (SEQ ID Nos. 129, 139, and 149) Determination of the whole base sequence of the cDNA
insert of clone HP10531 obtained from cDNA library of human osteosarcoma cell line Saos-2 revealed the structure consisting of a 55-by 5'-untranslated region, a 1035-by ORF, and a 1092-by 3'-untranslated region. The ORF codes for a protein consisting of 344 amino acid residues and there existed five putative transmembrane domains.' Figure 49 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight.
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. 850695) in ESTs, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention.
<HP10574> (SEQ ID Nos. 130, 140, and 150) Determination of the whole base sequence of the cDNA
insert of clone HP10574 obtained from cDNA library of human stomach cancer revealed the structure consisting of a 210-by 5'-untranslated region, a 1287-by ORF, and a 1276-by 3' untranslated region. The ORF codes for a protein consisting of 428 amino acid residues and there existed a putative secretory signal at the N-terminus and one putative transmembrane domain in the intermediate region. Figure 50 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of high molecular weight. Application of the (-3,-1) rule, a method for predicting the cleavage site of the secretory signal sequence, allows to expect that the mature protein starts from serine at position 36.
The search of the protein data base using the amino acid sequence of the present protein revealed that the protein was similar to the Drosophila melanogaster GOLIATH
protein (SWISS-PROT Accession No. Q06003). Table 32 shows the comparison between amino acid sequences of the human protein of the present invention (HP) and the D.
melanogaster GOLIATH protein (DM). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with that of the protein of the present invention, and an amino acid residue similar to that of the protein of the present invention, respectively. The intermediate region of 169 amino acids of the protein of the present invention shared a homology of 41.4% with the N-terminal region of the D. melanogaster GOLIATH protein.

Table 32 HP MGPPPGAGVSCRGGCGFSRLLAWCFLLALSPQAPGSRGAEAVWTAYLNVSWRVPHTGVNR
HP TVWELSEEGVYGQDSPLEPVAGVLVPPDGPGALNACNPHTNFTVPTVWGSTVQVSWLALI
HP QRGGGCTFADKIHLAYERGASGAVIFNFPGTRNEVIPMSHPGAVDIVAIMIGNLKGTKIL
.*.*... . * ..
DM MQLERMQIKGKTRNIAAVITYQNIGQDLS
HP QSIQRGIQVTMVIEVGKK---HGPWVNHYSIFFVSVSFFIITAATVGYFIFYSARRLRNA
....* .**. * *.. . .*. *..***.* **. .... ..*** .*,*
DM LTLDKGYNVTISIIEGRRGVRTISSLNRTSVLFVSIS-FIV-DDILCWLIFYYIQRFRYM
HP RAQSRKQRQLKADAKKAIGRLQLRTLKQGDKEIGPDGDSCAVCIELYKPNDLVRILTCNH
.*.... *.*' . .**** ... .* * ,* * , *,*,**,*** ***,* ,***,*,*
DM QARDQQSRNLCSVTKKAIMKIPTKTGKFSD-EKDLDSDCCAICIEAYRPTDTIRILPCRH
HP IFHKTCVDPWLLEHRTCPMCKCDILKALGIEVDVEDGSVSLQVPVSNEISNSASSHEEDN
***,*,****,********* *,** * *, DM EFHKNCIDPWLIEHRTCPMCKLDVLKFYGYWGDQIYQTPSPQHTAPIASIEEVPVIWA
HP RSETASSGYASVQGTDEPPLEEHVQSTNESLQLVNHEANSVAVDVIPHVDNPTFEEDETP
DM VPHGPQPLQPLQASNMSSFAPSHYFQSSRSPSSSVQQQLAPLTYQPHPQQAASERGRRNS
HP NQETAVREIKS
DM APATMPHAITASHQVTDV
Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the registration of sequences that shared a homology of 90% or more (for example, Accession No. AA155685) in ESTs, but, since they are partial sequences, it can not be judged whether or~not any of these sequences codes for the same protein as the protein of the present invention.

The present invention provides human proteins having hydrophobic domains, DNAs coding for these proteins, and expression vectors for these DNAs as well as eucaryotic cells expressing these DNAs. All of the proteins of the present invention are secreted or exist in the cell membrane, so that they are considered to be proteins controlling the proliferation and/or the differentiation of the cells.
Accordingly, the proteins of the present invention can be employed as pharmaceuticals such as carcinostatic agents which act to control the proliferation and/or the differentiation of the cells, or as antigens for preparing antibodies against these proteins. The DNAs of the present invention can be utilized as probes for the genetic diagnosis and gene sources for the gene therapy. Furthermore, the DNAs can be utilized for large-scale expression of these proteins. Cells into which these genes are introduced to express these proteins, can be utilized for detection of the corresponding receptors and ligands, screening of novel low-molecular pharmaceuticals, and so on.
The present invention also provides genes corresponding to the polynucleotide sequences disclosed herein.
"Corresponding genes" are the regions of the genome that are transcribed to produce the mRNAs from which cDNA
polynucleotide sequences are derived and may include contiguous regions of the genome necessary for the regulated expression of such genes. Corresponding genes may therefore include but are not limited to coding sequences, 5' and 3' untranslated regions, alternatively spliced exons, introns, promoters, enhancers, and silencer or suppressor elements.
The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials. An "isolated gene" is a gene that has been separated from the adjacent coding sequences, if any, present in the genome of the organism from which the gene was isolated.
Organisms that have enhanced, reduced, or modified expression of the genes) corresponding to the polynucleotide sequences disclosed herein are provided. The IO desired change in gene expression can be achieved through the use of antisense polynucleotides or ribozymes that bind and/or cleave the mRNA transcribed from the gene (Albert and Morris, 1994, Trends Pharmacol. Sci. 15(7): 250-254;
Lavarosky et al., 1997, Biochem. Mol. Med. 62(1): 11-22; and Hampel, 1998, Prog. Nucleic Acid Res. Mol. Biol. 58: 1-39;
all of which are incorporated by reference herein).
Transgenic animals that have multiple copies of the genes) corresponding to the polynucleotide sequences disclosed herein, preferably produced by transformation of cells with genetic constructs that are stably maintained within the transformed cells and their progeny, are provided.
Transgenic animals that have modified genetic control regions that increase or reduce gene expression levels, or that change temporal or spatial patterns of gene expression, are also provided (see European Patent No. 0 649 464 B1, incorporated by reference herein). In addition, organisms are provided in which the genes) corresponding to the polynucleotide sequences disclosed herein have been partially or completely inactivated, through insertion of extraneous sequences into the corresponding genes) or through deletion of all or part of the corresponding gene(s).
Partial or complete gene inactivation can be accomplished through insertion, preferably followed by imprecise excision, of transposable elements (Plasterk, 1992, Bioessays 14(9):
629-633; Zwaal et al., 1993, Proc. Natl. Acad. Sci. USA
90(16): 7431-7435; Clark et al., 1994, Proc. Natl. Acad. Sci.
USA 91(2): 719-722; all of which are incorporated by reference herein), or through homologous recombination, preferably detected by positive/negative genetic selection strategies (Mansour et al., 1988, Nature 336: 348-352; U.S.
Patent Nos. 5,464,764; 5,487,992; 5,627,059; 5,631,153;
5,614, 396; 5,616,491; and 5,679,523; all of which are incorporated by reference herein). These organisms with altered gene expression are preferably eukaryotes and more preferably are mammals. Such organisms are useful for the development of non-human models for the study of disorders involving the corresponding gene(s), and for the development of assay systems for the identification of molecules that interact with the protein products) of the corresponding gene(s). Where the protein of the present invention is membrane-bound (e. g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information.
Proteins and protein fragments of the present invention include proteins with amino acid sequence lengths that are at least 25%(more preferably at least 50%, and most preferably at least 75%) of the length of a disclosed protein and have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 95% identity) with that disclosed protein, where sequence identity is determined by comparing the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Also included in the present invention are proteins and protein fragments that contain a segment preferably comprising 8 or more (more preferably 20 or more, most preferably 30 or more) contiguous amino acids that shares at least 75%
sequence identity (more preferably, at least 85% identity;
most preferably at least 95% identity) with any such segment of any of the disclosed proteins.
Species homologs of the disclosed polynucleotides and proteins are also provided by the present invention. As used herein, a "species homologue" is a protein or polynucleotide with a different species of origin from that of a given protein or polynucleotide, but with significant sequence similarity to the given protein or polynucleotide, as determined by those of skill in the art. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species.
The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally occurring alternative forms of the isolated polynucleotide which also encode proteins which are identical, homologous, or related to that encoded by the polynucleotides.
The invention also includes polynucleotides with sequences complementary to those of the polynucleotides disclosed herein.
The present invention also includes polynucleotides WO 00/0536? PCT/JP99/03929 capable of hybridizing under reduced stringency conditions, more preferably stringent conditions, and most preferably highly stringent conditions, to polynucleotides described herein. Examples of stringency conditions are shown in the table 33 below: highly stringent conditions are those that are at least as stringent as, for example, conditions A-F;
stringent conditions are at least as stringent as, for example, conditions G-L; and reduced stringency conditions are at least as stringent as, for example, conditions M-R.

Table 33 StringencyPolynucleotideHybridHybridization TemperatureWash ConditionHybrid Lengthand Buffers Temperature and Buffers A DNA : DNA >_50 65C; lxSSC -or- 65C; 0.3xSSC
42C; lxSSC,50% formamide B DNA : DNA <50 TB*; lxSSC TB*; IxSSC

C DNA : RNA >_50 67C; lxSSC -or- 67~C; 0.3xSSC
45C; lxSSC,50% formamide D DNA : RNA <50 TD*; lxSSC To*; lxSSC

E RNA : RNA X50 70C; lxSSC -or- 70C; 0.3xSSC
50C; lxSSC,50% formamide F RNA : RNA <50 TF*; lxSSC Tr*; lxSSC

G DNA : DNA Z50 65C; 4xSSC -or- 65C; lxSSC
42C; 4xSSC,50% formamide H DNA : DNA <50 TH*; 4xSSC TH*; 4xSSC

I DNA : RNA X50 67~; 4xSSC -or- 67C; lxSSC
4590; 4xSSC,50% formamide J DNA : RNA <50 TJ*; 4xSSC Td*; 4xSSC

K RNA : RNA >_50 70~; 4xSSC -or- 6790; lxSSC
50qC; 4xSSC,50% formamide L RNA : RNA <50 TL*; 2xSSC TL*; 2xSSC

M DNA : DNA __>50 50~; 4xSSC -or- 50~C; 2xSSC
40C; 6xSSC,50% formamide N DNA : DNA <50 TH*; 6xSSC TN*; 6xSSC

O DNA : RNA >_50 55C; 4xSSC -or- 55~; 2xSSC
42~; 6xSSC,50% formamide P DNA : RNA <50 TP*; 6xSSC TP*; 6xSSC

Q RNA : RNA >_50 60C; 4xSSC -or- 60C; 2xSSC
45~; 6xSSC,50% formamide R RNA : RNA <50 TR*; 4xSSC TR*; 4xSSC

$ : The hybrid length is that anticipated for the hybridized regions) of the hybridizing polynucleotides. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is assumed to be that of the hybridizing polynucleotide. When polynucleotides of known sequencx are hybridized, the hybrid length can be determined by aligning the sequences of the polynucleotides and identifying the region or regions of optimal sequence complementarity.
f : SSPE (lxSSPE is 0.15M NaCI, lOmM NaH2P04, and 1.25mM EDTA, pH7.4) can be substituted for SSC (lxSSG is 0.15M NaCI and lSmM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes after hybridization is complete.
'"'TH - TR : The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10°C less than the melting temperature (T~ of the hybrid, where T~, is determined according to the following equations. For hybrids less than 18 base pairs in length, T~,(°C)=2(#of A + T bases) + 4(# of G + C
bases). For hybrids between 18 and 49 base pairs in length, Tm('C)=81.5 + 16.6(log,o[Na']) + 0.41 (%G+C) - (600/I~, where N is the number of bases in the hybrid, and [Na+] is the concentration of sodium ions in the hybridization buffer ([Na'] for lxSSC~.1651V1).
Additional examples of stringency conditions for polynucleotide hybridization are provided in Sambrook, J., E.F. Fritsch, and T. Maniatis, 1989, Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, chapters 9 and 11, and Current Protocols in Molecular Biology, 1995, F.M. Ausubel et al., eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, incorporated herein by reference.
Preferably, each such hybridizing polynucleotide has a length that is at least 25%(more preferably' at least 50%, and most preferably at least 75%) of the length of the polynucleotide of the present invention to which it hybridizes, and has at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 95% identity) with the polynucleotide of the present invention to which it hybridizes, where sequence identity is determined by comparing the sequences of the hybridizing polynucleotides when aligned so as to maximize overlap and identity while minimizing sequence gaps.

Sequence listing <110> Sagami Chemical Research Center; Protegene Inc.
<120> Human Proteins Having Hydrophobic Domains And DNAs Encoding These Proteins <130> 661102 <150> JP 10-208820 <151> 1998-07-24 <150> JP 10-224105 <151> 1998-08-07 <150> JP 10-238116 <151> 1998-08-25 <150> JP 10-254736 <151> 1998-09-09 <150> JP 10-275505 <I51> 1998-09-29 <160> 150 <170> Windows 95 (Word 98) <210> 1 <211> 125 <212> PRT
<213> Homo Sapiens <400> 1 Met Ala Lys Tyr Leu Ala Gln Ile Ile Val Met Gly Val Gln Val Val Gly Arg Ala Phe Ala Arg Ala Leu Arg Gln Glu Phe Ala Ala Ser Arg ' 20 25 30 Ala Ala Ala Asp Ala Arg Gly Arg Ala Gly His Arg Ser Ala Ala Ala Ser Asn Leu Ser Gly Leu Ser Leu Gln Glu Ala Gln Gln Ile Leu Asn Val Ser Lys Leu Ser Pro Glu Glu Val Gln Lys Asn Tyr Glu His Leu Phe Lys Val Asn Asp Lys Ser Val Gly Gly Ser Phe Tyr Leu Gln Ser 85 90 g5 Lys Val Val Arg Ala Lys Glu Arg Leu Asp Glu Glu Leu Lys Ile Gln Ala Gln Glu Asp Arg Glu Lys Gly Gln Met Pro His Thr <210> 2 <211> 131 <212> PRT
<213> Homo sapiens <400> 2 Met Ala Gly IIe Lys Ala Leu Ile Ser Leu Ser Phe Gly Gly Ala Ile Gly Leu Met Phe Leu Met Leu Gly Cys Ala Leu Pro Ile Tyr Asn Lys Tyr Trp Pro Leu Phe Val Leu Phe Phe Tyr Ile Leu Ser Pro Ile Pro Tyr Cys Ile Ala Arg Arg Leu Val Asp Asp Thr Asp Ala Met Ser Asn Ala Cys Lys Glu Leu Ala Ile Phe Leu Thr Thr Gly Ile Val Val Ser Ala Phe Gly Leu Pro Ile Val Phe Ala Arg Ala His Leu Ile Glu Trp 35 Gly Ala Cys Ala Leu Val Leu Thr Gly Asn Thr Val Ile Phe Ala Thr 3/17?

Ile Leu Gly Phe Phe Leu Val Phe Gly Ser Asn Asp Asp Phe Ser Trp Gln Gln Trp <210> 3 <211> 242 <212> PRT
<213> Homo sapiens <400> 3 Met Ala Lys His Glu Gln Ile Leu Val Leu Asp Pro Pro Thr Asp Leu Lys Phe Lys Gly Pro Phe Thr Asp Val Val Thr Thr Asn Leu Lys Leu Arg Asn Pro Ser Asp Arg Lys Val Cys Phe Lys Val Lys Thr Thr Ala Pro Arg Arg Tyr Cys Val Arg Pro Asn Ser Gly Ile Ile Asp Pro Gly Ser Thr Val Thr Val Sex Val Met Leu Gln Pro Phe Asp Tyr Asp Pro Asn Glu Lys Ser Lys His Lys Phe Met Val Gln Thr Ile Phe Ala Pro B5 90 g5 Pro Asn Thr Ser Asp Met Glu Ala Val Trp Lys Glu Ala Lys Pro Asp 100 105 lI0 Glu Leu Met Asp Ser Lys Leu Arg Cys Val Phe Glu Met Pro Asn Glu Asn Asp Lys Leu Asn Asp Met Glu Pro Ser Lys Ala Val Pro Leu Asn Ala Ser Lys Gln Asp Gly Pro Met Pro Lys Pro His Ser Val Ser Leu Asn Asp Thr Glu Thr Arg Lys Leu Met Glu Glu Cys Lys Arg Leu Gln Gly Glu Met Met Lys Leu Ser Glu Glu Asn Arg His Leu Arg Asp Glu Gly Leu Arg Leu Arg Lys Val Ala His Ser Asp Lys Pro Gly Ser Thr Ser Thr Ala Ser Phe Arg Asp Asn Val Thr Ser Pro Leu Pro Ser Leu Leu Val Val Ile Ala Ala Ile Phe Ile Gly Phe Phe Leu Gly Lys Phe Ile Leu <210> 4 <211> 264 <212> PRT
<213> Homo sapiens <400> 4 Met Phe Val Pro Cys Gly Glu Ser Ala Pro Asp Leu Ala Gly Phe Thr Leu Leu Met Pro Ala Val Ser Val Gly Asn Val Gly Gln Leu Ala Met 20 Asp Leu Ile Ile Ser Thr Leu Asn Met Sex Lys Ile Gly Tyr Phe Tyr Thr Asp Cys Leu Val Pro Met Val Gly Asn Asn Pro Tyr Ala Thr Thr Glu Gly Asn Ser Thr Glu Leu Ser Ile Asn Ala Glu Val Tyr Ser Leu Pro Ser Arg Lys Leu Val Ala Leu Gln Leu Arg Ser Ile Phe Ile Lys 85 90 g5 Tyr Lys Ser Lys Pro Phe Cys Glu Lys Leu Leu Ser Trp Val Lys Ser Ser Gly Cys Ala Arg Val Ile Val Leu Ser Ser Ser His Ser Tyr Gln Arg Asn Asp Leu Gln Leu Arg Ser Thr Pro Phe Arg Tyr Leu Leu Thr Pro Ser Met Gln Lys Ser Val Gln Asn Lys Ile Lys Ser Leu Asn Trp Glu Glu Met Glu Lys Ser Arg Cys Ile Pro Glu Ile Asp Asp Ser Glu 165 170 i~~
Phe Cys Ile Arg Ile Pro Gly Gly Gly Ile Thr Lys Thr Leu Tyr Asp Glu Ser Cys Ser Lys Glu Ile Gln Met Ala Val Leu Leu Lys Phe Val Ser Glu Gly Asp Asn Ile Pro Asp Ala Leu Gly Leu Val Glu Tyr Leu Asn Glu Trp Leu Gln Ile Leu Lys Pro Leu Ser Asp Asp Pro Thr Val Ser Ala Ser Arg Trp Lys Ile Pro Ser Ser Trp Arg Leu Leu Phe Gly Ser Gly Leu Pro Pro Ala Leu Phe <210> 5 <211> 112 <212> PRT

<213> Homo sapiens <400> 5 Met Gly Ser Arg Leu Ser Gln Pro Phe Glu Ser Tyr Ile Thr Ala Pro Pro Gly Thr Ala Ala Ala Pro Ala Lys Pro Ala Pro Pro Ale Thr Pro Gly Ala Pro Thr Ser Pro Ala Glu His Arg Leu Leu Lys Thr Cys Trp Ser Cys Arg Val Leu Ser Gly Leu Gly Leu Met Gly Ala Gly Gly Tyr 3U Val Tyr Trp Val Ala Arg Lys Pro Met Lys Met Gly Tyr Pro Pro Ser Pro Trp Thr Ile Thr Gln Met Val Ile Gly Leu Ser Ile Ala Thr Trp Gly Ile Val Val Met Ala Asp Pro Lys Gly Lys Ala Tyr Arg Val Val 35 loo l05 llo <210> 6 <211> 146 <212> PRT
<213> Homo sapiens <400> 6 Met Leu Ala Gly Ala Gly Arg Pro Gly Leu Pro Gln Gly Arg His Leu Cys Trp Leu Leu Cys Ala Phe Thr Leu Lys Leu Cys Gln Ala Glu Ala Pro Val Gln Glu Glu Lys Leu Ser Ala Ser Thr Ser Asn Leu Pro Cys Trp Leu Val Glu Glu Phe Val Val Ala Glu Glu Cys Ser Pro Cys Ser Asn Phe Arg Ala Lys Thr Thr Pro Glu Cys Gly Pro Thr Gly Tyr Val 65 70 75 8p Glu Lys Ile Thr Cys Ser Ser Ser Lys Arg Asn Glu Phe Lys Ser Cys 20 Arg Ser Ala Leu Met Glu Gln Arg Leu Phe Trp Lys Phe Glu Gly Ala Val Val Cys Val Ala Leu Ile Phe Ala Cys Leu Val Ile Ile Arg Gln Arg Gln Leu Asp Arg Lys Ala Leu Glu Lys Val Arg Lys Gln Ile Glu Ser Ile <210> 7 <211> 344 <212> PRT
<213> Homo Sapiens <400> 7 Met Asp Phe Leu Val Leu Phe Leu Phe Tyr Leu Ala Ser Val Leu Met Gly Leu Val Leu Ile Cys Val Cys Ser Lys Thr His Ser Leu Lys Gly Leu Ala Arg Gly Gly Ala Gln Ile Phe Ser Cys Ile Ile Pro Glu Cys Leu Gln Arg Ala Val His Gly Leu Leu His Tyr Leu Phe His Thr Arg Asn His Thr Phe Ile Val Leu His Leu Val Leu Gln Gly Met Vai Tyr Thr Glu Tyr Thr Trp Glu Val Phe Gly Tyr Cys Gln~Glu Leu Glu Leu Ser Leu His Tyr Leu Leu Leu Pro Tyr Leu Leu Leu Gly Val Asn Leu Phe Phe Phe Thr Leu Thr Cys Gly Thr Asn Pro Gly Ile Ile Thr Lys Ala Asn Glu Leu Leu Phe Leu His Val Tyr Glu Phe Asp Glu Val Met Phe Pro Lys Asn Val Arg Cys Ser Thr Cys Asp Leu Arg Lys Pro Als Arg Ser Lys His Cys Ser Val Cys Asn Trp Cys Val His Arg Phe Asp His His Cys Val Trp Val Asn Asn Cys Ile Gly Ala Trp Asn Ile Arg Tyr Phe Leu Ile Tyr Val Leu Thr Leu Thr Ala Ser Ala Ala Thr Val 2~ 195 200 205 Ala Ile Val Ser Thr Thr Phe Leu Val His Leu Val Val Met Ser Asp Leu Tyr Gln Glu Thr Tyr Ile Asp Asp Leu Gly His Leu His Val Met Asp Thr Val Phe Leu Ile Gln Tyr Leu Phe Leu Thr Phe Pro Arg Ile Val Phe Met Leu Gly Phe Val Val Val Leu Ser Phe Leu Leu Gly Gly Tyr Leu Leu Phe Val Leu Tyr Leu Ala Ala Thr Asn Gln Thr Thr Asn Glu Trp Tyr Arg Gly Asp Trp Ala Trp Cys Gln Arg Cys Pro Leu Val Ala Trp Pro Pro Ser Ala Glu Pro Gln Val His Arg Asn Ile His Ser His Gly Leu Arg Ser Asn Leu Gln Glu Ile Phe Leu Pro Ala Phe Pro Cys His Glu Arg Lys Lys Gln Glu <210> 8 <211> 97 <212> PRT
<2I3> Homo sapiens <400> a Met Thr Lys Lys Lys Arg Glu Asn Leu Gly Val Ala Leu Glu Ile Asp Gly Leu Glu Glu Lys Leu Ser Gln Cys Arg Arg Asp Leu Glu Ala Val 20 Asn Ser Arg Leu His Ser Arg Glu Leu Ser Pro Glu Ala Arg Arg Ser Leu Glu Lys Glu Lys Asn Ser Leu Met Asn Lys Ala Ser Asn Tyr Glu Lys Glu Leu Lys Phe Leu Arg Gln Glu Asn Arg Lys Asn Met Leu Leu 65 70 75 g0 Ser Val Ala Ile Phe Ile Leu Leu Thr Leu Val Tyr Ala Tyr Trp Thr Met <210> 9 <211> 124 <212> PRT

<213> Homo sapiens <400> 9 Tyr Leu Leu Phe Val Leu Tyr Leu Ala Met Ala Thr Ser Ser Met Ser Lys Gly Cys Phe Val Phe Lys Pro Asn Ser Lys Lys Arg Lys Ile Ser Leu Pro Ile Glu Asp Tyr Phe Asn Lys Gly Lys Asn Glu Pro Glu Asp Ser Lys Leu Arg Phe Glu Thr Tyr Gln Leu Ile Trp Gln Gln Met Lys Ser Glu Asn Glu Arg Leu Gln Glu Glu Leu Asn Lys Asn Leu Phe Asp Asn Leu Ile Glu Phe Leu Gln Lys Ser His Ser Gly Phe Gln Lys Asn Ser Arg Asp Leu Gly Gly Gln Ile Lys Leu Arg Glu Ile Pro Thr Ala Ala Leu Val Leu Gly Ile Tyr Ala Tyr Val Cys Ser Cys Met His Leu Cys Val Phe Arg Phe <210> 10 <211> 327 <212> PRT
<213> Homo sapiens <400> 10 Met Ala Glu Leu Pro Gly Pro Phe Leu Cys Gly Ala Leu Leu Gly Phe Leu Cys Leu Ser Gly Leu Ala Val Glu Val Lys Val Pro Thr Glu Pro Leu Ser Thr Pro Leu Gly Lys Thr Ala Glu Leu Thr Cys Thr Tyr Ser 30 Thr Ser Val Gly Asp Ser Phe Ala Leu Glu Trp Ser Phe Val Gln Pro Gly Lys Pro Ile Ser Glu Ser His Pro Ile Leu Tyr Phe Thr Asn Gly His Leu Tyr Pro Thr Gly Ser Lys Ser Lys Arg Val Ser Leu Leu Gln Asn Pro Pro Thr Val Gly Val Ala Thr Leu Lys Leu Thr Asp Val His Pro Ser Asp Thr Gly Thr Tyr Leu Cys Gln Val Asn Asn Pro Pro Asp Phe Tyr Thr Asn Gly Leu Gly Leu Ile Asn Leu Thr Val Leu Val Pro Pro Ser Asn Pro Leu Cys Ser Gln Ser Gly Gln Thr Ser Val Gly Gly Ser Thr Ala Leu Arg Cys Ser Ser Ser Glu Gly Ala Pro Lys Pro Val Tyr Asn Trp Val Arg Leu Gly Thr Phe Pro Thr Pro Ser Pro Gly Ser Met Val Gln Asp Glu Val Ser Gly Gln Leu Ile Leu Thr Asn Leu Ser Leu Thr Ser Ser Gly Thr Tyr Arg Cys Val Ala Thr Asn Gln Met Gly Ser Ala Ser Cys Glu Leu Thr Leu Ser Val Thr Glu Pro Ser Gln Gly Arg Val Ala Gly Ala Leu Ile Gly Val Leu Leu Gly Val Leu Leu Leu Ser Val Alc Ala Phe Cys Leu Val Arg Phe Gln Lys Glu Arg Gly Lys Lys Pro Lys Glu Thr Tyr Gly Gly Ser Asp Leu Arg Glu Asp Ala Ile Ala Pro Gly Ile Ser Glu His Thr Cys Met Arg Ala Asp Ser Ser Lys Gly Phe Leu Glu Arg Pro Ser Ser Ala Ser Thr Val Thr Thr Thr Lys Ser Lys Leu Pro Met Val Val <210> 11 <211> 375 <212> DNA

<213> Homo sapiens <400> 11 atggccaagt acctggcccagatcattgtgatgggcgtgcaggtggtgggcagggccttt60 gcacgggcct tgcggcaggagtttgcagccagccgggccgcagctgatgcccgaggacgc120 gctggacacc ggtctgcagccgcttccaacctctccggcctcagcctccaggaggcacag180 .

cagattctca acgtgtccaagctgagccctgaggaggtccagaagaactatgaacactta240 tttaaggtga atgataaatccgtgggtggctccttctacctgcagtcaaaggtggtccgc300 gcaaaggage gcctggatgaggaactcaaaatccaggcccaggaggacagagaaaaaggg360 cagatgcccc atacg 375 <210> 12 <211> 393 <212> DNA

<213> Homo sapiens <400> 12 atggcaggca tcaaagctttgattagtttgtcctttggaggagcaatcggactgatgttt60 ttgatgcttg gatgtgcccttccaatatacaacaaetactggcccctctttgttctattt120 ttttacatcc tttcacctattccatactgcatagcaagaagattagtggatgatacagat180 gctatgagta acgcttgtaaggaacttgccatctttcttacaacgggcattgtcgtgtca240 gcttttggac tccctattgtatttgccagagcacatctgattgagtggggagcttgtgca300 cttgttctca caggaaacacagtcatctttgcaactatactaggctttttcttggtcttt360 ggaagcaatg acgacttcagctggcagcagtgg 393 <210> 13 <211> 726 <212> DNA
<213> Homo sapiens <400> 13 atggcgeagc acgagcagatcctggtcctcgatccgcccacagacctcaaattcaaaggc60 cccttcacag atgtagtcactacaaatcttaaattgcgaaatccatcggatagaaaagtg120 tgtttcaaag tgaagactacagcacctcgccggtactgtgtgaggcccaacagtggaatt180 attgacccag ggtcaactgtgactgtttcagtaetgctacagccctttgactatgatccg240 aatgaaaaga gtaaacacaagtttatggtacagacaatttttgctccaccaaacacttca300 gatatggaag ctgtgtggaaagaggcaaaacctgatgaattaatggattccaaattgaga360 tgcgtatttg aaatgcccaatgaaaatgatasattgaatgatatggaacctagcaaagct420 gttccactga atgcatctsagcaagatggacctatgccaaaaccacacagtgtttcactt480 aatgataccg aaacaaggaaactaatggaagagtgtaaaagacttcagggagaaatgatg540 aagctatcag aagasaatcggcacctgagagatgaaggtttaaggctcagaaaggtagca600 cattcggata aacctggatcaacctcaactgcatccttcagagataatgtcaccagtcct660 cttccttcac ttcttgttgtaattgcagccattttcattggattctttctagggaaattc720 atcttg 726 <210> 14 <211> 792 <212> DNA
<213> Homo sapiens <400> I4 atgttcgttc cctgcggggagtcggcccccgaccttgccggcttcaccctcctaatgcca60 gcagtatctg ttggaastgttggccagcttgcaatggatctgattatttctacactgaat120 atgtctaaga ttggttacttctataccgattgtcttgtgccaatggttggaaacaatcca180 tatgcgacca cagaaggasattcaacagaacttagcataaatgctgaagtgtattcattg240 ccttcasgaa agctggtggctctacagttaagatccatttttattaagtataaatcaaag300 ccattetgtg aaaaactgctttcctgggtgaaaagcagtggctgtgccagagtcattgtt360 ctttcgagca gtcattcatatcagcgtaatgatctgcagcttcgtagtactcccttccgg420 tacctactta caccttccatgcaaaaaagtgttcaaaataaaataaagagccttasctgg480 gaagasatgg aaasaagccggtgcattcctgaaatagatgattccgagttttgtatccgc540 attccgggag gaggtatcacaaaaacactctatgatgaaagctgttctaaagaaatccaa600 atggcagttc tgctgaaatttgtttcagaaggggacaacatcccagatgcattaggtctt660 gttgagtatc ttaatgagtggcttcagataetcaaaccacttagcgatgaccccacagta720 tctgcctcac ggtggaaaataccaagttcttggagattactctttggcagtggtcttccc780 cctgcacttt tc 792 <210> 15 <211> 336 <212> DNA
<213> Homo Sapiens WO 00/05367 PC'T/JP99/03929 <400> 15 atggggtctc ggttgtcccagccttttgagtcctatatcactgcgcctcccggtaccgcc60 gccgcgcccg ccaaacctgcgcccccagctacacccggagcgccgacctccccagcagaa120 caccgcctgt tgaagacctgctggagctgtcgcgtgctttctgggttggggctgatgggg180 gcgggcgggt acgtgtactgggtggcacggaagcccatgaagatgggataccccccgagt240 ccatggacca ttacgcagatggtcatcggcctcagcattgccacctggggtatcgttgtc300 atggcagacc ccaaagggaaggcctaccgcgttgtt 336 <210> 16 <211> 438 <212> DNA
<213> Homo Sapiens <400> 16 atgcttgcgg gtgccgggaggcctggcctcccccagggccgccacctctgctggttgctc60 tgtgctttca ccttaaagctctgccaagcagaggctcccgtgcaggaagagaagctgtca120 gcaagcacct caaatttgccatgctggctggtggaagagtttgtggtagcageagagtgc180 tctccatgct ctaatttccgggctaaaactacccctgagtgtggtcccacaggatatgta240 gagsaaatca catgcagctcatctaagagaaatgagttcaaaagctgccgctcagctttg300 atggaacasc gcttattttggaagttcgaaggggctgtcgtgtgtgtggccctgatcttc360 gcttgtcttg tcatcattcgtcagcgacaattggacagaaaggctctggaaaaggtccgg420 aagcaaatcg agtccata 438 <210> 17 <211> 1032 <212> DNA
<213> Homo Sapiens <400> 17 atggactttc tggtcctcttcttgttctacctggcttcggtgctgatgggtcttgttctt60 atctgcgtct gctcgaaaacccatagcttgaaaggcctggccaggggaggagcacagata120 ttttcctgta taattccagaatgtcttcagagagccgtgcatggattgcttcattacctt180 ttccatacga gacaccacaccttcattgtcctgcacctggtcttgcaagggatggtttat240 actgagtaca cctgggaagtatttggctactgtcaggagctggagttgtccttgcattac300 cttcttctgc cctatctgctgctaggtgtaaacctgttttttttcaccctgacttgtgga360 accaatcctg gcattateacaaaagcaaetgaattattatttcttcatgtttatgaattt420 gatgaagtga tgtttccaaagaacgtgaggtgctctacttgtgatttaaggaaaccagct480 cgatccaagc actgcagtgtgtgtaactggtgtgtgcaccgtttcgaccatcactgtgtt540 tgggtgaaca actgcatcggggcctggaacatcaggtacttcctcatctacgtcttgacc600 ttgacggcct cggctgccaccgtcgccattgtgagcaccacttttctggtccacttggtg660 gtgatgtcag atttataccaggagacttacatcgatgaccttggacacctccatgttatg720 gacacggtct ttcttattcagtacctgttcctgacttttccacggattgtcttcatgctg780 ggctttgtcg tggttctgagcttcctcctgggtggctacctgttgtttgtcctgtatctg840 gcggccacca accagactactaacgagtggtacagaggtgactgggcctggtgccagcgt900 tgtccccttg tggcctggcctccgtcagcagagccccaagtccaccggaacattcactcc960 catgggcttc ggagcaaccttcaagagatctttctacctgcctttccatgtcatgagagg1020 aagaaacaag as 1032 <210> 18 <211> 291 <212> DNA

<213> Homo sapiens <400> 18 atgactaaaa agaagcgggagaatctgggcgtcgctctagagatcgatgggctagaggag60 aagctgtccc agtgtcggagagacctggaggccgtgaactccagactccacagccgggag120 ctgagcccag aggccaggaggtccctggagaaggagaaaaacagcctaatgaacaaagcc180 tccaactacg agaaggaactgaagtttcttcggcaagagaaccggaagaacatgctgctc240 tctgtggcca tctttatcctcctgacgctcgtctatgcctactggaccatg 291 <210> 19 <211> 372 <212> DNA
<213> Homo sapiens <400> 19 atggctacgt cctcgatgtc taagggttgc tttgttttta agccaaactc caaaaagaga 60 aagatctctc tgccaataga ggactatttt aacaaaggga aaaatgagcc tgaggacagt 120 sagcttcgat tcgaaactta tcagttgata tggcagcaga tgaaatctga aaatgagcga 180 ctaca8gagg sattaaataa aaacttgttt gacaatctga ttgaatttct gcaaaastca 240 cattctggat tccagaagaa ttcaagagac ttgggcggtc aaataaaact cagagaaatt 300 ccaactgctg ctcttgttct tggtatatat gcgtatgttt gttcatgcat gcatctctgt 360 gtatttcgtt tt 372 <210> 20 <211> 981 <212> DNA
<213> Homo Sapiens <400> 20 atggccgagc tcccggggcc ctttctctgc ggggccctgc taggcttcct gtgcctgagt 60 gggctggccg tggaggtgaa ggtacccaca gagccgctga gcacgcccct ggggaagaca 120 gccgagctga cctgcaccta cagcacgtcg gtgggagaca gcttcgccct ggagtggagc 180 tttgtgcagc ctgggaaacc catctctgag tcccatccaa tcctgtactt caccaatggc 240 catctgtatc caactggttctaagtcaaagcgggtcagcctgcttcagaacceccccaca300 gtgggggtgg ccacactgaaactgactgacgtccacccctcagatactggaacetacctc360 tgccaagtca acaacccaccagatttctacaccaatgggttggggctaatcaaccttact420 gtgctggttc cccccagtaatcccttatgcagtcagagtggacaaecctctgtgggaggc480 tctactgcac tgagatgcagctcttccgagggggctcctaagccagtgtacaactgggtg540 cgtcttggaa cttttcctacaccttctcctggcagcatggttcaagatgaggtgtctggc600 cagctcattc tcaccaacctctccctgacctcctcgggcacctaccgctgtgtggccacc660 aaccagatgg gcagtgcatcctgtgagctgaccctctctgtgaccgaaccctcccaaggc720 cgagtggccg gagctctgattggggtgctcctgggcgtgctgttgctgtcagttgctgcg780 ttctgcctgg tcaggttccagaasgagagggggaagaagcccaaggagacatatgggggt840 agtgaccttc gggaggatgccatcgctcctgggatctctgagcacacttgtatgagggct900 gattctagca aggggttcctggaaagaccctcgtctgccagcaccgtgacgaccaccaag960 tccaagctcc ctatggtcgtg 981 <210> 21 <211> 510 <212> DNA
<213> Homo Sapiens <220>
<221> CDS
<222> (66)...(443) <400> 21 acgcttgatc cccggccgcg gggccaggaa gtcggagttt ggcagagcgg60 gagccccgga ctgcc atg gcc aag tac ctg gcc cag atc att gtg 110 atg ggc gtg cag gtg Met Ala Lys Tyr Leu Ala Gln Ile Ile Val Met Gly Val Gln Val gtg ggc agg gcc ttt gca cgg gcc ttg cgg cag gcc agc 158 gag ttt gca Val Gly Arg Ala Phe Ala Arg Ala Leu Arg Gln Ala Ser Glu Phe Ala cgg gcc gca get gat gcc cga gga cgc get gga gca gcc 206 cac cgg tct Arg Ala Ala Ala Asp Ala Arg Gly Arg Ala Gly Ala Ala His Arg Ser get tcc aac ctc tcc ggc ctc agc ctc cag gag att ctc 254 gca cag cag Ala Ser Asn Leu Ser Gly Leu Ser Leu Gln Glu Ile Leu Ala Gln Gln eac gtg tcc aag ctg agc cct gag gag gtc cag gaa cac 302 aag aac tat Asn Val Ser Lys Leu Ser Pro Glu Glu Val Gln Glu His Lys Asn Tyr tta ttt asg gtg sat gat aaa tcc gtg ggt ggc ctg cag 350 tcc ttc tac Leu Phe Lys Val Asn Asp Lys Ser Val Gly Gly Leu Gln Ser Phe Tyr 80 85 90 g5 tca aag gtg gtc cgc gca aag gag cgc ctg gat aaa atc 398 gag gsa ctc Ser Lys Val Val Arg Ala Lys Glu Arg Leu Asp Lys Ile Glu Glu Leu cag gcc cag gag gac aga gaa asa ggg cag atg tgactgctc450 . ccc cat acg Gln Ala GIn Glu Asp Arg Glu Lys Gly Gln Met Pro His Thr gctccccccg cccaccccgc cgcctctaat ttatagcttg 510 gtaataaatt tcttttctgc <210> 22 <211> 697 <212> DNA

<213> Homo sapiens <220>

<221> cDs <222> (104)...(499) <400> 22 acttccgggt gttgtctggc ccgctgctgc 60 cgccgtagcg cgtcttgggt ctcccggctg cgc cgccgcctcgggtcgtg gcc atggcaggcatc 115 gagccaggag cgacgtcacc MetAlaGlyIle eaa get ttgattagtttgtccttt ggaggagcaatc ggactgatgttt 163 Lys Ala LeuIleSerLeuSerPhe GlyGlyAlaIle GlyLeuMetPhe ttg atg cttggatgtgcccttcca atatacaacaaa tactggcecctc 211 Leu Met LeuGlyCysAlaLeuPro IleT AsnL T T P
r s r y y y rp ro Leu ttt gtt ctatttttttacatcctt tcacctattcca tactgcatagca 259 Phe Val LeuPhePheTyrIleLeu SerProIlePro T C Il r y ys e Ala aga aga ttagtggatgatacagat getatgagtaac gettgtaaggaa 307 Arg Arg LeuValAspAspThrAsp AlaMetSerAsn AlaCysLysGlu ctt gcc atctttcttacaacgggc attgtcgtgtca gettttggactc 355 Leu Ala IlePheLeuThrThrGly IleValValSer AlaPheGlyLeu cct att gta ttt gcc aga gca cat ctg att gag tgg gga get tgt gca 403 Pro Ile Val Phe Ala Arg Ala His Leu Ile Glu Trp Gly Ala Cys Ala ctt gtt ctc aca gga aec aca gtc atc ttt gca act ata cta ggc ttt 45I
Leu Val Leu Thr Gly Asn Thr Val Ile Phe Ala Thr Ile Leu Gly Phe ttc ttg gtc ttt gga agc aat gac gac ttc agc tgg cag cag tgg tgaa 500 Phe Leu Val Phe Gly Ser Asn Asp Asp Phe Ser Trp Gln Gln Ttp aagaaattac tgaactattg tcaaatggac ttcctgtcat ttgttggcca ttcacgcaca 560 caggagatgg ggcagttaat gctgaatggt atagcaagcc tcttgggggt attttaggtg 620 ctcccttctc acttttattg taagcatact attttcacag agacttgctg aaggattaaa 680 aggattttct cttttgg 697 <210> 23 <211> 1619 <212> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (287)...(10/5) <400> 23 gcagaggccg tcacgtgggtcgccgaggctcgcaagtgcgcgtggccgtggcggctggtg60 tggggttgag tcagttgtgggacccggagctgctgacccagcgggtggcccaccgaaccg120 gtgacacagc ggcaggcgttagggctcgggagccgcgagcctggcctcgtcctagagctc180 ggccgagccg tcgccgccgtcgtcccccgcccccagtcagcaaaccgccgccgcgggcgc240 gcccccgctc tgcgctgtctctccgatggcgtccgcctcaggggcc gcg aag 295 atg Met Ala Lys cac gag cag atc ctg gtc ctc gat ccg ccc aca gac ctc aaa ttc aaa 343 His Glu Gln Ile Leu Val Leu Asp Pro Pro Thr Asp Leu Lys Phe Lys 5 l0 15 ggc ccc ttc aca gat gta gtc act aca aat ctt aaa ttg cga aat cca 391 Gly Pro Phe Thr Asp Val Val Thr Thr Asn Leu Lys Leu Arg Asn Pro tcg gat aga asa gtg tgt ttc aaa gtg aag act aca gca cct cgc cgg 439 Ser Asp Arg Lys Val Cys Phe Lys Val Lys Thr Thr Ala Pro Arg Arg tac tgt gtg agg ccc aac agt gga att att gac cca ggg tca act gtg 487 Tyr Cys Val Arg Pro Asn Ser Gly Ile Ile Asp Pro Gly Ser Thr Val act gtt tca gta atg cta cag ccc ttt gac tat gat ccg aat gaa aag 535 Thr Val Ser Val Met Leu Gln Pro Phe Asp Tyr Asp Pro Asn Glu Lys agt aaa cac aag ttt atg gta cag aca att ttt get cca cca aac act 583 Ser Lys His Lys Phe Met Val Gln Thr Ile Phe Ala Pro Pro Asn Thr tca gat atg gaa get gtg tgg aaa gag gca aaa cct gat gaa tta atg 631 Ser Asp Met Glu Ala Val Trp Lys Glu Ala Lys Pro Asp Glu Leu Met gat tcc saa ttg aga tgc gta ttt gaa atg ccc aat gsa aat gat aaa 679 Asp Ser Lys Leu Arg Cys Val Phe Glu Met Pro Asn Glu Asn Asp Lys ttg aat gat atg gaa cct agc aaa get gtt cca ctg aat gca tct aag 727 Leu Asn Asp Met Glu Pro Ser Lys Ala Val Pro Leu Asn Ala Ser Lys caa gat gga cct atg cca aaa cca cac agt gtt tca ctt aat gat acc 775 Gln Asp Gly Pro Met Pro Lys Pro His Ser Val Ser Leu Asn Asp Thr gaa aca agg saa cta atg gaa gag tgt saa aga ctt cag gga gaa atg 823 Glu Thr Arg Lys Leu Met Glu Glu Cys Lys Arg Leu Gln Gly Glu Met atg aag cta tca gaa gaa sat cgg cac ctg aga gat gaa ggt tta agg 87I
Met Lys Leu Ser Glu Glu Asn Arg His Leu Arg Asp Glu Gly Leu Arg ctc aga aag gta gca cat tcg gat saa ect gga tca acc tca act gca 919 Leu Arg Lys Val Ala His Ser Asp Lys Pro Gly Ser Thr Ser Thr Ale tcc ttc aga gat aat gtc acc agt cct ctt cct tca ctt ett gtt gta 967 Ser Phe Arg Asp Asn Val Thr Ser Pro Leu Pro Ser Leu Leu Val Val att gca ttt cta aea ttc 1012 gcc att ttc ggg atc ttg att gga ttc Ile Ala Ala le Gly Phe Leu Lys Phe Ile Phe I Phe Gly Ile Leu tagagtgaag catgcagagtgctgtttcttttttttttttttctcttgaccagaaaaa 1070 gatttgttta cctaccatttcattggtagtatggcccacggtgaccatttttttgtgtgt1130 acagcgtcat ataggctttgcctttaatgatctcttacggttagaaaacacaataaaeac1190 aaactgttcg gctactggacaggttgtatattaccagatcatcactagcagatgtcagtt1250 gcacattgag tcctttatgaaattcataaataaagaattgttctttctttgtggttttaa1310 taagagttca agasttgttcagagtcttgtaaatgttattttaataatccctttaaattt1370 tatctgttgc tgttacctcttgasatatgatttatttagattgctaatcccactcattca1430 ggaaatgcca agaggtattccttggggaaatggtgcctcttacagtgtaaatttttcctc1490 2aii77 ctttaccttt gctaatatca tggcagaatt tttcttatcc cttgtgaggc agttgttgac 1550 tgagtttttc atccttacaa tcctgtccca tggtatttaa cataaaaaaa aataaaactg 1610 ttaacagat 1619 <210> 24 <211> 1066 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (65)...(859) <400> 24 cttcttgctg ccctcgttct tgccggggcc gcggttagtc cctgctggcc accccactgc 60 gacc atg ttc gtt ccc tgc ggg gag tcg gcc ccc gac ctt gcc ggc ttc 109 Met Phe Val Pro Cys Gly Glu Ser Ala Pro Asp Leu Ala Gly Phe acc ctc cta atg cca gca gta tct gtt gga aat gtt ggc cag ctt gca 157 Thr Leu Leu Met Pro Ala Val Ser Val Gly Asn Val Gly Gln Leu Ala atg gat ctg att att tct aca ctg aat atg tct aag att ggt tac ttc 205 Met Asp Leu Ile Ile Ser Thr Leu Asn Met Ser Lys Ile Gly Tyr Phe tat acc gat tgt ctt gtg cca atg gtt gga aac eat cca tat gcg acc 253 Tyr Thr Asp Cys Leu Val Pro Met Val Gly Asn Asn Pro Tyr Ala Thr aca gaa gga aat tca aca gaa ctt agc ata aat get gaa gtg tat tca 301 Thr Glu Gly Asn Ser Thr Glu Leu Ser Ile Asn Ala Glu Val Tyr Ser 65 ~n ttg cct tca aga aag ctg gtg get cta cag tta aga tcc att ttt att 349 Leu Pro Ser Arg Lys Leu Val Ala Leu Gln Leu Arg Ser Ile Phe Ile aag tat aaa tca aag cca ttc tgt gaa aaa ctg ctt tcc tgg gtg aaa 397 Lys Tyr Lys Ser Lys Pro Phe Cys Glu Lys Leu Leu Ser Trp Val Lys loo 105 llo 21/1?7 agc agt ggc tgt gcc aga gtc att gtt ctt tcg agc agt cat tca tat 445 Ser Ser Gly Cys Ala Arg Val Ile Val Leu Ser Ser Ser His Ser Tyr cag cgt aat gat ctg cag ctt cgt agt act ccc ttc cgg tac cta ctt 493 Gln Arg Asn Asp Leu Gln Leu Arg Ser Thr Pro Phe Arg Tyr Leu Leu aca cct tcc atg caa aaa agt gtt caa aat aaa ata aag agc ctt aac 541 Thr Pro Ser Met Gln Lys Ser Val Gln Asn Lys Ile Lys Ser Leu Asn tgg gaa gaa atg gaa aaa agc cgg tgc att cct gaa ata gat gat tcc 589 Trp Glu Glu Met Glu Lys Ser Arg Cys Ile Pro Glu Ile Asp Asp Ser gag ttt tgt atc cgc att ccg gga gga ggt atc aca aaa aca ctc tat 637 Glu Phe Cys Ile Arg Ile Pro Gly Gly Gly Ile Thr Lys Thr Leu Tyr gat gaa agc tgt tct aaa gaa atc caa atg gca gtt ctg ctg aaa ttt 685 Asp Glu Ser Cys Ser Lys Glu Ile Gln Met Ala Val Leu Leu Lys Phe gtt tca gaa ggg gac aac atc cca gat gca tta ggt ctt gtt gag tat 733 Val Ser Glu Gly Asp Asn Ile Pro Asp Ala Leu Gly Leu Val Glu Tyr ctt aat gag tgg ctt cag ata ctc aaa cca ctt agc gat gac ccc aca 781 Leu Asn Glu Trp Leu Gln Ile Leu Lys Pro Leu Ser Asp Asp Pro Thr gta tct gcc tca cgg tgg aaa ata cca agt tct tgg aga tta-ctc ttt 829 Val Ser Ala Ser Arg Trp Lys Ile Pro Ser Ser Trp Arg Leu Leu Phe ggc agt ggt ctt ccc cct gca ctt ttc tgatctaatt tctgttttat acct 880 Gly Ser Gly Leu Pro Pro Ala Leu Phe tatacccaaa acacttacta ccaacacagc tgttaascat tctatacaaa aaaattgtat 940 gatctggtat taggaaatta ctttcacagt aaatatcaaa gaaaaaagat taagggtctc 1000 tttgccatgc ttttcatcat atgcaccaaa tgtaaatttt gtacaataaa attttatttc 1060 ctaagt 1066 22n~7 <210> 25 <211> 618 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (54)...(392) <400> 25 gtttacgcca gtttgaacca aagacgccca aggttgaggc cgagttccag56 agc atg Met ggg tct cgg ttg tcc cag cct ttt gag tcc tat atc act 104 gcg cct ccc Gly Ser Arg Leu 5er Gln Pro Phe Glu Ser Tyr Ile Thr Ala Pro Pro 5 to 15 ggt acc gcc gcc gcg ccc gcc aaa cct gcg cec cca get 152 aca ccc gga Gly Thr Ala Ala Ala Pro Ala Lys Pro Ala Pro Pro Ala Thr Pro Gly gcg ccg acc tcc cca gca gaa cac cgc ctg ttg aag acc 200 tgc tgg agc 20 Ala Pro Thr Ser Pro Ala Glu His Arg Leu Leu Lys Thr Cys Trp Ser tgt cgc gtg ctt tct ggg ttg ggg ctg atg ggg gcg ggc 248 ggg tac gtg Cys Arg Val Leu Ser Gly Leu Gly Leu Met Gly Ala Gly Gly Tyr Val tac tgg gtg gca cgg aag ccc atg aag atg gga tac ccc 296 ccg agt cca Tyr Trp Val Ala Arg Lys Pro Met Lys Met Gly Tyr Pro Pro Ser Pro tgg acc att acg cag atg gtc atc ggc ctc agc att gcc 344 acc tgg ggt Trp Thr Ile Thr Gln Met Val Ile Gly Leu Ser Ile Ala Thr Trp Gly atc gtt gtc atg gca gac ccc aaa ggg aag gcc tac cgc 390 gtt gtt t Ile Val Val Met Ala Asp Pro Lys Gly Lys Ala Tyr Arg Val Val gaeagtacca ccagtgaatc tgtcttctgt ctctgtccct ttccccgtga450 cacacacagc aggcatggaa tttaatgggt gttctggaca gacacttgta catggacaga510 catcactact gtggatacta caagactgag aagaaaatcg tatgttgtca ttctctggct atggagtgtt 570 tgtggccttc acagatttca caggaaccaa taaatccctc agagaagt 618 <210> 26 <211> 1021 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (413)...(853) <400> 26 aagactataa gccccagcgg gcgacgaccg aacgcccccg ggaacaccgg gccccgagct 60 cggtcccgcg cccgaggatc ctccacgggg ctagatggct gcgtcggggg cgggagcgga 120 ggtgagcggg cgctagggccgcgagcccccgccggccettcctccagcgccctgcggacc180 ccgcagaagg cgctcgcctccctagcccgcaaaaacatatcgatttttctcgctgtggca240 acggggacgt cctgatagatcctctgctccaataggcaactccggccttccctgccctga300 cctggaacct ctgggagggctgcagagtaagtgccgcctctgcgctccgacggaggcacg360 aggcctgtgg agtaggtccctctgttccgacaggtgcgacacttggcgctcc atg 418 ctt Met Leu gcg ggt gcc ggg agg cct ggc ctc ccc cag ggc cgc cac ctc tgc tgg 466 Ala Gly Ala Gly Arg Pro Gly Leu Pro Gln Gly Arg His Leu Cys Trp ttg ete tgt get tte ace tta aag cte tgc caa gca gag get ece gtg 514 Leu Leu Cys Ala Phe Thr Leu Lys Leu Cys Gln Ala Glu Ala Pro Val cag gaa gag aag ctg tca gca agc acc tca aat ttg cca tgc tgg ctg 562 Gln Glu Glu Lys Leu Ser Ala Ser Thr Ser Asn Leu Pro Cys Trp Leu 35 40 45 5n gtg gaa gag ttt gtg gta gca gaa gag tgc tct cca tgc tct aat ttc 610 Val Glu Glu Phe Val Val Ala Glu Glu Cys Ser Pro Cys Ser Asn Phe cgg get aaa act acc cct gag tgt ggt ccc aca gga tat gta gag eaa 658 Arg Ala Lys Thr Thr Pro Glu Cys Gly Pro Thr Gly Tyr Val Glu Lys atc aca tgc agc tca tct aag aga aat gag ttc aaa agc tgc cgc tca 706 Ile Thr Cys Ser Ser Ser Lys Arg Asn Giu Phe Lys Ser Cys Arg Ser get ttg atg gaa csa cgc tta ttt tgg aag ttc gaa ggg get gtc gtg 754 Ala Leu Met Glu Gln Arg Leu Phe Trp Lys Phe Glu Gly Ala Val Val tgt gtg gcc ctg atc ttc get tgt ctt gtc atc att cgt cag cga cea 802 Cys Val Ala Leu Ile Phe Ala Cys Leu Val Ile Ile Arg Gln Arg Gln ttg gac aga aag get ctg gaa aag gtc cgg aag caa atc gag tcc ata 850 Leu Asp Arg Lys Ala Leu Glu Lys Val Arg Lys Gln Ile Glu Ser Ile tagctacatt ccacccttgt atcctgggtc ttagagaccc tatctcagac agtgaaagtg 910 asatggactg atttgcactc ttggttcttt ggagccttgt ggtggaatcc ccttttcccc 970 atcttcttct ttcagatcat taatgagcag aataaaaaga gtaaaatggt t 1021 <210> 27 <211> 1432 <2I2> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (331)...(1365) <400> 27 atcgcgcccg ggaggcgccggagcccagcggctggcgggccgccgtcccacccccacctc60 gcccgagtcc ggggcggccccggtgtcccctccgagcctgctgcactccacgtcccccta120 ccagggctcc agcccccagggaaatctccgaccaggcccgcccaggagccagatccaggc180 tcctggaaga accatgtccggcagctactggtcatgccaggcacacactgctgcccaaga240 ggagctgctg tttgaattatctgtgaatgttgggaagaggaatgccagagctgccggctg300 saaattaccc aaccaagagaaatctgcaggatg gac ctg gtc 354 ttt ctc ttc ttg Met Asp Leu Val Phe Leu Phe Leu ttc tac ctg get tcg gtg ctg atg ggt ctt gtt ctt atc tgc gtc tgc 402 Phe Tyr Leu Ala Ser Val Leu Met Gly Leu Val Leu Ile Cys Val Cys tcg aaa acc cat agc ttg aaa ggc ctg gcc agg gga gga gca cag ata 450 Ser Lys Thr His Ser Leu Lys Gly Leu Ala Arg Gly Gly Ala Gln Ile ttt tcc tgt ata att cca gaa tgt ctt cag aga gcc gtg cat gga ttg 498 Phe Ser Cys Ile Ile Pro Glu Cys Leu Gln Arg Ala Val His Gly Leu ctt cat tac ctt ttc cat acg aga nac cac acc ttc att gtc ctg cac 546 10 Leu His Tyr Leu Phe His Thr Arg Asn His Thr Phe Ile Val Leu His ctg gtc ttg caa ggg atg gtt tat act gag tac acc tgg gaa gta ttt 594 Leu Val Leu Gln Gly Met Val Tyr Thr Glu Tyr Thr Trp Glu Val Phe ggc tac tgt cag gag ctg gag ttg tcc ttg cat tac ctt ctt ctg ccc 642 Gly Tyr Cys Gln Glu Leu Glu Leu Ser Leu His Tyr Leu Leu Leu Pro tat ctg ctg cta ggt gta aac ctg ttt ttt ttc acc ctg act tgt gga 690 Tyr Leu Leu Leu Gly Val Asn Leu Phe Phe Phe Thr Leu Thr Cys Gly acc aat cct ggc att ata aca aaa gca aat gaa tta tta ttt ctt cat 738 Thr Asn Pro Gly Ile Ile Thr Lys Ala Asn Glu Leu Leu Phe Leu His gtt tat gas ttt gat gae gtg atg ttt cca aag aac gtg agg tgc tct 786 Val Tyr Glu Phe Asp Glu Val Met Phe Pro Lys Asn Val Arg Cys Ser act tgt gat tta agg asa cca get cga tcc aag cac tgc agt gtg tgt 834 Thr Cys Asp Leu Arg Lys Pro Ala Arg Ser Lys His Cys Ser Val Cys aac tgg tgt gtg cac cgt ttc gac cat cac tgt gtt tgg gtg aac aac 882 Asn Trp Cys Val His Arg Phe Asp His His Cys Val Trp Val Asn Asn tgc atc ggg gcc tgg aac atc agg tac ttc ctc atc tac gtc ttg acc 930 Cys Ile Gly Ala Trp Asn Ile Arg Tyr Phe Leu Ile Tyr Val Leu Thr ttg acg gcc tcg get gcc acc gtc gcc att gtg agc acc act ttt ctg 978 Leu Thr Ala Ser Ala Ala Thr Val Ala Ile Val Ser Thr Thr Phe Leu gtc cac ttg gtg gtg atg tca gat tta tac cag gag act tac atc gat 1026 Val His Leu Val Val Met Ser Asp Leu Tyr Gln Glu Thr Tyr Ile Aap gac ctt gga cac ctc cat gtt atg gac acg gtc ttt ctt att cag tac 1074 Asp Leu Gly His Leu His Val Met Asp Thr Val Phe Leu Ile Gln Tyr ctg ttc ctg act ttt cca cgg att gtc ttc atg ctg ggc ttt gtc gtg 1122 Leu Phe Leu Thr Phe Pro Arg Ile Val Phe Met Leu Gly Phe Val Val Val Leu Ser Phe Leu Leu Gly Gly Tyr Leu Leu Phe Val Leu Tyr Leu 265 270 275 2g0 gcg gcc acc aac cag act act aac gag tgg tac aga ggt gac tgg gcc 1218 Ala Ala Thr Asn Gln Thr Thr Asn Glu Trp Tyr Arg Gly Asp Trp Ala tgg tgc cag cgt tgt ccc ctt gtg gcc tgg cct ccg tca gca gag ccc 1266 Trp Cys Gln Arg Cys Pro Leu Val Ala Trp Pro Pro Ser Ala Glu Pro caa gtc cac cgg aac att cac tcc cat ggg ctt cgg agc sac ett caa 1314 Gln Val His Arg Asn Ile His Ser His Gly Leu Arg Ser Asn Leu Gln gag atc ttt cta cct gcc ttt cca tgt cat gag agg aag aea caa gaa 1362 Glu Ile Phe Leu Pro Ala Phe Pro Cys His Glu Arg Lys Lys Gln Glu tgacaegtgt atgactgcct ttgagctgta gttcccgttt atttacacat gtggatcc 1420 tcgttttcca ag 1432 <210> 28 <211> 601 <212> DNA
<213> Homo sapiens <220>

<221> CDS
<222> (62)...(355) <400>

atgcgcacat agcgacttgg tgggggatcc cggcaagtaa60 tgggcgcgtc cagtgatgac c aa 109 atg aag act eag a cgg gag aat ctg ggc gtc get cta gag atc gat Met lu Ile Thr Asp Lys Lys Lys Arg Glu Asn Leu Gly Val Ala Leu G

ggg cta gag aag ctg cag tgt cgg gacctg gcc gtg 157 gag tcc aga gag Gly Leu Glu Lys Leu Gln Cys Arg AspLeu Ala Val Glu Ser Arg Glu aac tcc ctc cac agc gag ctg agc gaggcc agg tcc 205 aga cgg cca agg Asn Ser Leu His Ser Glu Leu Ser GluAla Arg Ser Arg Arg Pro Arg ctg gag gag eaa sac cta atg aac gcctcc tac gag 253 aag agc aaa aac Leu Glu Glu Lys Asn Leu Met Asn AlaSer Tyr Glu Lys Ser Lys Asn aag gaa aag ttt ctt caa gag aac aagaac ctg ctc 301 ctg cgg cgg atg Lys Glu Lys Phe Leu Gln Glu Asn LysAsn Leu Leu Leu Arg Arg Met tct gtg atc ttt atc ctg acg ctc tatgcc tgg acc 349 gcc ctc gtc tac Ser Val Ile Phe Ile Leu Thr Leu TyrAla Trp Thr Ala Leu Val Tyr atg tgagcctggc acttggcccct 400 acttccccac eaccagcaca ggcttcc Met tgatcaggat caagcaggca cttcaagcct caataggacc aaggtgctgg ggtgttcccc 460 tcccaaccta gtgttcaagc atggcttcct ggcggcccag gccttgcctc cctggcctgc 520 tggggggttc cgggtctcca gaaggacatg gtgctggtcc ctcccttagc ccaagggaga 580 ggcaataaag acacaaagct g 601 <210> 29 <211> 585 <212> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (78)...(452) <400>

actaacctct gccctgcagc cccgagtgca 60 cgcgagggcg tctggaatac cgcgggaaat gcagagtcag taagacc atggetacg tctnagggt 110 tcc tgc tcg ttt atg Met Ser Ser Ala Ser Lys Thr Met Gly Cys Phe gtt tttaagccaasc tccaaaaagaga aagatctctctgcca ata gag 158 Val PheLysProAsn SerLysLysArg LysIleSerLeuPro Ile Glu gac tattttsacaaa gggaaaaatgag cctgaggacagtaag ctt cga 206 Asp TyrPheAsnLys GlyLysAsnGlu ProGluAspSerLys Leu Arg ttc gaaacttatcag ttgatatggcag cagatgaaatctgaa aat gag 254 Phe GluThrTyrGln LeuIleTrpGln GlnMetLysSerGlu Asn Glu cga ctacaagaggaa ttaaataaaaac ttgtttgacaatctg att gaa 302 Arg LeuGlnGluGlu LeuAsnLysAsn LeuPheAspAsnLeu Ile Glu ttt ctgcaaaaatca cattctggattc cagaagaattcaaga gac ttg 350 Phe LeuGlnLysSer HisSerGlyPhe GlnLysAsnSerArg Asp Leu ggc ggtcaaataaaa ctcagagaaatt ccaactgetgetctt gtt ctt 398 Gly GlyGlnIleLys LeuArgGluIle ProThrAlaAlaLeu Val Leu ggt atatatgcgtat gtttgttcatgc atgcatctctgtgta ttt cgt 446 Gly IleTyrAlaTyr ValCysSerCys MetHisLeuCysVal Phe Arg ll0 115 120 ttt taaatttttt tttgatgagc 500 tttattgttg c agaatagtgg aaggacctgt Phe tattttgtct ctcttatttg tacaattaaa ccaactatag tttatattac atattttcaa 560 aaaccaataa aaattcctta tcttt 585 <210> 30 <211> 1100 <212> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (57)...(1040) <400> 30 agaccgacct tgaccgccca cctggcagga gcaggacagg acggccggac gcggcc atg 59 Met gcc gag ctcccggggccc tttctctgcggggccctg ctaggcttcctg 107 Ala Glu LeuProGlyPro PheLeuCysGlyAlaLeu LeuGlyPheLeu tgc ctg agtgggctggcc gtggaggtgaaggtaccc acagagccgctg 155 Cys Leu SerGlyLeuAla ValGluValLysValPro ThrGluProLeu agc acg cccctggggaag acagccgagctgacctgc acctacagcacg 203 Ser Thr ProLeuGlyLys ThrAlaGluLeuThrCys ThrTyrSerThr tcg gtg ggagacagcttc gccctggagtggagcttt gtgcagcctggg 251 Ser Val GlyAspSerPhe AlaLeuGluTrpSerPhe ValGlnProGly aaa ccc atctctgagtcc catccaatcctgtacttc accaatggccat 299 Lys Pro IleSerGluSer HisProIleLeuTyrPhe ThrAsnGlyHis ctg tat ccaactggttct aagtcasagcgggtcagc ctgcttcagaac 347 Leu Tyr ProThrGlySer LysSerLysArgValSer LeuLeuGlnAsn ccc ccc acagtgggggtg gccacactgaaactgact gacgtccacccc 395 Pro Pro ThrValGlyVal AlaThrLeuLysLeuThr AspValHisPro tca gat actggaacctac ctctgccaagtcaacaac ccaccagatttc 443 Ser Asp Thr Gly Thr Tyr Leu Cys Gln Val Asn Asn Pro Pro Asp Phe tac acc aat ggg ttg ggg cta atc aac ctt act gtg ctg gtt 491 ccc ccc Tyr Thr Asn Gly Leu Gly Leu Ile Asn Leu Thr Val Leu Val Pro Pro agt ast ccc tta tgc agt cag agt gga caa acc tct gtg gga 539 ggc tct Ser Asn Pro Leu Cys Ser Gln Ser Gly Gln Thr Ser Val Gly Gly Ser act gca ctg aga tgc agc tct tcc gag ggg get cct aag cca 587 gtg tac Thr Ala Leu Arg Cys Ser Ser Ser Glu Gly Ala Pro Lys Pro Val Tyr aac tgg gtg cgt ctt gga act ttt cct aca cct tct cct ggc 635 agc atg Asn Trp Val Arg Leu Gly Thr Phe Pro Thr Pro Ser Pro Gly Ser Met gtt caa gat gag gtg tct ggc cag ctc att ctc acc sac ctc 683 tcc ctg VaI Gln Asp Glu Val Ser Gly Gln Leu Ile Leu Thr Asn Leu Ser Leu acc tcc tcg ggc acc tac cgc tgt gtg gcc acc sac cag atg 731 ggc agt Thr Ser Ser Gly Thr Tyr Arg Cys Val Ala Thr Asn Gln Met Gly Ser gca tcc tgt gag ctg acc ctc tct gtg acc gsa ecc tcc cas ggc cga 779 Ala Ser Cys Glu Leu Thr Leu Ser Val Thr Glu Pro Ser Gln Gly Arg gtg gcc gga get ctg att gtg ctc ctg ggc gtg ctg ttg 827 ggg ctg tca Val Ala Gly Ala Leu Ile Val Leu Leu Gly Val Leu Leu Gly Leu Ser gtt get gcg ttc tgc ctg agg ttc cag aaa gag agg ggg 875 gtc aag eag Val Ala Ala Phe Cys Leu Arg Phe Gln Lys Glu Arg Gly Val Lys Lys ccc aag gag aca tat ggg agt gac ctt cgg gag gat gcc 923 ggt atc get Pro Lys Glu Thr Tyr Gly Ser Asp Leu Arg Glu Asp Ala Gly Ile Ala cct ggg atc tct gag cac tgt atg agg get gat tct agc 971 act aag ggq Pro Gly Ile Ser Glu His Cys Met Arg Ala Asp Ser Ser Thr Lys Gly ttc ctg gaa aga ccc tcg tct gcc agc acc gtg acg acc acc aag tcc 1019 Phe Leu Glu Arg Pro Ser Ser Ala Ser Thr Val Thr Thr Thr Lys Ser asg ctc cct atg gtc gtg tgacttctcc cgatccctga gggcggtgag ggg 1070 Lys Leu Pro Met Val Val gaatatcast aattaaagtc tgtgggtacc 1100 <210> 31 <211> 313 <212> PRT
<213> Homo sapiens <400> 31 Met Asn Gln Leu Ser Phe Leu Leu Phe Leu Ile Ala Thr Thr Arg Gly Trp Ser Thr Asp Glu Ala Asn Thr Tyr Phe Lys Glu Trp Thr Cys Ser Ser Ser Pro Ser Leu Pro Arg Ser Cys Lys Glu Ile Lys Asp Glu Cys Pro Ser Ala Phe Asp Gly Leu Tyr Phe Leu Arg Thr Glu Asn Gly Val Ile Tyr Gln Thr Phe Cys Asp Met Thr Ser Gly Gly Gly Gly Trp Thr Leu Val Ala Ser Val His Glu Asn Asp Met Arg Gly Lys Cys Thr Val Gly Asp Arg Trp Ser Ser Gln Gln Gly Ser Lys Als Asp Tyr Pro Glu Gly Asp Gly Asn Trp Ala Asn Tyr Asn Thr Phe Gly Ser Ala Glu Ala Ala Thr Ser Asp Asp Tyr Lys Asn Pro Gly Tyr Tyr Asp Ile Gln Ala Lys Asp Leu Gly Ile Trp His Val Pro Asn Lys Ser Pro Met Gln His Trp Arg Asn Ser Ser Leu Leu Arg Tyr Arg Thr Asp Thr Gly Phe Leu Gln Thr Leu Gly His Asn Leu Phe Gly Ile Tyr Gln Lys Tyr Pro Val Lys Tyr Gly Glu Gly Lys Cys Trp Thr Asp Asn Gly Pro Val Ile Pro Val Val Tyr Asp Phe Gly Asp Ala Gln Lys Thr Ala Ser Tyr Tyr Ser Pro Tyr Gly Gln Arg Glu Phe Thr Ala Gly Phe Val Gln Phe Arg Val Phe Asn Asri Glu Arg Ala Ala Asn Ala Leu Cys Als Gly Met Arg Val Thr Gly Cys Asn Thr Glu His His Cys Ile Gly Gly Gly Gly Tyr Phe Pro Glu Ala Ser Pro Gln Gln Cys Gly Asp Phe Ser Gly Phe Asp Trp Ser Gly Tyr Gly Thr His Val Gly Tyr Ser Ser Ser Arg Glu Ile Thr Glu Ala Ala Val Leu Leu Phe Tyr Arg <210>32 <211>229 <212>PRT

<213>Homo sapiens <400> 32 Met Gly Asp Lys Ile Trp Leu Pro Phe Pro Val Leu Leu Leu Ala Ala Leu Pro Pro Val Leu Leu Pro Gly Ala Ala Gly Phe Thr Pro Ser Leu Asp Ser Asp Phe Thr Phe Thr Leu Pro Ala Gly Gln Lys Glu Cys Phe Tyr Gln Pro Met Pro Leu Lys Ala Ser Leu Glu Ile Glu Tyr Gln Val 35 Leu Asp Gly Ala Gly Leu Asp Ile Asp Phe His Leu Ala Ser Pro Glu 33/17?

Gly Lys Thr Leu Val Phe Glu Gln Arg Lys Ser Asp Gly Val His Thr Val Glu Thr Glu Val Gly Asp Tyr Met Phe Cys Phe Asp Asn Thr Phe Ser Thr Ile Ser Glu Lys Val Ile Phe Phe Glu Leu Ile Leu Asp Asn Met Gly Glu Gln Ala Gln Glu Gln Glu Asp Trp Lys Lys Tyr Ile Thr 130 13s 140 Gly Thr Asp Ile Leu Asp Met Lys Leu Glu Asp Ile Leu Glu Ser Ile Asn Ser Ile Lys Ser Arg Leu Ser Lys Ser Gly His Ile Gln Ile Leu Leu Arg Ala Phe Glu Ala Arg Asp Arg Asn Ile Gln Glu Ser Asn Phe Asp Arg Val Asn Phe Trp Ser Met Val Asn Leu Val Val Met Val Val Val Ser Ala Ile Gln Val Tyr Met Leu Lys Ser Leu Phe Glu Asp Lys Arg Lys Ser Arg Thr <210> 33 <211> 467 <212> PRT
<213> Homo Sapiens <400> 33 Met Arg Pro Gln Glu Leu Pro Arg Leu Ala Phe Pro Leu Leu Leu Leu Leu Leu Leu Leu Leu Pro Pro Pro Pro Cys Pro Ala His Ser Ala Thr Arg Phe Asp Pro Thr Trp Glu Ser Leu Asp Ala Arg Gln Leu Pro Ala 35 Trp Phe Asp Gln Ala Lys Phe Gly Ile Phe Ile His Trp Gly Val Phe Ser Val Pro Ser Phe Gly Ser Glu Trp Phe Trp Trp Tyr Trp Gln Lys Glu Lys Ile Pro Lys Tyr Val Glu Phe Met Lys Asp Asn Tyr Pro Pro Ser Phe Lys Tyr Glu Asp Phe Gly Pro Leu Phe Thr Ala Lys Phe Phe Asn Ala Asn Gln Trp Ala Asp Ile Phe Gln Ala Ser Gly Ala Lys Tyr Ile Val Leu Thr Ser Lys His His Glu Gly Phe Thr Leu~Trp Gly Ser Glu Tyr Ser Trp Asn Trp Asn Ala Ile Asp Glu Gly Pro Lys Arg Asp Ile Val Lys Glu Leu Glu Val Ala Ile Arg Asn Arg Thr Asp Leu Arg 1~ 165 170 175 Phe Gly Leu Tyr Tyr Ser Leu Phe Glu Trp Phe His Pro Leu Phe Leu Glu Asp Glu Ser Ser Ser Phe His Lys Arg Gln Phe Pro VaI Ser Lys Thr Leu Pro Glu Leu Tyr Glu Leu Val Asn Asn Tyr Gln Pro Glu Val Leu Trp Ser Asp Gly Asp Gly Gly Ala Pro Asp Gln Tyr Trp Asn Ser Thr Gly Phe Leu Ala Trp Leu Tyr Asn Glu Ser Pro Val Arg Gly Thr Val Val Thr Asn Asp Arg Trp Gly Ala Gly Ser Ile Cys Lys His Gly Gly Phe Tyr Thr Cys Ser Asp Arg Tyr Asn Pro Gly His Leu Leu Pro His Lys Trp Glu Asn Cys Met Thr Ile Asp Lys Leu Ser Trp Gly Tyr Arg Arg Glu Ala Gly Ile Ser Asp Tyr Leu Thr Ile Glu Glu Leu Val Lys Gln Leu Val Glu Thr Val Ser Cys Gly Gly Asn Leu Leu Met Asn Ile Gly Pro Thr Leu Asp Gly Thr Ile Ser Val Val Phe Glu Glu Arg Leu Arg Gln Met Gly Ser Trp Leu Lys Val Asn Gly Glu Ala Ile Tyr Glu Thr His Thr Trp Arg Ser Gln Asn Asp Thr Val Thr Pro Asp Val Trp Tyr Thr ser Lys Pro Lys Glu Lys Leu Val Tyr Ala Ile Phe Leu Lys Trp Pro Thr Ser Gly Gln Leu Phe Leu Gly His Pro Lys Ala Ile 405 410 ' 415 Leu Gly Ala Thr Glu Val Lys Leu Leu Gly His Gly Gln Pro Leu Asn Trp Ile Ser Leu Glu Gln Asn Gly Ile Met Val Glu Leu Pro Gln Leu Thr Ile His Gln Met Pro Cys Lys Trp Gly Trp Ala Leu Ala Leu Thr Asn Val Ile <210> 34 <211> 99 <212> PRT
<2I3> Homo sapiens <400> 34 Met Asp Asn Val Gln Pro Lys Ile Lys His Arg Pro Phe Cys Phe Ser Val Lys Gly His Val Lys Met Leu Arg Leu Asp Ile Ile Asn Ser Leu Val Thr Thr Val Phe Met Leu Ile Val Ser Val Leu Ala Leu Ile Pro Glu Thr Thr Thr Leu Thr Val Gly Gly Gly Val Phe Ala Leu Val Thr Ala Val Cys Cys Leu Ala Asp Gly Ala Leu Ile Tyr Arg Lys Leu Leu Phe Asn Pro Ser Gly Pro Tyr Gln Gln Lys Pro Val His Glu Lys Lys Glu Val Leu <210> 35 <211> 189 <212> PRT
<213> Homo sapiens <400> 35 Met Glu Glu Gly Gly Asn Leu Gly Gly Leu Ile Lys Met Val His Leu Leu Val Leu Ser Gly Ala Trp Gly Met Gln Met Trp Val Thr Phe Val 15 Ser Gly Phe Leu Leu Phe Arg Ser Leu Pro Arg His Thr Phe Gly Leu Val Gln Ser Lys Leu Phe Pro Phe Tyr Phe His Ile Ser Met Gly Cys Ala Phe Ile Asn Leu Cys Ile Leu Ala Ser Gln His Ala Trp Ala Gln Leu Thr Phe Trp Glu Ala Ser Gln Leu Tyr Leu Leu Phe Leu Ser Leu Thr Leu Ala Thr Val Asn Ala Arg Trp Leu Glu Pro Arg Thr Thr Ala 100 105 lI0 Ala Met Trp Ala Leu Gln Thr Val Glu Lys Glu Arg Gly Leu Gly Gly 115 lzo 125 Glu Val Pro Gly Ser His Gln Gly Pro Asp Pro Tyr Arg Gln Leu Arg Glu Lys Asp Pro Lys Tyr Ser Ala Leu Arg Gln Asn Phe Phe Arg Tyr His Gly Leu Ser Ser Leu Cys Asn Leu Gly Cys Val Leu Ser Asn Gly Leu Cys Leu Ala Gly Leu Ala Leu Glu Ile Arg Ser Leu <210> 36 <211> 363 <212> PRT
<213> Homo Sapiens <400> 36 Met Val Asp Ser Leu Leu Ala Val Thr Leu Ala Gly Asn Leu Gly Leu Thr Phe Leu Arg Gly Ser Gln Thr Gln Ser His Pro Asp Leu Gly Thr Glu Gly Cys Trp Asp Gln Leu Ser Ale Pro Arg Thr Phe Thr Leu Leu Asp Pro Lys Ala Ser Leu Leu Thr Lys Ala Phe Leu Asn Gly Ala Leu Asp Gly Val Ile Leu Gly Asp Tyr Leu Ser Arg Thr Pro Glu Pro Arg Pro Ser Leu Ser His Leu Leu Ser Gln Tyr Tyr Gly Ala Gly Val Ala Arg Asp Pro Gly Phe Arg Ser Asn Phe Arg Arg Gln Asn Gly Ala Ala 100 l05 110 Leu Thr Ser Ala Ser Ile Leu Ala Gln Gln Val Trp Gly Thr Leu Val Leu Leu Gln Arg Leu Glu Pro Val His Leu Gln Leu Gln Cys Met Ser Gln Glu Gln Leu Ala Gln Val Ala Ala Asn Ale Thr Lys Glu Phe Thr Glu Ala Phe Leu Gly Cys Pro Ala Ile His Pro Arg Cys Arg Trp Gly Ala Als Pro Tyr Arg Gly Arg Pro Lys Leu Leu Gln Leu Pro Leu Gly Phe Leu Tyr Val His His Thr Tyr Val Pro Ala Pro Pro Cys Thr Asp Phe Thr Arg Cys Ala Ala Asn Met Arg Ser Met Gln Arg Tyr His Gln Asp Thr Gln Gly Trp Gly Asp Ile Gly Tyr Ser Phe Val Val Gly Ser Asp Gly Tyr Val Tyr Glu Gly Arg Gly Trp His Trp Val Gly Ala His Thr Leu Gly His Asn Ser Arg Gly Phe Gly Val Ala Ile Val Gly Asn Tyr Thr Ala Ala Leu Pro Thr Glu Ala Ala Leu Arg Thr Val Arg Asp Thr Leu Pro Ser Cys Ala val Arg Ala Gly Leu Leu Arg Pro Asp Tyr Ala Leu Leu Gly His Arg Gln Leu Val Arg Thr Asp Cys Pro Gly Asp Ala Leu Phe Asp Leu Leu Arg Thr Trp Pro His Phe Thr Ala Thr Val Lys Pro Arg Pro Ala Arg Ser Val Ser Lys Arg Ser Arg Arg Glu Pro Pro Pro Arg Thr Leu Pro Ala Thr Asp Leu Gln <210> 37 <211> 249 <212> PRT
<213> Homo Sapiens <400> 37 Met Gly Gly Pro Arg Gly Ala Gly Trp Val Ala Ala Gly Leu Leu Leu Gly Ala Gly Ala Cys Tyr Cys Ile Tyr Arg Leu Thr Arg Gly Arg Arg Arg Gly Asp Arg Glu Leu Gly Ile Arg Ser Ser Lys Ser Ala Glu Asp Leu Thr Asp Gly Ser Tyr Asp Asp Val Leu Asn Ala Glu Gln Leu Gln Lys Leu Leu Tyr Leu Leu Glu Ser Thr Glu Asp Pro Val Ile Ile Glu Arg Ala Leu Ile Thr Leu Gly Asn Asn Ala Ala Phe Ser Val Asn Gln WO 00/05367 PCf/JP99/03929 Ala Ile Ile Arg Glu Leu Gly Gly Ile Pro Ile Val Ala Asn Lys Ile Asn His Ser Asn Gln Ser Ile Lys Glu Lys Ala Leu Asn Ala Leu Asn Asn Leu Ser Val Asn Val Glu Asn Gln Ile Lys Ile Lys Val Gln Val Leu Lys Leu Leu Leu Asn Leu Ser Glu Asn Pro Ala Met Thr Glu Gly Leu Leu Arg Ala Gln Val Asp Ser Ser Phe Leu Ser Leu Tyr Asp Ser His VaI Ala Lys Glu Ile Leu Leu Arg Val Leu Thr Leu Phe Gln Asn Ile Lys Asn Cys Leu Lys Ile Glu Gly His Leu Ala Val GIn Pro Thr Phe Thr Glu Gly Ser Leu Phe Phe Leu Leu His Gly Glu Glu Cys Ala Gln Lys Ile Arg Ala Leu Val Asp His His Asp Ala Glu Val Lys Glu Lys Val Val Thr Ile Ile Pro Lys Ile <210> 38 <211> 98 <212> PRT
<213> Homo sapiens <400> 38 Met Ala Ser Leu Leu Cys Cys Gly Pro Lys Leu Ala Ala Cys Gly Ile 1 s l0 15 Val Leu Ser Ala Trp Gly Val Ile Met Leu Ile Met Leu Gly Ile Phe Phe Asn Val His Ser Ala Val Leu Ile Glu Asp Val Pro Phe Thr Glu 35 Lys Asp Phe Glu Asn Gly Pro Gln Asn Ile Tyr Asn Leu Tyr Glu Gln Val Ser Tyr Asn Cys Phe Ile Ala Ala Gly Leu Tyr Leu Leu Leu Gly Gly Phe Ser Phe Cys Gln Val Arg Leu Asn Lys Arg Lys Glu Tyr Met 85 90 g5 Val Arg <210> 39 <211> 172 <212> PRT
<213> Homo sapiens <400> 39 Met Val Gly Pro Ala Pro Arg Arg Arg Leu Arg Pro Leu Ala Ala Leu Ala Leu Val Leu Ala Leu Ala Pro Gly Leu Pro Thr Ala Arg Ala Gly Gln Thr Pro Arg Pro Ala Glu Arg Gly Pro Pro Val Arg Leu Phe Thr 20 Glu Glu Glu Leu Ala Arg Tyr Gly Gly Glu Glu Glu Asp Gln Pro Ile Tyr Leu Ala Val Lys Gly Val Val Phe Asp Val Thr Ser Gly Lys Glu Phe Tyr Gly Arg Gly Ala Pro Tyr Asn Ala Leu Thr Gly Lys Asp Ser Thr Arg Gly Val Ala Lys Met Ser Leu Asp Pro Ala Asp Leu Thr His Asp Thr Thr Gly Leu Thr Ala Lys Glu Leu Glu Ala Leu Asp Glu Val Phe Thr Lys Val Tyr Lys Ala Lys Tyr Pro Ile Val Gly Tyr Thr Ala Arg Arg Ile Leu Asn Glu Asp Gly Ser Pro Asn Leu Asp Phe Lys Pro Glu Asp Gln Pro His Phe Asp Ile Lys Asp Glu Phe lss 170 <210> 40 <211> 120 <212> PRT
<213> Homo sapiens <400> 40 Met Met Pro Ser Arg Thr Asn Leu Ala Thr Gly Ile Pro Ser Ser Lys Val Lys Tyr Ser Arg Leu Ser Ser Thr Asp Asp Gly Tyr Ile Asp Leu Gln Phe Lys Lys Thr Pro Pro Lys Ile Pro Tyr Lys Ala Ile Ala Leu Ala Thr Val Leu Phe Leu Ile Gly Ala Phe Leu Ile Ile Ile Gly Ser Leu Leu Leu Ser Gly Tyr Ile Ser Lys Gly Gly Ala Asp Arg Ala Val Pro Val Leu Ile Ile Gly Ile Leu Val Phe Leu Pro Gly Phe Tyr His 20 Leu Arg Ile Ala Tyr Tyr Ala Ser Lys Gly Tyr Arg Gly Tyr Ser Tyr Asp Asp Ile Pro Asp Phe Asp Asp <210> 41 <211> 939 <212> DNA
<213> Homo Sapiens <400> 41 atgaaccaac tcagcttcctgctgtttctcatagcgaccaccagaggatggagtacagat60 gaggctaata cttacttcaaggaatggacctgttcttcgtctccatctctgcccagaagc120 tgcaaggaaa tcaaagacgaatgtcctagtgcatttgatggcctgtattttctccgcact180 gagaatggtg ttatctaccagaccttctgtgacatgacctctgggggtggcggctggacc240 ctggtggccagcgtgcatgagaatgacatgcgtgggaagtgcacggtgggcgatcgctgg300 tccagtcagc agggcagcaaagcagactacccagagggggacggcaactgggccaactac360 aacacctttg gatctgcagaggcggccacg~agcgatgactacaagaaccctggctactac420 gacatccagg ccaaggacctgggcatctggcacgtgcccaataagtcccccatgcagcac480 tggagaaaca gctccctgctgaggtaccgcacggacactggcttcctccagacactggga540 cataatctgt ttggcatctaccagaaatatccagtgaaatatggagaaggaaegtgttgg600 actgacaacg gcccggtgatccctgtggtctatgattttggcgacgcccagaaaacagca660 tcttattact caccctatggccagcgggaattcactgcgggatttgttcagttcagggta720 tttaataacg agagagcagccaacgccttgtgtgctggaatgagggtcaccggatgtaac780 actgagcacc actgcattggtggaggaggatactttccagaggccagtccccagcagtgt840 ggagattttt ctggttttgattggagtggatatggaactcatgttggttacagcagcagc900 cgtgagataa ctgaggcagctgtgcttctattctatcgt gag <210> 42 <211> 687 <212> DNA
<213> Homo sapiens <400> 42 atgggcgaca agatctggct gcccttcccc gtgctccttc tggccgctct gcctccggtg 60 ctgctgcctg gggcggccggcttcacaccttccctcgatagcgacttcacctttaccctt120 cccgccggcc agaaggagtgcttctaccagcccatgcccctgaaggcctcgctggagatc180 gagtaccaag ttttagatggagcaggattagatattgatttccatcttgcctctccagaa240 ggcaaaacct tagtttttgaacaaagaaaatcagatggagttcacactgtagagactgaa300 gttggtgatt acatgttctgctttgacastacattcagcaccatttctgagaaggtgatt360 ttctttgaat taatcctggataatatgggagaacaggcacaagaacaagaagattggaag420 aaatatatta ctggcacagatatattggatatgaasctggaagacatcctggaatccatc480 aacagcatca agtccagactaagcaaaagtgggcacatacaaattctgcttagagcattt540 gaagctcgtg atcgaaacatacaagaaagcaactttgatagagtcaatttctggtctatg600 gttaatttag tggtcatggtggtggtgtcagccattcaagtttatatgctgaagagtctg660 tttgaagata agaggaaaagtagaact 687 <210> 43 <211> 1401 <212> DNA
<213> Homo sapiens <400> 43 atgcggccccaggagctccccaggctcgcgttcccgttgctgctgttgctgttgctgetg60 ctgccgccgccgccgtgccctgcccacagcgccacgcgcttcgaccccacctgggagtcc120 ctggacgcccgccagctgcccgcgtggtttgaccaggccaagttcggcatcttcatccac180 tggggagtgttttccgtgcccagcttcggtagcgagtggttctggtggtattggcaaeag240 gaaaagataccgaagtatgtggaatttatgaaagataattaccctcctagtttcaaatat300 gaagattttggaccactatttacagcaeaattttttaatgccaaccagtgggcagatatt360 tttcaggcctctggtgccaaatacattgtcttaacttccaascatcatgaaggctttacc420 ttgtgggggtcagaatattcgtggaactggaatgccatagatgaggggcccaagaggga~480 attgtcaaggaacttgaggtagccattaggaacagaactgacctgcgttttggactgtac540 tattccctttttgaatggtttcatccgctcttccttgaggatgaatccagttcattccat600 asgcggcaatttccagtttctaagacattgccagagctctatgagttagtgaacaactat660 cagcctgaggttctgtggtcggatggtgacggaggagcaccggatceatactggaacagc720 acaggcttcttggcctggttatataatgaaagcccagttcggggcacagtagtcaccaat780 gatcgttggggagctggtagcatctgtaagcatggtggcttctatacctgcagtgatcgt840 tataacccaggacatcttttgccacataastgggaaaactgcatgacaatagacaaactg900 tcctggggctataggagggaagctggaatctctgactatcttacaattgaageattggtg960 aagcaacttgtagagacagtttcatgtggaggaaatcttttgatgaatattgggcccaca1020 ctagatggcaccatttctgtagtttttgaggagcgactgaggcaaatggggtcctggcta1080 aaagtcaatggagaagctatttatgaaacccatacctggcgatcccagaatgacactgtc1140 accccagatgtgtggtacacatccaagcctaaagaaaaattagtctatgccatttttctt1200 aaatggcccacatcaggacagctgttccttggccatcccaaagctattctgggggcaaca1260 gaggtgaaactactgggccatggacagccacttaactggatttctttggagcasaatggc1320 attatggtagasctgccacagctaaccattcatcagatgccgtgtaaatggggctgggct1380 ctagccctga ctaatgtgat c 1401 <210> 44 <211> 297 <212> nrr.~

<213> Homo sapiens <400> 44 atggataacg tgcagccgaa aataaaacat cgccccttct gcttcagtgt gaaaggccac 60 gtgaagatgc tgcggctgga tattatcaac tcactggtaa caacagtatt catgctcatc 120 gtatctgtgt tggcactgat accagaaacc acaacattga cagttggtgg aggggtgttt 180 gcacttgtga cagcagtatg ctgtcttgcc gacggggccc ttatttaccg gaagcttctg 240 ttcaatccca gcggtcctta ccagcaaaag cctgtgcatg aaaaaaaaga agttttg 297 <210> 45 <211> 567 <212> DNA
<213> Homo sapiens <400> 45 atggaggaag gcgggaacctaggaggcctgattaagatggtccatctactggtcttgtca60 ggtgcctggg gcatgcaaatgtgggtgaccttcgtctcaggcttcctgcttttccgaagc120 cttccccgac ataccttcggactagtgcagagcaaactcttecccttctacttccacatc180 tccatgggct gtgccttcatcaacctctgcatcttggcttcacagcatgcttgggctcag240 ctcacattctgggaggccagccagctttacctgctgttcctgagccttacgctggccact300 gtcaacgccc gctggctggaaccccgcaccacagctgccatgtgggccctgcaaaccgtg360 gagaaggagc gaggcctgggtggggaggtaccaggcagccaccagggtcccgatccctac420 cgccagctgc gagagasggaccccaagtacagtgctctccgccagaatttcttccgctac480 catgggctgt cctctctttgcaatctgggctgcgtcctgagcaatgggctctgtctcgct540 ggccttgccctggaaataaggagcctc 567 <210> 46 <211> 1089 <212> DNA
<2I3> Homo sapiens <400> 46 atggtggaca gcctcctggc agtcaccctg gctggaaacc tgggcctgac cttcctccga 60 ggttcccaga cccagagcca tccagacctg ggaactgagg gctgctggga ccagctctct 120 gcccctcggacctttacgcttttggaccccaaggcatctctgttsaccaaggccttcctc180 aatggcgccc tggatggggtcatccttggagactacctgagccggactcctgagccccgg240 ccatccctca gccacttgctgagccagtactatggggctggggtggccagagacccaggg300 ttccgcagca acttccgacggcagaacggtgctgctctgacttcagcctccatcctggcc360 cagcaggtgt ggggaacccttgtccttctacagaggctggagccagtacacctccagctt420 cagtgcatgagccaagaacagctggcccaggtggctgccaatgctaccaaggaattcact480 gaggccttcc tgggatgcccggccatccacccccgctgccgctggggagcggcgccttat540 cggggccgcc cgaagctgctgcagctgccgctgggattcttgtacgtgcatcacacctac600 gtgcctgcac caccctgcacggacttcacgcgctgcgcagccaacatgcgctccatgcag660 cgctaccacc aggacacgcaaggctggggagacatcggctacagtttcgtggtgggctcg720 gacggctacg tgtacgagggacgcggctggcactgggtgggcgcccacacgctcggccac780 eactcccggg gcttcggcgtggccatagtgggcaactacaccgcggcgctgcccaccgag840 gccgctctgc gcacggtgcgcgacacgctcccgagttgtgcggtgcgcgccggcctcctg900 cggccagact acgcgctgctgggccaccgccagctggtgcgcaccgactgccccggcgac960 gcgctcttcg acctgctgcgcacctggccgcacttcaccgcgactgttaagccaagacct1020 gccaggagtg tctctaagagatccaggagggagccacccccaaggaccctgccagccaca1080 gacctccaa 1089 <210> 47 <211> 747 <212> DNA
<213> Homo sapiens <400> 47 atgggtggcc cccggggcgc gggctgggtg gcggcgggcc tgctgctcgg cgcgggcgcc 60 tgctactgca tttacaggctgacccggggtcggcggcggggcgaccgcgagctcgggata 120 cgctcttcga agtccgcagaagacttaactgatggttcatatgatgatgttctaaatgct 180 gaacaacttc agaaactcctttacctgctggagtcaacggaggatcctgtaattattgaa 240 agagctttga ttactttgggtascaatgcagccttttcagttaacceagctattattcgt 300 gaattgggtg gtattccaattgttgcaaacaaaatcaaccattccaaccagagtattaaa 360 gagaeagctt taaatgcactaaataacctgagtgtgaatgttgaaaatcasatcaagata 420 aaggtgcaag ttttgaaactgcttttgaatttgtctgaaaatccagccatgacagaagga 480 cttctccgtg cccaagtggattcatcattcctttccctttatgacagccacgtagcaaag 540 gagattcttc ttcgagtacttacgctatttcagaatataaagaactgcctcaaaatagaa 600 ggccatttag ctgtgcagcctactttcactgaaggttcattgtttttcctgttacatgga 660 gaagaatgtg cccagaaaatsagagctttagttgatcaccatgatgcagaggtgaaggaa 720 aaggttgtaa caataatacccaaeatc 747 <210> 48 <211> 294 <212> DNA

<213> Homo sapiens <400> 48 atggcgtcgc tcctgtgctg tgggccgaag ctggccgcct gcggcatcgt cctcagcgcc 60 tggggagtga tcatgttgat aatgctcgga atatttttca atgtccattc cgctgtgttg 120 attgaggacg ttcccttcac ggagaaagat tttgagaatg gcccccagaa catatacaac 180 ctttacgagc aagtcagcta caactgtttc atcgctgcag gcctttacct cctcctcgga 240 ggcttctctt tctgccaagt tcggctcaat aagcgcaagg aatacatggt gcgc 2g4 <210> 49 <211> 516 <212> DNA
<213> Homo sapiens <400> 49 atggtgggcc ccgcgccgcggcggcggctgcggccgctggcagcgctggccctggtcctg60 gcgctggccc cggggctgcccacagcccgggccgggcagacaccgcgccctgccgagcgg120 gggcccccag tgcggcttttcaccgaggaggagctggcccgctatggcggggaggaggaa180 gatcagccca tctacttggcagtgaagggagtggtgtttgatgtcacctccggaaaggag240 ttttatggac gaggagccccctacaatgccttgacggggaaggactccactagaggggta300 gccasgatgt ccttggatcctgcagacctcacccatgacactacgggtctcacggccasg360 gaactggagg ccctggatgaggtcttcaccaaagtgtacaaagccaaataccccatcgtc420 ggctacactg cccggagaattctcaatgaggatggcagccctaacctggacttcaagcct480 gaagaccagc cccattttgacatcaaggatgagttc 516 <210> 50 <211> 360 <212> DNA
<213> Homo sapiens <400> 50 atgatgccgt cccgtaccaa cctggctact ggaatcccca gtagtaaagt gaaatattca 60 aggctctcca gcacagacga tggctacatt gaccttcagt ttaagaaaac ccctcctaag 120 atcccttata aggccatcgc acttgccact gtgctgtttt tgattggcgc ctttctcatt 180 attataggct ccctcctgct gtcaggctac atcagcaaag ggggggcaga ccgggccgtt 240 ccagtgctga tcattggcat tctggtgttc ctacccggat tttaccacct gcgcatcgct 300 tactatgcat ccaaaggcta ccgtggttac tcctatgatg acattccaga ctttgatgac 360 <210> 51 <211> 1065 <212> DNA
<213> Homo Sapiens <220>
<221> CDS
<222> (2)...(943) <400> 51 a atg aac caa ctc agc ttc ctg ctg ttt ctc ata gcg acc acc aga gga 49 Met Asn Gln Leu Ser Phe Leu Leu Phe Leu Ile Ala Thr Thr Arg Gly tgg agt aca gat gag get sat act tac ttc aag gaa tgg acc tgt tct 97 Trp Ser Thr Asp Glu Ala Asn Thr Tyr Phe Lys Glu Trp Thr Cys Ser tcg tct cca tct ctg ccc aga agc tgc aag gaa atc aaa gac gaa tgt 145 20 Ser Ser Pro Ser Leu Pro Arg Ser Cys Lys Glu Ile Lys Asp Glu Cys cct agt gca ttt gat ggc ctg tat ttt ctc cgc act gag aat ggt gtt 193 Pro Ser Ala Phe Asp Gly Leu Tyr Phe Leu Arg Thr Glu Asn Gly Val atc tac cag acc ttc tgt gac atg acc tct ggg ggt ggc ggc tgg acc 241 Ile Tyr Gln Thr Phe Cys Asp Met Thr Ser Gly Gly Gly Gly Trp Thr ctg gtg gcc agc gtg cat gag sat gac atg cgt ggg aag tgc acg gtg 289 Leu Val Ala Ser Val His Glu Asn Asp Met Arg Gly Lys Cys Thr Val ggc gat cgc tgg tcc agt cag cag ggc agc aaa gca gac tac cca gag 337 Gly Asp Arg Trp Ser Ser Gln Gln Gly Ser Lys Ala Asp Tyr Pro Glu ggg gac ggc aac tgg gcc aac tac aac acc ttt gga tct gca gag gcg 385 Gly Asp Gly Asn Trp Ala Asn Tyr Asn Thr Phe Gly Ser Ala Glu Ala gcc acgagcgatgactac eagaaccctggctactacgac atccaggcc 433 Ala ThrSerAspAspTyr LysAsnProGlyTyrTyrAsp IleGlnAla aag gacctgggcatctgg cacgtgcccaataagtccccc atgcagcac 481 Lys AspLeuGlyIleTrp HisValProAsnLysSerPro MetGlnHis tgg agaaacagctccctg ctgaggtaccgcacggacact ggcttcetc 529 Trp ArgAsnSerSerLeu LeuArgTyrArgThrAspThr GlyPheLeu cag acactgggacataat ctgtttggcatctaccagaaa tatccagtg 577 Gln ThrLeuGlyHisAsn LeuPheGlyIleTyrGlnLys TyrProVal aaa tatggagaaggaaag tgttggactgacaacggcccg gtgatccct 625 Lys TyrGlyGluGlyLys CysTrpThrAspAsnGlyPro ValIlePro gtg gtctatgattttggc gacgcccagaaaacagcatct tattactca 673 Val ValTyrAspPheGly AspAlaGlnLysThrAlaSer TyrTyrSer ccc tatggccagcgggaa ttcactgcgggatttgttcag ttcagggta 721 Pro TyrGlyGlnArgGlu PheThrAlaGlyPheValGln PheArgVal ttt aataacgagagagca gccaacgccttgtgtgetgga atgagggtc 769 Phe AsnAsnGluArgAla AlaAsnAlaLeuCysAlaGly MetArgVal acc gga tgt eac act gag cac cac tgc att ggt gga gga gga tac ttt 817 Thr Gly Cys Asn Thr Glu His His Cys Ile Gly Gly Gly Gly Tyr Phe cca gag gcc agt ccc cag cag tgt gga gat ttt tct ggt ttt gat tgg 865 Pro Glu Ala Ser Pro Gln Gln Cys Gly Asp Phe Ser Gly Phe Asp Trp agt gga tat gga act cat gtt ggt tac agc agc agc cgt gag ata act 913 Ser Gly Tyr Gly Thr His Val Gly Tyr Ser Ser Ser Arg Glu Ile Thr gag gca get gtg ctt cta ttc tat cgt tgagagtttt gtgggaggga 960 Glu Ala Ala Val Leu Leu Phe Tyr Arg acccagacct etcctcccaa ccatgagatc ccaaggatgg agaacaactt acccagtagc 1020 tagaatgtta atggcagaag agaaaacaat aaatcatatt gactc 1065 <210> 52 <211> 937 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (177)...(866) <400> 52 cttttggaga actgcgcttc ccgccgccgc ggccgccacc 60 tctttcggag ggagtgttcg tggagtttct tcagactcca ggagtccaga gaggasacgc 120 gatttccctg tcaaccacga ggagcggaga caacagtacc gatcgcccca gcaggg 176 tgacgcctct ttcagcccgg atg ggc aag atctggctgccc ttccccgtgctccttctggcc get 224 gac Met Gly Lys IleTrpLeuPro PheProValLeuLeuLeuAla Ala Asp 1 5 io 15 ctg cct gtg ctgctgcctggg gcggccggcttcacaccttcc ctc 272 ccg Leu Pro Val LeuLeuProGly AlaAlaGlyPheThrProSer Leu Pro gat agc ttc acctttaccctt cccgccggccagaaggagtgc ttc 320 gac Asp Ser Phe ThrPheThrLeu ProAlsGlyGlnLysGluCys Phe Asp tac cag atg cccctgaaggcc tcgctggagatcgagtaccaa gtt 368 ccc Tyr Gln Met ProLeuLysAla SerLeuGluIleGluTyrGln Val Pro 30 tta gat gca ggattagatatt gatttccatcttgcctctcca gaa 416 gga Leu Asp Ala GlyLeuAspIle AspPheHisLeuAlaSerPro Glu Gly ggc aaa tta gtttttgaacaa agaaaatcagatggagttcac act 464 acc Gly Lys Leu ValPheGluGln ArgLysSerAspGlyValHis Thr Thr gta gag gaa gtt gattac atg aat aca 512 act ggt ttc ttc tgc ttt gac Val GluThrGlu ValGlyAspTyr Met Asn ThrPhe Phe Cys Phe Asp agc accatttct gagasggtgatt ttctttgaa atcctg gataat 560 tta Ser ThrIleSer GluLysValIle PhePheGlu IleLeu AspAsn Leu atg ggagaacag gcacaagaacan gaagattgg aaatat attact 608 aag Met GlyGluGln AlaGInGluGln GluAspTrp LysTyr IleThr Lys ggc acagatata ttggatatgaaa ctggaagac ctggaa tccatc 656 atc Gly ThrAspIle LeuAspMetLys LeuGluAsp LeuGlu SerIle Ile aac agcatcaag tccagaetaagc saaagtggg atacaa attctg 704 cac Asn SerIleLys SerArgLeuSer LysSerGly IleGln IleLeu His ctt agagcattt gaagetcgtgat cgaaacata gaaagc aacttt 752 csa Leu ArgAlaPhe GluAlaArgAsp ArgAsnIle GluSer AsnPhe Gln gat agagtcaat ttctggtctatg gttaattta gtcatg gtggtg 800 gtg Asp ArgValAsn PheTrpSerMet ValAsnLeu ValMet ValVal Val gtg tcagccatt caagtttatatg ctgaagagt tttgan gataag 848 ctg Val SerAlaIle ValTyr LysSer PheGlu Gln Met Leu As Leu L

p ys agg saaagtaga taaaactcca gagtn attganaaatg gOp act aacta cgtaac Arg Ser Lys Arg Thr aggcataaaa atgcaataaa ctgttacagt caagacc g37 <210> 53 <211> 1678 <212> DNA

<213> Homo sapiens <220>

<221> cns <222> (56)...(1459) <400> 53 agcgctcccg aggccgcggg agcctgcaga gaggacagcc ggcctgcgcc gggac 55 atg cgg ccc cag gag ctc ccc agg ctc gcg ttc ccg ttg ctg ctg ttg 103 Met Arg Pro Gln Glu Leu Pro Arg Leu Ala Phe Pro Leu Leu Leu Leu ctg ttg ctg ctg ctg ccg ccg ccg ccg tgc cct gcc cac agc gcc acg 151 Leu Leu Leu Leu Leu Pro Pro Pro Pro Cys Pro Ala His Ser Ala Thr cgc ttc gac ccc acc tgg gag tcc ctg gac gcc cgc cag ctg ccc gcg 199 Arg Phe Asp Pro Thr Trp Glu Ser Leu Asp Ala Arg Gln Leu Pro Ala tgg tttgaccaggcc aagttcggcatcttc atccactggggagtg ttt 247 Trp PheAspGlnAla LysPheGlyIlePhe IleHisTrpGlyVal Phe tcc gtgcccagcttc ggtagcgagtggttc tggtggtattggcaa aeg 295 Ser ValProSerPhe GlySerGluTrpPhe TrpTrpTyrTrpGln Lys gaa aagataccgaag tatgtggaatttatg aaagataattaccct cct 343 Glu LysIleProLys TyrValGluPheMet LysAspAsnTyrPro Pro agt ttcaaatatgaa gattttggaccacta tttacagcaaaattt ttt 391 Ser PheLysTyrGlu AspPheGlyProLeu PheThrAlaLysPhe Phe loo los 110 aat gcc aac cag tgg gca gat att ttt cag gcc tct ggt gcc aaa tac 439 Asn Ala Asn Gln Trp Ala Asp Ile Phe Gln Ala Ser Gly Ala Lys Tyr att gtc tta act tcc saa cat cat gaa ggc ttt acc ttg tgg ggg tca 487 Ile Val Leu Thr Ser Lys His His Glu Gly Phe Thr Leu Trp Gly Ser gaa tat tcg tgg aac tgg aat gcc ata gat gag ggg ccc sag agg gac 535 Glu Tyr Ser Trp Asn Trp Asn Ala Ile Asp Glu Gly Pro Lys Arg Asp att gtc aag gaa ett gag gta gcc att agg aac aga act gac ctg cgt 583 Ile Val Lys Glu Leu Glu Val Ala Ile Arg Asn Arg Thr Asp Leu Arg ttt gga ctg tac tat tcc ctt ttt gaa tgg ttt cat ccg ctc ttc ctt 631 Phe Gly Leu Tyr Tyr Ser Leu Phe Glu Trp Phe His Pro Leu Phe Leu 180 185 . 190 gag gat gaa tcc agt tca ttc cat aag cgg caa ttt cca gtt tct aag 679 Glu Asp Glu Ser Ser Ser Phe His Lys Arg Gln Phe Pro Val Ser Lys aca ttg cca gag ctc tat gag tta gtg aac aac tat cag cct gag gtt 727 Thr Leu Pro Glu Leu Tyr Glu Leu Val Asn Asn Tyr Gln Pro Glu Val ctg tgg tcg gat ggt gac gga gga gca ccg gat cas tac tgg aac agc 775 Leu Trp Ser Asp Gly Asp Gly Gly Ala Pro Asp Gln Tyr Trp Asn Ser aca ggc ttc ttg gcc tgg tta tat aat gaa agc cca gtt cgg ggc aca 823 Thr Gly Phe Leu Ala Trp Leu Tyr Asn Glu Ser Pro Val Arg Gly Thr gta gtc acc aat gat cgt tgg gga get ggt agc atc tgt aag cat ggt 871 Val Val Thr Asn Asp Arg Trp Gly Ala Gly Ser Ile Cys Lys His Gly ggc ttc tat acc tgc agt gat cgt tat aac cca gga cat ctt ttg cca 919 Gly Phe Tyr Thr Cys Ser Asp Arg Tyr Asn Pro Gly His Leu Leu Pro cat aaa tgg gaa aac tgc atg aca ata gac aaa ctg tcc tgg ggc tat 967 His Lys Trp Glu Asn Cys Met Thr Ile Asp Lys Leu Ser Trp Gly Tyr agg agg gaa get gga atc tct gac tat ctt aca att gaa gas ttg gtg -1015 Arg Arg Glu Ala Gly Ile Ser Asp Tyr Leu Thr Ile Glu Glu Leu Val aag caa ctt gta gag aca gtt tca tgt gga gga aat ctt ttg atg aat 1063 Lys Gln Leu Val Glu Thr Val Ser Cys Gly Gly Asn Leu Leu Met Asn att ggg ccc aca cta gat ggc acc att tct gta gtt ttt gag gag cga 1111 Ile Gly Pro Thr Leu Asp Gly Thr Ile Ser Val Val Phe Glu Glu Arg ctg agg caa atg ggg tcc tgg cta aaa gtc aat gga gaa get att tat 1159 Leu Arg Gln Met Gly Ser Trp Leu Lys Val Asn Gly Glu Ala Ile Tyr gaa acc cat acc tgg cga tcc cag aat gac act gtc acc cca gat gtg 1207 Glu Thr His Thr Trp Arg Ser Gln Asn Asp Thr Val Thr Pro Asp Val tgg tacacatccaagcctaaa gaaaaattagtc tatgccatttttctt 1255 Trp TyrThrSerLysProLys GluLysLeuVal TyrAlaIlePheLeu aaa tggcccacatcaggacag ctgttccttggc catcccaaagetatt 1303 Lys TrpProThrSerGlyGln LeuPheLeuGly HisProLysAlaIle ctg ggggcaacagaggtgaaa ctactgggccat ggacagccacttaac 1351 Leu GlyAlaThrGluValLys LeuLeuGlyHis GlyGlnProLeuAsn tgg atttctttggagcaaaat ggcattatggta gaactgccaca eta 1399 g Trp IleSerLeuGluGlnAsn GlyIleMetVal GluLeuProGl L

n eu acc attcatcagatgccgtgt aaatggggctgg getctagccctgact 1447 Thr IleHisGlnMetProCys LysTrpGlyTrp AlaLeuAlaLeuThr eat gtg atc taaagtgcag cagagtggct gatgctgcaa gttatgtcta aggc 1500 Asn Val Ile taggaactat caggtgtcta taattgtagc acatggagaa agcasatgta saactggata 1560 agaaaattat tttggcagtt cagccctttc cctttttccc actaaatttt ttcttaeatt 1620 acccatgtaa ccattttaac tctccagtgc actttgccat tsaagtctct tcacattg 1678 <210> 54 <2I1> 467 <212> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (114)...(413) 54/1??
<400>

aggggagggc ggtgctcc gc gcggtggc g gttgctatcg cgcagaa cctactcagg c ctt cagccagctg agaagagttg gggaaagtg ctgctgctgg tgcagac gcgatg a gtc ~t gat aacgtg cagccgaaaataaaa cat cccttctgcttc agtgtg 164 cgc Asp AsnVal GlnProLysIleLys His ProPheCysPhe SerVal Arg aaa ggccac gtgaagatgctgcgg ctg attatcaactca ctggta 212 gat Lys GlyHis ValLysMetLeuArg Leu IleIleAsnSer LeuVal Asp aca acagta ttcatgctcatcgta tct ttggcactgata ccagaa 260 gtg Thr ThrVal PheMetLeuIleVal Ser LeuAlaLeuIle ProGlu Val acc acaaca ttgacagttggtgga ggg tttgcacttgtg acagca 308 gtg Thr ThrThr LeuThrValGlyGly Gly PheAlaLeuVal ThrAla Val gta tgctgt cttgccgacggggcc ctt taccggaagctt ctgttc 356 att Val CysCys LeuAlaAspGlyAla Leu TyrArgLysLeu LeuPhe Ile aat cccagc ggtccttaccagcaa aag gtgcatgaaaaa aaagaa 404 cct Asn ProSer GlyProTyrGlnGln Lys ValHisGluLys LysGlu Pro gtt ttgtaattttata tacttttt a ttgatactaagtatt aaa 450 t gt Val Leu catatttctg tattctt ~ 467 <210> 55 <211> 875 <212> DNA
<213> Homo sapiens <220>
<221> cns <222> (272)...(841) <400> 55 attggttggg ggaaacccac gaggggacgc ggccgaggag ggtcgctgtc cacccggggg 60 cgtgggagtg aggtaccaga ttcagcccat ttggccccga cgcctctgtt ctcggaatcc 120 gggtgctgcg gattgaggtc ccggttccta acgaatctct gctggattgg ccgtaaccct 180 gtccccgagc gggctcacag ggtctgaagg ccacgcatga ggcaaaggta aagttctgag 240 ccacccggtg cctccttccc aggactgcaa g atg gag gaa ggc ggg aac cta 292 Met Glu Glu Gly Gly Asn Leu gga ggc ctg att aag atg gtc cat cta ctg gtc ttg tca ggt gcc tgg 340 Gly Gly Leu Ile Lys Met Val His Leu Leu Val Leu Ser Gly Ala Trp ggc atg caa atg tgg gtg acc ttc gtc tca ggc ttc ctg ctt ttc cga 388 Gly Met Gln Met Trp Val Thr Phe Val Ser Gly Phe Leu Leu Phe Arg agc ctt ccc cga cat acc ttc gga cta gtg cag agc aaa etc ttc ccc 436 Ser Leu Pro Arg His Thr Phe Gly Leu Val Gln Ser Lys Leu Phe Pro 20 ttc tac ttc cac atc tcc atg ggc tgt gcc ttc atc aac ctc tgc atc 484 Phe Tyr Phe His Ile Ser Met Gly Cys Ala Phe Ile Asn Leu Cys Ile ttg get tca cag cat get tgg get cag ctc aca ttc tgg gag gcc agc 532 Leu Ala Ser Gln His Ala Trp Ala Gln Leu Thr Phe Trp Glu Ala Ser cag ctt tac ctg ctg ttc ctg agc ctt acg ctg gcc act gtc aac gcc 580 Gln Leu Tyr Leu Leu Phe Leu Ser Leu Thr Leu Ala Thr Val Asn Ala cgc tgg ctg gaa cec cgc acc aca get gcc atg tgg gcc ctg caa acc 628 Arg Trp Leu Glu Pro Arg Thr Thr Ala Ala Met Trp Ala Leu Gln Thr gtg gag aag gag cga ggc ctg ggt ggg gag gta cca ggc agc cac cag 676 Val Glu Lys Glu Arg Gly Leu Gly Gly Glu Val Pro Gly Ser His Gln ggt ccc gat ccc tac cgc cag ctg cga gag aag gac ccc aag tac agt 724 Gly Pro Asp Pro Tyr Arg Gln Leu Arg Glu Lys Asp Pro Lys Tyr Ser get ctc cgc cag aat ttc ttc cgc tac cat ggg ctg tcc tct ctt tgc 772 Ala Leu Arg Gln Asn Phe Phe Arg Tyr His Gly Leu Ser Ser Leu Cys ast ctg ggc tgc gtc ctg agc aat ggg ctc tgt ctc get ggc ctt gcc 820 Asn Leu Gly Cys Val Leu Ser Asn Gly Leu Cys Leu Ala Gly Leu Ala ctg gaa ata egg agc ctc tagcatgggc cctgcatgct aataaatgct tcttcag 875 Leu Glu Ile Arg Ser Leu <210> 56 <211> 1256 <212> rn~A

<213> Homo Sapiens <220>

<221> CDS

<222> (150)...(1241) <400> 56 atgtaagagc cacctcctcc ccaggactca gggatggctc tccagatgtc accactgcag 60 atattggagc caacactcca gatgctacaa aaggctgtcc agatgtccaa gcttccttgc I20 cagatgccaa agccaagtcc ccaccgacc atg gtg gac agc ctc ctg gca gtc 173 Met Val Asp Ser Leu Leu Ala Val acc ctq get gga aac ctg ggc ctg acc ttc ctc cga ggt tcc cag acc 221 Thr Leu Ala Gly Asn Leu Gly Leu Thr Phe Leu Arg Gly Ser Gln Thr cag agc cat cca gac ctg gga act gag ggc tgc tgg gac cag ctc tct 269 Gln Ser His Pro Asp Leu Gly Thr Glu Gly Cys Trp Asp Gln Leu Ser gcc cct cgg acc ttt acg ctt ttg gac ccc aag gca tct ctg tta acc 31?
Ala Pro Arg Thr Phe Thr Leu Leu Asp Pro Lys Ala Ser Leu Leu Thr aag gcc ttc ctc aat ggc gcc ctg gat ggg gtc atc ctt gga gac tac 365 Lys Ala Phe Leu Asn Gly Ala Leu Asp Gly Val Ile Leu Gly Asp Tyr ctg agc cgg act cct gag ccc cgg cca tcc ctc agc cac ttg ctg agc 413 Leu Ser Arg Thr Pro Glu Pro Arg Pro Ser Leu Ser His Leu Leu Ser cag tac tat ggg get ggg gtg gcc aga gac cca ggg ttc cgc agc aac 461 Gln Tyr Tyr Gly Ala Gly Val Ala Arg Asp Pro Gly Phe Arg Ser Asn ttc cga cgg cag aac ggt get get ctg act tca gcc tcc atc ctg gcc 509 Phe Arg Arg Gln Asn Gly Ala Ala Leu Thr Ser Ala Ser Ile Leu Ala cag cag gtg tgg gga acc ctt gtc ctt cta cag agg ctg gag cca gta 557 Gln Gln Val Trp Gly Thr Leu Val Leu Leu Gln Arg Leu Glu Pro Val cac ctc cag ctt cag tgc atg agc caa gaa cag ctg gcc cag gtg get 605 His Leu Gln Leu Gln Cys Met Ser Gln Glu Gln Leu Ala Gln Val Ala gcc aat get acc aag gaa ttc act gag gcc ttc ctg gga tgc ccg gcc 653 Ala Asn Ala Thr Lys Glu Phe Thr Glu Ala Phe Leu Gly Cys Pro Ala atc cac ccc cgc tgc cgc tgg gga gcg gcg cct tat cgg ggc cgc ccg 701 Ile His Pro Arg Cys Arg Trp Gly Ala Ala Pro Tyr Arg Gly Arg Pro aag ctg ctg cag ctg ccg ctg gga ttc ttg tac gtg cat cac acc tac 749 Lys Leu Leu Gln Leu Pro Leu Gly Phe Leu Tyr Val His His Thr Tyr gtg cct gca cca ccc tgc acg gac ttc acg cgc tgc gca gcc asc atg 797 Val Pro Ala Pro Pro Cys Thr Asp Phe Thr Arg Cys Ala Ala Asn Met cgc tcc atg cag cgc tac cac cag gac acg caa ggc tgg gga gac atc 845 Arg Ser Met Gln Arg Tyr His Gln Asp Thr Gln Gly Trp Gly Asp Ile ggc tac agt ttc gtg gtg ggc tcg gac ggc tac gtg tac gag gga cgc 893 Gly Tyr Ser Phe Val Val Gly Ser Asp Gly Tyr Val Tyr Glu Gly Arg ggc tgg cac tgg gtg ggc gcc cac acg ctc ggc cac aac 941 tcc cgg ggc Gly Trp His Trp Val Gly Ala His Thr Leu Gly His Asn Ser Arg Gly ttc ggc gtg gcc ata gtg ggc aac tac acc gcg gcg ctg 989 ccc acc gag Phe Gly Val Ala Ile Val Gly Asn Tyr Thr Ala Ala Leu Pro Thr Glu gcc get ctg cgc acg gtg cgc gac acg ctc ccg agt tgt 1037 gcg gtg.cgc.

Ala Ala Leu Arg Thr Val Arg Asp Thr Leu Pro Ser Cys Ala Val Arg gcc ggc ctc ctg cgg cca gac tac gcg ctg ctg ggc cac 1085 cgc cag ctg Ala Gly Leu Leu Arg Pro Asp Tyr Ala Leu Leu Gly His Arg Gln Leu gtg cgc acc gac tgc ccc ggc gac gcg ctc ttc gac ctg 1133 ctg cgc acc Val Arg Thr Asp Cys Pro Gly Asp Ala Leu Phe Asp Leu Leu Arg Thr tgg ccg cac ttc acc gcg act gtt aag cca aga cct gcc 1181 agg agt gtc Trp Pro His Phe Thr Ala Thr Val Lys Pro Arg Pro Ala Arg Ser Val tct aag aga tcc agg agg gag cca ccc cca agg acc ctg 1229 cca gcc aca Ser Lys Arg Ser Arg Arg Glu Pro Pro Pro Arg Thr Leu Pro Ala Thr gac ctc caa tasagacagc atggaaac 1256 Asp Leu Gln <210> 57 <211> 884 <212> DNA
<213> Homo Sapiens <220>
<221> CDS
<222> (135)...(884) <400> 57 catttccttt ctccacatcc aggtcaggtg gcgtttgctg tggcggctag gcccgcgtgc 60 gctggagacc tccgcgctgg cccccgcgag cctcctgccc tggcccggcg ctgcggctct 120 gccgcggcgg cagc atg ggt ggc ccc cgg ggc gcg ggc tgg gtg gcg gcg 170 Met Giy Gly Pro Arg Gly Ala Gly Trp Val Ala Ala ggc ctg ctg ctc ggc gcg ggc gcc tgc tac tgc att tac agg ctg acc 218 Gly Leu Leu Leu Gly Ala Gly Ala Cys Tyr Cys Ile Tyr Arg Leu Thr cgg ggt cgg cgg cgg ggc gac cgc gag ctc ggg ata cgc tct tcg aag 266 Arg Gly Arg Arg Arg Gly Asp Arg Glu Leu Gly Ile Arg Ser Ser Lys tcc gca gaa gac tta act gat ggt tca tat gat gat gtt cta aat get 314 Ser Ala Glu Asp Leu Thr Asp Gly Ser Tyr Asp Asp VaI Leu Asn Ala gaa caa ctt cag aaa ctc ctt tac ctg ctg gag tca acg gag gat cct 362 15 Glu Gin Leu Gln Lys Leu Leu Tyr Leu Leu Glu Ser Thr Glu Asp Pro gta att att gaa aga get ttg att act ttg ggt aac ast gca gcc ttt 410 Val Ile Ile Glu Arg Ala Leu Ile Thr Leu Gly Asn Asn Ala Ala Phe tca gtt asc caa get att att cgt gaa ttg ggt ggt att cca att gtt 458 Ser Val Asn Gln Ala Ile Ile Arg Glu Leu Gly Gly Ile Pro Ile Val gca aac aaa atc aac cat tcc aac cag agt att aaa gag aaa get tta 506 Ala Asn Lys Ile Asn His Ser Asn Gln Ser Ile Lys Glu Lys Ala Leu aat gca cta aat aac ctg agt gtg aat gtt gaa ant can atc aag ata 554 Asn Ala Leu Asn Asn Leu Ser Val Asn Val Glu Asn Gln Ile Lys Ile aag gtg caa gtt ttg aaa ctg ctt ttg aat ttg tct gaa aat cca gcc 602 Lys Val Gln Val Leu Lys Leu Leu Leu Asn Leu Ser Glu Asn Pro Ala atg aca gaa gga ctt ctc cgt gcc caa gtg gat tcn tca ttc ctt tcc 650 Met Thr Glu Gly Leu Leu Arg Ala Gln Val Asp Ser Ser Phe Leu Ser ctt tat gac agc cac gta gca aag gag att ctt ctt cga gta ctt acg 698 60!177 Leu TyrAspSerHis ValAlaLysGlu Ile Leu Val LeuThr Leu Arg cta tttcagaatata aagaactgcctc aaaatagaaggccat ttaget 746 Leu PheGlnAsnIle LysAsnCysLeu LysIleGluGIyHis LeuAla gtg cagectactttc actgaaggttca ttgtttttcctgtta catgga 794 Val GlnProThrPhe ThrGluGlySer LeuPhePheLeuLeu HisGly gaa gaatgtgcccag aaaataagaget ttagttgatcaccat gatgca 842 Glu GluCysAlaGln LysIleArgAla LeuValAspHisHis AspAla gag gtgaaggaaaag gttgtaacaata atacccsaaatctga 884 Glu ValLysGluLys ValValThrIle IleProLysIle <210> 58 <211> 589 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (48). ..(344) <400> 58 gctttccgag cccgcttgca cttcttt atggcg tcg 56 cctcggcgat ccccgactcc MetAla Ser ctc ctg tgc tgt ccgaagctggccgcc tgcggcatcgtcctc agc 104 ggg Leu Leu Cys Cys ProLysLeuAlaAla CysGlyIleValLeu Ser Gly gcc tgg gga gtg atgttgataatgctc ggaatatttttcaat gtc 152 atc Ala Trp Gly Val MetLeuIleMetLeu GlyIlePhePheAsn Val Ile cat tcc get gtg attgaggacgttccc ttcacggagasagat ttt 200 ttg His Ser Ala Val Leu Ile Glu Asp Val Pro Phe Thr Glu Lys Asp Phe .
WO 00/05367 PCT/JP99/0392~
s lim7 gag aat ggc ccc aac ata aac ctt gag caa gtc agc 248 cag tac tac tac Glu Asn Gly Pro Asn Ile Asn Leu Glu Gln Val Ser Gln Tyr Tyr Tyr sac tgt ttc atc gca ggc tac ctc ctc gga ggc ttc 296 get ctt ctc tct Asn Cys Phe Ile Ala Gly Tyr Leu Leu Gly Gly Phe Ala Leu Leu Ser ttc tgc caa gtt ctc aat cgc aag tac atg gtg cgc 341 cgg aag gaa Phe Cys Gln Val Leu Asn Arg Lys Tyr Met Val Arg Arg Lys Glu tagggcccc ggcgcgtttccccgctccagcccctcctct 400 atttaaagac tccctgcacc gtgtcaccca ggtcgcgtcc cacccttgccggcgccctctgtgggactgg gtttcccggg460 cgagagactg aatcccttct cccatctctggcatccggcccccgtggaga gggctgaggc520 tggggggctg ttccgtctct ctgtgtcccgtatctcaata aagagaatct580 ccacccttcg gctctcttc 589 <210> 59 <211> 673 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (25)...(543) <900> 59 cttgccttgc gctgcgcgct cacc atg gtg ggc ccc gcg ccg cgg cgg cgg 51 Met Val Gly Pro Ala Pro Arg Arg Arg ctg cgg ccg ctg gca gcg ctg gcc ctg gtc ctg gcg ctg gcc ccg ggg gg Leu Arg pro Leu Ala Ala Leu Ala Leu Val Leu Ala Leu Ala Pro Gly ctg ccc aca gcc cgg gcc ggg cag aca ccg cgc cct gcc gag cgg ggg 147 Leu Pro Thr Ala Arg Ala Gly Gln Thr Pro Arg Pro Ala Glu Arg Gly cec cca gtg cgg ctt ttc acc gag gag gag ctg gcc cgc tat ggc ggg 195 Pro Pro Val Arg Leu Phe Thr Glu Glu Glu Leu Ala Arg Tyr Gly Gly gag gag gsa gat cag ccc atc tac ttg gca gtg aag gga gtg gtg ttt 243 Glu Glu Glu Asp Gln Pro Ile Tyr Leu Ala Val Lys Gly Val Val Phe gat gtc acc tcc gga aag gag ttt tat gga cga gga gcc ccc tac aat 291 Asp Val Thr Ser Gly Lys Glu Phe Tyr Gly Arg Gly Ala Pro Tyr Asn gcc ttg acg ggg aag gac tcc act aga ggg gta gcc aag atg tcc ttg 339 Ala Leu Thr Gly Lys Asp Ser Thr Arg Gly Val Ala Lys Met Ser Leu gat cct gca gac ctc acc cat gac act acg ggt ctc acg gcc aag gaa 387 Asp Pro Ala Asp Leu Thr His Asp Thr Thr Gly Leu Thr Ala Lys Glu ctg gag gcc ctg gat gag gtc ttc acc aaa gtg tac aaa gcc aaa tac 435 Leu Glu Ala Leu Asp Glu Val Phe Thr Lys Val Tyr Lys Ala Lys Tyr ccc atc gtc ggc tac act gcc cgg aga att ctc aat gag gat ggc agc 483 Pro Ile Val Gly Tyr Thr Ala Arg Arg Ile Leu Asn Glu Asp Gly Ser cct aac ctg gac ttc aag cct gaa gac cag ccc cat ttt gac atc aag 531 Pro Asn Leu Asp Phe Lys Pro Glu Asp Gln Pro His Phe Asp Ile Lys gat gag ttc tgatgttccc cctgcaggag caggttcttg ggagcgtgag 580 Asp Glu Phe gcaggaagac actaggtgct gaatctcctg caaaactggc tgcctggagg ccctgagcca 640 cccagatctg aataaaacag atgcttaccc tgg 673 <210> 60 <211> 1425 <212> DNA
<213> Homo Sapiens <220>
<221> cDs <222> (127)...(489) <400> 60 tcccgcctgg ggccggctga gccatgcaac cttgggcgct gtggcactta agcgggccat gcc aaccgtg ggcgagctct gcggcgctcc gctgtgtcag gggtgtgcgg gcggcctggc cgt gttatg atgccgtcccgtacc aacctggetactgga atccccagt 168 Met MetProSer Thr LeuAlaThrGly ZleProSer Arg Asn agt eaagtg aaatattcaaggctc tccagcacagacgat ggctacatt 216 Ser Lysval LysTyrSerArgLeu SerSerThrAspAsp GlyTyrIle gac cttcag tttsagaaaacccct cctaagatcccttat caggccatc 264 Asp LeuGln PheLysLysThrPro ProLysIleProTyr LysAlaIle 15 gca cttgcc actgtgctgtttttg attggcgcctttctc attattata 312 Ala LeuAla ThrValLeuPheLeu IleGlyAlaPheLeu IleIleIle ggc tccctc ctgctgtcaggctac atcagcaaagggggg gcagaccgg 360 Gly SerLeu LeuLeuSerGlyTyr IleSerLysGlyGly AlaAspArg gcc gttcca gtgctgatcattggc attctggtgttccta cccggattt 408 Ala ValPro ValLeuIleIleGly IleLeuValPheLeu ProGlyPhe tac cacctg cgcatcgettactat gcatccaaaggctac cgtggttac 456 Tyr HisLeu ArgIleAlaTyrTyr AlaSexLysGlyTyr ArgGlyTyr tcc tat gat gac att cca gac ttt gat gac tagcacccac ccca 500 Ser Tyr Asp Asp Ile Pro Asp Phe Asp Asp tagctgagga ggagtcacagtggaactgtcccagctttaagatatctagcagaaactata560 gctgaggact aaggaattctgcagcttgcagatgtttaagaaaataatggccagattttt620 tgggtccttc ccaasgatgttaagtgaacctacagttagctaattaggacsagctctatt680 tttcatccct gggccctgacaagtttttccacaggaatatgtatcatggaagaatagagg740 ttattctgta atggaasagtgttgcctgccaccaccctctgtagagctgagcatttcttt800 taaatagtct tcattgccaatttgttcttgtagcaaatggaacaatgtggtatggctaat860 WO 00/05367 PC1'/JP991039Z9 ttcttattat taagtagtttattttaaaaatatctgagtatattatcctgtacacttatc920 cctaccttca tgttccagtggaagaccttagtaaaatcaaagatcagtgagttcatctgt980 aatatttttt ttacttgctttcttactgacagcaaccaggaatttttttatcctgcagag1040 caagttttca aaatgtaaatacttcctctgtttaacagtccttggaccattctgatccag1100 ttcaccagta ggttggacagcatataatttgcatcattttgtcccttgtaaatcaagatg1160 ttctgcagat tattcctttaacggccggacttttggctgtttcctaatgaeacatgtagt1220 ggttattatt tagagtttatagccgtattgctagcaccttgtagtatgtcatcattctgc1280 tcatgattcc aaggatcagcctggatgcctagaggactagatcaccttagtttgattcta1340 ttttttagct tgcaaaaagtgacttatattccaaagaaattaaaatgttgaaatccaaat1400 cctagaaata aaatgagttaacttc 1425 <210> 61 <211> 307 <212> PRT
<213> Homo sapiens <400> 61 Met Ser Met Ile Leu Ser Ala Ser Val Ile Arg Val Arg Asp Gly Leu Pro Leu Ser Ala Ser Thr Asp Tyr Glu Gln Ser Thr Gly Met Gln Glu Cys Arg Lys Tyr Phe Lys Met Leu Ser Arg Lys Leu Ala Gln Leu Pro Asp Arg Cys Thr Leu Lys Thr Gly His Tyr Asn Ile Asn Phe Ile Ser Ser Leu Gly Val Ser Tyr Met Met Leu Cys Thr Glu Asn Tyr Pro Asn Val Leu Ala Phe Ser Phe Leu Asp Glu Leu Gln Lys Glu Phe Ile Thr Thr Tyr Asn Met Met Lys Thr Asn Thr Ala Val Arg Pro Tyr Cys Phe Ile Glu Phe Asp Asn Phe Ile Gln Arg Thr Lys Gln Arg Tyr Asn Asn Pro Arg Ser Leu Ser Thr Lys Ile Asn Leu Ser Asp Met Gln Thr Glu Ile Lys Leu Arg Pro Pro Tyr Gln Ile Ser Met Cys Glu Leu Gly Ser Ala Asn Gly Val Thr Ser Ala Phe Ser Val Asp Cys Lys Gly Ale Gly Lys Ile Ser Ser Ala His Gln Arg Leu Glu Pro Ala Thr Leu Ser Gly Ile Val Gly Phe Ile Leu Ser Leu Leu Cys Gly Ala Leu Asn Leu Ile Arg Gly Phe His Ala Ile Glu Ser Leu Leu Gln Ser Asp Gly Asp Asp Phe Asn Tyr Ile Ile Ala Phe Phe Leu Gly Thr Ala Ala Cys Leu Tyr Gln Cys Tyr Leu Leu Val Tyr Tyr Thr Gly Trp Arg Asn Val Lys Ser Phe Leu Thr Phe Gly Leu Ile Cys Leu Cys Asn Met Tyr Leu Tyr Glu Leu Arg Asn Leu Trp Gln Leu Phe Phe His Val Thr Val Gly Ala Phe Val Thr Leu Gln Ile Trp Leu Arg Gln Ala Gln Gly Lys Ala Pro Asp Tyr Asp Val <210> 62 <211> 183 <212> PRT
<213> Homo sapiens <400> 62 Met Thr Ala Gln Gly Gly Leu Val Ale Asn Arg Gly Arg Arg Phe Lys Trp Ala Ile Glu Leu Ser Gly Pro Gly Gly Gly Ser Arg Gly Arg Ser Asp Arg Gly ser Gly Gln Gly Asp Ser Leu Tyr Pro Val Gly Tyr Leu WO 00/05367 PCT/JP99/0392~

Asp Lys Gln Val Pro Asp Thr Ser Val Gln Glu Thr Asp Arg Ile Leu Val Glu Lys Arg Cys Trp Asp Ile Ala Leu Gly Pro Leu Lys Gln Ile Pro Met Asn Leu Phe Ile Met Tyr Met Ala Gly Asn Thr Ile Ser Ile Phe Pro Thr Met Met Val Cys Met Met Ala Trp Arg Pro Ile Gln Ala Leu Met Ala Ile Ser Ala Thr Phe Lys Met Leu Glu Ser Ser Ser Gln Lys Phe Leu Gln Gly Leu Val Tyr Leu Ile Gly Asn Leu Met Gly Leu Als Leu Ala Val Tyr Lys Cys Gln Ser Met Gly Leu Leu Pro Thr His Ala Ser Asp Trp Leu Ala Phe Ile Glu Pro Pro Glu Arg Met Glu Phe Ser Gly Gly Gly Leu Leu Leu <210> 63 <211> 327 <212> PRT
<213> Homo sapiens <400> 63 Met Arg Ala Leu Pro Gly Leu Leu Glu Ala Arg Ala Arg Thr Pro Arg Leu Leu Leu Leu Gln Cys Leu Leu Ala Ala Ala Arg Pro Ser Ser Ale Asp Gly Ser Ala Pro Asp Ser Pro Phe Thr Ser Pro Pro Leu Arg Glu an v5 Glu Ile Met Ala Asn Asn Phe Ser Leu Glu Ser His Asn Ile Ser Leu Thr Glu His Ser Ser Met Pro Val Glu Lys Asn Ile Thr Leu Glu Arg Pro Ser Asn Val Asn Leu Thr Cys Gln Phe Thr Thr Ser Gly Asp Leu Asn Ala Val Asn Val Thr Trp Lys Lys Asp Gly Glu Gln Leu Glu Asn Asn Tyr Leu Val Ser Ala Thr Gly Ser Thr Leu Tyr Thr Gln Tyr Arg Phe Thr Ile Ile Asn Ser Lys Gln Met Gly Ser Tyr Ser Cys Phe Phe Arg Glu Glu Lys Glu Gln Arg Gly Thr Phe Asn Phe Lys Val Pro Glu Leu His Gly Lys Asn Lys Pro Leu Ile Ser Tyr Val Gly Asp Ser Thr Val Leu Thr Cys Lys Cys Gln Asn Cys Phe Pro Leu Asn Trp Thr Trp Tyr Ser Ser Asn Gly Ser Val Lys Val Pro Val Gly Val Gln Met Asn Lys Tyr Val Ile Asn Gly Thr Tyr Ala Asn Glu Thr Lys Leu Lys Ile Thr Gln Leu Leu Glu Glu Asp Gly Glu Ser Tyr Trp Cys Arg Ala Leu Phe Gln Leu Gly Glu Ser Glu Glu His Ile Glu Leu Val Val Leu Ser Tyr Leu Val Pro Leu Lys Pro Phe Leu Val Ile Val Ala Glu Val Ile Leu Leu Val Ala Thr Ile Leu Leu Cys Glu Lys Tyr Thr Gln Lys Lys Lys Lys His Ser Asp Glu Gly Lys Glu Phe Glu Gln Ile Glu Gln Leu Lys Ser Asp Asp Ser Asn Gly Ile Glu Asn Asn Val Pro Arg His Arg Lys Asn Glu Ser Leu Gly Gln <210> 64 <211> 223 <212> PRT
<213> Homo sapiens <400> 64 Met Lys Phe Val Pro Cys Leu Leu Leu Val Thr Leu Ser Cys Leu Gly Thr Leu Gly Gln Ala Pro Arg Gln Lys Gln Gly Ser Thr Gly Glu Glu Phe His Phe Gln Thr Gly Gly Arg Asp Ser Cys Thr Met Arg Pro Ser 35 40 45 ' Ser Leu Gly Gln Gly Ala Gly Glu Val Trp Leu Arg Val Asp Cys Arg Asn Thr Asp Gln Thr Tyr Trp Cys Glu Tyr Arg Gly Gln Pro Ser Met Cys Gln Ala Phe Ala Ala Asp Pro Lys Ser Tyr Trp Asn Gln Ala Leu 85 90 g5 Gln Glu Leu Arg Arg Leu His His Ala Cys Gln Gly Ala Pro Val Leu loo los llo Arg Pro Ser Val Cys Arg Glu Ala Gly Pro Gln Ala His Met Gln Gln Val Thr Ser Ser Leu Lys Gly Ser Pro Glu Pro Asn Gln Gln Pro Glu Ala Gly Thr Pro Ser Leu Arg Pro Lys Ala Thr Val Lys Leu Thr Glu Ala Thr Gln Leu Gly Lys Asp Ser Met Glu Glu Leu Gly Lys Als Lys Pro Thr Thr Arg pro Thr Ala Lys Pro Thr Gln Pro Gly Pro Arg Pro Gly Gly Asn Glu Glu Ala Lys Lys Lys Ala Trp Glu His Cys Trp Lys Pro Phe Gln Ala Leu Cys Ala Phe Leu Ile Ser Phe Phe Arg Gly <210> 65 <2I1> 4B

<212> PRT
<213> Homo Sapiens <400> 65 Met Arg Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Ala Met Val Arg Ser Glu Ala Ser Ala Asn Leu Gly Gly Val Pro Ser Lys Arg Leu Lys Met Gln Tyr Ala Thr Gly Pro Leu Leu Lys Phe Gln Ile Cys Val Ser <210> 66 <211> 371 <212> PRT

<213> Homo Sapiens <400> 66 Met Ala Trp Thr Lys Tyr Gln Leu Phe Leu Ala Gly Leu Met Leu Val Thr Gly Ser Ile Asn Thr Leu Ser Ala Lys Trp Ala Asp Asn Phe Met Ala Glu Gly Cys Gly Gly Ser Lys Glu His Ser Phe Gln His Pro Phe Leu Gln Ala Val Gly Met Phe Leu Gly Glu Phe Ser Cys Leu Ala Ala 5o s~
Phe Tyr Leu Leu Arg Cys Arg Ala Ala Gly Gln Ser Asp Ser Ser Val 65 70 75 g0 Asp Pro Gln Gln Pro Phe Asn Pro Leu Leu Phe Leu Pro Pro Ala Leu Cys Asp Met Thr Gly Thr Ser Leu Met Tyr Val Ala Leu Asn Met Thr Ser Ala Ser Ser Phe Gln Met Leu Arg Gly Ala Val Ile Ile Phe Thr Gly Leu Phe Ser Val Ala Phe Leu Gly Arg Arg Leu Val Leu Ser Gln Trp Leu Gly Ile Leu Ala Thr Ile Ala Gly Leu Val Val Val Gly Leu Ala Asp Leu Leu Ser Lys His Asp Ser Gln His Lys Leu Ser Glu Val Ile Thr Gly Asp Leu Leu Ile Ile Met Ala Gln Ile Ile Val Ala Ile Gln Met Val Leu Glu Glu Lys Phe Val Tyr Lys His Asn Val His Pro Leu Arg Ala Val Gly Thr Glu Gly Leu Phe Gly Phe Val Ile Leu Ser Leu Leu Leu Val Pro Met Tyr Tyr Ile Pro Ala Gly Ser Phe Ser Gly Asn Pro Arg Gly Thr Leu Glu Asp Ala Leu Asp Ala Phe Cys Gln Val I5 Gly Gln Gin Pro Leu Ile Ala Val Ala Leu Leu Gly Asn Ile Ser Ser Ile Ala Phe Phe Asn Phe Ala Gly Ile Ser Val Thr Lys Glu Leu Ser Ala Thr Thr Arg Met Val Leu Asp Ser Leu Arg Thr Val Val Ile Trp Ala Leu Ser Leu Ala Leu Gly Trp Glu Ala Phe His Ala Leu Gln Ile Leu Gly Phe Leu Ile Leu Leu Ile Gly Thr Ala Leu Tyr Asn Gly Leu His Arg Pro Leu Leu Gly Arg Leu Ser Arg Gly Arg Pro Leu Ala Glu Glu Ser Glu Gln Glu Arg Leu Leu Gly Gly Thr Arg Thr Pro Ile Asn Asp Ala Ser 3fl 370 <210> 67 <211> 90 <212> PRT
<213> Homo sapiens <400> 67 Met Phe His Gln Ile Trp Ala Ala Leu Leu Tyr Phe Tyr Gly Ile Ile Leu Asn Ser Ile Tyr Gln Cys Pro Glu His Ser Gln Leu Thr Thr Leu Gly Val Asp Gly Lys Glu Phe Pro Glu Val His Leu Gly Gln Trp Tyr Phe Ile Ala Gly Ala Ala Pro Thr Lys Glu Glu Leu Ala Thr Phe Asp Pro Val Asp Asn Ile Val Phe Asn Met Ala Ala Gly Ser Ala Pro Met Gln Leu His Leu Arg Ala Thr Ile Arg Met <210>68 <211>499 <212>PRT

<213>Homo sapiens <400> 68 Met Val Asp Arg Gly Pro Leu Leu Thr Ser Ala Ile Ile Phe Tyr Leu i 5 10 15 Ala Ile Gly Ala Ala Ile Phe Glu Val Leu Glu Glu Pro His Trp Lys Glu Ala Lys Lys Asn Tyr Tyr Thr Gln Lys Leu His Leu Leu Lys Glu Phe Pro Cys Leu Gly Gln Glu Gly Leu Asp Lys Ile Leu Glu Val Val 30 Ser Asp Ale Ala Gly Gln Gly Val Ala Ile Thr Gly Asn Gln Thr Phe Asn Asn Trp Asn Trp Pro Asn Ala Met Ile Phe Ala Ala Thr Val Ile Thr Thr Ile Gly Tyr Gly Asn Val Ala Pro Lys Thr Pro Ala Gly Arg 35 loo 105 110 Leu Phe Cys Val Phe Tyr Gly Leu Phe Gly Val Pro Leu Cys Leu Thr Trp Ile Ser Ala Leu Gly Lys Phe Phe Gly Gly Arg Ala Lys Arg Leu Gly Gln Phe Leu Thr Lys Arg Gly Val Ser Leu Arg Lya Ala Gln Ile Thr Cys Thr Val Ile Phe Ile Val Trp Gly Val Leu Val His Leu Val Ile Pro Pro Phe Val Phe Met Val Thr Glu Gly Trp Asn Tyr Ile Glu Gly Leu Tyr Tyr Ser Phe Ile Thr Ile Ser Thr Ile Gly Phe Gly Asp Phe Val Ala Gly Val Asn Pro Ser Ala Asn Tyr His Ala Leu Tyr Arg Tyr Phe Val Glu Leu Trp Ile Tyr Leu Gly Leu Ala Trp Leu Ser Leu Phe Val Asn Trp Lys Val Ser Met Phe Val Glu Val His Lys Ala Ile Lys Lys Arg Arg Arg Arg Arg Lys Glu Ser Phe Glu Ser Ser Pro His Ser Arg Lys Ala Leu Gln Val Lys Gly Ser Thr Ala Ser Lys Asp Val Asn Ile Phe Ser Phe Leu Ser Lys Lys Glu Glu Thr Tyr Asn Asp Leu Ile Lys Gln Ile Gly Lys Lys Ala Met Lys Thr Ser Gly Gly Gly Glu Thr Gly Pro Gly Pro Gly Leu Gly Pro Gln Gly Gly Gly Leu Pro Ala Leu Pro Pro Ser Leu Val Pro Leu Val Val Tyr Ser Lys Asn Arg Val Pro Thr Leu Glu Glu Val Ser Gln Thr Leu Arg Ser Lys Gly His Val Ser Arg Ser Pro Asp Glu Glu Ala Val Ala Arg Ala Pro Glu Asp Ser Ser Pro Ala Pro Glu Val Phe Met Asn Gln Leu Asp Arg Ile Ser Glu Glu Cys Glu Pro Trp Asp Ala Gln Asp Tyr His Pro Leu Ile Phe Gln Asp Ala Ser Ile Thr Phe Val Asn Thr Glu Ala Gly Leu Ser Asp Glu Glu Thr Ser Lys Ser Ser Leu Glu Asp Asn Leu Ala Gly Glu Glu Ser Pro Gln Gln Gly Ala Glu Ala Lys Ala Pro Leu Asn Met Gly Glu Phe Pro Ser Ser Ser Glu Ser Thr Phe Thr Ser Thr Glu Ser Glu Leu Ser Val Pro Tyr Glu Gln Leu Met Asn Glu Tyr Asn Lys Ale Asn Ser Pro Lys Gly Thr <210> 69 <211> 106 <212> PRT

<213> Homo sapiens <400> 69 Met Ala Ser Ser Gly Ala Gly Asp Pro Leu Asp Ser Lys Arg Gly Glu Ala pro Phe Ala Gln Arg Ile Asp Pro Thr Arg Glu Lys Leu Thr Pro Glu Gln Leu His Ser Met Arg Gln Ala Glu Leu Als Gln Trp Gln Lys Val Leu Pro Arg Arg Arg Thr Arg Asn Ile Val Thr Gly Leu Gly Ile Gly Ala Leu Val Leu Ala Ile Tyr Gly Tyr Thr Phe Tyr Ser Ile Ser Gln Glu Arg Phe Leu Asp Glu Leu Glu Asp Glu Ala Lys Ala Ala Arg 35 Ala Arg Ala Leu Ala Arg Ala Ser Gly Ser <210> 70 <211> 152 <212> PRT
<213> Homo sapiens <400> 70 Met Asp Tyr Val Cys Cys Ala Tyr Asn Asn Ile Thr Gly Arg Gln Asp Glu Thr His Phe Thr Val Ile Ile Thr Ser Val Gly Leu Glu Lys Leu Ala Gln Lys Gly Lys Ser Leu Ser Pro Leu Ala Ser Ile Thr Gly Ile 15 Ser Leu Phe Leu Ile Ile Ser Met Cys Leu Leu Phe Leu Tip Lys Lys Tyr Gln Pro Tyr Lys Val Ile Lys Gln Lys Leu Glu Gly Arg Pro Glu Thr Glu Tyr Arg Lys Ala Gln Thr Phe Ser Gly His Glu Asp Ala Leu Asp Asp Phe Gly Ile Tyr Glu Phe Val Ala Phe Pro Asp Val Ser Gly Val Ser Arg Ile Pro Ser Arg Ser Val Pro Ala Ser Asp Cys Val Ser Gly Gln Asp Leu His Ser Thr Val Tyr Glu Val Ile Gln His Ile Pro Als Gln Gln Gln Asp His Pro Glu <210> 71 <211> 921 <212> DNA
<213> Homo sapiens <400> 71 atgtctatga ttttatctgcctcagtcattcgtgtcagagatggactgccactttctgct60 tctactgatt atgaacaaagcacaggaatgcaggagtgcagaaagtattttaaaatgctt120 tcgaggaaac ttgctcaacttcctgatagatgtacactgaaaactggacattataacatt180 aettttatta gctctctgggagtgagctacatgatgttgtgcactgaaaattacccaaat240 gttctcgcct tctctttcctggatgagcttcagaaggagttcattactacttataacatg300 atgaagacaa atactgctgtcagaccatactgtttcattgeatttgataacttcattcag360 aggaccaagc agcgatataataatcccaggtctctttcaacaaegataaatctttctgac420 atgcagacgg aaatcaagctgaggcctccttatcaaatttccatgtgcgaactggggtca480 gccaetggag tcacatcagcattttctgttgactgtaaeggtgctggtaagatttcttct540 gctcaccagc gactggaaccagcaactctgtcagggattgtaggatttatccttagtctt600 ttatgtggag ctctgaatttaattcgaggctttcatgctatagaaagtctcctgcagagt660 gatggtgatg attttaattacatcattgcatttttccttggaacagcagcctgcctttac720 cagtgttatt tacttgtctactacaccggctggcggaatgtcaaatcttttttgactttt780 ggcttaatct gtctatgcaacatgtatctctatgaactgcgcaacctctggcagcttttc840 I5 tttcatgtga ctgtgggagcatttgttacactacagatctggctaaggcaagcccagggc900 aaggctcccg attatgatgt c 921 <210> 72 <211> 549 <212> DNA

<213> Homo Sapiens <400> 72 atgacggccc aggggggcct ggtggctaac cgaggccggc gcttcaagtg ggccattgag 60 ctaagcgggc ctggaggaggcagcaggggtcgaagtgaccggggcagtggccagggagac120 tcgctctacc cagtcggttacttggacaagcaagtgcctgataccagcgtgcaagagaca180 gaccggatcc tggtggagaagcgctgctgggacatcgccttgggtcccctcaaacagatt240 cccatgaatc tcttcatcatgtacatggcaggcaatactatctccatcttccctactatg300 atggtgtgta tgatggcctggcgacccattcaggcacttatggccatttcagccactttc360 aagatgttag aaagttcaagccagaagtttcttcagggtttggtctatctcattgggaac420 ctgatgggtt tggcattggc tgtttacaag tgccagtcca tgggactgtt acctacacat 480 gcatcggatt ggttagcctt cattgagccc cctgagagaa tggagttcag tggtggagga 540 ctgcttttg 549 <210> 73 <211> 981 <212> DNA
<213> Homo sapi.ens <400> 73 atgcgcgccc tccccggcctgctggaggccagggcgcgta 60 cgccccggct gctcctectc cagtgccttc tcgctgccgcgcgcccaagctcggcggacggcagtgcccc 120 agattcgcct tttacaagtc cacctctcagagaagaaataatggcaaataacttttccttggagagtcat180 aacatatcac tgactgaacattctagtatgccagtagaaaaaaatatcactttagaaagg240 ccttctaatg taaatctcacatgccagttcacaacatctggggatttgaatgcagtaaat300 gtgacttgga aaaaagatggtgaacaacttgagaataattatcttgtcagtgcaacagga360 agcaccttgt atacccaatacaggttcaccatcattaatagcaaacasatgggaagttat420 tcttgtttct ttcgagaggaasaggaecaaaggggaacatttaatttcaaagtccctgaa480 cttcatggga aaaacaagccattgatctcttacgtaggggattctactgtcttgacatgt540 aastgtcaaa attgttttcctttaaattggacctggtacagtagtaatgggagtgtaaag600 gttcctgttg gtgttcaaatgaataaatatgtgatcaatggaacatatgctaacgeaaca660 aagctgaaga taacacaacttttggaggaagatggggsatcttactggtgccgtgcacta720 ttcceattag gcgagagtgaagaacacattgagcttgtggtgctgagctatttggtgccc780 ctcaaaccat ttcttgtaatagtggctgaggtgattcttttagtggccaccattctgctt840 tgtgaaaagt acacacaaaagaasaagaagcactcagatgaggggaaagaatttgagcag900 attgaacagc tgaaatcaga ggtatagaaaataatgtccccaggcataga960 tgatagcaat aaaaatgagt 981 ctctgggcca g <210> 74 <211> 669 <212> DNA

<213> Homo sapiens <400> 74 atgaagttcg tcccctgcctcctgctggtgaccttgtcctgcctggggactttgggtcag 60 gccccgaggc aaaagcaaggaagcactggggaggaattccatttccagactggagggaga 120 gattcctgca ctatgcgtcccagcagcttggggcaaggtgctggagaegtctggcttcgc 180 gtcgactgcc gcaacacagaccagacctactggtgtgagtacagggggcagcccagcatg 240 tgccaggctt tcgctgctgaccccasatcttactggaatcaagccctgcaggagctgagg 300 cgccttcacc atgcgtgccagggggccccggtgcttaggccatccgtgtgcagggaggct 360 ggaccccagg cccatatgcagcaggtgacttccagcctcaagggcagcccagagcccaac420 cagcagcctg aggctgggacgccatctctgaggcccaaggccacagtgaeactcacagaa480 gcaacacagc tgggaaaggactcgatggaagagctgggaaaagccaaacccaccacccga540 cccacagcca aacctacccagcctggacccaggcccggagggaatgaggaagceaagaag600 aaggcctggg aacattgttggaaacccttccaggccctgtgcgcctttctcatcagcttc660 ttccgaggg 669 <210> 75 <211> 144 <212> DNA
<213> Homo sapiens <400> 75 atgaggcttc tgctgcttct cctagtggcg gcgtctgcga tggtccggag cgaggcctcg 60 gccaatctgg gcggcgtgcc cagcaagaga ttsaagatgc agtacgccac ggggccgctg 120 ctcaagttcc agatttgtgt ttcc 144 <210> 76 <211> 1113 <212> DNA
<213> Homo sapiens <400> 76 atggcctgga ccaagtacca gctgttcctg gccgggctca tgcttgttac cggctccatc 60 aacacgctct cggcaaaatgggcggacaatttcatggccgagggctgtggagggagcaag120 gagcacagct tccagcatcccttcctccaggcagtgggcatgttcctgggagaattctcc180 tgcctggctg ccttctacctcctccgatgcagagctgcagggcaatcagactccagcgta240 gacccccagc agcccttcaaccctcttcttttcctgcccccagcgctctgtgacatgaca300 gggaccagcc tcatgtatgtggctctgaacatgaccagtgcctccagcttccagatgctg360 cggggtgcag tgatcatattcactggcctgttctcggtggccttcctgggccggaggctg420 , gtgctgagcc agtggctgggcatcctagccaccatcgcggggctggtggtcgtgggcctg480 gctgacctcc tgagcaagcacgacagtcagcacaagctcagcgaagtgatcacaggggac540 ctgttgatca tcatggcccagatcatcgttgccatccagatggtgctagaggagaagttc600 gtctacaaec acaatgtgcacccactgcgggcagttggcactgagggcctctttggcttt660 gtgatcctct ccctgctgctggtgcccatgtactacatccccgccggctccttcagcgga720 78/x77 aaccctcgtg ggacactggaggatgcattggacgccttctgccaggtgggccagcagccg780 ctcattgccg tggcactgctgggcaacatcagcagcattgccttcttcaacttcgcaggc840 atcagcgtca ccaaggaactgagcgccaccacccgcatggtgttggacagcttgcgeacc900 gttgtcatct gggcactgagcctggcactgggctgggaggccttccatgcactgcagatc960 cttggcttcc tcatactccttataggcactgccctctacaatgggctacaccgtccgctg1020 ctgggccgcc tgtccaggggccggcccctggcagaggagsgcgagcaggagagactgctg1080 ggtggcaccc gcactcccatcaatgatgccagc 1113 <210> 77 <211> 270 <212> DNA
<213> Homo sapiens <400> 77 atgttccaccsaatttgggcagctctgctctacttctatggtattatccttaactccatc60 taccagtgcc ctgagcacagtcaactgacaactctgggcgtggatgggaaggagttccca120 gaggtccact tgggccagtggtactttatcgcaggggcagctcccaccaaggaggagttg180 gcaacttttg accctgtggacaacattgtcttcaatatggctgctggctctgccccgatg240 cagctccacc ttcgtgctaccatccgcatg 270 <210>78 <211>1497 <212>DNA

<213>Homo sapiens <400> 78 atggtggacc ggggccctctgctcacctcggccatcatcttctacctggccatcggggcg60 gcgatcttcg aagtgctggaggagccacactggaaggaggccaagaaaaactactacaca120 cagaagctgc atctgctcaaggagttcccgtgcctgggtcaggagggcctggacaagatc180 ctagaggtggtatctgatgctgcaggacagggtgtggccatcacagggaaccagaccttc240 aacaactgga actggcccaatgcaatgatttttgcagcgaccgtcattaccaccattgga300 tatggcaatg tggctcccaagacccccgccggtcgcctcttctgtgttttctatggtctc360 ttcggggtgc cgctctgcctgacgtggatcagtgccctgggcaagttcttcgggggacgt420 gceaagagac tagggcagttccttaccaagagaggtgtgagtctgcggaaggcgcagatc480 acgtgcacagtcatcttcatcgtgtggggcgtcctagtccacctggtgatcccacccttc540 WO 00/05367 PCT/JP99/0392~

gtattcatgg tgactgaggg gtggaactac atcgagggcc tctactactc cttcatcacc 600 atctccacca tcggcttcgg tgactttgtg gccggtgtga accccagcgc caactaccac 660 gccctgtacc gctacttcgt ggagctctgg atctacttgg ggctggcctg gctgtccctt 720 tttgtcaact ggaaggtgag catgtttgtg gaagtccaca aagccattaa gaagcggegg 780 cggcgacgga aggagtcctt tgagagctcc ccacactccc ggaaggccct gcaggtgaag 840 gggagcacag cctccaagga cgtcaacatc ttcagctttc tttccaagaa ggaagagacc 900 tacaaegacc tcatcaagca gatcgggaag aaggccatga agacaagcgg gggtggggag 960 acgggcccgg gcccagggct ggggcctcaa ggcggtgggc tcccagcact gcccccttcc 1020 ctggtgcccc tggtagtcta ctccaagaac cgggtgccca ccttggaaga ggtgtcacag 1080 acactgagga gcaaaggccs cgtatcaagg tccccagatg aggaggctgt ggcacgggcc 1140 cctgaagaca gctcccctgc ccccgaggtg ttcstgaacc agctggaccg catcagcgag 1200 gaatgcgagc catgggacgc ccaggactac cacccactca tcttccaggs cgccagcatc 1260 accttcgtga acacggaggc tggcctctca gacgaggaga cctccaagtc ctcgctagag 1320 gacaacttgg caggggagga gagcccccag cagggggctg aagccaaggc gcccctgaac 1380 atgggcgagt tcccctcctc ctccgagtcc accttcacca gcactgagtc tgagctctct 1440 gtgccttacg aacagctgat gaatgagtac aacaaggcta acagccccaa gggcaca 1497 <210> 79 <211> 318 <212> DNA
<213> Homo sapiens <400> 79 atggcgtctt cgggagctgg tgaccctctg gattctaagc gtggagaggc cccgttcgct 60 cagcgtatcg acccgactcgggagaagctgacacccgagcaactgcattccatgcggcag120 gcggagcttg cccagtggcagaaggtcctsccacggcggcgaacccggaacatcgtgacc180 ggcctaggca tcggggccctggtgttggctatttatggttacaccttctactcgatttcc240 caggagcgtt tcctagatgagctagaagacgaggccaaagctgcccgagcccgagctctg300 gcaagggcgt cagggtcc 318 <210> 80 <211> 456 <212> DNA

<213> Homo Sapiens <400> 80 atggactatg tgtgctgtgcttacaacaacataaccggcaggcaagatgaaactcatttc60 acagttatca tcacttccgtaggactggagaagcttgcacagaaaggaaaatcattgtca120 cctttagcaa gtataactggaatatcactatttttgattatatccatgtgtcttctcttc180 ctatggaaaa aatatcaaccctacaeagttataaaacagaaactagaaggcaggccagaa240 acagaataca ggaaagctcaaacattttcaggccatgaagatgctctggatgacttcgga300 atatatgaat ttgttgcttttccagatgtttctggtgtttccaggatcccaegcaggtct360 gttccagcct ctgattgtgtatcggggcaagatttgcacagtacagtgtatgaagttatt420 cagcacatcc ctgcccagcagcaagaccatccagag 456 <210> 81 <211> 1436 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (66)...(989) <400> 81 gcacttcggg gcgcgtcact cggagcggcg ggtcccgtct cgacaggtct tctctgttgg 60 ttgaa atg tct atg att tta tct gcc tca gtc att cgt gtc aga gat 107 Met Ser Met Ile Leu Set Ala Ser Val Ile Arg Val Arg Asp 1 5 ~ 10 gga ctg cca ctt tet get tct act gat tat gas caa agc aca gga atg 155 Gly Leu Pro Leu Ser Ala Ser Thr Asp Tyr Glu Gln Ser Thr Gly Met cag gag tgc aga aag tat ttt aaa atg ctt tcg agg aaa ctt get caa 203 Gln Glu Cys Arg Lys Tyr Phe Lys Met Leu Ser Arg Lys Leu Ala Gln 40 dS
30 ctt cct gat aga tgt aca ctg aaa act gga cat tat aac att aat ttt 251 Leu Pro Asp Arg Cys Thr Leu Lys Thr Gly His Tyr Asn Ile Asn Phe 50 55 ~n att agc tct ctg gga gtg agc tac atg atg ttg tgc act gaa aat tac 299 Ile Ser Ser Leu Gly Val Ser Tyr Met Met Leu Cys Thr Glu Asn Tyr cca aat gtt ctc gcc ttc tct ttc ctg gat gag ctt cag aag gag ttc 347 Pro Asn Val Leu Ala Phe Ser Phe Leu Asp Glu Leu Gln Lys Glu Phe att act act tat aac atg atg.aag aca aat act get gtc aga cca tac 395 Ile Thr Thr Tyr Asn Met Met Lys Thr Asn Thr Ala Val Arg Pro Tyr tgt ttc att gaa ttt gat aac ttc att cag agg acc aag cag cga tat 443 Cys Phe Ile Glu Phe Asp Asn Phe Ile Gln Arg Thr Lys Gln Arg Tyr ~10 aat aatcccagg tctctttcaacaaagata aatctttctgac atgcag 491 Asn AsnProArg SerLeuSerThrLysIle AsnLeuSerAsp MetGln acg gaaatcaag ctgaggcctccttatcaa atttccatgtgc gaactg 539 Thr GluIleLys LeuArgProProTyrGln IleSerMetCys GluLeu ggg tcagccaat ggagtcacatcagcattt tctgttgactgt aaaggt 587 Gly SerAlaAsn GlyValThrSerAlaPhe SerValAspCys LysGly get ggtaagatt tcttctgetcaccagcga ctggaaccagca actctg 635 Ala GlyLysIle SerSerAlaHisGlnArg LeuGluProAla ThrLeu tca gggattgta ggatttatcettagtctt ttatgtggaget ctgaat 683 Ser GlyIleVal GlyPheIleLeuSerLeu LeuCysGlyAla LeuAsn tta attcgaggc tttcatgetatagaaagt ctcctgcagagt gatggt 731 Leu IleArgGly PheHisAlaIleGluSer LeuLeuGlnSer AspGly gat gattttaat tacatcattgcatttttc cttggaacagca gcctgc 779 Asp AspPheAsn TyrIleIleAlaPhePhe LeuGlyThrAla AlaCys ctt tac cag tgt tat tta ctt gtc tac tac acc ggc tgg cgg aat gtc 827 Leu Tyr Gln Cys Tyr Leu Leu Val Tyr Tyr Thr Gly Trp Arg Asn Val aaa tct ttt ttg act ttt ggc tta atc tgt cta tgc aac atg tat ctc 875 Lys Ser Phe Leu Thr Phe Gly Leu Ile Cys Leu Cys Asn Met Tyr Leu tat gas ctg cgc aac ctc tgg cag ctt ttc ttt cat gtg act gtg gga 923 Tyr Glu Leu Arg Asn Leu Trp Gln Leu Phe Phe His Val Thr Val Gly gca ttt gtt aca cta cag atc tgg cta agg caa gcc cag ggc aeg get 971 Ala Phe Val Thr Leu Gln Ile Trp Leu Arg Gln Ala Gln Gly Lys Ala ccc gat tat gat gtc tgacaccatc cttcagatct attgccttgg cttc 1020 Pro Asp Tyr Asp Val agggggataa ggagggaacatatcatasctgcactgtgatgaagaagctgttccccacag1080 aggagaagct ctgctttctttctctccaactttccttttttaaaatcagcatgatgtgcc1140 tgtgagcatg gsagagtcctctcagaagaatgttggccatgagactatcattcagaggag1200 gaggggattt ctctcttcaaggccataacagtggaagaacagtcatatgccattggaagt1260 cttggccagc agtcctgaatccttcctgaagagttcagaaaatagatgtggtattgctct1320 gaggaccagg caggaggaactctacaacctgagtttgcctttgtgaggcattagtataga1380 ccaaatasaa agctgcagaaattggaaagtttatgttttaastaaatgactgtgat 1936 <210> 82 <211> 997 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (87)...(638) <400> 82 gagacaeagc ggagaacgct ggtgggcctg ttgtggagta cgctttggac tgagaagcat 60 cgaggctata ggacgcagct gttgcc atg acg gcc cag ggg ggc ctg gtg 110 Met Thr Ala Gln Gly Gly Leu Val get sac cga ggc cgg cgc ttc asg tgg gcc att gag cta agc ggg cct 158 Ala Asn Arg Gly Arg Arg Phe Lys Trp Ala Ile Glu Leu Ser Gly Pro gga gga ggc agc agg ggt cga agt gac cgg ggc agt ggc cag gga gac 206 Gly Gly Gly Ser Arg Gly Arg Ser Asp Arg Gly Ser Gly Gln Gly Asp tcg ctc tac cca gtc ggt tac ttg gac aag caa gtg cct gat acc agc 254 Ser Leu Tyr Pro Val Gly Tyr Leu Asp Lys Gln Val Pro Asp Thr Ser gtg caa gag aca gac cgg atc ctg gtg gag aag cgc tgc tgg gac atc 302 Val Gln Glu Thr Asp Arg Ile Leu Val Glu Lys Arg Cys Trp Asp Ile gcc ttg ggt ccc ctc aaa cag att ccc atg aat ctc ttc atc atg tac 350 Ala Leu Gly Pro Leu Lys Gln Ile Pro Met Asn Leu Phe Ile Met Tyr atg gca ggc aat act atc tcc atc ttc cct act atg atg gtg tgt atg 398 Met Ala Gly Asn Thr Ile Ser Ile Phe Pro Thr Met Met Val Cys Met atg gcc tgg cga ccc att cag ctt atg att tca gcc act 446 gca gcc ttc Met Ala Trp Arg Pro Ile Gln Leu Met Ile Ser Ala Thr Ala Ala Phe aag atg tta gas agt tca agc aag ttt cag ggt ttg gtc 494 cag ctt tat Lys Met Leu Glu Ser Ser Ser Lys Phe Gln Gly Leu Val Gln Leu Tyr ctc att ggg aac ctg atg ggt gca ttg gtt tac aag tgc 542 ttg get cag Leu Ile Gly Asn Leu Met Gly Ala Leu Val Tyr Lys Cys Leu Ala Gln tcc atg gga ctg tta cct aca gca tcg tgg tta gcc ttc 590 cat gat att Ser Met Gly Leu Leu Pro Thr Ala Ser Trp Leu Ala Phe His Asp Ile gag ccc cct gag aga atg gag agt ggt gga ctg ctt ttg 640 ttc gga tgaac Glu Pro Pro Glu Arg Met Glu Ser Gly Gly Leu Leu Leu Phe Gly atgagaaagc agcgcctggt ccctatgtatttgggtcttatttacatcct tctttaagcc700 cagtggctcc tcagcatact cttasactaatcacttatgttaaaaagasc caaaagactc760 ttttctccat ggtggggtga caggtcctagaaggacaatgtgcatattac gacaaacaca820 aagaaactat accataaccc aaggctgaaaataatgtagaaaactttatt tttgtttcca880 gtacagagca aaacsacaec aaaaaaacataactatgtaaacaagagaat aactgctgct940 saatcaagaa ctgttgcagc atctcctttcaataaattaaatggttgaga acaatgc997 ccaaatas <210> 83 <211> 1753 <212> DNA
<213> Homo Sapiens <220>
<221> CDS
<222> {134)...(1117) <400> 83 tcttcagcgt cctacccgcg gcactggctg cgagcgccgg gccacctgcg agtgtgcgca 60 gggactctgg acacccgcgg cggcgagctg agggagcagt ctccacgagg acccaggcgg 120 accctctggc gcc atg cgc gcc ctc ccc ggc ctg ctg gag gcc agg gcg 169 Met Arg Ala Leu Pro Gly Leu Leu Glu Ala Arg Ala cgt acg ccc cgg ctg ctc ctc ctc cag tgc ctt ctc get gcc gcg cgc 217 Arg Thr Pro Arg Leu Leu Leu Leu Gln Cys Leu Leu Ala Ala Ale Arg cca agc tcg gcg gac ggc agt gcc cca gat tcg cct ttt aca agt cca 265 Pro Ser Ser Ala Asp Gly Ser Ala Pro Asp Ser Pro Phe Thr Ser Pro cct ctc aga gaa gaa ata atg gca aat eac ttt tcc ttg gag agt cat 313 Pro Leu Arg Glu Glu Ile Met Ala Asn Asn Phe Ser Leu Glu Ser His eac ata tca ctg act gaa cat tct agt atg cca gta gaa aaa aat atc 361 Asn Ile Ser Leu Thr Glu His Ser Ser Met Pro Val Glu Lys Asn Ile act tta gaa agg cct tct aat gta aat ctc aca tgc cag ttc aca aca 409 Thr Leu Glu Arg Pro Ser Asn Val Asn Leu Thr Cys Gln Phe Thr Thr tct ggg gat ttg aat gca gta sat gtg act tgg aaa aaa gat ggt gaa 457 Ser Gly Asp Leu Asn Ala Val Asn Val Thr Trp Lys Lys Asp Gly Glu caa ctt gag aat aat tat ctt gtc agt gca aca gga agc acc ttg tat 505 Gln Leu Glu Asn Asn Tyr Leu Val Ser Ala Thr Gly Ser Thr Leu Tyr WO 00/05367 PCT/,1P99/0392~

acc caa tac agg ttc acc atc att sat agc aaa caa atg gga agt tat 553 Thr Gln Tyr Arg Phe Thr Ile Ile Asn Ser Lys Gln Met Gly Ser Tyr tct tgt ttc ttt cga gag gaa aag gaa caa agg gga aca ttt aat ttc 601 Ser Cys Phe Phe Arg Glu Glu Lys Glu Gln Arg Gly Thr Phe Asn Phe aaa gtc cct gaa ctt cat ggg aea aac aag cca ttg atc tct tac gta 649 Lys Val Pro Glu Leu His Gly Lys Asn Lys Pro Leu Ile Ser Tyr Val ggg gat tct act gtc ttg aca tgt saa tgt caa aat tgt ttt cct tta 697 Gly Asp Ser Thr Val Leu Thr Cys Lys Cys Gln Asn Cys Phe Pro Leu aat tgg acc tgg tac agt agt aat ggg agt gta aag gtt cct gtt ggt 745 Asn Trp Thr Trp Tyr Ser Ser Asn Gly Ser Val Lys Val Pro Val Gly gtt caa atg aat aaa tat gtg atc aat gga aca tat get aac gaa aca 793 Val Gln Met Asn Lys Tyr Val Ile Asn Gly Thr Tyr Ala Asn Glu Thr eag ctg aag ata aca caa ctt ttg gag gaa gat ggg gaa tct tac tgg 841 Lys Leu Lys Ile Thr Gln Leu Leu Glu Glu Asp Gly Glu Ser Tyr Trp tgc cgt gca cta ttc caa tta ggc gag agt gaa gaa cac att gag ctt 889 Cys Arg Ala Leu Phe Gln Leu Gly Glu Ser Glu Glu His Ile Glu Leu gtg gtg ctg agc tat ttg gtg ccc ctc aaa cca ttt ctt gta ata gtg 937 Val Val Leu Ser Tyr Leu Val Pro Leu Lys Pro Phe Leu Val Ile Val get gag gtg att ctt tta gtg gcc acc att ctg ctt tgt gaa aag tac 985 Ala Glu Val Ile Leu Leu Val Als Thr Ile Leu Leu Cys Glu Lys Tyr acs caa sag aaa asg aag cac tca gat gag ggg aaa gaa ttt gag cag 1033 Thr Gln Lys Lys Lys Lys His Ser Asp Glu Gly Lys Glu Phe Glu Glri att gaa cag ctg aaa tca gat gat agc eat ggt ata gaa aat aat gtc 1081 Ile Glu Gln Leu Lys Ser Asp Asp Ser Asn Gly Ile Glu Asn Asn Val ccc agg cat aga aaa aat gag tct ctg ggc cag tgaatacaaa acatca 1130 Pro Arg His Arg Lys Asn Glu Ser Leu Gly Gln tgtcgagaat cattggaaga tatacagagt tcgtatttca gctttattta tccttcctgt 1190 taagagcctc tgagttttta gttttaaaag gatgaaaagc ttatgcaaca tgctcagcag 1250 gagcttcatc aacgatatat gtcagatcta aaggtatatt ttcattctgt aattatgtta 1310 cataasagca atgtaaatca gaataaatat gttagaccag aataaaatta attatattct 1370 ggtcttcaaa ggacacacag aacagatatc agcagaatca cttaatactt catagaacaa 1430 aaatcactca aaacctgttt ataaccaaag aattcatgaa aaagaaagcc tttgccattt 1490 gtcttagaaa gttatttttt taaaasaaat catacttact attagtatct atggaagtat 1550 atgtaacaat ttttatgtaa aggtcatctt tctgtgatag tgaasaaata tgtctttact 1610 aagttgaaat gaatactttc tgcctttgct catgatagtt attctacaat ctccacaaga 1670 aaaatatacc ttttatccgg saatattggt ttaaggcaaa taaataaaac tgtgcttgct 1730 cteaagctct gcactacaae agc 1753 <210> 84 <211> 1117 <212> DrrA
<213> Homo sapiens <220>
<221> CDS
<222> (62)...(733) <400> 84 cgtcccactt gtgttctctc tcctggtgca gagttgcaag caagtttatc ggagtatcgc 60 c atg aag ttc gtc ccc tgc ctc ctg ctg gtg acc ttg tcc tgc ctg 106 Met Lys Phe Val Pro Cys Leu Leu Leu Val Thr Leu Ser Cys Leu ggg act ttg ggt cag gcc ccg agg caa aag caa gga agc act ggg gag 154 Gly Thr Leu Gly Gln Ala Pro Arg Gln Lys Gln Gly Ser Thr Gly Glu gaa ttc cat ttc cag act gga ggg aga gat tcc tgc act atg cgt ccc 202 Glu Phe His Phe Gln Thr Gly Gly Arg Asp Ser Cys Thr Met Arg pro agc agc ttg ggg caa ggt get gga gea gtc tgg ctt cgc gtc gac tgc 250 Ser Ser Leu Gly Gln Gly Ala Gly Glu Val Trp Leu Arg Val Asp Cys cgc aac aca gac cag acc tac tgg tgt gag tac agg ggg cag ccc agc 298 Arg Asn Thr Asp Gln Thr Tyr Trp Cys Glu Tyr Arg Gly Gln Pro Ser atg tgc cag get ttc get get gac ccc aaa tct tac tgg aat caa gcc 346 Met Cys Gln Als Phe Ala Ala Asp Pro Lys Ser Tyr Trp Asn Gln Ala 80 B5 90 g5 ctg cag gag ctg agg cgc ctt cac cat gcg tgc cag ggg gcc ccg gtg 394 Leu Gln Glu Leu Arg Arg Leu His His Ala Cys Gln Gly Ala Pro Val ctt agg cca tcc gtg tgc agg gag get gga ccc cag gcc cat atg cag 442 Leu Arg Pro Ser Val Cys Arg Glu Ala Gly Pro Gln Ala His Met Gln cag gtg act tcc agc ctc aag ggc agc cca gag ccc aac cag cag cct 490 Gln Val Thr Ser Sex Leu Lys Gly Ser Pro Glu Pro Asn Gln Gln Pro gag get ggg acg cca tct ctg agg cec aag gcc aca gtg aaa ctc aca 538 Glu Ala Gly Thr Pro Ser Leu Arg Pro Lys Ala Thr Val Lys Leu Thr gaa gca aca cag ctg gga aag gac tcg atg gaa gag ctg gga saa gcc 586 Glu Ala Thr Gln Leu Gly Lys Asp Ser Met Glu Glu Leu Gly Lys Ala aaa ccc acc acc cga ccc aca gcc aaa cct acc cag cct gga ccc agg 634 Lys Pro Thr Thr Arg Pro Thr Ala Lys Pro Thr Gln Pro Gly Pro Arg ccc gga ggg aat gag gaa gca aag aag aag gcc tgg gaa cat tgt tgg 682 Pro GIy Gly Asn Glu Glu AIa Lys Lys Lys Ala Trp Glu His Cys Trp aaa ccc ttc cag gcc ctg tgc gcc ttt ctc atc agc ttc ttc cga ggg 730 Lys Pro Phe Gln Ala Leu Cys Ala Phe Leu Ile Ser Phe Phe Arg Gly tgacaggtga aagaccccta cagatctgac ctctccctga cagacaacca tctcttttta 790 tattatgccg ctttcaatccaacgttctcacactggaagaagagagtttctaatcagatg850 caacggccca aattcttgatctgcagcttctctgaagtttggaaaagaaaccttcctttc910 tggagtttgc agagttcagcastatgatagggaacaggtgctgatgggcccaagagtgac970 aagcatacac aactacttattatctgtagaagttttgctttgttgatctgagccttctat1030 gaaagtttaa atatgteacgcattcatgaatttccagtgttcagtaaetagcagctatgt1090 gtgtgcaaaa taaaagaatgatttcag 1117 <210> 85 <211> 1380 <212> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (43)...(189) <400> 85 gcagtctgtc tgagggcggc cgaagtggct ggctcattta ag atg agg ctt ctg 54 Met Arg Leu Leu ctg ctt ctc cta gtg gcg gcg tct gcg atg gtc cgg agc gag gcc tcg 102 Leu Leu Leu Leu Val Ala Ala Ser Ala Met Val Arg Ser Glu Ala Ser gcc aat ctg ggc ggc gtg ccc agc aag aga tta aag atg cag tac gcc 150 Ala Asn Leu Gly Gly Val Pro Ser Lys Arg Leu Lys Met Gln Tyr Ala acg ggg ccg ctg ctc aag ttc cag att tgt gtt tcc tgag 190 Thr Gly Pro Leu Leu Lys Phe Gln Ile Cys Val Ser gttataggcg ggtgtttgag gagtacatgc gggttattag ccagcggtac ccagacatcc 250 gcattgaagg agagaattacctccctcaaccaatatatagacacatagcatctttcctgt 310 cagtcttcaa actagtattaataggcttaataattgttggcaaggatccttttgctttct 370 ttggcatgca agctcctagcatctggcagtggggccaagaaaataaggtttatgcatgta 430 tgatggtttt cttcttgagcaacatgattgagaaccagtgtatgtcaacaggtgcatttg 490 agataacttt aaatgatgtacctgtgtggtctaagctggaatctggtcaccttccatcca 550 tgcaacaact tgttcaaattcttgacaatgaaatgaagctcaatgtgcatatggattcaa 610 tcccacacca tcgatcatag caccacctat cagcactgaa aactcttttg cattaaggga 670 tcattgcaag agcagcgtga ctgacattat gaaggcctgt actgaagaca gceagctgtt 730 agtacagacc agatgctttc ttggcaggct cgttgtacct cttggaaaac ctcaatgeaa 790 gatagtgttt cagtgctggc atattttgga attctgcaca ttcatggagt gcaataatac 850 tgtatagctt tccccacctc ccacaaeatc acccagttaa tgtgtgtgtg tgtttttttt 910 tttaaggtea acattactac ttgtaacttt ttttcttagt catatttgaa eaagtagaaa 970 attgagttac satttgattt tttttccaaa gatgtctgtt aaatctgttg tgcttttata 1030 tgaatatttg ttttttatag tttaaaattg atcctttggg aatccagttg aagttcccaa 1090 atactttata agagtttatc agacatctct aatttggcca tgtccagttt atacagttta 1150 caaaatatag cagatgcaag attatggggg asatcctata ttcagagtac tctataaatt 1210 tttgtgtatg tgtgtatgtg cgtgtgatta ccagagaact actaaaaaaa ccaactgctt 1270 tttaaatcct attgtgtagt taaagtgtca tgccttgacc aatctaatga attgattaat 1330 tsactgggcc tttatactta actaaatasa aaactaagca gatatgagtt 1380 <210> e6 <211> 1503 <212> DNA
<213> Homo sapiens <220>
<221> CDS
<222> (51)...(1166) <400> 86 gtgacggggc ccggcgccgc taactggagc gaaccccagc gtccgccgac atg gcc 56 Met Ala tgg acc aag tac cag ctg ttc ctg gcc ggg ctc atg ctt gtt acc ggc 104 Trp Thr Lys Tyr Gln Leu Phe Leu Ala Gly Leu Met Leu Val Thr Gly 5 in is tcc atc aac acg ctc tcg gca aaa tgg gcg gac aat ttc atg gcc gag 152 Ser Ile Asn Thr Leu Ser Ala Lys Trp Ala Asp Asn Phe Met Ala Glu ggc tgt gga ggg agc aag gag cac agc ttc cag cat ccc ttc ctc cag 200 Gly Cys Gly Gly Ser Lys Glu His Ser Phe Gln His Pro Phe Leu Gln gca gtg ggc atg ttc ctg gga gaa ttc tcc tgc ctg get gcc ttc tac 248 Ala Val Gly Met Phe Leu Gly Glu Phe Ser Cys Leu Ala Ala Phe Tyr ctc ctc cga tgc aga get gca ggg caa tca gac tcc agc gta gac ccc 296 Leu Leu Arg Cys Arg Ala Ala Gly Gln Ser Asp Ser Ser Val Asp Pro cag cagcccttc aaccctcttctt ttcctgcccccagcgctc tgt gac 344 Gln GlnProPhe AsnProLeuLeu PheLeuProProAlaLeu Cys Asp atg acagggacc agcctcatgtat gtggetctgcacatgacc agt gcc 392 Met ThrGlyThr SerLeuMetTyr ValAlaLeuAsnMetThr Ser Ala tcc agcttccag atgctgcggggt gcagtgatcatattcact ggc ctg 440 Ser SerPheGln MetLeuArgGly AlaValIleIlePheThr Gly Leu 115 120 125. 130 ttc tcggtggcc ttcctgggccgg aggctggtgctgagccag tgg ctg 488 Phe SerValAla PheLeuGlyArg ArgLeuValLeuSerGln Trp Leu ggc atc cta gcc acc atc gcg ggg ctg gtg gtc gtg ggc ctg get gac 536 Gly Ile Leu Ala Thr Ile Ala Gly Leu Val Val Val Gly Leu Ala Asp ctc ctg agc aag cac gac agt cag cac aag ctc agc gaa gtg atc aca 584 Leu Leu Ser Lys His Asp Ser Gln His Lys Leu Ser Glu Val Ile Thr ggg gac ctg ttg atc atc atg gcc cag atc atc gtt gcc atc cag atg 632 Gly Asp Leu Leu Ile Ile Met Ala Gln Ile Ile Val Ala Ile Gln Met gtg cta gag gag aag ttc gtc tac aaa cac aat gtg cac cca ctg cgg 680 Val Leu Glu Glu Lys Phe Val Tyr Lys His Asn Val His Pro Leu Arg gca gtt ggc act gag ggc ctc ttt ggc ttt gtg atc ctc tcc ctg ctg 728 Ala Val Gly Thr Glu Gly Leu Phe Gly Phe Val Ile Leu Ser Leu Leu ctg gtg ccc atg tac tac atc ccc gcc ggc tcc ttc agc gga aac cct 776 Leu Val Pro Met Tyr Tyr Ile Pro Ala Gly Ser Phe Ser Gly Asn Pro cgt ggg aca ctg gag gat gca ttg gac gcc ttc tgc cag gtg ggc cag 824 Arg Gly Thr Leu Glu Asp Ala Leu Asp Ala Phe Cys Gln Val Gly Gln cag ccg ctc att gcc gtg gca ctg ctg ggc aac atc agc agc att gcc 872 Gln Pro Leu Ile Ala Val Ala Leu Leu Gly Asn Ile Ser Ser Ile Ala ttc ttc aac ttc gca ggc atc agc gtc acc aag gaa ctg agc gcc acc 920 Phe Phe Asn Phe Ala Gly Ile Ser Val Thr Lys Glu Leu Ser Ala Thr acc cgc atg gtg ttg gac agc ttg cgc acc gtt gtc atc tgg gca ctg 968 Thr Arg Met Val Leu Asp Ser Leu Arg Thr Val Val Ile Trp Ala Leu agc ctg gca ctg ggc tgg gag gcc ttc cat gca ctg cag atc ctt ggc 1016 Ser Leu Ala Leu Gly Trp Glu Ala Phe His Ala Leu Gln Ile Leu Gly ttc ctc ata ctc ctt ata ggc act gcc ctc tac aat ggg cta cac cgt 1064 Phe Leu Ile Leu Leu Ile Gly Thr Ala Leu Tyr Asn Gly Leu His Arg ccg ctg ctg ggc cgc ctg tcc agg ggc cgg ccc ctg gca gag gag agc 1112 Pro Leu Leu Gly Arg Leu Ser Arg Gly Arg Pro Leu Ala Glu Glu Ser gag cag gag aga ctg ctg ggt ggc acc cgc act ccc atc aat gat gcc 1160 Glu Gln Glu Arg Leu Leu Gly Gly Thr Arg Thr Pro Ile Asn Asp Ala agc tgaggttccc tggaggcttc tactgccacc cgggtgctcc ttctccc 1210 Ser tgagactgag gccacacagg ctggtgggcc ccgaatgccc tatccccaag gcctcaccct 1270 gtcccctccc tgcagaaccc ccagggcagc tgctgccaca gaagataaca acacccaagt 1330 cctctttttc tcactaccac ctgcagggtg gtgttaccca gcccccacaa gcctgagtgc 1390 agtggcagac ctcagctctc tggacccctc ctacagcact agagctaaat catgaagttg 1450 aattgtagga atttaccacc gtagtgtatc tgaatcataa actagattat cat 1503 <210> 87 <211> 733 <212> DNA
<2I3> Homo sapiens <220>
<221> CDS
<222> (40)...(312) <400> 87 gttaaggcac acagagcacc agctccctcc tgcctgaag atg ttc cac caa att 54 Met Phe His Gln Ile tgg gca get ctg ctc tac ttc tat ggt att atc ctt aac tcc atc tac 102 Trp Ala Ala Leu Leu Tyr Phe Tyr Gly Ile Ile Leu Asn Ser Ile Tyr I5 cag tgc cct gag cac agt caa ctg aca act ctg ggc gtg gat ggg aag 150 Gln Cys Pro Glu His Ser Gln Leu Thr Thr Leu Gly Val Asp Gly Lys gag ttc cca gag gtc cac ttg ggc cag tgg tac ttt atc gca ggg gca 198 Glu Phe Pro Glu Val His Leu Gly Gln Trp Tyr Phe Ile Ala Gly Ala get cec acc aag gag gag ttg gca act ttt gac cct gtg gac aac att 246 Ala Pro Thr Lys Glu Glu Leu Ala Thr Phe Asp Pro Val Asp Asn Ile gtc ttc aat atg get get ggc tct gcc ccg atg cag ctc cac ctt cgt 294 Val Phe Asn Met Ala Ala Gly Ser Ala Pro Met Gln Leu His Leu Arg get acc atc cgc atg tgagtggaaa gatgggctct gtgtgccccg g 340 Ala Thr Ile Arg Met 30 aaetggatct accacctgactgaagggagcacagatctcagaactgaaggccgccctgac400 atgaagactg agctcttttccagctcatgcccaggtggaatcatgctgaatgagacaggc460 cagggttacc agcgctttctcctctacaatcgctcaccacatcctcccgaaaagtgtgtg520 gaggaattca agtccctgacttcctgcctggactccaaagccttcttattgactcctagg580 eatcaegagg cctgtgagctgtccaataactgacctgtaacttcatctaagtccccagat640 35 gggtacaatg ggagctgagttgttggagggagaagctggagacttccagctccagctccc700 actcaagata ataaagataa tttttcaatc ctc 733 <210> 88 <211> 3768 <212> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (358)...(1857) <400> 88 gctagtggcg cgcggaggagcgacgcgtggagaegcggcccacgtgtctgcccagagtca60 agtcctgtgt tcttcccgctccttacgcatccgcggtccagggcgccctttcagccccgc120 tggtgttcgc ccaccccgggccgcgtgagtggggccccacgcagctccccgcactccgtg180 ggccaacttg gccaagcaactctgtccggggagcggtgcttgcggggggtgagtaccggg240 cactgcgcat gcggagctccaaattcaaacagctgttttcagaggctggagggcgggcgg300 actggtagca gctggggctaggagaggctttctctaggaggcggccgctcgggagcc 357 atg gtg gac cgg ggc cct ctg ctc acc tcg gcc atc atc 405 ttc tac ctg Met Val Asp Arg Gly Pro Leu Leu Thr Ser Ala Ile Ile Phe Tyr Leu gcc atc ggg gcg gcg atc ttc gaa gtg ctg gag gag cca 453 cac tgg aag Ala Ile Gly Ala Ala Ile Phe Glu Val Leu Glu Glu Pro Hi s Trp Lys gag gcc aag aaa aac tac tac aca cag aag ctg cat ctg 501 ctc aag gag Glu Ala Lys Lys Asn Tyr Tyr Thr Gln Lys Leu His Leu Leu Lys Glu ttc ccg tgc ctg ggt cag gag ggc ctg gac aag atc cta 549 gag gtg gta 30 Phe Pro Cys Leu Gly Gln Glu Gly Leu Asp Lys Ile Leu Glu Val Val tct gat get gca gga cag ggt gtg gcc atc aca ggg aac 597 cag acc ttc Ser Asp Ala Ala Gly Gln Gly Val Ala Ile Thr Gly Asn Gln Thr Phe 35 aac aac tgg aac tgg ccc aat gca atg att ttt gca gcg 695 acc gtc att Asn Asn Trp Asn Trp Pro Asn Ala Met Ile Phe Ala Ala Thr Val Ile acc acc att gga tat ggc aat gtg get ccc aag acc ccc gcc ggt cgc 693 Thr Thr Ile Gly Tyr Gly Asn Val Ala Pro Lys Thr Pro Ala Gly Arg loo l05 llo ctc ttc tgt gtt ttc tat ggt ctc ttc ggg gtg ccg ctc tgc ctg acg 741 Leu Phe Cys Val Phe Tyr Gly Leu Phe Gly Val Pro Leu Cys Leu Thr tgg atc agt gcc ctg ggc aag ttc ttc ggg gga cgt gcc asg aga eta 789 Trp Ile Ser Ala Leu Gly Lys Phe Phe Gly Gly Arg Ala Lys Arg Leu ggg cag ttc ctt acc aag aga ggt gtg agt ctg cgg aag gcg cag atc 837 Gly Gln Phe Leu Thr Lys Arg Gly Val Ser Leu Arg Lys Ala Gln Ile acg tgc aca gtc atc ttc atc gtg tgg ggc gtc cta gtc cac ctg gtg 885 Thr Cys Thr Val Ile Phe Ile Val Trp Gly Val Leu Val His Leu Val atc cca ccc ttc gta ttc atg gtg act gag ggg tgg aac tac atc gag 933 Ile Pro Pro Phe Val Phe Met Val Thr Glu Gly Trp Asn Tyr Ile Glu ggc ctc tac tac tcc ttc atc acc atc tcc acc atc ggc ttc ggt gac 981 Gly Leu Tyr Tyr Ser Phe Ile Thr Ile Ser Thr Ile Gly Phe Gly Asp ttt gtg gcc ggt gtg sac ccc agc gcc sac tac cac gcc ctg tac cgc 1029 Phe Val Ala Gly Val Asn Pro Ser Ala Asn Tyr His Ala Leu Tyr Arg 210 215 2~n tac ttc gtg gag ctc tgg atc tac ttg ggg ctg gcc tgg ctg tec ett 1077 Tyr Phe Val Glu Leu Trp Ile Tyr Leu Gly Leu Ala Trp Leu Ser Leu 225 230 235 ~dn ttt gtc aac tgg aag gtg agc atg ttt gtg gaa gtc cac aaa gcc att 1125 Phe VaI Asn Trp Lys Val Ser Met Phe Val Glu Val His Lys Ala.Ile aag eag cgg cgg cgg cga cgg aag gag tcc ttt gag agc tcc cca cac 1173 Lys Lys Arg Arg Arg Arg Arg Lys Glu Ser Phe Glu Ser Ser Pro His tcc cgg aag gcc ctg cag gtg eag ggg agc aca gcc tcc aag gac gtc 1221 Ser Arg Lys Ala Leu Gln Val Lys Gly Ser Thr Ala Ser Lys Asp Val aac ttc aag aac gac 1269 atc agc aag ctc ttt gaa ctt gag tcc acc tac Asn Phe Lys Asn Asp Ile Ser Lys Leu Phe Glu Leu Glu Ser Thr Tyr atc aag cag gcc agc ggt ggg I3I7 atc atg ggg gag ggg aag aag aca aag Ile Lys Gln Lys Ala Ser Gly Gly Ile Met Gly Glu Gly Lys Lys Thr acg ggc ccg cca ctg ggg caa ggt ctc cca 1365 ggc ggg cct ggc ggg gca Thr Gly Pro Pro Leu Gly Gln Gly Leu Pro Gly Gly Pro Gly Gly Ala ctg ccc cct ctg ccc ctg gtc tcc aac cgg 1413 tcc gtg gta tac aag gtg Leu Pro Pro Leu Pro Leu Val Ser Asn Arg Ser Val Val Tyr Lys Val ccc acc ttg gag tca cag ctg agc ggc cac 1461 gaa gtg aca agg aaa gta Pro Thr Leu Glu Ser Gln Leu Ser Gly His Glu Val Thr Arg Lys Val tca agg tcc gat gag get gca gcc gaa gac 1509 cca gag gtg cgg cct agc 2a Ser Arg Ser Asp Glu Ala Ala Ala Glu Asp Pro Glu Val Arg Pro Ser tcc cct gcc gag ttc atg cag gac atc agc 1557 ccc gtg aac ctg cgc gag Ser Pro Ala Glu Phe Gln Asp Ile Ser Pro Val Met Leu Arg Glu Asn gaa tgc gag tgg gcc tac cca atc ttc 1605 cca gac cag cac ctc cag gac Glu Cys Trp Ala Tyr Pro Ile Phe Glu Asp Gln His Leu Gln Pro Asp gac gcc acc gtg gag ggc 1653 agc ttc eac get ctc atc acg tca gac gag Asp Thr Glu Ala Phe Ala Ser Val Gly Ile Asn Leu Thr Ser Asp Glu 420 425 a3n gag acc tcc aag tcc tcg cta gag gac aac ttg gca ggg gag gag agc 1701 Glu Thr Ser Lys Ser Ser Leu Glu Asp Asn Leu Ala Gly Glu Glu Ser ccc cag cag ggg get gaa gcc sag gcg ccc ctg aac atg ggc gag ttc 1749 Pro Gln Gln Gly Ala Glu Ala Lys Ala Pro Leu Asn Met Gly Glu Phe ccc tcc tcc tcc gag tcc acc ttc acc agc act gag tct gag ctc tct 1797 Pro Ser Ser Ser Glu Ser Thr Phe Thr Ser Thr Glu Ser Glu Leu Ser gtg cct tac gsa cag ctg atg aat gag tac aac aag get aac agc ccc 1845 Val Pro Tyr Glu Gln Leu Met Asn Glu Tyr Asn Lys Ala Asn Ser Pro aag ggc aca tgaggcaggg ccggctcccc accccacctt tgatgg 1890 Lys Gly Thr cctcttcccc cctcacccta gggtgtcccg agatgaccgg gacgcctggc ccctggtggg 1950 ggggcagcct cggaactggg agtggggggc caggggcctt cctaaccttc catcatcccc 2010 agctagatgt atgcccggga cagggcctct gttctccagc tgaaccatac cctggctgtg 2070 ggggcatctg tcctgagctt ggctggtgta tctcacaatg caaagacatg ctggctggcg 2130 ggacaggtgg gcaggactga ccctgaggag gccttgcctg cagggtcttt gtcccaccat 2190 ttggtggagt atcacacggt tctctgaggt ccggggcctc agctgtttaa gtttaccggt 2250 attactgagc tcggcatttg gagagqgagc tctgaagtgt ctggggaggt accgctgtgc 2310 gtggggtcag gtgtttccgt accacagcag gagcagggcc cgcccgcatc ccagctgtgg 2370 gcctgccggt caggtcgggc acctactaca aaccgtagtg gggtggaggc tgctggaggt 2430 gggagtgagg agatgagggc agggtctcaa acagtcctga ctcacagggc ctggaaacaa 2490 gtcctatgtg ggcctggggc ctggggtcct catcctcctt gttggtctac tcaggcccag 2550 cccagagctg tgttccctgt ctcaggtcaa gcagtggcag acgcaaggct ttctgtgggc 2610 ccccaagtgg taggagggag agtagcagag catgggttac tggaagccgg gactgctagg 2670 gctggtggcc agggagctgc asgagtgagg ctcagctctg gctggttctg cccttacccc 2730 tcctgcccgc cggagaactg cacaccctgc ccgctggccc caggacctgc actcccaatc 2790 ctgctgtctt ctccttccct gtgccctgaa caaggacctc actgcccgcc ttcccctccc 2850 accagccccc ttgggccagg cagggtgagg ccasattgct cttggcccac aaatgggtga 2910 tggtcagata tgtgaatcaa gctcctttct ctagctagtg tttgatgtgc acgtgtgtgt 2970 gcacagtgcg tgtgtgcaca cgcacacctg tgcactcgtg tgtgtttaag aaaggaaagg 3030 atttgggctg gggagcaaaa gataatgtga aactgttggt ggactctctg gtgaggggtg 3090 ggcagaactt gctgctacta gagttcttgg gttctccatg atgttcaccc tggggctggc 3150 ccactgtgtc ctgaatgttt ttgttatttt ttgttttatt ttttaaacaa actgctgttt 3210 ttatatacct ggaatctgtt gttggcttca gagccagtgg ttaaagagca gggtcccaag 3270 gattgggaga tctagtgtct gccctcctgc cctgcaactc aattgggcct ttttcggtga 3330 cctcatccaa ggccatgatg tcaagggcca tgtccccaag cagaggtgga gaaggggaca 3390 WO 00/0536? PCT/JP99/03929 ctgaggtgag caaaagcaggaaggggcatccactgcgggtgactggaggccgggcaggaa3450 gcaagtcatc agagccgctcagctccgttcactctctgccttctgccccactactgtggg3510 gcagtggggc cagagcccacctccecaacatgtgaagacagtgatgggcacgtgcccaca3570 cccccacttc tctagccgtttgcagaggccgccacccagcaggggcctgaaaaggagcag3630 cctcgtattt ttctgtgaaatgttttaatgaaccatgttgttgctggttgtcctggcatc3690 gcgcacactg tatgtacatactggcaacgatgtcsaatgtaatttattttaacattttta3750 caataaaaca tgaggtgg 3768 <210> 89 <211> 770 <212> DNA
<213> Homo sapiens <220>
<221> CDS
I5 <222> (24)...(344) <400> 89 accgcgaagg gaggagtggc aac atg gcg tct tcg gga get ggt gac cct ctg 53 Met Ala Ser Ser Gly Ala Gly Asp Pro Leu 1 5 to gat tct aag cgt gga gag gcc ccg ttc get cag cgt atc gac ccg act 101 Asp Ser Lys Arg Gly Glu Ala Pro Phe Ala Gln Arg Ile Asp Pro Thr cgg gag aag ctg aca ccc gag caa ctg cat tcc atg cgg cag gcg gag 149 Arg Glu Lys Leu Thr Pro Glu Gln Leu His Ser Met Arg Gln Ala Glu ctt gcc cag tgg cag asg gtc cta cca cgg cgg cga acc cgg aac atc 197 Leu Ala Gln Trp Gln Lys Val Leu Pro Arg Arg Arg Thr Arg Asn Ile gtg acc ggc cta ggc atc ggg gcc ctg gtg ttg get att tat ggt tac 245 Val Thr Gly Leu Gly Ile Gly Ala Leu Val Leu Ala Ile Tyr Gly Tyr acc ttc tac tcg att tcc cag gag cgt ttc cta gat gag cta gaa gac 293 Thr Phe Tyr Ser Ile Ser Gln Glu Arg Phe Leu Asp Glu Leu Glu Asp 75 80 85 gp gag gcc aaa get gcc cga gcc cga get ctg gca agg gcg tca ggg tcc 341 Glu Ala Lys Ala Ala Arg Ala Arg Ala Leu Ala Arg Ala Ser Gly Ser taatctgga tgggtattga tcatgtccaa cctgctggag ccccttcaca tggtggatga 400 tgccccatga ccctgtagaaattgaatcctgctcacaacattgttggccttcttactaac460 cttggaccgt gattgagcccaagaaaccagggacttacgcatttggccaatgtcaaaaga520 acagaacttt gcccactgcacacttgctgtgtacaatgactgagccctttcttgtagttt580 gtttccttgt ttgagaggtgtgcatgcgaccgtggcttttcccaaagtttctgactttgt640 ggtttacccc cttcaccttccagggacgcagttgttacgaggttagacgtggcagctctg700 tgcagtgttt gagcctacagtgggatacatagggtcasattgagsataataaactgagtc760 attctcctgg 770 <210> 90 <211> 1229 <2I2> DNA

<213> Homo sapiens <220>

<221> CDS

<222> (96)...(554}

<400> 90 cctactcctg gattaggagg actgacaata ctacatatat cattaagcat gggcctcgct 60 tagaagttgc atctgagaaa gtagcccaga agaca atg gac tat gtg tgc tgt 113 Met Asp Tyr Val Cys Cys get tac aac aac ata acc ggc agg caa gat gsa act cat ttc aca gtt 161 Ala Tyr Asn Asn Ile Thr Gly Arg Gln Asp Glu Thr His Phe Thr Val atc atc act tcc gta gga ctg gag aag ctt gca cag aaa gga aaa tca 209 Ile Ile Thr Ser Val Gly Leu Glu Lys Leu Ala Gln Lys Gly Lys Ser ttg tca cct tta gca agt ata act gga ata tca cta ttt ttg att ata 257 Leu Ser Pro Leu Ala Ser Ile Thr Gly Ile Ser Leu Phe Leu Ile Ile 35 tcc atg tgt ctt ctc ttc cta tgg aaa aaa tat caa ccc tac aaa gtt 305 Ser Met Cys Leu Leu Phe Leu Trp Lys Lys Tyr Gln Pro Tyr Lys Val ata aaa cag aaa cta gaa ggc agg cca gaa aca gaa tac agg aaa get 353 Ile Lys Gln Lys Leu Glu Gly Arg Pro Glu Thr Glu Tyr Arg Lys Ala caa aca ttt tca ggc cat gaa gat get ctg gat gac ttc gga ata tat 401 Gln Thr Phe Ser Gly His Glu Asp Ala Leu Asp Asp Phe Gly Ile Tyr gaa ttt gtt get ttt cca gat gtt tct ggt gtt tcc agg atc cca agc 449 Glu Phe Val Ala Phe Pro Asp Val Ser Gly Val Ser Arg Ile Pro Ser agg tct gtt cca gcc tct gat tgt gta tcg ggg caa gat ttg cac agt 497 Arg Ser Val Pro Ala Ser Asp Cys Val Ser Gly Gln Asp Leu His Ser aca gtg tat gas gtt att cag cac atc cct gcc cag cag caa gac cat 545 Thr Val Tyr Glu Val Ile Gln His Ile Pro Ala Gln Gln Gln Asp His cca gag tgaactttca tgggctaaac agtacattcg agtgaaattc tgaagaaac 600 Pro Glu attttaagga aaaacagtggaaaagtatattaatctggaatcagtgasgaaaccaagacc660 sacacctctt actcattattcctttacatgcagaatagaggcatttatgcaaattgaact720 gcaggttttt cagcatatacacaatgtcttgtgcaacagaaaaacatgttggggaaatat780 tcctcagtgg agagtcgttctcatgctgacggggagaacgaeagtgacaggggtttcctc840 ataegttttg tatgaaatatctctacaaecctcaettagttctactctacactttcacta900 tcatcaacac tgagactatcctgtctcacctaceaatgtggaaactttacattgttcgat960 ttttcagcag actttgttttattaaatttttattagtgttaagaatgctaaagtttcaat1020 tttatttcca eatttctatcttgttatttgtacaacaaagtaataaggatggttgtcaca1080 aaaacaaaac tatgccttctcttttttttcaatcaccagtagtatttttgagaagacttg1140 tgaacactta aggaaatgactattaaagtcttatttttatttttttcaaggaaagatgga1200 ttcaaataaa ttattctgtttttgctttt 1229 <210> 91 <211> 358 <212> PRT

<213> Homo sapience <400> 91 Met Ala Pro Gln Asn Leu Ser Thr Phe Cys Leu Leu Leu Leu Tyr Leu Ile Gly Ala Val Ile Ala Gly Arg Asp Phe Tyr Lys Ile Leu Gly Val Pro Arg Ser Ala Ser Ile Lys Asp Ile Lys Lys Ala Tyr Arg Lys Leu Ala Leu Gln Leu His Pro Asp Arg Asn Pro Asp Asp Pro Gln Ala Gln Glu Lys Phe Gln Asp Leu Gly Ala Ala Tyr Glu Val Leu Ser Asp Ser Glu Lys Arg Lys Gln Tyr Asp Thr Tyr Gly Glu Glu Gly Leu Lys Asp Gly His Gln Ser Ser His Gly Asp Ile Phe Ser His Phe Phe Gly Asp Phe Gly Phe Met Phe Gly Gly Thr Pro Arg Gln Gln Asp Arg Asn Ile Pro Arg Gly Ser Asp Ile Ile Val Asp Leu Glu Val Thr Leu Glu Glu Val Tyr Ala Gly Asn Phe Val Glu Val Val Arg Asn Lys Pro Val Ala Arg Gln Ala Pro Gly Lys Arg Lys Cys Asn Cys Arg Gln Glu Met Arg 165 170 17s Thr Thr Glri Leu Gly Pro Gly Arg Phe Gln Met Thr Gln Glu Val Val Cys Asp Glu Cys Pro Asn Val Lys Leu Val Asn Glu Glu Arg Thr Leu Glu Val Glu Ile Glu Pro Gly Val Arg Asp Gly Met Glu Tyr Pro Phe Ile Gly Glu Gly Glu Pro His Val Asp Gly Glu Pro Gly Asp Leu Arg Phe Arg Ile Lys Val Val Lys His Pro Ile Phe Glu Arg Arg Gly Asp WO 00/05367 PCT/JP99/0392~

Asp Leu Tyr Thr Asn Val Thr Ile Ser Leu Val Glu Ser Leu Val Gly Phe Glu Met Asp Ile Thr His Leu Asp Gly His Lys Val His Ile Ser Arg Asp Lys Ile Thr Arg Pro Gly Ala Lys Leu Trp Lys Lys Gly Glu Gly Leu Pro Asn Phe Asp Asn Asn Asn Ile Lys Gly Ser Leu Ile Ile Thr Phe Asp Val Asp Phe Pro Lys Glu Gln Leu Thr Glu Glu Ala Arg Glu Gly Ile Lys Gln Leu Leu Lys Gln Gly Ser Val Gln Lys Val Tyr Asn Gly Leu Gln Gly Tyr <210> 92 <211> 226 <zl2> PRT
<213> Homo sapience <400> 92 Met Lys Met Val Ala Pro Trp Thr Arg Phe Tyr Ser Asn Ser Cys Cys Leu Cys Cys His Val Arg Thr Gly Thr Ile Leu Leu Gly Val Trp Tyr Leu Ile Ile Asn Ala Val Val Leu Leu Ile Leu Leu Ser Ala Leu Ala Asp Pro Asp Gln Tyr Asn Phe Ser Ser Ser Glu Leu Gly Gly Asp Phe 30 Glu Phe Met Asp Asp Ala Asn Met Cys Ile Ala Ile Ala Ile Ser Leu Leu Met Ile Leu Ile Cys Ala Met Ala Thr Tyr Gly Ala Tyr Lys Gln Arg Ala Ala Trp Ile Ile Pro Phe Phe Cys Tyr Gln Ile Phe Asp Phe 35 loo l05 110 Ala Leu Asn Met Leu Val Ala Ile Thr Val Leu Ile Tyr Pro Asn Ser Ile Gln Glu Tyr Ile Arg Gln Leu Pro Pro Asn Phe Pro Tyr Arg Asp Asp Val Met Ser Val Asn Pro Thr Cys Leu Val Leu Ile Ile Leu Leu Phe Ile Ser Ile Ile Leu Thr Phe Lys Gly Tyr Leu Ile Ser Cys Val Trp Asn Cys Tyr Arg Tyr Ile Asn Gly Arg Asn Ser Ser Asp Val Leu Val Tyr Val Thr Ser Asn Asp Thr Thr Val Leu Leu Pro Pro Tyr Asp Asp Ala Thr Val Asn Gly Ala Ala Lys Glu Pro Pro Pro Pro Tyr Val ser Ala <210> 93 <211> 195 <2I2> PRT
<213> Homo sapience <400> 93 Met Arg Leu Leu Leu Leu Leu Leu VaI Ala Ala Ser Ala Met Val Arg Ser Glu Ala Ser Ala Asn Leu Gly Gly Val Pro Ser Lys Arg Leu Lys Met Gln Tyr Ala Thr Gly Pro Leu Leu Lys Phe Gln Ile Cys Val Ser 30 Xaa Gly Tyr Arg Arg Val Phe Glu Glu Tyr Met Arg Val Ile Ser Gln Arg Tyr Pro Asp Ile Arg Ile Glu Gly Glu Asn Tyr Leu Pro Gln Pro Ile Tyr Arg His Ile Ala Ser Phe Leu Ser Val Phe Lys Leu Val Leu Ile Gly Leu Ile Ile Val Gly Lys Asp Pro Phe Ala Phe Phe Gly Met Gln Ala Pro Ser Ile Trp Gln Trp Gly Gln Glu Asn Lys Val Tyr Ala Cys Met Met Val Phe Phe Leu Ser Asn Met Ile Glu Asn Gln Cys Met Ser Thr Gly Ala Phe Glu Ile Thr Leu Asn Aap Val Pro Val Trp Ser Lys Leu Glu Ser Gly His Leu Pro Ser Met Gln Gln Leu Val Gln Ile Leu Asp Asn Glu Met Lys Leu Asn Val His Met Asp Ser Ile Pro His His Arg Ser <210>94 <211>339 <212>PRT

<213>Homo sapience <400> 94 Met Asn Trp Glu Leu Leu Leu Trp Leu Leu Val Leu Cys Ala Leu Leu i 5 10 15 Leu Leu Leu Val Gln Leu Leu Arg Phe Leu Arg Ala Asp Gly Asp Leu Thr Leu Leu Trp Ala Glu Trp Gln Gly Arg Arg Pro Glu Trp Glu Leu Thr Asp Met Val Val Trp Val Thr Gly Ala Ser Ser Gly Ile Gly Glu 30 Glu Leu Ala Tyr Gln Leu Ser Lys Leu Gly Val Ser Leu Val Leu Ser Ala Arg Arg Val His Glu Leu Glu Arg Val Lys Arg Arg Cys Leu Glu Asn Gly Asn Leu Lys Glu Lys Asp Ile Leu Val Leu Pro Leu Asp Leu 35 loo io5 110 Thr Asp Thr Gly Ser His Glu Ale Ala Thr Lys Ala Val Leu Gln Glu Phe Gly Arg Ile Asp Ile Leu Val Asn Asn Gly Gly Met Ser Gln Arg Ser Leu Cys Mat Asp Thr Ser Leu Asp Val Tyr Arg Lys Leu Ile Glu Leu Asn Tyr Leu Gly Thr Val Ser Leu Thr Lys Cys Val Leu Pro His Met Ile Glu Arg Lys Gln Gly Lys Ile Val Thr Val Asn Ser Ile Leu Gly Ile Ile Ser Val Pro Leu Ser Ile Gly Tyr Cys Ala Ser Lys His Ala Leu Arg Gly Phe Phe Asn Gly Leu Arg Thr Glu Leu Ala Thr Tyr Pro Gly Ile Ile Val Ser Asn Ile Cys Pro Gly Pro Val Gln Ser Asn Ile Val Glu Asn Ser Leu Ala Gly Glu Val Thr Lys Thr Ile Gly Asn Asn Gly Asp Gln Ser His Lys Met Thr Thr Ser Arg Cys Val Arg Leu Met Leu Ile Ser Met Ala Asn Asp Leu Lys Glu Val Trp Ile Ser Glu Gln Pro Phe Leu Leu Val Thr Tyr Leu Trp Gln Tyr Met Pro Thr Trp Ala Trp Trp Ile Thr Asn Lys Met Gly Lys Lys Arg Ile Glu Asn Phe Lys Ser Gly Val Asp Ala Asp Ser Ser Tyr Phe Lys Ile Phe Lys Thr Lya His Asp <210> 95 <211> 487 <212> PRT
<213> Homo sapience <400> 95 Met Asp Gly Thr Glu Thr Arg Gln Arg Arg Leu Asp Ser Cys Gly Lys Pro Gly Glu Leu Gly Leu Pro His Pro Leu Ser Thr Gly Gly Leu Pro Val Ala Ser Glu Asp Gly Ala Leu Arg Ala Pro Glu Ser Gln Ser Val Thr Pro Lys Pro Leu Glu Thr Glu Pro Ser Arg Glu Thr Ala Trp Ser Ile Gly Leu Gln Val Thr Val Pro Phe Met Phe Ala Gly Leu Gly Leu 65 70 ?5 80 Ser Trp Ala Gly Met Leu Leu Asp Tyr Phe Gln His Trp Pro Val Phe Val Glu Val Lys Asp Leu Leu Thr Leu Val Pro Pro Leu Val Gly Leu loo l05 110 Lys Gly Asn Leu Glu Met Thr Leu Ala Ser Arg Leu Ser Thr Ala Ala Asn Thr Gly Gln Ile Asp Asp Pro Gln Glu Gln His Arg Val Ile Ser Ser Asn Leu Ala Leu Ile Gln Val Gln Ala Thr Val Val Gly Leu Leu Ala Ala Val Ala Ala Leu Leu Leu Gly Val Val Ser Arg Glu Glu Val Asp Val Als Lys Val Glu Leu Leu Cys Ala Ser Ser Val Leu Thr Ala Phe Leu Ala Ala Phe Ala Leu Gly Val Leu Met Val Cys Ile Val Ile Gly Ala Arg Lys Leu Gly Val Asn Pro Asp Asn Ile Ala Thr Pro Ile Ala Ala Ser Leu Gly Asp Leu Ile Thr Leu Ser Ile Leu Ala Leu Val Ser Ser Phe Phe Tyr Arg His Lys Asp Ser Arg Tyr Leu Thr Pro Leu Val Cys Leu Ser Phe Ala Ala Leu Thr Pro Val Trp Val Leu Ile Ala Lys Gln Ser Pro Pro Ile Val Lys Ile Leu Lys Phe Gly Trp Phe Pro Ile Ile Leu Ala Met Val Ile Ser Ser Phe Gly Gly Leu Ile Leu Ser Lys Thr Val Ser Lys Gln Gln Tyr Lys Gly Met Ala Ile Phe Thr Pro Val Ile Cys Gly Val Gly Gly Asn Leu Val Ala Ile Gln Thr Ser Arg Ile Ser Thr Tyr Leu His Met Trp Ser Ala Pro Gly Val Leu Pro Leu Gln Met Lys Lys Phe Trp Pro Asn Pro Cys Ser Thr Phe Cys Thr Ser Glu Ile Asn Ser Met Ser Ala Arg Val Leu Leu Leu Leu Val Val Pro Gly His Leu Ile Phe Phe Tyr Ile Ile Tyr Leu Val Glu Gly Gln Ser Val Ile Asn Ser Gln Thr Phe Val Val Leu Tyr Leu Leu Ala Gly Leu Ile Gln Val Thr Ile Leu Leu Tyr Leu Ala Glu Val Met Val Arg Leu Thr Trp His Gln Ala Leu Asp Pro Asp Asn His Cys Ile Pro Tyr Leu Thr Gly Leu Gly Asp Leu Leu Gly Thr Gly Leu Leu Ala Leu Cys Phe Phe Thr Asp Trp Leu Leu Lys Ser Lys Ala Glu Leu Gly Gly Ile Ser Glu Leu Ala Ser Gly Pro Pro <210> 96 <211> 393 <212> PRT
<2I3> Homo sapience <400> 96 WO 00/05367 PCT/JP99/039Zg Met Arg Thr Leu Phe Asn Leu Leu Trp Leu Ala Leu Ala Cys Ser Pro Val His Thr Thr Leu Ser Lys Ser Asp Ala Lys Lys Ala Ala Ser Lys Thr Leu Leu Glu Lys Ser Gln Phe Ser Asp Lys Pro Val Gln Asp Arg Gly Leu Val Val Thr Asp Leu Lys Ala Glu Ser Val Val Leu Glu His Arg Ser Tyr Cys Ser Ala Lys Ala Arg Asp Arg His Phe Ala Gly Asp Val Leu Gly Tyr Val Thr Pro Trp Asn Ser His Gly Tyr Asp Val Thr 85 90 g5 Lys Val Phe Gly Ser Lys Phe Thr Gln Ile Ser Pro Val Trp Leu Gln Leu Lys Arg Arg Gly Arg Glu Met Phe Glu Val Thr Gly Leu His Asp Val Asp Gln Gly Trp Met Arg Ala Val Arg Lys His Ala Lys Gly Leu His Ile Val Pro Arg Leu Leu Phe Glu Asp Trp Thr Tyr Asp Asp Phe Arg Asn Val Leu Asp Ser Glu Asp Glu Ile Glu Glu Leu Ser Lys Thr Val Val Gln Val Ala Lys Asn Gln His Phe Asp Gly Phe Val Val Glu Val Trp Asn Gln Leu Leu Ser Gln Lys Arg Val Gly Leu Ile His Met Leu Thr His Leu Ala Glu Ala Leu His Gln Ala Arg Leu Leu Ala Leu Leu Val Ile Pro Pro Ala Ile Thr Pro Gly Thr Asp Gln Leu Gly Met Phe Thr His Lys Glu Phe Glu Gln Leu Ala Pro Val Leu Asp Gly Phe Ser Leu Met Thr Tyr Asp Tyr Ser Thr Ala His Gln Pro Gly Pro Asn Ala Pro Leu Ser Trp Val Arg Ala Cys Val Gln Val Leu Asp Pro Lys Ser Lys Trp Arg Ser Lys Ile Leu Leu Gly Leu Asn Phe Tyr Gly Met Asp Tyr Ala Thr Ser Lys Asp Ala Arg Glu Pro Val Val Gly Ala Arg Tyr Ile Gln Thr Leu Lys Asp His Arg Pro Arg Met Val Trp Asp Ser Gln Ala Ser Glu His Phe Phe Glu Tyr Lys Lys Ser Arg Ser Gly Arg Hie Val Val Phe Tyr Pro Thr Leu Lys Ser Leu Gln Val Arg Leu Glu Leu Ala Arg Glu Leu Gly Val Gly Val Ser Ile Trp Glu Leu Gly Gln Gly Leu Asp Tyr Phe Tyr Asp Leu Leu <210> 97 <211> 196 <212> PRT
<213> Homo sapience <400> 97 Met Trp Arg Val Pro Gly Thr Thr Arg Arg Pro Val Thr Gly Glu Ser Pro Gly Met His Arg Pro Glu Ala Met Leu Leu Leu Leu Thr Leu Ala Leu Leu Gly Gly Pro Thr Trp Ala Gly Lys Met Tyr Gly Pro Gly Gly Gly Lys Tyr Phe Ser Thr Thr Glu Asp Tyr Asp His Glu Ile Thr Gly Leu Arg Val Ser Val Gly Leu Leu Leu Val Lys Ser Val Gln Val Lys 65 70 75 g0 Leu Gly Asp Ser Trp Asp Val Lys Leu Gly Ala Leu Gly Gly Asn Thr 35 Gln Glu Val Thr Leu Gln Pro Gly Glu Tyr Ile Thr Lys Val Phe Val loo los llo Ala Phe Gln Ala Phe Leu Arg Gly Met Val Met Tyr Thr Ser Lys Asp Arg Tyr Phe Tyr Phe Gly Lys Leu Asp Gly Gln Ile Ser Ser Ala Tyr Pro Ser Gln Glu Gly Gln Val Leu Val Gly Ile Tyr Gly Gln Tyr Gln Leu Leu Gly Ile Lys Ser Ile Gly Phe Glu Trp Asn Tyr Pro Leu Glu Glu Pro Thr Thr Glu Pro Pro Val Asn Leu Thr Tyr Ser Ala Asn Ser Pro Val Gly Arg <210> 98 <211> 107 <212> PRT
<213> Homo sapience <400> 98 Met Glu Gln Lys Leu Val GIu Glu Ile Leu Gln Ala Ile Thr Met Ser Thr Asp Thr Gly Val Ser Leu Pro Ser Tyr Glu Glu Asp Gln Gly Ser Lys Leu Ile Arg Lys Ala Lys Glu Ala Pro Phe Val Pro Val Gly Ile Ala Gly Phe Ala Ala Ile Val Ala Tyr Gly Leu Tyr Lys Leu Lys Ser Arg Gly Asn Thr Lys Met Ser Ile His Leu Ile His Met Arg Val Ala Ala Glu Gly Phe Val Val Gly Ala Met Thr Val Gly Met Gly Tyr Ser Met Tyr Arg Glu Phe Trp Ala Lys Pro Lys Pro <210> 99 <211> 350 <212> PRT

<213> Homo sapience <400> 99 Met Ser Glu Val Lys Ser Arg Lys Lys Ser Gly Pro Lys Gly Ala Pro Ala Ala Glu Pro Gly Lys Arg Ser Glu Gly Gly Lys Thr Pro Val Ala Arg Ser Ser Gly Gly Gly Gly Trp Ala Asp Pro Arg Thr Cys Leu Ser Leu Leu Ser Leu Gly Thr Cys Leu Gly Leu Ala Trp Phe Val Phe Gln Glri Ser Glu Lys Phe Ala Lys Val Glu Asn Gln Tyr Gln Leu Leu Lys Leu Glu Thr Asn Glu Phe Gln Gln Leu Gln Ser Lys Ile Ser Leu Ile Ser Glu Lys Trp Gln Lys Ser Glu Ala Ile Met Glu Gln Leu Lys Ser Phe Gln Ile Ile Ala His Leu Lys Arg Leu Gln Glu Glu Ile Asn Glu Val Lys Thr Trp Ser Asn Arg Ile Thr Glu Lys Gln Asp Ile Leu Asn Asn Ser Leu Thr Thr Leu Ser Gln Asp Ile Thr Lys Val Asp Gln Ser Thr Thr Ser Met Ala Lys Asp Val Gly Leu Lys Ile Thr Ser Val Lys Thr Asp Ile Arg Arg Ile Ser Gly Leu Val Thr Asp Val Ile Ser Leu Thr Asp Ser Val Gln Glu Leu Glu Asn Lys Ile Glu Lys Val Glu Lys Asn Thr Val Lys Asn Ile Gly Asp Leu Leu Ser Ser Ser Ile Asp Arg Thr Ala Thr Leu Arg Lys Thr Ala Ser Glu Asn Ser Gln Arg Ile Asn Ser Val Lys Lys Thr Leu Thr Glu Leu Lys Ser Asp Phe Asp Lys His Thr Asp Arg Phe Leu Ser Leu Glu Gly Asp Arg Ala Lys Val Leu Lys Thr Val Thr Phe Ala Asn Asp Leu Lys Pro Lys Val Tyr Asn Leu Lys Lys Asp Phe Ser Arg Leu Glu Pro Leu Val Asn Asp Leu Thr Leu Arg Ile Gly Arg Leu Val Thr Asp Leu Leu Gln Arg Glu Lys Glu Ile Ala Phe Leu Ser Glu Lys Ile Ser Asn Leu Thr Ile Val Gln Ala Glu Ile Lys Asp Ile Lys Asp Glu Ile Ala His Ile Ser Asp Met Asn <210> 100 <211> 107 <212> PRT

<213> Homo sapience <400> 100 Met Ser Ser Ala Gly Thr Ala Thr Pro Leu Glu Met Asp His Lys Leu Thr Ser Gln Pro Gly Arg Pro Ser Phe Tyr Cys Asn Ser Arg His Ser Ile Val Gly Ser Ser His Gln Leu Gly Phe Trp Phe Ser His Leu Glu Ser Ser Gly Leu Lys Val Phe Gln Val Ser Leu Pro Cys Glu Cys Val Asn Leu Pro Thr Arg Ile Ala Ser Val Val Leu Ser Leu Met Ser Leu Leu Val Val Gly Gln Ala Pro Ala Trp Glu Gly Ser Leu Leu Arg Gly 35 Arg Pro Ala Gly Gly Ala His Leu Cys Ala Ala 112/1?7 <210> 101 <211> 1074 <212> DNA
<213> Homo Sapience <400> 101 atggctccgcagaacctgagcaccttttgcctgttgctgctatacctcatcggggcggtg60 attgccggacgagatttctataagatcttgggggtgcctcgaagtgcctctataaaggat120 attaaaaaggcctataggaaactagccctgcagcttcatcccgaccggaaccctgatgat180 ccacaagcccaggagaaattccaggatctgggtgctgcttatgaggttctgtcagatagt240 gagaaacggaaacagtacgatacttatggtgaagaaggattaaaagatggtcatcagagc300 tcccatggagacattttttcacacttctttggggattttggtttcatgtttggaggaacc360 cctcgtcagcaagacagaaatattccaagaggaagtgatattattgtagatctagaagtc420 actttggaagaagtatatgcaggaaattttgtggaagtagttagaascaaacctgtggca480 aggcaggctcctggcaaacggaagtgcaattgtcggcaagagatgcggaccacccagctg540 ggccctgggcgcttccaaatgacccaggaggtggtctgcgacgaatgccctaatgtcaaa600 ctagtgaatgaagaacgaacgctggaagtagaaatagagcctggggtgagagacggcatg660 gagtacccctttattggagaaggtgagcctcacgtggatggggagcctggagatttacgg720 ttccgsatcaaagttgtcaagcacccaatatttgaaaggagaggagatgatttgtacaca780 aatgtgacaatctcattagttgagtcactggttggctttgagatggatattactcacttg840 gatggtcacaaggtacatatttcccgggataagatcaccaggccaggagcgaagctatgg900 aagaaaggggaagggctccccaactttgacaacaacaatatcaagggctctttgataatc960 acttttgatgtggattttccasaagaacagttaacagaggaagcgagagaaggtatcaaa1020 cagctactgaaacaagggtcagtgcagaaggtatacaatggactgcaaggatat 1074 <210> 102 <211> 678 <212> DNA

<213> Homo Sapience <400> 102 atgaagatgg tcgcgccctg gacgcggttc tactccaaca gctgctgctt gtgctgccat 60 gtccgcaccg gcaccatcct gctcggcgtc tggtatctga tcatcaatgc tgtggtactg 120 ttgattttat tgagtgccctggctgatccggatcagtataacttttcaagttctgaactg180 ggaggtgact ttgagttcatggatgatgccaacatgtgcattgccattgcgatttctctt240 ctcatgatcc tgatatgtgctatggctacttacggagcgtacaagcaacgcgcagcctgg300 atcatcccat tcttctgttaccagatctttgactttgccctgaacatgttggttgcaatc360 actgtgctta tttatccaaactccattcaggaatacatacggceactgcctcctaatttt420 ccctacagag atgatgtcatgtcagtgaatcctacctgtttggtccttattattcttctg480 tttattagca ttatcttgacttttaagggttacttgattagctgtgtttggaactgctac540 cgatacatca atggtaggaactcctctgatgtcctggtttatgttaccagcaatgacact600 acggtgctgc tacccccgtatgatgatgccactgtgaatggtgctgccaaggagccaccg660 ccaccttacg tgtctgcc 678 <210> 103 <21I> 585 <212> DNA

<213> Homo Sapience <400> 103 atgaggcttc tgctgcttct cctagtggcg gcgtctgcga tggtccggag cgaggcctcg 60 gccaatctgg gcggcgtgcc cagcaagaga ttaaagatgc agtacgccac ggggccgctg 120 ctcaagttcc agatttgtgtttcctgaggttataggcgggtgtttgaggagtacatgcgg180 gttattagcc agcggtacccagacatccgcattgaaggagagaattacctccctcaacca240 atatatagac acatagcatctttcctgtcagtcttcaaactagtattaataggcttaata300 attgttggca aggatccttttgctttctttggcatgcaagctcctagcatctggcagtgg360 ggccaagaaa ataaggtttatgcatgtatgatggttttcttcttgagcaacatgattgag420 aaccagtgta tgtcaacaggtgcatttgagataactttaaatgatgtacctgtgtggtct480 aagctggaat ctggtcaccttccatccatgcaacaacttgttcaaattcttgacaatgas540 atgaegctca atgtgcatatggattcaatcccacaccatcgatca 585 <210> 104 <21I> 1017 <212> DNA
<213> Homo Sapience <400> 104 atgaactggg agctgctgct gtggctgctg gtgctgtgcg cgctgctcct gctcttggtg 60 cagctgctgc gcttcctgagggctgacggcgacctgacgctactatgggccgagtggcag120 ggacgacgcc cagaatgggagctgactgatatggtggtgtgggtgactggagcctcgagt180 ggaattggtg aggagctggcttaccagttgtctaaactaggagtttctcttgtgctgtca240 gccagaagag tgcatgagctggaaagggtgaaaagaagatgcctagagaatggcaattta300 aaagaasaag atatacttgttttgccccttgacctgaccgacactggttcccatgaagcg360 gctaccaaag ctgttctccaggagtttggtagaatcgacattctggtcaacaatggtgga420 atgtcccagc gttctctgtgcatggataccagcttggatgtctacagaaagctaatagag480 cttaactact tagggacggtgtccttgacaaaatgtgttctgcctcacatgatcgagagg540 aagcaaggaa agattgttactgtgaatagcatcctgggtatcatatctgtacctctttcc600 attggatact gtgctagcasgcatgctctccggggtttttttaatggccttcgaecagae660 cttgccacat acccaggtat aatagtttct aacatttgcc caggacctgt gcactcaaat 720 attgtggaga attccctagc tggagaagtc acaaagacta taggcaataa tggagaccag 780 tcccacaaga tgacaaccag tcgttgtgtg cggctgatgt taatcagcat ggccaatgat 840 ttgaaagaag tttggatctc agaacaacct ttcttgttag taacatattt gtggcaatac 900 atgccaacct gggcctggtg gataaccaac aagatgggga agaaaaggat tgagaacttt 960 sagagtggtg tggatgcaga ctcttcttat tttaaaatct ttaagacaaa acatgac 1017 <210> 105 <211> 1461 <212> DNA

<213> Homo Sapience <400> 105 atggatggga cagagacccg gcagcggagg ctggacagct gtggcaagcc aggggagctg 60 gggcttcctc accccctcag cacaggagga ctccctgtag cctcagaaga tggagctctc 120 agggcccctg agagccaaagcgtgacccccaagccactggagactgagcctagcagggag180 accgcctggt ccataggccttcaggtgaccgtgcccttcatgtttgcaggcctgggactg240 tcctgggccg gcatgcttctggactatttccagcactggcctgtgtttgtggaggtgaaa300 gaccttttga cattggtgccgcccctggtgggcctgaaggggaacctggagatgacactg360 gcatccagac tctccacagctgccaacactggacaaattgatgacccccaggagcagcac420 agagtcatca gcagcaacct ggccctcatc caggtgcagg ccactgtcgt ggggctcttg 480 gctgctgtgg ctgcgctgct gttgggcgtg gtgtctcgag aggaagtgga tgtcgccaag 540 gtggagttgc tgtgtgccag cagtgtcctc actgccttcc ttgcagcctt tgccctgggg 600 gtgctgatgg tctgtatagt gattggtgct cgaaagctcg gggtcaaccc agacaacatt 660 gccacgccca ttgcagccag cctgggagac ctcatcacac tgtccattct ggctttggtt 720 agcagcttct tctacagaca caaagatagt cggtatctga cgccgctggt ctgcctcagc 780 tttgcggctc tgaccccagt gtgggtcctc attgccaagc agagcccacc catcgtgaag 840 atcctgaagt ttggctggtt cccaatcatc ctggccatgg tcatcagcag tttcggagga 900 ctcatcttga gcaaaaccgt ttctasacag cagtacaaag gcatggcgat atttaccccc 960 gtcatatgtg gtgttggtgg caatctggtg gccattcaga ccagccgaat ctcaacctac 1020 ctgcacatgt ggagtgcacc tggcgtcctg cccctccaga tgaagaaatt ctggcccaac 1080 ccgtgttcta ctttctgcac gtcagasatc aattccatgt cagctcgagt cctgctcttg 1140 ctggtggtcc caggccatct gattttcttc tacatcatct acctggtgga gggtcagtca 1200 gtcataaaca gccagacctt tgtggtgctc tacctgctgg caggcctgat ccaggtgaca 1260 atcctgctgt acctggcaga agtgatggtt cggctgactt ggcaccaggc cctggatcct' 1320 gacaaccact gcatccccta ccttacaggg ctgggggacc tgctcggtac tggcctcctg 1380 gcactctgct ttttcactga ctggctactg aagagcaagg cagagctggg tggcatctca 1440 gaactggcat ctggacctcc c 1461 <210> 106 <211> 1179 <212> DNA
<213> Homo Sapience <400> 106 atgcggacac tcttcaacct cctctggctt gccctggcct gcagccctgt tcacactacc 60 ctgtcaaagt cagatgccaa aaaagccgcc tcaaegacgc tgctggagaa gagtcagttt 120 tcagataagc cggtgcaaga ccggggtttg gtggtgacgg acctcasagc tgagagtgtg 180 gttcttgagc atcgcagcta ctgctcggca aaggcccggg acagacactt tgctggggat 240 gtactgggct atgtcactccatggaacagccatggctacgatgtcaccaaggtctttggg300 agceagttca cacagatctcacccgtctggctgcagctgaagagacgtggccgtgagatg360 tttgaggtca cgggcctccacgacgtggaccaagggtggatgcgagctgtcaggaagcat420 gccaagggcc tgcacatagtgcctcggctcctgtttgaggactggacttacgatgatttc480 cggaacgtct tagacagtgaggatgagatagaggagctgagcaagaccgtggtccaggtg540 gcaaagaacc agcatttcgatggcttcgtggtggaggtctggaaccagctgctaagccag600 sagcgcgtgg gcctcatccacatgctcacccacttggccgaggctctgcaccaggcccgg660 ctgctggccc tcctggtcatcccgcctgccatcacccccgggaccgaccagctgggcatg720 ttcacgcaca aggagtttgagcagctggcccccgtgctggatggtttcagcctcatgacc780 tacgactact ctacagcgcatcagcctggccctaatgcacccctgtcctgggttcgagcc840 tgcgtccagg tcctggacccgsagtccaagtggcgaagcaaaatcctcctggggctcaac900 ttctatggta tggactacgcgacctccaaggatgcccgtgagcctgttgtcggggccagg960 tacatccaga cactgaaggaccacaggccccggatggtgtgggacagccaggcctcagag1020 cacttcttcg agtacaagaagagccgcagtgggaggcacgtcgtcttctacccaaccctg1080 aagtccctgc aggtgcggctggagctggcccgggagctgggcgttggggtctctatctgg1140 gagctgggcc agggcctggactacttctacgacctgctc 1179 <210> 107 <211> 588 <212> DNA
<213> Homo Sapience <400> 107 atgtggaggg tgcccggcac aaccagacgc ccagtcacag gcgagagccc tgggatgcac 60 cggccagagg ccatgctgct gctgctcacg cttgccctcc tggggggccc cacctgggca 120 gggaagatgt atggccctggaggaggcaagtatttcagcaccactgaagactacgaccat180 gaastcacag ggctgcgggtgtctgtaggtcttctcctggtgaaaagtgtccaggtgaaa240 cttggagact cctgggacgtgaaactgggagccttaggtgggaatacccaggaagtcacc300 ctgcagccag gcgaatacatcacaaaagtctttgtcgccttccaagctttcctccggggt360 atggtcatgt acaccagcaaggaccgctatttctattttgggaagcttgatggccagatc420 tcctctgcct accccagccaagaggggcaggtgctggtgggcatctatggccagtatcaa480 ctccttggca tcaagagcattggctttgaatggaattatccactagaggagccgaccact540 gagccaccag ttaatctcacatactcagcasactcacccgtgggtcgc 588 <210> 108 <211> 321 <212> DNA
<213> Homo Sapience <400> 108 atggagcaga agcttgtggaggagattcttcaagcaatcactatgtcaacagacacaggt60 gtttcccttc cttcatatgaggaagatcagggatcaaaactcattcgaaaagctaaagag120 gcaccattcg tacccgttggaatagcgggttttgcagcaattgttgcatatggattatat180 aaactgaaga gcaggggaaatactaaastgtccattcatctgatccacatgcgtgtggca240 gcccaaggct ttgttgtaggagcaatgactgttggtatgggctattccatgtatcgggaa300 ttctgggcaa aacctaagcct 321 <210> 109 <211> 1050 <212> DNA
<213> Homo Sapience <400> 109 atgtctgaggtgaagagccggaagaagtcggggcccaagggagcccctgctgcggagccc60 gggaagcggagcgagggcgggaagacccccgtggcccggagcagcggaggcgggggctgg120 gcagacccccgaacgtgcctgagcctgctgtcgctggggacgtgcctgggcctggcctgg180 tttgtatttcagcagtcagaaaaatttgcaaaggtggaaaaccaataccagttactgaaa240 ctagaaaccaatgaattccaacaacttcaaagtaaaatcagtttaatttcagaaaagtgg300 cagaaatctgaagctatcatggaacaattgaagtcttttcaastaattgctcatctasag360 cgtctacaggaagsaattaatgaggtaaaaacttggtccaataggataactgaaaaacag420 gatatactgaacaacagtctgacgacgctttctcaagacattacaaaagtagaccaaagt480 acaacttccatggcaaasgatgttggtctcsagattacaagtgtaaaaacagatatacga540 cggatttcaggtttagtaactgatgtaatatcattgacagattctgtgcaagaactagaa600 sataaaatagagaaagtagaaaaeaatacagtaaaaaatataggtgatcttctttcaagc660 agtattgatcgaacagcaacgctccgasagacagcatctgaaaattcacaaagaattaac720 tctgttaagaagacgctaaccgaactasagagtgacttcgacaaacatacagatagattt780 ctaagcttagaaggtgacagagccaaagttctgaagacagtgacttttgcaaatgatcta840 asaccaseggtgtataatctaaagaaggacttttcccgtttagaaccattagtasatgat900 ttaacactacgcattgggagattggttaccgacttactacaaagagagaaagaaattgct960 ttcttaagtgaaaasatatctaatttaacaatagtccaagctgagattaaggatattaaa1020 gatgaaatagcacacatttcagatatgaat 1050 <210> 110 <211> 321 <212> DNA

<213> HomoSapience <400> 110 atgtcctcag caggcacagc aacccctctg gaaatggatc acaaactcac ttctcagcca 60 ggcaggccaa gcttctattg taacagtagg cacagtatag tcggatcatc acatcagctg 120 ggtttttggt ttagtcatct agagtcgtct ggactaaagg tctttcaggt ctccttgccc 180 11$/17?
tgtgagtgcg tgascctccc cacccgaatt gcctcagttg tcctgagcct catgtctctc 240 ctggtggtgg gccaggcccc tgcatgggaa gggagcctgc tgcggggcag gccagctggg 300 ggtgctcacc tatgcgcagc a 321 <210> 111 <211> 1619 <212> DNA

<213> Homo Sapience <220>

IO <221> CDS

<222> (158)...(1234) <400> 111 agaagagggg gctagctagc tgtctctgcg gaccagggag acccccgcgc ccccccggtg 60 I5 tgaggcggcc tcacagggcc gggtgggctg gcgagccgac gcggcggcgg aggaggctgt 120 gaggagtgtg tggaacagga cccgggacag aggaacc atg get ccg cag aac ctg 175 Met Ala Pro Gln Asn Leu agc accttttgc ctgttgctgcta tacctcatcggggcg attgcc 223 gtg 20 Ser ThrPheCys LeuLeuLeuLeu TyrLeuIleGlyAlaVal IleAla 10 15 ~ 20 gga cgagatttc tataagatcttg ggggtgcctcgaagtgcc tctata 271 Gly ArgAspPhe TyrLysIleLeu GlyValProArgSerAla SerIle 25 aag gatattaaa saggcctatagg aaactagccctgcagctt catccc 319 Lys AspIleLys LysAlsTyrArg LysLeuAlaLeuGlnLeu HisPro gac cggaaccct gatgatccacaa gcccaggagaaattccag gatctg 367 Asp ArgAsnPro AspAspProGln AlaGlnGluLysPheGln AspLeu ggt getgettat gaggttctgtca gatagtgagaaacggaaa cagtac 415 Gly AlaAlaTyr GluValLeuSer AspSerGluLysArgLys GlnTyr gat acttatggt gasgaaggatta aaagatggtcatcagagc tcccat 463 35 Asp Thr Tyr Gly Glu Glu Gly Leu Lys Asp Gly His Gln Ser Ser His gga gac att ttt tca cac ttc ttt ggg gat ttt ggt ttc atg ttt gga 511 Gly Asp Ile Phe Ser His Phe Phe Gly Asp Phe Gly Phe Met Phe Gly gga acc cct cgt cag caa gac aga aat att cca aga gga agt gat att 559 Gly Thr Pro Arg Gln Gln Asp Arg Asn Ile Pro Arg Gly Ser Asp Ile att gta gat cta gaa gtc act ttg gaa gaa gta tat gca gga aat ttt 607 Ile Val Asp Leu Glu Val Thr Leu Glu Glu Val Tyr Ala Gly Asn Phe 135 140 145 ~5n gtg gaa gta gtt aga aac asa cct gtg gca agg cag get cct ggc aaa 655 Val Glu Val Val Arg Asn Lys Pro Val Ala Arg Gln Ala Pro Gly Lys cgg aag tgc aat tgt cgg caa gag atg cgg acc acc cag ctg ggc cct 703 Arg Lys Cys Asn Cys Arg Gln Glu Met Arg Thr Thr Gln Leu Gly Pro ggg cgc ttc caa atg acc cag gag gtg gtc tgc gac gaa tgc cct sat 751 Gly Arg Phe Gln Met Thr Gln Glu Val Val Cys Asp Glu Cys Pro Asn gtc aaa cta gtg aat gaa gaa cga acg ctg gaa gta gaa ata gag cct 799 Val Lys Leu Val Asn Glu Glu Arg Thr Leu Glu Val Glu Ile Glu Pro ggg gtg aga gac ggc atg gag tac ccc ttt att gga gaa ggt gag cct 847 Gly Val Arg Asp Gly Met Glu Tyr Pro Phe Ile Gly Glu Gly Glu Pro cac gtg gat ggg gag cct gga gat tta cgg ttc cga atc aas gtt gtc 895 His Val Asp Gly Glu Pro Gly Asp Leu Arg Phe Arg Ile Lys Val Val aag cac cca ata ttt gaa agg aga gga gat gat ttg tac aca aat gtg ' 943 Lys His Pro Ile Phe Glu Arg Arg Gly Asp Asp Leu Tyr Thr Asn Val aca atc tca tta gtt gag tca ctg gtt ggc ttt gag atg gat att act 991 Thr Ile Ser Leu Val Glu Ser Leu Val Gly Phe Glu Met Asp Ile Thr cac ttg gat ggt cac aag gta cat att tcc cgg gat aag atc acc agg 1039 WO 00/05367 PCT/JP99/0392'9 His Leu Asp Gly His Lys Val His Ile Ser Arg Asp Lys Ile Thr Arg cca gga gcg aag cta tgg aag aaa ggg gaa ggg ctc ccc eac ttt gac 1087 Pro Gly Ala Lys Leu Trp Lys Lys Gly Glu Gly Leu Pro Asn Phe Asp aac aac aat atc aag ggc tct ttg ata atc act ttt gat gtg gat ttt 1135 Asn Asn Asn Ile Lys Gly Ser Leu Ile Ile Thr Phe Asp Val Asp Phe cca aaa gaa cag tta aca gag gaa gcg aga gaa ggt atc aaa cag cta 1183 Pro Lys Glu Gln Leu Thr Glu Glu Ala Arg Glu Gly Ile Lys Gln Leu ctg aaa caa ggg tca gtg cag aag gta tac aat gga ctg caa gga tat 1231 Leu Lys Gln Gly Ser Val Gln Lys Val Tyr Asn Gly Leu Gln Gly Tyr tgagagtga actttgttta ataagcgatatttattatct1290 ataaeattgg aaataagtga gcaaggtttttttgtgtgtgtttttgtttttattttcaatatgcaagttaggcttaattt1350 ttttatctaatgatcatcatgaaatgaataagagggcttaagaatttgtccatttgcatt1410 cggaaaagaatgaccagcaaaaggtttactaatacctctccctttggggatttaatgtct1470 ggtgctgccgcctgagtttcaagaattasagctgcaagaggactccaggagcasaagasa1530 cacaatatagagggttggagttgttagcaatttcattcaaaatgcceactggagaagtct1590 gtttttaastacattttgttgttattttt 1619 <210> 112 <211> 2054 <212> DNA

<213> HomoSapience <220>

<221> CDS

<222> (254)...(934) <400> 112 cacatggcca agtccgcccc gccccctccc cgtccccgcc gctgcagcgg tcgccttcgg 60 agcgaagggt accgacccgg cagaagctcg gagctctcgg ggtatcgagg aggcaggccc 120 gcgggcgcac gggcgagcgg gccgggagcc ggagcggcgg aggagccggc agcagcggcg 180 cggcgggctc caggcgaggc ggtcgacgct cctgaaaact tgcgcgcgcg ctcgcgccac 240 tgcgcccgga gcg atg sag atg gtc gcg ccc tgg acg cgg ttc tac tcc 289 Met Lys Met Val Ala Pro Trp Thr Arg Phe Tyr Ser aac agc tgc tgc ttg tgc tgc cat gtc cgc acc ggc acc atc ctg ctc 337 Asn Ser Cys Cys Leu Cys Cys His Val Arg Thr Gly Thr Ile Leu Leu ggc gtc tgg tat ctg atc atc aat get gtg gta ctg ttg att tta ttg 385 Gly Val Trp Tyr Leu Ile Ile Asn Ala Val Val Leu Leu Ile Leu Leu 30 35 ~ 40 10 agt gcc ctg get gat ccg gat cag tat aac ttt tca agt tct gaa ctg 433 Ser Ala Leu Ala Asp Pro Asp Gln Tyr Asn Phe Ser Ser Ser Glu Leu gga ggt gac ttt gag ttc atg gat gat gcc aac atg tgc att gcc att 481 Gly Gly Asp Phe Glu Phe Met Asp Asp Ala Asn Met Cys Ile Ala Ile gcg att tct ctt ctc atg atc ctg ata tgt get atg get act tac gga 529 Ala Ile Ser Leu Leu Met Ile Leu Ile Cys Ala Met Ala Thr Tyr Gly gcg tac aag caa cgc gca gcc tgg atc atc cca ttc ttc tgt tac cag 577 Ala Tyr Lys Gln Arg Ala Ala Trp Ile Ile Pro Phe Phe Cys Tyr Gln atc ttt gac ttt gcc ctg aac atg ttg gtt gca atc act gtg ctt att 625 Ile Phe Asp Phe Ala Leu Asn Met Leu Val Ala Ile Thr Val Leu Ile tat cca aac tcc att cag gaa tac ata cgg caa ctg cct cct eat ttt 673 Tyr Pro Asn Ser Ile Gln Glu Tyr Ile Arg Gln Leu Pro Pro Asn Phe ccc tac aga gat gat gtc atg tca gtg aat cct acc tgt ttg gtc ctt 721 Pro Tyr Arg Asp Asp Val Met Ser Val Asn Pro Thr Cys Leu Val Leu att att ctt ctg ttt att agc att atc ttg act ttt aag ggt tac ttg 769 Ile Ile Leu Leu Phe Ile Ser Ile Ile Leu Thr Phe Lys Gly Tyr Leu att agc tgt gtt tgg aac tgc tac cga tac atc aat ggt agg aac tcc 8I7 Ile Ser Cys Val Trp Asn Cys Tyr Arg Tyr Ile Asn Gly Arg Asn Ser 122/1??

tct gat gtc ctg gtt tat gtt acc agc aat gac act acg gtg ctg cta 865 Ser Asp Val Leu Val Tyr Val Thr Ser Asn Asp Thr Thr Val Leu Leu ccc ccg tat gat gat gcc act gtg eat ggt get gcc eag gag cca ccg 913 Pro Pro Tyr Asp Asp Ala Thr Val Asn Gly Ala Ala Lys Glu Pro Pro cca cct tac gtg tct gcc taagccttca agtgggcgga gctgagggc 960 Pro Pro Tyr Val Ser Ala agcagcttga ctttgcagac atctgagcaa tagttctgtt atttcacttt tgccatgagc 1020 ctctctgagc ttgtttgttg ctgaaatgct actttttaaa atttagatgt tagattgaaa 1080 actgtagttt tcaacatatg ctttgctgga acactgtgat agattaactg tagsattctt 1140 cctgtacgat tggggatata atgggcttca ctaaccttcc ctaggcattg aaacttcccc 1200 caaatctgat ggacctagaagtctgcttttgtacctgctgggccccasagttgggcattt1260 ttctctctgt tccctctcttttgaaaatgtaaaataaaaccasaaatagacaactttttc1320 ttcagccatt ccagcatagagaacaaaaccttatggaaacaggaatgtcaattgtgtaat1380 cattgttcta attaggtaaatagaagtccttatgtatgtgttacaagaatttcccccaca1440 acatccttta tgactgaagttcaatgacagtttgtgtttggtggtasaggattttctcca1500 tggcctgaat taagaccattagaaagcaccaggccgtgggagcagtgaccatctgctgac1560 tgttcttgtg gatcttgtgtccagggacatggggtgacatgcctcgtatgtgttagaggg1620 tggaatggat gtgtttggcgctgcatgggatctggtgcccctcttctcctggattcacat1680 ccccacccag ggcccgcttttactaagtgttctgccctagattggttcaaggaggtcatc1740 caactgactt tatcaagtggaattgggatatatttgatatacttctgcctaacaacatgg1800 aaaagggttt tcttttccctgcaagctacatcctactgctttgaacttccaagtatgtct1860 agtcaccttt taaaatgtaaacattttcagaasaatgaggattgccttccttgtatgcgc1920 tttttacctt gactacctgaattgcaagggatttttatatattcatatgttacasagtca1980 gcaactctcc tgttggttcattattgaatgtgctgtaaattaagttgtttgcaattaaaa2040 caaggtttgc ccac 2054 <210>113 <211>1380 <212>DNA

<213>Homo Sapience <220>

<221> CDS
<222> (43)...(630) <400> 113 gcagtctgtc tgagggcggc cgaagtggct ggctcattta ag atg agg ctt ctg 54 Met Arg Leu Leu ctg ctt ctc cta gtg gcg gcg tct gcg atg gtc cgg agc gag gcc tcg 102 Leu Leu Leu Leu Val Ala Ala Ser Ala Met Val Arg Ser Glu Ala Ser 5 10 15 2p gcc aat ctg ggc ggc gtg ccc agc aag aga tta aag atg cag tac gcc 150 Ala Asn Leu Gly Gly Val Pro Ser Lys Arg Leu Lys Met Gln Tyr Ala acg ggg ccg ctg ctc aag ttc cag att tgt gtt tcc tga ggt tat agg 198 Thz Gly Pro Leu Leu Lys Phe Gln Ile Cys Val Ser Xaa Gly Tyr Arg cgg gtg ttt gag gag tac atg cgg gtt att agc cag cgg tac cca gac 246 Arg Val Phe Glu Glu Tyr Met Arg VaI Ile Ser Gln Arg Tyr Pro Asp atc cgc att gaa gga gag aat tac ctc cct caa cca ata tat aga cac 294 Ile Arg Ile Glu Gly Glu Asn Tyr Leu Pro Gln Pro Ile Tyr Arg His ata gca tct ttc ctg tca gtc ttc saa cta gta tta ata ggc tta ata 342 Ile Ala Ser Phe Leu Ser Val Phe Lys Leu Val Leu Ile Gly Leu Ile att gtt ggc aag gat cct ttt get ttc ttt ggc atg caa get cct agc 390 Ile Val Gly Lys Asp Pro Phe Ala Phe Phe Gly Met Gln Ala Pro Ser atc tgg cag tgg ggc caa gaa aat aag gtt tat gca tgt atg atg gtt 438 Ile Trp Gln Trp Gly Gln Glu Asn Lys Val Tyr Ala Cys Met Met Val ttc ttc ttg agc aac atg att gag eac cag tgt atg tca aca ggt gca 486 Phe Phe Leu Ser Asn Met Ile Glu Asn Gln Cys Met Ser Thr Gly Ala ttt gag ata act tta aat gat gta cct gtg tgg tct aag ctg gaa tct 534 Phe Glu Ile Thr Leu Asn Asp Val Pro Val Trp Ser Lys Leu Glu Ser ggt cac ctt gtt att ctt 582 ctt cca caa gac aat tcc atg gaa caa caa Gly His Leu Val Ile Leu Leu Pro Gln Asp Asn Ser Met Glu Gln Gln atg sag at atg tca atc cac cat 627 ctc aat gat cca cga tca gtg c Met Lys is Met Ser Ile His His Leu Asn Asp Pro Arg Ser VaI H

tag caccacctat 680 cagcactgaa aactcttttg cattaaggga tcattgcaag agcagcgtgactgacattatg~aggcctgtactgaagacagcaagctgttagtacagacc740 agatgctttcttggcaggctcgttgtacctcttggaaaacctcaatgcaagatagtgttt800 cagtgctggcatattttggaattctgcacattcatggagtgcaataatactgtatagctt860 tccccacctcccacaaaatcacccagttaatgtgtgtgtgtgtttttttttttaaggtaa920 acattactacttgtasctttttttcttagtcatatttgaaaaagtagaaaattgagttac980 aatttgattttttttecaaagatgtctgttsaatctgttgtgcttttatatgaatatttg1040 ttttttatagtttaaaattgatcctttgggaatccagttgaagttcccasatactttata1100 agagtttatcagacatctctaatttggccatgtccagtttatacagtttacaaaatatag1160 cagatgcaagattatgggggaaatcctatattcagagtactctataaatttttgtgtatg1220 tgtgtatgtgcgtgtgattaccagagaactactaaanaaaccaactgctttttaastcct1280 attgtgtagttasagtgtcatgccttgaccaatctaatgaattgattaattaactgggcc1340 tttatacttaactaaataaasaactaagcagatatgagtt 1380 <210> 114 <211> 1292 <212> nrrA

<213> Homo Sapience <220>
<221> CDS
<222> {113)...(1132) <400> 114 aaaagtgcgg ctctgggctg gccgaagggg tggcgctgcg atcccgcagg gcagcgacgc 60 gactctggtg cgggccgtct tcttcccccc gagctgggcg tgcgcggccg ca atg aac I18 Met Asn WO 00/05367 PC'T/JP99/03929 tgg gag ctg ctg ctg tgg ctg ctg gtg ctg tgc gcg ctg ctc ctg ctc 166 Trp Glu Leu Leu Leu Trp Leu Leu Val Leu Cys Ala Leu Leu Leu Leu ttg gtg cag ctg ctg cgc ttc ctg agg get gac ggc gac ctg acg cta 214 5 Leu Val Gln Leu Leu Arg Phe Leu Arg Ala Asp Gly Asp Leu Thr Leu cta tgg gcc gag tgg cag gga cga cgc cca gaa tgg gag ctg act gat 262 Leu Trp Ala Glu Trp Gln Gly Arg Arg Pro Glu Trp Glu Leu Thr Asp atg gtg gtg tgg gtg act gga gcc tcg agt gga att ggt gag gag ctg 310 Met Val Val Trp Val Thr Gly Ala Ser Ser Gly Ile Gly Glu Glu Leu get tac cag ttg tct aaa cts gga gtt tct ctt gtg ctg tca gcc aga 358 Ala Tyr Gln Leu Ser Lys Leu Gly Val Ser Leu Val Leu Ser Ala Arg 70 75 so aga gtg cat gag ctg gas agg gtg aaa aga aga tgc cta gag aat ggc 406 Arg Val His Glu Leu Glu Arg Val Lys Arg Arg Cys Leu Glu Asn Gly aat tta aaa gaa saa gat ata ctt gtt ttg ccc ctt gac ctg acc gac 454 Asn Leu Lys Glu Lys Asp Ile Leu Val Leu Pro Leu Asp Leu Thr Asp act ggt tcc cat gaa gcg get acc aaa get gtt ctc cag gag ttt ggt 502 Thr Gly Ser His Glu Ala Ala Thr Lys Ala Val Leu Gln Glu Phe Gly aga atc gac att ctg gtc aac aat ggt gga atg tcc cag cgt tct ctg 550 Arg Ile Asp Ile Leu Val Asn Asn Gly Gly Met Ser Gln Arg Ser Leu tgc atg gat acc agc ttg gat gtc tac aga aag cta ata gag ctt aac 598 Cys Met Asp Thr Ser Leu Asp Val Tyr Arg Lys Leu Ile Glu Leu Asn tac tta ggg acg gtg tcc ttg aca aaa tgt gtt ctg cct cac atg atc 646 Tyr Leu Gly Thr Val Ser Leu Thr Lys Cys Val Leu Pro His Met IIe gag agg aag caa gga aag att gtt act gtg aat agc atc ctg ggt atc 694 Glu Arg Lys Gln Gly Lys Ile Val Thr Val Asn Ser Ile Leu Gly Ile ata tctgtacctctttccatt ggatactgtgetagcaag catgetctc 742 Ile SerValProLeuSerIle GlyTyrCysAlaSerLys HisAlaLeu cgg ggtttttttsatggcctt cgaacagaacttgccaca tacccaggt 790 Arg GlyPhePheAsnGlyLeu ArgThrGluLeuAlaThr TyrProGly ata atagtttctaacatttgc ccaggacctgtgcaatca aatattgtg 838 Ile IleValSerAsnIleCys ProGlyProValGlnSer AsnIleVal gag aattccctagetggagae gtcacaasgactataggc aataatgga 886 Glu AsnSerLeuAlaGlyGlu ValThrLysThrIleGly AsnAsnGly gac cagtcccacaagatgaca accagtcgttgtgtgcgg ctgatgtta 934 Asp GlnSerHisLysMetThr ThrSerArgCysValArg LeuMetLeu atc agcatggccaatgatttg aaagaagtttggatctca gaacaacct 982 Ile SerMetAlaAsnAspLeu LysGluValTrpIleSer GluGlnPro ttc ttgttagtaacatatttg tggcaatacatgccaacc tgggcctgg 1030 Phe LeuLeuValThrTyrLeu TrpGlnTyrMetProThr TrpAlaTrp tgg ataaccaacaagatgggg aagsaaaggattgagsac tttaagagt 1078 Trp IleThrAsnLysMetGly LysLysArgIleGluAsn PheLysSer ggt gtggatgcagactcttct tattttaaaatctttaag acaaaacat 1126 Gly ValAspAlaAspSerSer TyrPheLysIlePheLys ThrLysHis gac tgaaaagagc tctgtactt tggagggaaa aatggaaa ac a ttcaagccac a Asp tgaaaacagc aatcttctta tgcttctgaa taatcaaaga ctaetttgtg gttttacttt 1240 ttaatagata tgactttgct tccaacatgg aatgasataa aaaataagta at 1292 <210> 115 12?/177 <211> 2168 <212> DNA
<213> Homo Sapience <220>
<221> CDS
<222> (56)...(1519) <400>

tttccgccgc cgcctgggag cccagctgtg 55 gggacccggg cccag ctgccaggcg atg gatggg acagagacc cggcagcggaggctggac agctgtggcaag 103 Met AspGly ThrGluThr ArgGlnArgArgLeuAsp SerCysGlyLys cca ggggag ctggggctt cctcaccccctcagcaca ggaggactccct 151 Pro GlyGlu LeuGlyLeu ProHisProLeuSerThr GlyGlyLeuPro gta gcctca gasgatgga getetcagggcccctgag agccaaagcgtg 199 Val AlaSer GluAspGly AlaLeuArgAlaProGlu SerGlnSerVal acc eccsag ccactggag actgagcctagcagggag accgcctggtcc 247 Thr ProLys ProLeuGlu ThrGluProSerArgGlu ThrAlaTrpSer ata ggcctt caggtgacc gtgcccttcatgtttgca ggcctgggactg 295 Ile GlyLeu GlnValThr ValProPheMetPheAla GlyLeuGlyLeu tcc tgggcc ggcatgctt ctggactatttccagcac tggcctgtgttt 343 Ser TrpAla GlyMetLeu LeuAspTyrPheGlnHis TrpProValPhe gtg gaggtg aaagacctt ttgacattggtgccgccc ctggtgggcctg 391 Val GluVal LysAspLeu LeuThrLeuValProPro LeuValGlyLeu aag gggaac ctggagatg acactggcatccagactc tccacagetgcc 439 Lys GlyAsn LeuGluMet ThrLeuAlaSerArgLeu SerThrAlaAla aac actgga caaattgat gacccccaggagcagcac agagtcatcagc 487 Asn Thr Gly Gln Ile Asp Asp Pro Gln Glu Gln His Arg Val Ile Ser DEMANDES OU BREVETS VOLUMINEUX
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COMPREND PLUS D'UN TOME. ~ _ CECI EST LE TOME . ~ DE
NOTE: Pour les tomes additionels, veuiitez co~tacter !e Bureau canadien des brevets JUMBO APPLlCATIONS/PATEnITS
THIS SECT10N OF THE APPLICATiON/PATENT CONTAINS MORE
THAN ONE VOLUME

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Claims (6)

122

1. A protein comprising any one of an amino acid sequence selected from the group consisting of SEQ ID Nos. 1 to 10, 31 to 40, 61 to 70, 91 to 100, and 121 to 130.

2. An isolated DNA coding for the protein according to Claim 1.

3. An isolated cDNA comprising any one of a base sequence selected from the group consisting of SEQ ID Nos.
11 to 20, 41 to 50, 71 to 80, 101 to 110, and 131 to 140.

4. The cDNA according to Claim 3 consisting of any one of a base sequence selected from the group consisting of SEQ ID Nos. 21 to 30, 51 to 60, 81 to 90, 111 to 120, and 141 to 150.

5. An expression vector that is capable of expressing the DNA according to any one of Claim 2 to Claim 4 by in vitro translation or in eucaryotic cells.

6. A transformed eucaryotic cell that is capable of expressing the DNA according to any one of Claim 2 to Claim 4 and of producing the protein according to Claim 1.