SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM

PROTEINES SECRETEES ET POLYNUCLEOTIDES LES CODANT

English Abstract

Novel polynucleotides and the proteins encoded thereby are disclosed.

French Abstract

La présente invention concerne, d'une part des polynucléotides nouvellement découverts, et d'autre part les protéines codées par ces polynucléotides.

Claims

What is claimed is:
1. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:1;
(b) the nucleotide sequence of SEQ ID NO:1 from nucleotide 126 to
nucleotide 485;
(c) the nucleotide sequence of SEQ ID NO:1 from nucleotide 207 to
nucleotide 485;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb2_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb2_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:2;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:2, the fragment comprising eight
contiguous amino acids of SEQ ID NO:2;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:1.
2. The polynucleotide of claim 1 wherein said polynucleotide is operably
linked to at least one expression control sequence.
3. A host cell transformed with the polynucleotide of claim 2.
175

4. The host cell of claim 3, wherein said cell is a mammalian cell.
5. A process for producing a protein encoded by the polynucleotide of claim
2, which process comprises:
(a) growing a culture of a host cell transformed with the
polynucleotide of claim 2 in a suitable culture medium; and
(b) purifying said protein from the culture.
6. A protein produced according to the process of claim 5.
7. An isolated polynucleotide encoding the protein of claim 6.
8. The polynucleotide of claim 7, wherein the polynucleotide comprises the
cDNA insert of clone vb2_1 deposited under accession number ATCC 98804.
9. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:2;
(b) a fragment of the amino acid sequence of SEQ ID NO:2, the
fragment comprising eight contiguous amino acids of SEQ ID NO:2; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb2_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
10. The protein of claim 9, wherein said protein comprises the amino acid
sequence of SEQ ID NO:2.
11. A composition comprising the protein of claim 9 and a pharmaceutically
acceptable carrier.
12. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:3;
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(b) the nucleotide sequence of SEQ ID NO:3 from nucleotide 130 to
nucleotide 2286;
(c) the nucleotide sequence of SEQ ID NO:3 from nucleotide 214 to
nucleotide 2286;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb3_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb3_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:4;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight
contiguous amino acids of SEQ ID NO:4;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:3.
13. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:4;
(b) a fragment of the amino acid sequence of SEQ ID NO:4, the
fragment comprising eight contiguous amino acids of SEQ ID NO:4; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
177

14. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:5;
(b) the nucleotide sequence of SEQ ID NO:5 from nucleotide 172 to
nucleotide 522;
(c) the nucleotide sequence of SEQ ID NO:5 from nucleotide 214 to
nucleotide 522;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb4_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb4_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:6;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:6, the fragment comprising eight
contiguous amino acids of SEQ ID NO:6;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:5.
15. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:6;
(b) a fragment of the amino acid sequence of SEQ ID NO:6, the
fragment comprising eight contiguous amino acids of SEQ ID NO:6; and
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(c) the amino acid sequence encoded by the cDNA insert of clone
vb4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
16. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:7;
(b) the nucleotide sequence of SEQ ID NO:7 from nucleotide 119 to
nucleotide 502;
(c) the nucleotide sequence of SEQ ID NO:7 from nucleotide 176 to
nucleotide 502;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb5_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb5_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:8;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:8, the fragment comprising eight
contiguous amino acids of SEQ ID NO:8;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:7.
17. A protein comprising an amino acid sequence selected from the group
consisting of:
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(a) the amino acid sequence of SEQ ID NO:8;
(b) a fragment of the amino acid sequence of SEQ ID NO:8, the
fragment comprising eight contiguous amino acids of SEQ ID NO:8; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb5_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
18. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:9;
(b) the nucleotide sequence of SEQ ID NO:9 from nucleotide 128 to
nucleotide 436;
(c) the nucleotide sequence of SEQ ID NO:9 from nucleotide 203 to
nucleotide 436;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb6_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb6_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:10;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:10, the fragment comprising eight
contiguous amino acids of SEQ ID NO:10;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:9.
180

19. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID NO:10, the
fragment comprising eight contiguous amino acids of SEQ ID NO:10; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb6_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
20. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:11;
(b) the nucleotide sequence of SEQ ID NO:11 from nucleotide 138 to
nucleotide 1250;
(c) the nucleotide sequence of SEQ ID NO:11 from nucleotide 279 to
nucleotide 1250;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb7_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb7_1 deposited under accession number ATCC 98804;
(g} a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb7_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:12;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:12, the fragment comprising eight
contiguous amino acids of SEQ ID NO:12;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
181

C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:11.
21. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:12;
(b} a fragment of the amino acid sequence of SEQ ID NO:12, the
fragment comprising eight contiguous amino acids of SEQ ID NO:12; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb7_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
22. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:13;
(b) the nucleotide sequence of SEQ ID NO:13 from nucleotide 615 to
nucleotide 869;
(c) the nucleotide sequence of the full-length protein coding sequence
of clone vb8_1 deposited under accession number ATCC 98804;
(d) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:14;
(f) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:14, the fragment comprising eight
contiguous amino acids of SEQ ID NO:14;
(g) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and
(h) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(d),
and
that has a length that is at least 25% of the length of SEQ ID NO:13.
182

23. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:14;
(b) a fragment of the amino acid sequence of SEQ ID NO:14, the
fragment comprising eight contiguous amino acids of SEQ ID NO:14; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
24. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:15;
(b) the nucleotide sequence of SEQ ID NO:15 from nucleotide 148 to
nucleotide 1470;
(c) the nucleotide sequence of SEQ ID NO:15 from nucleotide 193 to
nucleotide 1470;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb9_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vb9_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:16;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:16, the fragment comprising eight
contiguous amino acids of SEQ ID NO:16;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
183

C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:15.
25. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:16;
(b) a fragment of the amino acid sequence of SEQ ID NO:16, the
fragment comprising eight contiguous amino acids of SEQ ID NO:16; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb9_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
26. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:17;
(b) the nucleotide sequence of SEQ ID NO:17 from nucleotide 109 to
nucleotide 414;
(c) the nucleotide sequence of SEQ ID NO:17 from nucleotide 217 to
nucleotide 414;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc3_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc3_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:18;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight
contiguous amino acids of SEQ ID NO:18;
184

(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:17.
27. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:18;
(b) a fragment of the amino acid sequence of SEQ ID NO:18, the
fragment comprising eight contiguous amino acids of SEQ ID NO:18; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc3_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
28. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:19;
(b) the nucleotide sequence of SEQ ID NO:19 from nucleotide 169 to
nucleotide 840;
(c) the nucleotide sequence of SEQ ID NO:19 from nucleotide 211 to
nucleotide 840;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc4_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc4_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:20;
185

(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:20; the fragment comprising eight
contiguous amino acids of SEQ ID NO:20;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:19.
29. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:20;
(b) a fragment of the amino acid sequence of SEQ ID NO:20, the
fragment comprising eight contiguous amino acids of SEQ ID NO:20; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc4_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
30. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:21;
(b) the nucleotide sequence of SEQ ID NO:21 from nucleotide 508 to
nucleotide 951;
(c) the nucleotide sequence of SEQ ID NO:21 from nucleotide 733 to
nucleotide 951;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc5_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the foil-length protein encoded by
the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc5_1 deposited under accession number ATCC 98748;
186

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:22;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:22, the fragment comprising eight
contiguous amino acids of SEQ ID NO:22;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:21.
31. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:22;
(b) a fragment of the amino acid sequence of SEQ ID NO:22, the
fragment comprising eight contiguous amino acids of SEQ ID NO:22; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc5_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
32. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:23;
(b) the nucleotide sequence of SEQ ID NO:23 from nucleotide 125 to
nucleotide 493;
(c) the nucleotide sequence of the full-length protein coding sequence
of clone vc7_1 deposited under accession number ATCC 98748;
(d) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
187

(e) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:24;
(f) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:24, the fragment comprising eight
contiguous amino acids of SEQ ID NO:24;
(g) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and
(h) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(d),
and
that has a length that is at least 25% of the length of SEQ ID NO:23.
33. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:24;
(b) a fragment of the amino acid sequence of SEQ ID NO:24, the
fragment comprising eight contiguous amino acids of SEQ ID NO:24; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc7_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
34. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:25;
(b) the nucleotide sequence of SEQ ID NO:25 from nucleotide 33 to
nucleotide 407;
(c) the nucleotide sequence of SEQ ID NO:25 from nucleotide 99 to
nucleotide 407;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc9_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
188

(f) the nucleotide sequence of a mature protein coding sequence of
clone vc9_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:26;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:26, the fragment comprising eight
contiguous amino acids of SEQ ID NO:6;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:25.
35. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:26;
(b) a fragment of the amino acid sequence of SEQ ID NO:26, the
fragment comprising eight contiguous amino acids of SEQ ID NO:26; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc9_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
36. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:27;
(b) the nucleotide sequence of SEQ ID NO:27 from nucleotide 176 to
nucleotide 871;
(c) the nucleotide sequence of the full-length protein coding sequence
of clone vc10_1 deposited under accession number ATCC 98748;
189

(d) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc10_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:28;
(f) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:28, the fragment comprising eight
contiguous amino acids of SEQ ID NO:28;
(g) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and
(h) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(d),
and
that has a length that is at least 25% of the length of SEQ ID NO:27.
37. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:28;
(b) a fragment of the amino acid sequence of SEQ ID NO:28, the
fragment comprising eight contiguous amino acids of SEQ ID NO:28; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc10_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
38. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:29;
(b) the nucleotide sequence of SEQ ID NO:29 from nucleotide 160 to
nucleotide 657;
(c) the nucleotide sequence of SEQ ID NO:29 from nucleotide 214 to
nucleotide 657;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc11_1 deposited under accession number ATCC 98748;
190

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc11_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:30;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:30, the fragment comprising eight
contiguous amino acids of SEQ ID NO:30;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:29.
39. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:30;
(b) a fragment of the amino acid sequence of SEQ ID NO:30, the
fragment comprising eight contiguous amino acids of SEQ ID NO:30; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc11_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
40. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:31;
(b) the nucleotide sequence of SEQ ID NO:31 from nucleotide 228 to
nucleotide 662;
191

(c) the nucleotide sequence of SEQ ID NO:31 from nucleotide 327 to
nucleotide 662;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc14_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc14_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:32;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:32, the fragment comprising eight
contiguous amino acids of SEQ ID NO:32;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:31.
41. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:32;
(b) a fragment of the amino acid sequence of SEQ ID NO:32, the
fragment comprising eight contiguous amino acids of SEQ ID NO:32; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc14_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
42. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
192

(a) the nucleotide sequence of SEQ ID NO:33;
(b) the nucleotide sequence of SEQ ID NO:33 from nucleotide 101 to
nucleotide 667;
(c) the nucleotide sequence of SEQ ID NO:33 from nucleotide 182 to
nucleotide 667;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc16_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc16_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:34;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:34, the fragment comprising eight
contiguous amino acids of SEQ ID NO:34;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:33.
43. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:34;
(b) a fragment of the amino acid sequence of SEQ ID NO:34, the
fragment comprising eight contiguous amino acids of SEQ ID NO:34; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc16_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
193

44. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:35;
(b) the nucleotide sequence of SEQ ID NO:35 from nucleotide 8 to
nucleotide 355;
(c) the nucleotide sequence of SEQ ID NO:35 from nucleotide 134 to
nucleotide 355;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc17_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc17_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc17_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc17_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:36;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight
contiguous amino acids of SEQ ID NO:36;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:35.
45. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:36;
(b) a fragment of the amino acid sequence of SEQ ID NO:36, the
fragment comprising eight contiguous amino acids of SEQ ID NO:36; and
194

(c) the amino acid sequence encoded by the cDNA insert of clone
vc17-1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
46. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:37;
(b) the nucleotide sequence of SEQ ID NO:37 from nucleotide 1031 to
nucleotide 1252;
(c) the nucleotide sequence of SEQ ID NO:37 from nucleotide 1100 to
nucleotide 1252;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc21_1 deposited under accession number ATCC 98785;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc21_1 deposited under accession number ATCC 98785;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:38;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:38, the fragment comprising eight
contiguous amino acids of SEQ ID NO:38;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:37.
47. A protein comprising an amino acid sequence selected from the group
consisting of:
195

(a) the amino acid sequence of SEQ ID NO:38;
(b) the amino acid sequence of SEQ ID NO:38 from amino acid 29 to
amino acid 74;
(c) a fragment of the amino acid sequence of SEQ ID NO:38, the
fragment comprising eight contiguous amino acids of SEQ ID NO:38; and
(d) the amino acid sequence encoded by the cDNA insert of clone
vc21_1 deposited under accession number ATCC 98785;
the protein being substantially free from other mammalian proteins.
48. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:39;
(b) the nucleotide sequence of SEQ ID NO:39 from nucleotide 94 to
nucleotide 1482;
(c) the nucleotide sequence of SEQ ID NO:39 from nucleotide 214 to
nucleotide 1482;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc23_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc23_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:40;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:40, the fragment comprising eight
contiguous amino acids of SEQ ID NO:40;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
196

C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:39.
49. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:40;
(b) a fragment of the amino acid sequence of SEQ ID NO:40, the
fragment comprising eight contiguous amino acids of SEQ ID NO:40; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc23_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
50. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:41;
(b) the nucleotide sequence of SEQ ID NO:41 from nucleotide 153 to
nucleotide 413;
(c) the nucleotide sequence of SEQ ID NO:41 from nucleotide 264 to
nucleotide 413;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc25_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc25_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:42;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:42, the fragment comprising eight
contiguous amino acids of SEQ ID NO:42;
197

(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:41.
51. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:42;
(b) a fragment of the amino acid sequence of SEQ ID NO:42, the
fragment comprising eight contiguous amino acids of SEQ ID NO:42; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc25_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
52. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:43;
(b) the nucleotide sequence of SEQ ID NO:43 from nucleotide 87 to
nucleotide 1409;
(c) the nucleotide sequence of SEQ ID NO:43 from nucleotide 156 to
nucleotide 1409;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc26_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc26_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:44;
198

(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight
contiguous amino acids of SEQ ID NO:44;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:43.
53. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:44;
(b) a fragment of the amino acid sequence of SEQ ID NO:44, the
fragment comprising eight contiguous amino acids of SEQ ID NO:44; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc26_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
54. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:45;
(b) the nucleotide sequence of SEQ ID NO:45 from nucleotide 63 to
nucleotide 428;
(c) the nucleotide sequence of SEQ ID NO:45 from nucleotide 156 to
nucleotide 428;
(d) the nucleotide sequence of SEQ ID NO:45 from nucleotide 356 to
nucleotide 1773;
(e) the nucleotide sequence of the full-length protein coding sequence
of clone vc30_1 deposited under accession number ATCC 98804;
(f) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
199

(g) the nucleotide sequence of a mature protein coding sequence of
clone vc30_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(i) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:46;
(j) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:46, the fragment comprising eight
contiguous amino acids of SEQ ID NO:46;
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(h);
and
(l) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(h),
and
that has a length that is at least 25% of the length of SEQ ID NO:45.
55. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:46;
(b) the amino acid sequence of SEQ ID NO:46 from amino acid 1 to
amino acid 97;
(c) a fragment of the amino acid sequence of SEQ ID NO:46, the
fragment comprising eight contiguous amino acids of SEQ ID NO:46; and
(d) the amino acid sequence encoded by the cDNA insert of clone
vc30_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
56. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:47;
(b) the nucleotide sequence of SEQ ID NO:47 from nucleotide 30 to
nucleotide 1799;
200

(c) the nucleotide sequence of SEQ ID NO:47 from nucleotide 90 to
nucleotide 1799;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vd1_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vd1_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:48;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:48, the fragment comprising eight
contiguous amino acids of SEQ ID NO:48;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:47.
57. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:48;
(b) a fragment of the amino acid sequence of SEQ ID NO:48, the
fragment comprising eight contiguous amino acids of SEQ ID NO:48; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vd1_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
58. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
201

(a) the nucleotide sequence of SEQ ID NO:49;
(b) the nucleotide sequence of SEQ ID NO:49 from nucleotide 69 to
nucleotide 443;
(c) the nucleotide sequence of SEQ ID NO:49 from nucleotide 111 to
nucleotide 443;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vd2_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vd2_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:50;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight
contiguous amino acids of SEQ ID NO:50;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:49.
59. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:50;
(b) a fragment of the amino acid sequence of SEQ ID NO:50, the
fragment comprising eight contiguous amino acids of SEQ ID NO:50; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vd2_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
202

60. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:51;
(b) the nucleotide sequence of SEQ ID NO:51 from nucleotide 176 to
nucleotide 1249;
(c) the nucleotide sequence of SEQ ID NO:51 from nucleotide 227 to
nucleotide 1249;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vd3_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vd3_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:52;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:52, the fragment comprising eight
contiguous amino acids of SEQ ID NO:52;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (ar(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:51.
61. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:52;
(b) a fragment of the amino acid sequence of SEQ ID NO:52, the
fragment comprising eight contiguous amino acids of SEQ ID NO:52; and
203

(c) the amino acid sequence encoded by the cDNA insert of clone
vd3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
62. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:53;
(b) the nucleotide sequence of SEQ ID NO:53 from nucleotide 94 to
nucleotide 1530;
(c) the nucleotide sequence of SEQ ID NO:53 from nucleotide 145 to
nucleotide 1530;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vd4_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vd4_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:54;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:54, the fragment comprising eight
contiguous amino acids of SEQ ID NO:54;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:53.
63. A protein comprising an amino acid sequence selected from the group
consisting of:
204

(a) the amino acid sequence of SEQ ID NO:54;
(b) a fragment of the amino acid sequence of SEQ ID NO:54, the
fragment comprising eight contiguous amino acids of SEQ ID NO:54; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vd4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
64. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:55;
(b) the nucleotide sequence of SEQ ID NO:55 from nucleotide 71 to
nucleotide 1300;
(c) the nucleotide sequence of SEQ ID NO:55 from nucleotide 182 to
nucleotide 1300;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone ve4_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone ve4_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:56;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:56, the fragment comprising eight
contiguous amino acids of SEQ ID NO:56;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:55.
205

65. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:56;
(b) a fragment of the amino acid sequence of SEQ ID NO:56, the
fragment comprising eight contiguous amino acids of SEQ ID NO:56; and
(c) the amino acid sequence encoded by the cDNA insert of clone
ve4_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
66. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:57;
(b) the nucleotide sequence of SEQ ID NO:57 from nucleotide 57 to
nucleotide 785;
(c) the nucleotide sequence of SEQ ID NO:57 from nucleotide 147 to
nucleotide 785;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone ve8_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone ve8_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:58;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:58, the fragment comprising eight
contiguous amino acids of SEQ ID NO:58;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
206

C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:57.
67. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:58;
(b) a fragment of the amino acid sequence of SEQ ID NO:58, the
fragment comprising eight contiguous amino acids of SEQ ID NO:58; and
(c) the amino acid sequence encoded by the cDNA insert of clone
ve8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
68. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:59;
(b) the nucleotide sequence of SEQ ID NO:59 from nucleotide 64 to
nucleotide 1002;
(c) the nucleotide sequence of SEQ ID NO:59 from nucleotide 139 to
nucleotide 1002;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vf1_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vf1_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:60;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:60, the fragment comprising eight
contiguous amino acids of SEQ ID NO:60;
207

(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:59.
69. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID NO:60, the
fragment comprising eight contiguous amino acids of SEQ ID NO:60; and
(c) the amino acid sequence encoded by the cDNA insert of clone vf1_1
deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
70. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:61;
(b) the nucleotide sequence of SEQ ID NO:61 from nucleotide 588 to
nucleotide 995;
(c) the nucleotide sequence of SEQ ID NO:61 from nucleotide 750 to
nucleotide 995;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vh1_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vh1_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:62;
208

(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight
contiguous amino acids of SEQ ID NO:62;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:61.
71. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:62;
(b) a fragment of the amino acid sequence of SEQ ID NO:62, the
fragment comprising eight contiguous amino acids of SEQ ID NO:62; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vh1_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
72. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:63;
(b) the nucleotide sequence of SEQ ID NO:63 from nucleotide 29 to
nucleotide 1369;
(c) the nucleotide sequence of SEQ ID NO:63 from nucleotide 104 to
nucleotide 1369;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vi1_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vi1_1 deposited under accession number ATCC 98804;
209

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino
acid sequence of SEQ ID NO:64;
(i) a nucleotide sequence encoding a protein comprising a fragment
of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight
contiguous amino acids of SEQ ID NO:64;
(j) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and
(k) the nucleotide sequence of a polynucleotide that hybridizes under
conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40
degrees
C with 50% formamide, to any one of the polynucleotides specified by (a)-(g),
and
that has a length that is at least 25% of the length of SEQ ID NO:63.
73. A protein comprising an amino acid sequence selected from the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:64;
(b) a fragment of the amino acid sequence of SEQ ID NO:64, the
fragment comprising eight contiguous amino acids of SEQ ID NO:64; and
(c) the amino acid sequence encoded by the cDNA insert of clone vi1_1
deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
210

Description

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SECRETED PROTEINS AND POLYNUCLEOT1DES ENCODING THEM
15
FIELD OF THE INVENTION
The present invention provides novel polynucleotides and proteins encoded by
such polynucleotides, along with therapeutic, diagnostic and research
utilities for these
polynucleotides and proteins.
BACKGROUND QF THE INVENTION
Technology aimed at the discovery of protein factors (including e.g.,
cytokines,
such as lymphokines, interferons, CSFs and interleukins) has matured rapidly
over the
past decade. The now routine hybridization cloning and expression cloning
techniques
2 5 clone novel polynucleotides "directly" in the sense that they rely on
information directly
related to the discovered protein (i.e., partial DNA/amino acid sequence of
the protein
in the case of hybridization cloning; activity of the protein in the case of
expression
cloning). More recent "indirect" cloning techniques such as signal sequence
cloning, which
isolates DNA sequences based on the presence of a now well-recognized
secretory leader
3 0 sequence motif, as well as various PCR-based or low stringency
hybridization cloning
techniques, have advanced the state of the art by making available large
numbers of
DNA/amino acid sequences for proteins that are known to have biological
activity by
virtue of their secreted nature in the case of leader sequence cloning, or by
virtue of the
cell or tissue source in the case of PCR-based techniques. It is to these
proteins and the
3 5 polynucleotides encoding them that the present invention is directed.

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SUMMARY OF THE INVENTION
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:1;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 126 to nucleotide 485;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 207 to nucleotide 485;
(d) a polynudeotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb2_1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb2_1 deposited under accession number ATCC
98804;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
insert of clone vb2_1 deposited under accession number ATCC 98804;
2 0 (h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:2;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:2 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:2;
2 5 (j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a palynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
3 0 one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:1.
2

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Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:1 from nucleotide 126 to nucleotide 485; the nucleotide sequence of SEQ ID
NO:1 from
nucleotide 207 to nucleotide 485; the nucleotide sequence of the full-length
protein coding
sequence of clone vb2_1 deposited under accession number ATCC 98804; or the
nucleotide sequence of a mature protein coding sequence of clone vb2_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb2_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:2 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:2, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:2 having biological activity,
the
fragment comprising the amino acid sequence from amino acid 55 to amino acid
64 of SEQ
ID N0:2.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:1.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i} preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID NO:1, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:1; and
(ab) the nucleotide sequence of the cDNA insert of clone
vb2_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
3 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
3

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(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID NO:1, but excluding the poly(A) tail at the
3' end of SEQ ID N0:1; and
(bb) the nucleotide sequence of the cDNA insert of clone
vb2_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:1, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
NO:1 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:1 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:1. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:1 from nucleotide 126 to nucleotide 485, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
2 0 SEQ ID N0:1 from nucleotide 126 to nucleotide 485, to a nucleotide
sequence
corresponding to the 3' end of said sequence of SEQ ID N0:1 from nucleotide
126 to
nucleotide 485. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
NO:1 from nucleotide 207 to nucleotide 485, and extending contiguously from a
2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:1 from
nucleotide 207 to nucleotide 485, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID NO:1 from nucleotide 207 to nucleotide 485.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:2;
(b) a fragment of the amino acid sequence of SEQ ID N0:2, the
fragment comprising eight contiguous amino acids of SEQ ID N0:2; and
4

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(c) the amino acid sequence encoded by the cDNA insert of clone
vb2_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:2. In further preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:2 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:2, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:2 having biological activity, the fragment comprising the amino acid
sequence from
amino acid 55 to amino acid 64 of SEQ ID N0:2.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 130 to nucleotide 2286;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286;
(d) a polynucleotide comprising the nucleotide sequence of the full-
2 0 length protein coding sequence of clone vb3_1 deposited under accession
number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 5 protein coding sequence of clone vb3_1 deposited under accession number
ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb3_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
3 0 sequence of SEQ ID N0:4;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:4 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:4;
5

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(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:3.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:3 from nucleotide 130 to nucleotide 2286; the nucleotide sequence of SEQ ID
N0:3
from nucleotide 214 to nucleotide 2286; the nucleotide sequence of the full-
length protein
coding sequence of clone vb3_1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone vb3_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb3_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:4 having biological activity, the
fragment
2 0 preferably comprising eight (more preferably twenty, most preferably
thirty) contiguous
amino acids of SEQ ID N0:4, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:4 having biological activity,
the
fragment comprising the amino acid sequence from amino acid 354 to amino acid
363 of
SEQ ID N0:4.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of
SEQ
ID N0:3.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:3, but excluding the poly(A) tail at the
3' end of SEQ ID N0:3; and
6

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(ab) the nucleotide sequence of the cDNA insert of done
vb3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynudeotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:3, but excluding the poly(A) tail at the
3' end of SEQ ID N0:3; and
(bb) the nucleotide sequence of the cDNA insert of done
vb3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynudeotide products of step (b)(iii).
2 0 Preferably the polynudeotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:3, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:3 to
a nucleotide sequence cosesponding to the 3' end of SEQ ID N0:3 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:3. Also preferably the polynudeotide
isolated
2 5 according to the above process comprises a nucleotide sequence
corresponding to the
cDNA sequence of SEQ ID N0:3 from nucleotide 130 to nucleotide 2286, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:3 from nucleotide 130 to nucleotide 2286, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide
130 to
3 0 nucleotide 2286. Also preferably the polynudeotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:3 from
7

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nucleotide 214 to nucleotide 2286, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:3 from nucleotide 214 to nucleotide 2286.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:4;
(b) a fragment of the amino acid sequence of SEQ ID N0:4, the
fragment comprising eight contiguous amino acids of SEQ ID N0:4; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb3 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:4. In further preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:4 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:4, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:4 having biological activity, the fragment comprising the amino acid
sequence from
amino acid 354 to amino and 363 of SEQ ID N0:4.
In one embodiment, the present invention provides a composition comprising an
2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 172 to nucleotide 522;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb4_1 deposited under accession number
ATCC 98804;
3 0 (e) a polynucleatide encoding the full-length protein encoded by the
cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb4_1 deposited under accession number ATCC
98804;
8

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(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb4_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:6;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:6 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:6;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:5.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:5 from nucleotide 172 to nucleotide 522; the nucleotide sequence of SEQ ID
N0:5 from
nucleotide 214 to nucleotide 522; the nucleotide sequence of the full-length
protein coding
2 0 sequence of clone vb4_1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone vb4_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb4_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
2 5 present invention provides a polynucleotide encoding a protein comprising
a fragment
of the amino acid sequence of SEQ ID N0:6 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:6, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:6 having biological activity,
the
3 0 fragment comprising the amino acid sequence from amino acid 53 to amino
acid 62 of SEQ
ID N0:6.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:5.
9

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Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:5, but excluding the poiy(A) tail at the
3' end of SEQ ID N0:5; and
(ab) the nucleotide sequence of the cDNA insert of clone
vb4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 0 (ba) SEQ ID N0:5, but excluding the poly(A) tail at the
3' end of SEQ ID N0:5; and
(bb) the nucleotide sequence of the cDNA insert of clone
vb4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:5, and
extending
3 0 contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:5 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:5 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:5. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522, and
extending

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contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:5 from nucleotide 172 to nucleotide 522, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:5 from nucleotide
172 to
nucleotide 522. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:5 from nucleotide 214 to nucleotide 522, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:5 from
nucleotide 214 to nucleotide 522, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:5 from nucleotide 214 to nucleotide 522.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:6;
(b) a fragment of the amino acid sequence of SEQ ID N0:6, the
fragment comprising eight contiguous amino acids of SEQ ID N0:6; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:6. In further preferred
2 0 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:6 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:6, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:6 having biological activity, the fragment comprising the amino acid
sequence from
2 5 amino acid 53 to amino acid 62 of SEQ ID N0:6.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 119 to nucleotide 502;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502;
11

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(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb5_1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
S cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb5_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb5_1 deposited under accession number ATCC 98804;
(h) a polynudeotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:8;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:8 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:8;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the profiein
of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a}-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:7.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:7 from nucleotide 119 to nucleotide 502; the nucleotide sequence of SEQ ID
N0:7 from
nucleotide 176 to nucleotide 502; the nucleotide sequence of the full-length
protein coding
sequence of clone vb5_1 deposited under accession number ATCC 98804; or the
nucleotide sequence of a mature protein coding sequence of clone vb5_1
deposited under
3 0 accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb5_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:8 having biological activity, the
fragment
12

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preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:8, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:8 having biological activity,
the
fragment comprising the amino acid sequence from amino acid 59 to amino acid
68 of SEQ
ID N0:8.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:7.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:7, but excluding the poly(A) tail at the
3' end of SEQ ID N0:7; and
(ab) the nucleotide sequence of the cDNA insert of clone
vb5_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:7, but excluding the poly(A) tail at the
3' end of SEQ ID N0:7; and
(bb) the nucleotide sequence of the cDNA insert of clone
3 0 vb5_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
13

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Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:7, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:7 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:7 , but
excluding the
poly{A) tail at the 3' end of SEQ ID N0:7. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:7 from nucleotide 119 to nucleotide 502, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide
119 to
nucleotide 502. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:7 from nucleotide 176 to nucleotide 502, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:7 from
nucleotide 176 to nucleotide 502, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:7 from nucleotide 176 to nucleotide 502.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:8;
(b) a fragment of the amino acid sequence of SEQ ID N0:8, the
fragment comprising eight contiguous amino acids of SEQ ID N0:8; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb5_1 deposited under accession number ATCC 98804;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such
protein comprises the amino acid sequence of SEQ ID N0:8. In further preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:8 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty} contiguous
amino ands
3 0 of SEQ ID N0:8, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:8 having biological activity, the fragment comprising the amino acid
sequence from
amino acid 59 to amino acid 68 of SEQ ID N0:8.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
14

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(a} a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 128 to nucleotide 436;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb6_1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb6_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb6_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID NO:10;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 0 amino acid sequence of SEQ ID N0:10 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID NO:10;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(i); and
(m} a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
3 0 25% of the length of SEQ ID N0:9.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:9 from nucleotide 128 to nucleotide 436; the nucleotide sequence of SEQ ID
N0:9 from
nucleotide 203 to nucleotide 436; the nucleotide sequence of the full-length
protein coding
sequence of clone vb6_1 deposited under accession number ATCC 98804; or the

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nucleotide sequence of a mature protein coding sequence of clone vb6_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb6_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:10 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID NO:10, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID NO:10 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 46 to amino and 55
of SEQ
ID N0:10.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:9.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
2 0 (aa) SEQ ID N0:9, but excluding the poly(A) tail at the
3' end of SEQ ID N0:9; and
(ab) the nucleotide sequence of the cDNA insert of clone
vb6_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:9, but excluding the poly(A) tail at the
3' end of SEQ ID N0:9; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vb6_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:9, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:9 to
a nucleotide sequence corresponding to the 3' end of SEQ ID N0:9 , but
excluding the
poly(A) tail at the 3' end of SEQ ID N0:9. Also preferably the polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:9 from nucleotide 128 to nucleotide 436, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:9 from nucleotide
128 to
nucleotide 436. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:9 from nucleotide 203 to nucleotide 436, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:9 from
nucleotide 203 to nucleotide 436, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:9 from nucleotide 203 to nucleotide 436.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID N0:10, the
fragment comprising eight contiguous amino acids of SEQ ID N0:10; and
{c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vb6_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID NO:10. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:10 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID NO:10, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID NO:10 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 46 to amino acid 55 of SEQ ID NO:10.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:11;
{b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 138 to nucleotide 1250;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb7 1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb7 1 deposited under accession number ATCC
2 0 98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb7 1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:12;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:12 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:12;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
18

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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i) and that has a length that is
at least
25% of the length of SEQ ID N0:11.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:11 from nucleotide 138 to nucleotide 1250; the nucleotide sequence of SEQ
ID NO:11
from nucleotide 279 to nucleotide 1250; the nucleotide sequence of the full-
length protein
coding sequence of clone vb7_1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone vb7 1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb7_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:12 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:12, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:12 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 180 to amino acid
189 of
SEQ ID N0:12.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:11.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:11, but excluding the poly(A) tail at the
3' end of SEQ ID N0:11; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vb7_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:11, but excluding the poly(A) tail at the
3' end of SEQ ID N0:11; and
(bb) the nucleotide sequence of the cDNA insert of clone
vb7 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:11; and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:11 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:11,
but
excluding the poly(A) tail at the 3' end of SEQ ID N0:11. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:11 from nucleotide 138 to
nucleotide
1250, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID NO:11 from nucleotide 138 to nucleotide 1250, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:11 from
nucleotide
138 to nucleotide 1250. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:11 from
nucleotide 279 to nucleotide 1250, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:11 from nucleotide 279 to nucleotide 1250.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:12;

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(b) a fragment of the amino acid sequence of SEQ ID N0:12, the
fragment comprising eight contiguous amino acids of SEQ ID N0:12; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb7 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:12. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:12 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:12, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:12 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 180 to amino acid 189 of SEQ ID N0:12.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13 from nucleotide 615 to nucleotide 869;
(c) a polynucleotide comprising the nucleotide sequence of the full-
2 0 length protein coding sequence of clone vb8_1 deposited under accession
number
ATCC 98804;
(d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(e) a polynucleotide comprising the nucleotide sequence of a mature
2 5 protein coding sequence of clone vb8_1 deposited under accession number
ATCC
98804;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb8_1 deposited under accession number ATCC 98804;
(g) a polynucleotide encoding a protein comprising the amino acid
3 0 sequence of SEQ ID N0:14;
(h) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:14 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:14;
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(i) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein
of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h) and that has a length that is
at least
25% of the length of SEQ ID N0:13.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:13 from nucleotide 615 to nucleotide 869; the nucleotide sequence of the
full-length
protein coding sequence of clone vb8_1 deposited under accession number ATCC
98804;
or the nucleotide sequence of a mature protein coding sequence of clone vb8_1
deposited
under accession number ATCC 98804. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vb8_1 deposited under accession number ATCC 98804. In further
preferred
embodiments, the present invention provides a polynucleotide encoding a
protein
comprising a fragment of the amino acid sequence of SEQ ID N0:14 having
biological
activity, the fragment preferably comprising eight (more preferably twenty,
most
2 0 preferably thirty) contiguous amino acids of SEQ ID N0:14, or a
polynucleotide encoding
a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14
having
biological activity, the fragment comprising the amino acid sequence from
amino acid 37
to amino acid 46 of SEQ ID N0:14.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 5 ID N0:13.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
3 0 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:13, but excluding the poly(A) tail at the
3' end of SEQ ID N0:13; and
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(ab) the nucleotide sequence of the cDNA insert of clone
vb8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:13, but excluding the poly(A) tail at the
3' end of SEQ ID N0:13; and
(bb) the nucleotide sequence of the cDNA insert of clone
vb8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:13 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:13
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:13. Also preferably the
2 5 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:13 fram nucleotide 615 to
nucleotide
869, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:13 from nucleotide 615 to nucleotide 869, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:13 from
nucleotide
3 0 615 to nucleotide 869.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:14;
23

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(b) a fragment of the amino acid sequence of SEQ ID N0:14, the
fragment comprising eight contiguous amino acids of SEQ ID N0:14; and
{c) the amino acid sequence encoded by the cDNA insert of clone
vb8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:14. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:14 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:14, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:14 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 37 to amino acid 46 of SEQ ID N0:14.
In one embodiment, the present invention provides a composition comprising an
isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:15;
{b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 148 to nucleotide 1470;
(c) a polynudeotide comprising the nucleotide sequence of SEQ iD
2 0 N0:15 from nucleotide 193 to nucleotide 1470;
(d) a polynudeotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb9_1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
2 5 cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(f) a polynudeotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb9_1 deposited under accession number ATCC
98804;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
3 0 insert of done vb9_1 deposited under accession number ATCC 98804;
(h) a polynudeotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:16;
24

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(i) a polynucleohde encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:16 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:16;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:15.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:15 from nucleotide 148 to nucleotide 1470; the nucleotide sequence of SEQ
ID N0:15
from nucleotide 193 to nucleotide 1470; the nucleotide sequence of the full-
length protein
coding sequence of clone vb9_1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone vb9_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vb9_1
2 0 deposited under accession number ATCC 98804. In further preferred
embodiments, the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:16 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:16, or a polynucleotide encoding a protein comprising
a
2 5 fragment of the amino acid sequence of SEQ ID N0:16 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 215 to amino acid
224 of
SEQ ID N0:16.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:15.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:

CA 02327551 2000-10-31
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(i) preparing one or more polynudeotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:15, but excluding the poly(A) tail at the
3' end of SEQ ID N0:15; and
(ab) the nucleotide sequence of the cDNA insert of clone
vb9_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes} to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynudeotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:15, but excluding the poly(A) tail at the
3' end of SEQ ID N0:15; and
(bb} the nucleotide sequence of the cDNA insert of done
2 0 vb9_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii} amplifying human DNA sequences; and
(iv} isolating the polynudeotide products of step (b)(iii).
2 5 Preferably the polynudeotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:15, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:15 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:15
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:15. Also preferably the
3 0 polynudeotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:15 from nucleotide 148 to
nucleotide
1470, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from
nucleotide
26

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148 to nucleotide 1470. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:15 from nucleotide 193 to nucleotide 1470, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:15 from
nucleotide 193 to nucleotide 1470, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:15 from nucleotide 193 to nucleotide 1470.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:16;
(b) a fragment of the amino acid sequence of SEQ ID N0:16, the
fragment comprising eight contiguous amino acids of SEQ ID N0:16; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vb9_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:16. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:16 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:16, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:16 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 215 to amino acid 224 of SEQ ID N0:16.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
2 5 {a) a polynudeotide comprising the nucleotide sequence of SEQ ID
NO:I7;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 109 to nucleotide 414;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:17 from nucleotide 217 to nucleotide 414;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc3_1 deposited under accession number
ATCC 98748;
27

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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc3_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc3_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:18;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:18 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:18;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
2 0 ane of the polynucleotides specified in (a)-(i) and that has a length that
is at least
25% of the length of SEQ ID N0:17.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:17 from nucleotide 109 to nucleotide 414; the nucleotide sequence of SEQ ID
N0:17
from nucleotide 217 to nucleotide 414; the nucleotide sequence of the full-
length protein
2 5 coding sequence of clone vc3_1 deposited under accession number ATCC
98748; or the
nucleotide sequence of a mature protein coding sequence of clone vc3_1
deposited under
accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc3_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
3 0 present invention provides a polynucleotide encoding a protein comprising
a fragment
of the amino acid sequence of SEQ ID N0:18 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:18, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:18 having biological
activity, the
28

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fragment comprising the amino acid sequence from amino acid 46 to amino acid
55 of SEQ
ID N0:18.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:17.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:17, but excluding the poly(A) tail at the
3' end of SEQ ID N0:17; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc3_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
2 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID NO:17, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:17; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc3_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
3 0 (iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:17, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
29

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ID N0:17 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:17
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:17. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:17 from nucleotide 109 to
nucleotide
414, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from
nucleotide
109 to nucleotide 414. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:17 from nucleotide 217 to nucleotide 414, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:17 from
nucleotide 217 to nucleotide 414, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:17 from nucleotide 217 to nucleotide 414.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:18;
(b) a fragment of the amino acid sequence of SEQ ID NO:18, the
fragment comprising eight contiguous amino acids of SEQ ID N0:18; and
2 0 (c) the amino acid sequence encoded by the cDNA insert of clone
vc3_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:18. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
2 5 amino acid sequence of SEQ ID N0:18 having biological activity, the
fragment preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ 117 N0:18, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:18 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 46 to amino acid 55 of SEQ ID N0:18.
3 0 In one embodiment, the present invention provides a composition comprising
an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19;

CA 02327551 2000-10-31
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 169 to nucleotide 840;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc4_1 deposited under accession number
ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc4_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc4_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:20;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:20 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:20;
2 0 (j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
2 5 one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:19.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
3 0 N0:19 from nucleotide 169 to nucleotide 840; the nucleotide sequence of
SEQ ID N0:19
from nucleotide 211 to nucleotide 840; the nucleotide sequence of the full-
length protein
coding sequence of clone vc4_1 deposited under accession number ATCC 98748; or
the
nucleotide sequence of a mature protein coding sequence of clone vc4_1
deposited under
accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
31

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encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc4_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:20 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:20, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:20 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 107 to amino acid
116 of
SEQ ID N0:20.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:19.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:19, but excluding the poly(A) tail at the
3' end of SEQ ID N0:19; and
2 0 (ab) the nucleotide sequence of the cDNA insert of clone
vc4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
2 5 probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
3 0 the group consisting of:
(ba) SEQ ID N0:19, but excluding the poly(A) tail at the
3' end of SEQ ID N0:19; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc4_1 deposited under accession number ATCC 98748;
32

CA 02327551 2000-10-31
wo mssn~ rc~rius99rosso4
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:19, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:19 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:19
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:19. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:19 from nucleotide 169 to
nucleotide
840, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:19 from
nucleotide
169 to nucleotide 840. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:19 from nucleotide 211 to nucleotide 840, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:19 from
nucleotide 211 to nucleotide 840, to a nucleotide sequence corresponding to
the 3' end of
2 0 said sequence of SEQ ID N0:19 from nucleotide 211 to nucleotide 840.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:20;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:20, the
fragment comprising eight contiguous amino acids of SEQ ID N0:20; and
(c) the amino acld sequence encoded by the cDNA insert of clone
vc4_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
3 0 protein comprises the amino acid sequence of SEQ ID N0:20. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:20 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino atids
of SEQ ID N0:20, or a protein comprising a fragment of the amino acid sequence
of SEQ
33

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ID N0:20 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 107 to amino acid 116 of SEQ ID N0:20.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 508 to nucleotide 951;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone v~ 1 deposited under accession number
ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc5_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone vc5_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:22;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:22 having biological activity, the fragment
2 5 comprising eight contiguous amino acids of SEQ ID N0:22;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
{k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:21.
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Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:21 from nucleotide 508 to nucleotide 951; the nucleotide sequence of SEQ ID
N0:21
from nucleotide 733 to nucleotide 951; the nucleotide sequence of the full-
length protein
coding sequence of clone vc5_1 deposited under accession number ATCC 98748; or
the
nucleotide sequence of a mature protein coding sequence of clone vc5_1
deposited under
accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc5_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:22 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:22, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:22 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 69 to amino acid
78 of SEQ
ID N0:22.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:21.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:21, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:21; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc5_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
3 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:

CA 02327551 2000-10-31
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(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:21, but excluding the poly(A) tail at the
3' end of SEQ ID N0:21; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc5_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b}(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:21, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:21 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:21,
but
excluding the poly(A) tail at the 3' end of SEQ ID N0:21. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:21 from nucleotide 508 to
nucleotide
951, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
2 0 of said sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951, to
a nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from
nucleotide
508 to nucleotide 951. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:21 from nucleotide 733 to nucleotide 951, and extending contiguously from a
2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:21 from
nucleotide 733 to nucleotide 951, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:21 from nucleotide 733 to nucleotide 951.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:22;
(b) a fragment of the amino acid sequence of SEQ ID N0:22, the
fragment comprising eight contiguous amino acids of SEQ ID N0:22; and
36

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(c) the amino acid sequence encoded by the cDNA insert of clone
vc5_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:22. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:22 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:22, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:22 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 69 to amino acid 78 of SEQ ID N0:22.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23 from nucleotide 125 to nucleotide 493;
(c) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc7 1 deposited under accession number
ATCC 98748;
2 0 (d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc7_1 deposited under accession number ATCC
98748;
2 5 (f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc7_1 deposited under accession number ATCC 98748;
(g) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:24;
(h) a polynucleotide encoding a protein comprising a fragment of the
3 0 amino acid sequence of SEQ ID N0:24 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:24;
(i) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(f) above;
37

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(j) a polynucleotide which encodes a species homologue of the protein
of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(h) and that has a length that is
at least
25% of the length of SEQ ID N0:23.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:23 from nucleotide 125 to nucleotide 493; the nucleotide sequence of the
full-length
protein coding sequence of clone vc7_1 deposited under accession number ATCC
98748;
or the nucleotide sequence of a mature protein coding sequence of clone vc7 1
deposited
under accession number ATCC 98748. In othex preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
of clone vc7_1 deposited under accession number ATCC 98748. In further
preferred
embodiments, the present invention provides a polynucleotide encoding a
protein
comprising a fragment of the amino acid sequence of SEQ ID N0:24 having
biological
activity, the fragment preferably comprising eight (more preferably twenty,
most
preferably thirty) contiguous amino acids of SEQ ID N0:24, or a polynucleotide
encoding
a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24
having
2 0 biological activity, the fragment comprising the amino acid sequence from
amino acid 56
to amino acid 65 of SEQ ID N0:24.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:23.
Further embodiments of the invention provide isolated polynucleotides produced
2 5 according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
3 0 (aa) SEQ ID N0:23, but excluding the poly(A) tail at the
3' end of SEQ ID N0:23; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc7_1 deposited under accession number ATCC 98748;
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(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynudeotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:23, but excluding the poly(A) tail at the
3' end of SEQ ID N0:23; and
(bb) the nucleotide sequence of the cDNA insert of done
vc7_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynudeotide isolated according to the above process comprises
a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:23, and
2 0 extending contiguously from a nucleotide sequence corresponding to the 5'
end of SEQ
ID N0:23 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:23
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:23. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:23 from nucleotide 125 to
nucleotide
2 5 493, and extending contiguously from a nucleotide sequence corresponding
to the 5' end
of said sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 493, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:23 from
nucleotide
125 to nucleotide 493.
In other embodiments, the present invention provides a composition comprising
3 0 a protein, wherein said protein comprises an amino acid sequence selected
from the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:24;
(b) a fragment of the amino acid sequence of SEQ ID N0:24, the
fragment comprising eight contiguous amino acids of SEQ ID N0:24; and
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(c) the amino acid sequence encoded by the cDNA insert of clone
vc7_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:24. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:24 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:24, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:24 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 56 to amino acid 65 of SEQ ID N0:24.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 33 to nucleotide 407;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407;
(d) a polynucleotide comprising the nucleotide sequence of the full-
2 0 length protein coding sequence of clone vc9_1 deposited under accession
number
ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 5 protein coding sequence of clone v~ 1 deposited under accession number
ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc9_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
3 0 sequence of SEQ ID N0:26;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:26 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:26;

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(j} a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i) and that has a length that is
at least
25% of the length of SEQ ID N0:25.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:25 from nucleotide 33 to nucleotide 407; the nucleotide sequence of SEQ ID
N0:25
from nucleotide 99 to nucleotide 407; the nucleotide sequence of the full-
length protein
coding sequence of clone vc9_1 deposited under accession number ATCC 98748; or
the
nucleotide sequence of a mature protein coding sequence of clone v~ 1
deposited under
accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone v~ 1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
presient invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:26 having biological activity, the
fragment
2 0 preferably comprising eight (more preferably twenty, most preferably
thirty) contiguous
amino acids of SEQ ID N0:26, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:26 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 57 to amino acid
66 of SEQ
ID N0:26.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of
SEQ
ID N0:25.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:25, but excluding the poly(A) tail at the
3' end of SEQ ID N0:25; and
41

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(ab) the nucleotide sequence of the cDNA insert of clone
vc9_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:25, but excluding the poly(A) tail at the
3' end of SEQ ID N0:25; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc9_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:25, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:25 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:25
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:25. Also preferably the
2 5 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:25 from nucleotide 33 to
nucleotide
407, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:25 from nucleotide 33 to nucleotide 407, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from
nucleotide
3 0 33 to nucleotide 407. Also preferably the polynucleotide isolated
according to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:25 from nucleotide 99 to nucleotide 407, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:25 from
42

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nucleotide 99 to nucleotide 407, to a nucleotide sequence corresponding to the
3' end of
said sequence of SEQ ID N0:25 from nucleotide 99 to nucleotide 407.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) ~ the amino acid sequence of SEQ ID N0:26;
(b) a fragment of the amino acid sequence of SEQ ID N0:26, the
fragment comprising eight contiguous amino acids of SEQ ID N0:26; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc9_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:26. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:26 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:26, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:26 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 57 to amino acid 66 of SEQ ID N0:26.
In one embodiment, the present invention provides a composition comprising an
2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27 from nucleotide 176 to nucleotide 871;
2 5 (c) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vcl0_1 deposited under accession
number
ATCC 98748;
(d) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
3 0 (e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vcl0_1 deposited under accession number ATCC
98748;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl0_1 deposited under accession number ATCC 98748;
43

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(g) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:28;
(h) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:28 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:28;
(i) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein
of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(h) and that has a length that is
at least
25% of the length of SEQ ID N0:27.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:27 from nucleotide 176 to nucleotide 871; the nucleotide sequence of the
full-length
protein coding sequence of clone vcl0_1 deposited under accession number ATCC
98748;
or the nucleotide sequence of a mature protein coding sequence of clone vcl0_1
deposited
under accession number ATCC 98748. In other preferred embodiments, the
2 0 polynucleotide encodes the full-length or a mature protein encoded by the
cDNA insert
of clone vcl0_1 deposited under accession number ATCC 98748. In further
preferred
embodiments, the present invention provides a polynucleotide encoding a
protein
comprising a fragment of the amino acid sequence of SEQ ID N0:28 having
biological
activity, the fragment preferably comprising eight (more preferably twenty,
most
2 5 preferably thirty) contiguous amino acids of SEQ ID N0:28, or a
polynucleotide encoding
a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28
having
biological activity, the fragment comprising the amino acid sequence from
amino and 111
to amino acid 120 of SEQ ID N0:28.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
3 0 ID N0:27.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
44

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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:27, but excluding the poly(A) tail at the
3' end of SEQ ID N0:27; and
(ab) the nucleotide sequence of the cDNA insert of clone
vcl0_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:27, but excluding the poly(A) tail at the
3' end of SEQ ID N0:27; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vcl0_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:27, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:27 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:27
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:27. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:27 from nucleotide 176 to
nucleotide
871, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871, to a
nucleotide

CA 02327551 2000-10-31
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sequence corresponding to the 3' end of said sequence of SEQ ID N0:27 from
nucleotide
176 to nucleotide 871.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:28;
(b) a fragment of the amino acid sequence of SEQ ID N0:28, the
fragment comprising eight contiguous amino acids of SEQ ID N0:28; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vcl0_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:28. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:28 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:28, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:28 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 111 to amino acid 120 of SEQ ID N0:28.
In one embodiment, the present invention provides a composition comprising an
2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 160 to nucleotide 657;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vcl l_1 deposited under accession
number
ATCC 98748;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vcll_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vcll_1 deposited under accession number ATCC
98748;
46

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(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcll 1 deposited under accession number ATCC 98748;
(h} a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:30;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:30 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:30;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i) and that has a length that is
at least
25% of the length of SEQ ID N0:29.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:29 from nucleotide 160 to nucleotide 657; the nucleotide sequence of SEQ ID
N0:29
from nucleotide 214 to nucleotide 657; the nucleotide sequence of the full-
length protein
2 0 coding sequence of clone vcll_1 deposited under accession number ATCC
98748; or the
nucleotide sequence of a mature protein coding sequence of clone vcl l_1
deposited under
accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vcll_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
2 5 present invention provides a polynucleotide encoding a protein comprising
a fragment
of the amino acid sequence of SEQ ID N0:30 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty}
contiguous
amino acids of SEQ ID N0:30, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:30 having biological
activity, the
3 0 fragment comprising the amino acid sequence from amino and 78 to amino
acid 87 of SEQ
ID N0:30.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:29.
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Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:29, but excluding the poly(A) tail at the
3' end of SEQ ID N0:29; and
(ab) the nucleotide sequence of the cUNA insert or clone
vcll 1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 0 (ba) SEQ ID N0:29, but excluding the poly(A) tail at the
3' end of SEQ ID N0:29; and
(bb) the nucleotide sequence of the cDNA insert of clone
vcll_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29, and
3 0 extending contiguously from a nucleotide sequence corresponding to the 5'
end of SEQ
ID N0:29 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:29
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:29. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:29 from nucleotide 160 to
nucleotide
48

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657, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from
nucleotide
160 to nucleotide 657. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:29 from nucleotide 214 to nucleotide 657, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:29 from
nucleotide 214 to nucleotide 657, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:29 from nucleotide 214 to nucleotide 657.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:30;
(b) a fragment of the amino acid sequence of SEQ ID N0:30, the
fragment comprising eight contiguous amino acids of SEQ ID N0:30; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vcl l_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:30. In further
preferred
2 0 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:30 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty} contiguous
amino acids
of SEQ ID N0:30, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:30 having biological activity, the fragment comprising the amino acid
sequence
2 5 from amino acid 78 to amino acid 87 of SEQ ID N0:30.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 228 to nucleotide 662;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662;
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(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vcl4_1 deposited under accession
number
ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA _insert of clone vcl4_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vcl4_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl4_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:32;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:32 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:32;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(i); and
(m} a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:31.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:31 from nucleotide 228 to nucleotide 662; the nucleotide sequence of SEQ ID
N0:31
from nucleotide 327 to nucleotide 662; the nucleotide sequence of the full-
length protein
coding sequence of clone vcl4_1 deposited under accession number ATCC 98748;
or the
nucleotide sequence of a mature protein coding sequence of clone vcl4_1
deposited under
3 0 accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vcl4_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:32 having biological activity, the
fragment

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preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:32, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:32 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 67 to amino acid
76 of SEQ
ID N0:32.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:31.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:31, but excluding the poly(A) tail at the
3' end of SEQ ID N0:31; and
(ab) the nucleotide sequence of the cDNA insert of clone
vcl4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
2 5 hybridize in 6X 5SC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:31, but excluding the poly(A) tail at the
3' end of SEQ ID N0:31; and
(bb) the nucleotide sequence of the cDNA insert of clone
3 0 vcl4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
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Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:31, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:31 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:31
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:31. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:31 from nucleotide 228 to
nucleotide
662, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from
nucleotide
228 to nucleotide 662. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:31 from nucleotide 327 to nucleotide 662, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:31 from
nucleotide 327 to nucleotide 662, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:31 from nucleotide 327 to nucleotide 662.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:32;
(b) a fragment of the amino acid sequence of SEQ ID N0:32, the
fragment comprising eight contiguous amino acids of SEQ ID N0:32; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vcl4_1 deposited under accession number ATCC 98748;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such
protein comprises the amino acid sequence of SEQ ID N0:32. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:32 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
3 0 of SEQ ID N0:32, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:32 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 67 to amino acid 76 of SEQ ID N0:32.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
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(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 101 to nucleotide 667;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vcl6_1 deposited under accession
number
ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vcl6_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl6_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:34;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 0 amino acid sequence of SEQ ID N0:34 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:34;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
3 0 25% of the length of SEQ ID N0:33.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:33 from nucleotide 101 to nucleotide 667; the nucleotide sequence of SEQ ID
N0:33
from nucleotide 182 to nucleotide 667; the nucleotide sequence of the full-
length protein
coding sequence of clone vcl6_1 deposited under accession number ATCC 98784;
or the
53

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nucleotide sequence of a mature protein coding sequence of clone vcl6_1
deposited under
accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vcl6_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:34 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:34, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:34 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 89 to amino acid
98 of SEQ
ID N0:34.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:33.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
2 0 (aa) SEQ ID N0:33, but excluding the poly(A) tail at the
3' end of SEQ ID N0:33; and
(ab) the nucleotide sequence of the cDNA insert of clone
vcl6_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b} a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:33, but excluding the poly(A) tail at the
3' end of SEQ ID N0:33; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vcl6_1 deposited under accession number ATCC 98784;
(ii} hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:33, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:33 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:33
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:33. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:33 from nucleotide 101 to
nucleotide
667, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from
nucleotide
101 to nucleotide 667. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:33 from nucleotide 182 to nucleotide 667, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:33 from
nucleotide 182 to nucleotide 667, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:33 from nucleotide 182 to nucleotide 667.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:34;
(b) a fragment of the amino acid sequence of SEQ ID N0:34, the
fragment comprising eight contiguous amino acids of SEQ ID N0:34; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vcl6_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:34. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:34 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino ands
of SEQ ID N0:34, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:34 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 89 to amino acid 98 of SEQ ID N0:34.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 8 to nucleotide 355;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vcl7 1 deposited under accession
number
ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vcl7 1 deposited under accession number ATCC
2 0 98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl7_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:36;
2 5 (i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:36 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:36;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a}-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i} above ;
(1) a polynudeotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a}-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:35.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:35 from nucleotide 8 to nucleotide 355; the nucleotide sequence of SEQ ID
N0:35 from
nucleotide 134 to nucleotide 355; the nucleotide sequence of the full-length
protein coding
sequence of clone vcl7_1 deposited under accession number ATCC 98784; or the
nucleotide sequence of a mature protein coding sequence of clone vcl7_1
deposited under
accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vcl7_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:36 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:36, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:36 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 53 to amino acid
62 of SEQ
ID N0:36.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:35.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:35, but excluding the poly(A) tail at the
3' end of SEQ ID N0:35; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vcl7 1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:35, but excluding the poly(A) tail at the
3' end of SEQ ID N0:35; and
(bb) the nucleotide sequence of the cDNA insert of clone
vcl7_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:35, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:35 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:35
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:35. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:35 from nucleotide 8 to
nucleotide
355, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from
nucleotide
8 to nucleotide 355. Also preferably the polynucleotide isolated according to
the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:35 from
nucleotide 134 to nucleotide 355, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:35 from nucleotide 134 to nucleotide 355.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:36;
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(b) a fragment of the amino acid sequence of SEQ ID N0:36, the
fragment comprising eight contiguous amino acids of SEQ ID N0:36; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vcl7 1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:36. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:36 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:36, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:36 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 53 to amino acid 62 of SEQ ID N0:36.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37 from nucleotide 1031 to nucleotide 1252;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:37 from nucleotide 1100 to nucleotide 1252;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc21_1 deposited under accession
number
ATCC 98785;
(e) a polynucleotide encoding the full-length protein encoded by the
2 5 cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(f) a polynucleotlde comprising the nucleotide sequence of a mature
protein coding sequence of clone vc21 1 deposited under accession number ATCC
98785;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
3 0 insert of clone vc21 1 deposited under accession number ATCC 98785;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:38;
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:38 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:38;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i) and that has a length that is
at least
25% of the length of SEQ ID N0:37.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:37 from nucleotide 1031 to nucleotide 1252; the nucleotide sequence of SEQ
ID N0:37
from nucleotide 1100 to nucleotide 1252; the nucleotide sequence of the full-
length
protein coding sequence of clone vc21 1 deposited under accession number ATCC
98785;
or the nucleotide sequence of a mature protein coding sequence of clone vc21 1
deposited
under accession number ATCC 98785. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert
2 0 of clone vc21 1 deposited under accession number ATCC 98785. In yet other
preferred
embodiments, the present invention provides a polynucleotide encoding a
protein
comprising the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino
acid
74. In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38
2 5 having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:38, or a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:38 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 32 to amino acid 41 of SEQ ID N0:38.
3 0 Other embodiments provide the gene corresponding to the cDNA sequence of
SEQ
ID N0:37.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:

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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:37, but excluding the poly(A) tail at the
3' end of SEQ ID N0:37; and
(ab) the nucleotide sequence of the cDNA insert of done
vc21 1 deposited under accession number ATCC 98785;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:37, but excluding the poly(A) tail at the
3' end of SEQ ID N0:37; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vc21 1 deposited under accession number ATCC 98785;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:37, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:37 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:37
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:37. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:37 from nucleotide 1031 to
nucleotide
1252, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from
nucleotide
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1031 to nucleotide 1252. Also preferably the polynucleotide isolated according
to the
above process comprises a nucleotide sequence corresponding to the cDNA
sequence of
SEQ ID N0:37 from nucleotide 1100 to nucleotide 1252, and extending
contiguously from
a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:37 from
nucleotide 1100 to nucleotide 1252, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:37 from nucleotide 1100 to nucleotide 1252.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:38;
(b) the amino acid sequence of SEQ ID N0:38 from amino acid 29 to
amino acid 74;
(c) a fragment of the amino acid sequence of SEQ ID N0:38, the
fragment comprising eight contiguous amino acids of SEQ ID N0:38; and
(d) the amino acid sequence encoded by the cDNA insert of clone
vc21 1 deposited under accession number ATCC 98785;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:38 or the amino acid
sequence
of SEQ ID N0:38 from amino acid 29 to amino acid 74. In further preferred
embodiments,
2 0 the present invention provides a protein comprising a fragment of the
amino acid
sequence of SEQ ID N0:38 having biological activity, the fragment preferably
comprising
eight (more preferably twenty, most preferably thirty) contiguous amino acids
of SEQ ID
N0:38, or a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38
having biological activity, the fragment comprising the amino acid sequence
from amino
2 5 acid 32 to amino acid 41 of SEQ ID N0:38.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 94 to nucleotide 1482;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482;
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(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc23_1 deposited under accession
number
ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc23_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc23_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:40;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:40 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:40;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:39.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:39 from nucleotide 94 to nucleotide 1482; the nucleotide sequence of SEQ ID
N0:39
from nucleotide 214 to nucleotide 1482; the nucleotide sequence of the full-
length protein
coding sequence of clone v~ 1 deposited under accession number ATCC 98784; or
the
nucleotide sequence of a mature protein coding sequence of clone vc23 1
deposited under
3 0 accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc23_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:40 having biological activity, the
fragment
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preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:40, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:40 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 226 to amino acid
235 of
SEQ ID N0:40.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:39.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:39, but excluding the poly(A) tail at the
3' end of SEQ ID N0:39; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc23_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:39, but excluding the poly(A) tail at the
3' end of SEQ ID N0:39; and
(bb) the nucleotide sequence of the cDNA insert of clone
3 0 vc23_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
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Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:39, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:39 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:39
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:39. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:39 from nucleotide 94 to
nucleotide
1482, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from
nucleotide
94 to nucleotide 1482. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:39 from
nucleotide 214 to nucleotide 1482, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:39 from nucleotide 214 to nucleotide 1482.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:40;
(b) a fragment of the amino acid sequence of SEQ ID N0:40, the
fragment comprising eight contiguous amino acids of SEQ ID N0:40; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc23_1 deposited under accession number ATCC 98784;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such
protein comprises the amino acid sequence of SEQ ID N0:40. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:40 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
3 0 of SEQ ID N0:40, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:40 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 226 to amino acid 235 of SEQ ID N0:40.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:

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(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 153 to nucleotide 413;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone v~ 1 deposited under accession number
ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc25_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of done vc25_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:42;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 0 amino acid sequence of SEQ ID N0:42 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:42;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
{m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a}-(i) and that has a length that is
at least
3 0 25% of the length of SEQ ID N0:41.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:41 from nucleotide 153 to nucleotide 413; the nucleotide sequence of SEQ ID
N0:41
from nucleotide 264 to nucleotide 413; the nucleotide sequence of the full-
length protein
coding sequence of clone vc~ 1 deposited under accession number ATCC 98784; or
the
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nucleotide sequence of a mature protein coding sequence of clone v~ 1
deposited under
accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc25_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:42 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:42, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:42 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 38 to amino acid
47 of SEQ
ID N0:42.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:41.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
2 0 (aa) SEQ ID N0:41, but excluding the poly(A) tail at the
3' end of SEQ ID N0:41; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc25_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:41, but excluding the poly(A) tail at the
3' end of SEQ ID N0:41; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vc25_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii} amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:41, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
TD N0:41 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:41,
but
excluding the poly(A) tail at the 3' end of SEQ ID N0:41. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:41 from nucleotide 153 to
nucleotide
413, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from
nucleotide
153 to nucleotide 413. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:41 from nucleotide 264 to nucleotide 413, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:41 from
nucleotide 264 to nucleotide 413, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:41 from nucleotide 264 to nucleotide 413.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a} the amino acid sequence of SEQ ID N0:42;
(b) a fragment of the amino acid sequence of SEQ ID N0:42, the
fragment comprising eight contiguous amino acids of SEQ ID N0:42; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vc25_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:42. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:42 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:42, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:42 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 38 to amino acid 47 of SEQ ID N0:42.
In one embodiment, the present invention provides a composition comprising an
isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43;
(b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 87 to nucleotide 1409;
(c) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409;
(d) a polynudeotide comprising the nucleotide sequence of the full-
length protein coding sequence of done vc26_1 deposited under accession number
ATCC 98784;
(e) a polynudeotide encoding the full-length protein encoded by the
cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(f) a polynudeotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc26_1 deposited under accession number ATCC
2 0 98784;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
insert of clone vc26_1 deposited under accession number ATCC 98784;
(h) a polynudeotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:44;
2 5 (i) a polynudeotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:44 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:44;
(j) a polynudeotide which is an allelic variant of a polynudeotide of
(a)-(g) above;
3 0 (k) a polynudeotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynudeotide that hybridizes under stringent conditions to any
one of the polynudeotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:43.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:43 from nucleotide 87 to nucleotide 1409; the nucleotide sequence of SEQ ID
N0:43
from nucleotide 156 to nucleotide 1409; the nucleotide sequence of the full-
length protein
coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
or the
nucleotide sequence of a mature protein coding sequence of clone vc26_1
deposited under
accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc26_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:44 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:44, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:44 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 215 to amino acid
224 of
SEQ ID N0:44.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:43.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:43, but excluding the poly(A) tail at the
3' end of SEQ ID N0:43; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vc26_1 deposited under accession number ATCC 98784;
{ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);

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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:43, but excluding the poly(A) tail at the
3' end of SEQ ID N0:43; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc26_1 deposited under accession number ATCC 98784;
(ii} hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:43, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:43 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:43
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:43. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:43 from nucleotide 87 to
nucleotide
1409, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from
nucleotide
87 to nucleotide 1409. Also preferably the polynucleotide isolated according
to the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:43 from
nucleotide 156 to nucleotide 1409, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:43 from nucleotide 156 to nucleotide 1409.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:44;
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(b) a fragment of the amino acid sequence of SEQ ID N0:44, the
fragment comprising eight contiguous amino acids of SEQ ID N0:44; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vc26_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:44. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:44 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:44, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:44 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 215 to amino acid 224 of SEQ ID N0:44.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 63 to nucleotide 428;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:45 from nucleotide 156 to nucleotide 428;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 356 to nucleotide 1773;
{e) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone v~ 1 deposited under accession number
2 5 ATCC 98804;
(f) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc30-1 deposited under accession number ATCC 98804;
(g) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone v~ 1 deposited under accession number ATCC
3 0 98804;
(h) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc30_1 deposited under accession number ATCC 98804;
(i) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:46;
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(j) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:46 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:46;
(k) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(h) above;
(1) a polynucleotide which encodes a species homologue of the protein
of (i) or (j) above ;
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(j); and
(n) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(j) and that has a length that is
at least
25% of the length of SEQ ID N0:45.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:45 from nucleotide 63 to nucleotide 428; the nucleotide sequence of SEQ ID
N0:45
from nucleotide 156 to nucleotide 428; the nucleotide sequence of SEQ ID N0:45
from
nucleotide 356 to nucleotide 1773; the nucleotide sequence of the full-length
protein
coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
or the
nucleotide sequence of a mature protein coding sequence of clone v~ 1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
2 0 encodes the full-length or a mature protein encoded by the cDNA insert of
clone vc30_1
deposited under accession number ATCC 98804. In yet other preferred
embodiments,
the present invention provides a polynucleotide encoding a protein comprising
the amino
acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97. In further
preferred
embodiments, the present invention provides a polynucleotide encoding a
protein
2 5 comprising a fragment of the amino acid sequence of SEQ ID N0:46 having
biological
activity, the fragment preferably comprising eight (more preferably twenty,
most
preferably thirty) contiguous amino acids of SEQ ID N0:46, or a polynucleotide
encoding
a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46
having
biological activity, the fragment comprising the amino acid sequence from
amino acid 56
3 0 to amino acid 65 of SEQ ID N0:46.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:45.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
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(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa} SEQ ID N0:45, but excluding the poly(A) tail at the
3' end of SEQ ID N0:45; and
(ab} the nucleotide sequence of the cDNA insert of clone
vc30_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:45, but excluding the poly(A) tail at the
3' end of SEQ ID N0:45; and
2 0 (bb) the nucleotide sequence of the cDNA insert of clone
vc30_I deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
2 5 (iv) isolating the polynucleotide products of step (b}(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:45 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:45
, but
3 0 excluding the poly(A) tail at the 3' end of SEQ ID N0:45. Also preferably
the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 63 to
nucleotide
428, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428, to a
nucleotide
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sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from
nucleotide
63 to nucleotide 428. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:45 from nucleotide 156 to nucleotide 428, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:45 from
nucleotide 156 to nucleotide 428, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:45 from nucleotide 156 to nucleotide 428. Also
preferably
the polynucleotide isolated according to the above process comprises a
nucleotide
sequence corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide
356 to
nucleotide 1773, and extending contiguously from a nucleotide sequence
corresponding
to the 5' end of said sequence of SEQ ID N0:45 from nucleotide 356 to
nucleotide 1773, to
a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID
N0:45 from
nucleotide 356 to nucleotide 1773.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:46;
(b) the amino acid sequence of SEQ ID N0:46 from amino acid 1 to
amino acid 97;
2 0 (c) a fragment of the amino acid sequence of SEQ ID N0:46, the
fragment comprising eight contiguous amino acids of SEQ ID N0:46; and
(d) the amino acid sequence encoded by the cDNA insert of clone
vc30_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
2 5 protein comprises the amino acid sequence of SEQ ID N0:46 or the amino
acid sequence
of SEQ ID N0:46 from amino acid 1 to amino acid 97. In further preferred
embodiments,
the present invention provides a protein comprising a fragment of the amino
acid
sequence of SEQ ID N0:46 having biological activity, the fragment preferably
comprising
eight (more preferably twenty, most preferably thirty) contiguous amino acids
of SEQ ID
3 0 N0:46, or a protein comprising a fragment of the amino acid sequence of
SEQ ID N0:46
having biological activity, the fragment comprising the amino acid sequence
from amino
acid 56 to amino acid 65 of SEQ ID N0:46.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:

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(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 30 to nucleotide 1799;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vdl 1 deposited under accession number
ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vdl_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vdl 1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd1 1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:48;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 0 amino acid sequence of SEQ ID N0:48 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:48;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k} a polynucleotide which encodes a species homologue of the protein
2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
3 0 25% of the length of SEQ ID N0:47.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:47 from nucleotide 30 to nucleotide 1799; the nucleotide sequence of SEQ ID
N0:47
from nucleotide 90 to nucleotide 1799; the nucleotide sequence of the full-
length protein
coding sequence of clone vd1 1 deposited under accession number ATCC 98748; or
the
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nucleotide sequence of a mature protein coding sequence of clone vdl 1
deposited under
accession number ATCC 98748. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vd1_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:48 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:48, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:48 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 290 to amino acid
299 of
SEQ ID N0:48.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:47.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
2 0 (aa) SEQ ID N0:47, but excluding the poly(A) tail at the
3' end of SEQ ID N0:47; and
(ab) the nucleotide sequence of the cDNA insert of clone
vdl_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:47, but excluding the poly(A) tail at the
3' end of SEQ TD N0:47; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vdl 1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:47, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:47 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:47
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:47. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:47 from nucleotide 30 to
nucleotide
1799, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from
nucleotide
30 to nucleotide 1799. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799, and extending contiguously from a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:47 from
nucleotide 90 to nucleotide 1799, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:47 from nucleotide 90 to nucleotide 1799.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:48;
(b) a fragment of the amino acid sequence of SEQ ID N0:48, the
fragment comprising eight contiguous amino acids of SEQ ID N0:48; and
(c) the amino acid sequence encoded by the cDNA insert of clone
3 0 vd1_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:48. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:48 having biological activity, the fragment
preferably
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comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID NO:48, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:48 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 290 to amino acid 299 of SEQ ID N0:48.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 69 to nucleotide 443;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vd2_1 deposited under accession number
ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vd2_1 deposited under accession number ATCC
2 0 98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd2_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:50;
2 5 (i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:50 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:50;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein
of {h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
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(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:49.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:49 from nucleotide 69 to nucleotide 443; the nucleotide sequence of SEQ ID
NO:49
from nucleotide 111 to nucleotide 443; the nucleotide sequence of the full-
length protein
coding sequence of clone vd2_1 deposited under accession number ATCC 98748; or
the
nucleotide sequence of a mature protein coding sequence of clone vd2_1
deposited under
accession number ATCC 98748. In other preferred embodiments, the polynudeotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vd2_1
deposited under accession number ATCC 98748. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:50 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:50, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:50 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 57 to amino acid
66 of SEQ
ID N0:50.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:49.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:49, but excluding the poly(A) tail at the
3' end of SEQ ID N0:49; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vd2 1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);

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and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:49, but excluding the poly(A) tail at the
3' end of SEQ ID N0:49; and
(bb) the nucleotide sequence of the cDNA insert of clone
vd2_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:49, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:49 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:49
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:49. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 0 corresponding to the cDNA sequence of SEQ ID N0:49 from nucleotide 69 to
nucleotide
443, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from
nucleotide
69 to nucleotide 443. Also preferably the polynucleotide isolated according to
the above
2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:49 from
nucleotide 111 to nucleotide 443, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:49 from nucleotide 111 to nucleotide 443.
3 0 In other embodiments, the present invention provides a composition
comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:50;
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(b) a fragment of the amino acid sequence of SEQ ID N0:50, the
fragment comprising eight contiguous amino acids of SEQ ID N0:50; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vd2_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:50. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:50 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:50, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:50 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 57 to amino acid 66 of SEQ ID N0:50.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51 from nucleotide 176 to nucleotide 1249;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:51 from nucleotide 227 to nucleotide 1249;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vd3_1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
2 5 cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vd3_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
3 0 insert of clone vd3_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:52;
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(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:52 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:52;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a}-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:51.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:51 from nucleotide 176 to nucleotide 1249; the nucleotide sequence of SEQ
ID N0:51
from nucleotide 227 to nucleotide 1249; the nucleoiide sequence of the full-
length protein
coding sequence of clone vd3_1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone vd3_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vd3_1
2 0 deposited under accession number ATCC 98804. In further preferred
embodiments, the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:52 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:52, or a polynucleotide encoding a protein comprising
a
2 5 fragment of the amino acid sequence of SEQ ID N0:52 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 174 to amino acid
183 of
SEQ ID N0:52.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:51.
3 0 Further embodiments of the invention provide isolated polynucleotides
produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
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(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:51, but excluding the poly(A) tail at the
3' end of SEQ ID N0:51; and
(ab) the nucleotide sequence of the cDNA insert of clone
vd3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:51, but excluding the poly(A) tail at the
3' end of SEQ ID N0:51; and
(bb) the nucleotide sequence of the cDNA insert of clone
2 0 vd3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:51, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:51 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:51
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:51. Also preferably the
3 0 polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:51 from nucleotide 176 to
nucleotide
1249, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from
nucleotide
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176 to nucleotide 1249. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:51 from nucleotide 227 to nucleotide 1249, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:51 from
nucleotide 227 to nucleotide 1249, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:51 from nucleotide 227 to nucleotide 1249.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:52;
(b) a fragment of the amino and sequence of SEQ ID N0:52, the
fragment comprising eight contiguous amino acids of SEQ ID N0:52; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vd3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:52. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:52 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
2 0 of SEQ ID N0:52, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:52 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 174 to amino acid 183 of SEQ ID N0:52.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
2 5 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53 from nucleotide 94 to nucleotide 1530;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:53 from nucleotide 145 to nucleotide 1530;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vd4_1 deposited under accession number
ATCC 98804;

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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vd4_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd4_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:54;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:54 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:54;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m} a polynucleotide that hybridizes under stringent conditions to any
2 0 one of the polynucleotides specified in (a)-(i) and that has a length that
is at least
25% of the length of SEQ ID N0:53.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:53 from nucleotide 94 to nucleotide 1530; the nucleotide sequence of SEQ ID
N0:53
from nucleotide 145 to nucleotide 1530; the nucleotide sequence of the full-
length protein
2 5 coding sequence of clone vd4_1 deposited under accession number ATCC
98804; or the
nucleotide sequence of a mature protein coding sequence of clone vd4_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vd4_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
3 0 present invention provides a polynucleotide encoding a protein comprising
a fragment
of the amino acid sequence of SEQ ID N0:54 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:54, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:54 having biological
activity, the
86

CA 02327551 2000-10-31
wo mss~z~ pcTiusmossoa
fragment comprising the amino acid sequence from amino acid 234 to amino acid
243 of
SEQ ID N0:54.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:53.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:53, but excluding the poly(A) tail at the
3' end of SEQ ID N0:53; and
(ab) the nucleotide sequence of the cDNA insert of clone
vd4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe(s);
and
2 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) 5EQ ID N0:53, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:53; and
(bb) the nucleotide sequence of the cDNA insert of clone
vd4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
3 0 (iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step {b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:53, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
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ID N0:53 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:53
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:53. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:53 from nucleotide 94 to
nucleotide
1530, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from
nucleotide
94 to nucleotide 1530. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:53 from
nucleotide 145 to nucleotide 1530, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:53 from nucleotide 145 to nucleotide 1530.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:54;
(b) a fragment of the amino acid sequence of SEQ ID N0:54, the
fragment comprising eight contiguous amino acids of SEQ ID N0:54; and
2 0 (c) the amino acid sequence encoded by the cDNA insert of clone
vd4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:54. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
2 5 amino acid sequence of SEQ ID N0:54 having biological activity, the
fragment preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:54, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:54 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 234 to amino acid 243 of SEQ ID N0:54.
3 0 In one embodiment, the present invention provides a composition comprising
an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55;
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(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 71 to nucleotide 1300;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone ve4_1 deposited under accession number
ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone ve4_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone ve4_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:56;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:56 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:56;
2 0 (j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
2 5 one of the polynucleotides specified in (ar(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:55.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
3 0 N0:55 from nucleotide 71 to nucleotide 1300; the nucleotide sequence of
SEQ ID N0:55
from nucleotide 182 to nucleotide 1300; the nucleotide sequence of the full-
length protein
coding sequence of clone ve4_1 deposited under accession number ATCC 98784; or
the
nucleotide sequence of a mature protein coding sequence of clone ve4_1
deposited under
accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
89

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encodes the full-length or a mature protein encoded by the cDNA insert of
clone ve4_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:56 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:56, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:56 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 200 to amino acid
209 of
SEQ ID N0:56.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:55.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:55, but excluding the poly(A) tail at the
3' end of SEQ ID N0:55; and
2 0 (ab) the nucleotide sequence of the cDNA insert of clone
ve4_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
2 5 probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
3 0 the group consisting of:
{ba) SEQ ID N0:55, but excluding the poly(A) tail at the
3' end of SEQ ID N0:55; and
(bb) the nucleotide sequence of the cDNA insert of clone
ve4_I deposited under accession number ATCC 98784;

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(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:55, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:55 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:55
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:55. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:55 from nucleotide 71 to
nucleotide
1300, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:55 from
nucleotide
71 to nucleotide 1300. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:55 from
nucleotide 182 to nucleotide 1300, to a nucleotide sequence corresponding to
the 3' end
2 0 of said sequence of SEQ ID N0:55 from nucleotide 182 to nucleotide 1300.
1n other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:56;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:56, the
fragment comprising eight contiguous amino acids of SEQ ID N0:56; and
(c) the amino acid sequence encoded by the cDNA insert of clone
ve4_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably
such
3 0 protein comprises the amino acid sequence of SEQ ID N0:56. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:56 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:56, or a protein comprising a fragment of the amino acid sequence
of SEQ
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ID N0:56 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 200 to amino acid 209 of SEQ ID N0:56.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57; '
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 57 to nucleotide 785;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785;
(d} a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone ve8_1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone ve8_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone ve8_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:58;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:58 having biological activity, the fragment
2 5 comprising eight contiguous amino acids of SEQ ID N0:58;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(ar(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-{i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:57.
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Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:57 from nucleotide 57 to nucleotide 785; the nucleotide sequence of SEQ ID
N0:57
from nucleotide 147 to nucleotide 785; the nucleotide sequence of the full-
length protein
coding sequence of clone ve8_1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone ve8_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone ve8_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:58 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:58, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:58 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 116 to amino acid
125 of
SEQ ID N0:58.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:57.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:57, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:57; and
(ab) the nucleotide sequence of the cDNA insert of clone
ve8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
3 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
(b) a process comprising the steps of:
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(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:57, but excluding the poly{A) tail at the
3' end of SEQ ID N0:57; and
(bb) the nucleotide sequence of the cDNA insert of done
ve8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step {b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:57, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:57 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:57
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:57. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:57 from nucleotide 57 to
nucleotide
785, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
2 0 of said sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785, to
a nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from
nucleotide
57 to nucleotide 785. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:57 from nucleotide 147 to nucleotide 785, and extending contiguously from a
2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:57 from
nucleotide 147 to nucleotide 785, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:57 from nucleotide 147 to nucleotide 785.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:58;
(b) a fragment of the amino acid sequence of SEQ ID N0:58, the
fragment comprising eight contiguous amino acids of SEQ ID N0:58; and
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(c) the amino acid sequence encoded by the cDNA insert of clone
ve8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:58. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:58 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:58, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:58 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 116 to amino acid 125 of SEQ ID N0:58.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 64 to nucleotide 1002;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002;
(d) a polynucleotide comprising the nucleotide sequence of the full-
2 0 length protein coding sequence of clone vfl 1 deposited under accession
number
ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vfl 1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature
2 5 protein coding sequence of clone vfl 1 deposited under accession number
ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vfl_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid
3 0 sequence of SEQ ID N0:60;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:60 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:60;

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(j} a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:59.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:59 from nucleotide 64 to nucleotide 1002; the nucleotide sequence of SEQ ID
N0:59
from nucleotide 139 to nucleotide 1002; the nucleotide sequence of the full-
length protein
coding sequence of clone vfl_1 deposited under accession number ATCC 98784; or
the
nucleotide sequence of a mature protein coding sequence of clone vfl 1
deposited under
accession number ATCC 98784. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vf1_1
deposited under accession number ATCC 98784. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:60 having biological activity, the
fragment
2 0 preferably comprising eight (more preferably twenty, most preferably
thirty) contiguous
amino acids of SEQ ID N0:60, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:60 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 151 to amino acid
160 of
SEQ ID N0:60.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of
SEQ
ID N0:59.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:59, but excluding the poly(A) tail at the
3' end of SEQ ID N0:59; and
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(ab) the nucleotide sequence of the cDNA insert of clone
vfl 1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynudeotides detected with the
probe(s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ ID N0:59, but excluding the poly(A) tail at the
3' end of SEQ ID N0:59; and
(bb) the nucleotide sequence of the cDNA insert of done
vf1 1 deposited under accession number ATCC 98784;
(ii) hybridizing said primer{s) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynudeotide products of step (b)(iii).
2 0 Preferably the polynudeotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:59, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:59 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:59
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:59. Also preferably the
2 5 polynudeotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:59 from nucleotide 64 to
nucleotide
1002, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:59 from nucleotide 64 to nucleotide 1002, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from
nucleotide
3 0 64 to nucleotide 1002. Also preferably the polynudeotide isolated
according to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:59 from
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nucleotide 139 to nucleotide 1002, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:59 from nucleotide 139 to nucleotide 1002.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID N0:60, the
fragment comprising eight contiguous amino acids of SEQ ID N0:60; and
(c) the amino acid sequence encoded by the cDNA insert of clone vf1 1
deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:60. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:60 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:60, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:60 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 151 to amino acid 160 of SEQ ID N0:60.
In one embodiment, the present invention provides a composition comprising an
2 0 isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61;
(b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 588 to nucleotide 995;
2 5 (c) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995;
(d) a polynudeotide comprising the nucleotide sequence of the full-
length protein coding sequence of done vhf 1 deposited under accession number
ATCC 98804;
3 0 (e) a polynudeotide encoding the full-length protein encoded by the
cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(f) a polynudeotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vh1_1 deposited under accession number ATCC
98804;
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(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vhl 1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:62;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:62 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:62;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the profiein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a~(i) and that has a length that is
at least
25% of the length of SEQ ID N0:61.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:61 from nucleotide 588 to nucleotide 995; the nucleotide sequence of SEQ ID
N0:61
from nucleotide 750 to nucleotide 995; the nucleotide sequence of the full-
length protein
2 0 coding sequence of clone vhl 1 deposited under accession number ATCC
98804; or the
nucleotide sequence of a mature protein coding sequence of clone vhl_1
deposited under
accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vhf 1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
2 5 present invention provides a polynucleotide encoding a protein comprising
a fragment
of the amino acid sequence of SEQ ID N0:62 having biological activity, the
fragment
preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:62, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:62 having biological
activity, the
3 0 fragment comprising the amino acid sequence from amino acid 63 to amino
acid 72 of SEQ
ID N0:62.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:61.
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Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:61, but excluding the poly(A) tail at the
3' end of SEQ ID N0:61; and
(ab) the nucleotide sequence of the cDNA insert of clone
vhl 1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
(iii) isolating the DNA polynucleotides detected with the
probe{s);
and
(b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that
hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
2 0 (ba) SEQ ID N0:61, but excluding the poly(A) tail at the
3' end of SEQ ID N0:61; and
(bb) the nucleotide sequence of the cDNA insert of clone
vhl 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:61, and
3 0 extending contiguously from a nucleotide sequence corresponding to the 5'
end of SEQ
ID N0:61 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:61
, but
excluding the poly(A} tail at the 3' end of SEQ ID N0:61. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:61 from nucleotide 588 to
nucleotide
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995, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from
nucleotide
588 to nucleotide 995. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:61 from nucleotide 750 to nucleotide 995, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:61 from
nucleotide 750 to nucleotide 995, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:61 from nucleotide 750 to nucleotide 995.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
(a) the amino acid sequence of SEQ ID N0:62;
(b) a fragment of the amino acid sequence of SEQ ID N0:62, the
fragment comprising eight contiguous amino acids of SEQ ID N0:62; and
(c) the amino acid sequence encoded by the cDNA insert of clone
vhf 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:62. In further
preferred
2 0 embodiments, the present invention provides a protein comprising a
fragment of the
amino acid sequence of SEQ ID N0:62 having biological activity, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:62, or a protein comprising a fragment of the amino acid sequence
of SEQ
ID N0:62 having biological activity, the fragment comprising the amino acid
sequence
2 5 from amino acid 63 to amino acid 72 of SEQ ID N0:62.
In one embodiment, the present invention provides a composition comprising an
isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 29 to nucleotide 1369;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369;
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(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vi1 1 deposited under accession number
ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vil 1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vil 1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vil I deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:64;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:64 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:64;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein
of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (ar(i); and
{m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i) and that has a length that is
at least
25% of the length of SEQ ID N0:63.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:63 from nucleotide 29 to nucleotide 1369; the nucleotide sequence of SEQ ID
N0:63
from nucleotide 104 to nucleotide 1369; the nucleotide sequence of the full-
length protein
coding sequence of clone vi1 1 deposited under accession number ATCC 98804; or
the
nucleotide sequence of a mature protein coding sequence of clone vil_1
deposited under
3 0 accession number ATCC 98804. In other preferred embodiments, the
polynucleotide
encodes the full-length or a mature protein encoded by the cDNA insert of
clone vi1_1
deposited under accession number ATCC 98804. In further preferred embodiments,
the
present invention provides a polynucleotide encoding a protein comprising a
fragment
of the amino acid sequence of SEQ ID N0:64 having biological activity, the
fragment
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preferably comprising eight (more preferably twenty, most preferably thirty)
contiguous
amino acids of SEQ ID N0:64, or a polynucleotide encoding a protein comprising
a
fragment of the amino acid sequence of SEQ ID N0:64 having biological
activity, the
fragment comprising the amino acid sequence from amino acid 218 to amino acid
227 of
SEQ ID N0:64.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:63.
Further embodiments of the invention provide isolated polynucleotides produced
according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:63, but excluding the poly(A) tail at the
3' end of SEQ ID N0:63; and
(ab) the nucleotide sequence of the cDNA insert of clone
vi1 1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
2 0 (iii) isolating the DNA polynucleotides detected with the
probe(s);
and
{b} a process comprising the steps of:
(i} preparing one or more polynucleotide primers that
2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from
the group consisting of:
(ba) SEQ 1D N0:63, but excluding the poly(A) tail at the
3' end of SEQ ID N0:63; and
(bb) the nucleotide sequence of the cDNA insert of clone
3 0 vil 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the polynucleotide products of step (b)(iii).
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Preferably the polynucleotide isolated according to the above process
comprises a
nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:63, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ
ID N0:63 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:63
, but
excluding the poly(A) tail at the 3' end of SEQ ID N0:63. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:63 from nucleotide 29 to
nucleotide
1369, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:63 from
nucleotide
29 to nucleotide 1369. Also preferably the polynudeotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:63 from
nucleotide 104 to nucleotide 1369, to a nucleotide sequence corresponding to
the 3' end
of said sequence of SEQ ID N0:63 from nucleotide 104 to nucleotide 1369.
In other embodiments, the present invention provides a composition comprising
a protein, wherein said protein comprises an amino acid sequence selected from
the group
consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:64;
(b) a fragment of the amino acid sequence of SEQ ID N0:64, the
fragment comprising eight contiguous amino acids of SEQ ID N0:64; and
(c) the amino acid sequence encoded by the cDNA insert of clone vi1 1
deposited under accession number ATCC 98804;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such
protein comprises the amino acid sequence of SEQ ID N0:64. In further
preferred
embodiments, the present invention provides a protein comprising a fragment of
the
amino acid sequence of SEQ ID N0:64 having biological activify, the fragment
preferably
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
3 0 of SEQ ID N0:64, or a protein comprising a fragment of the amino acid
sequence of SEQ
ID N0:64 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 218 to amino acid 227 of SEQ ID N0:64.
In certain preferred embodiments, the polynucleotide is operably linked to an
expression control sequence. The invention also provides a host cell,
including bacterial,
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yeast, insect and mammalian cells, transformed with such polynucleotide
compositions.
Also provided by the present invention are organisms that have enhanced,
reduced, or
modified expression of the genes) corresponding to the polynucleotide
sequences
disclosed herein.
Processes are also provided for producing a protein, which comprise:
(a) growing a culture of the host cell transformed with such
polynucleotide compositions in a suitable culture medium; and
(b) purifying the protein from the culture.
The protein produced according to such methods is also provided by the present
invention.
Protein compositions of the present invention may further comprise a
pharmaceutically acceptable Garner. Compositions comprising an antibody which
specifically reacts with such protein are also provided by the present
invention.
Methods are also provided for preventing, treating or ameliorating a medical
condition which comprises administering to a mammalian subject a
therapeutically
effective amount of a composition comprising a protein of the present
invention and a
pharmaceutically acceptable carrier.
BRIEF DESCRIPTION OF THE DRAWINGS
2 0 Figures 1A and 1B are schematic representations of the pED6 and pNOTs
vectors,
respectively, used for deposit of clones disclosed herein.
DETAILED DESCRIPTION
ISOLATED PROTEINS AND POLYNUCLEOTIDES
2 5 Nucleotide and amino acid sequences, as presently determined, are reported
below for each clone and protein disclosed in the present application. The
nucleotide
sequence of each clone can readily be determined by sequencing of the
deposited clone
in accordance with known methods. The predicted amino acid sequence (both full-
length
and mature forms) can then be determined from such nucleotide sequence. The
amino
3 0 acid sequence of the protein encoded by a particular clone can also be
determined by
expression of the clone in a suitable host cell, collecting the protein and
determining its
sequence. For each disclosed protein applicants have identified what they have
determined to be the reading frame best identifiable with sequence information
available
at the time of filing.
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As used herein a "secreted" protein is one which, when expressed in a suitable
host
cell, is transported across or through a membrane, including transport as a
result of signal
sequences in its amino acid sequence. "Secreted" proteins include without
limitation
proteins secreted wholly (e.g., soluble proteins) or partially (e.g. ,
receptors) from the cell
in which they are expressed. "Secreted" proteins also include without
limitation proteins
which are transported across the membrane of the endoplasmic reticulum.
Clone"vb2 1"
A polynucleotide of the present invention has been identified as clone
"vb2_1".
vb2_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb2_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb2_1 protein").
The nucleotide sequence of vb2_1 as presently determined is reported in SEQ ID
NO:1, and includes a poly(A} tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vb2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:2. Amino acids
15 to 27
of SEQ ID N0:2 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 28. Due to the hydrophobic nature of the
predicted
2 0 leader/signal sequence, it is likely to act as a transmembrane domain
should the predicted
leader/signal sequence not be separated from the remainder of the vb2_1
protein.
If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:1 by
deleting one of the adenine residues at positions 315 and 316, another
potential vb2_1
reading frame and predicted amino acid sequence could be encoded by basepairs
126 to
2 5 381 of SEQ ID N0:1 and is reported in SEQ ID N0:97. Amino acids 15 to 27
of SEQID
N0:97 are a predicted leader/signal sequence, with the predicted mature amino
acid
sequence beginning at amino acid 28 of SEQ ID N0:97, or are a transmembrane
domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb2_1 should be approximately 2342 bp.
3 0 The nucleotide sequence disclosed herein for vb2_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb2_1 demonstrated at least some similarity with
sequences
identified as AA308563 (EST179381 HCC cell line (matastasis to liver in mouse)
II Homo
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Sapiens cDNA 5' end, mRNA sequence). Based upon sequence similarity, vb2_1
proteins
and each similar protein or peptide may share at least some activity.
Clone "vb3 1"
A polynucleotide of the present invention has been identified as clone
"vb3_1".
vb3_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb3_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb3_1 protein").
The nucleotide sequence of vb3 1 as presently determined is reported in SEQ ID
N0:3, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vb3_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:4. Amino acids
16 to 28
of SEQ ID N0:4 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 29. Due to the hydrophobic nature of the
predicted
leader/signal sequence, it is likely to act as a transmembrane domain should
the predicted
leader/signal sequence not be separated from the remainder of the vb3_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb3_1 should be approximately 2498 bp.
2 0 The nucleotide sequence disclosed herein for vb3_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb3_1 demonstrated at least some similarity with
sequences
identified as AA098874 (zn45f I l .s 1 Stratagene HeLa cell s3 937216 Homo
sapiens cDNA
clone 550413 3', mRNA sequence) and T26482 (Human gene signature HUMGS08724).
2 5 Based upon sequence similarity, vb3_1 proteins and each similar protein or
peptide may
share at least some activity.
Clone "vb4 1"
A polynucleotide of the present invention has been identified as clone
"vb4_1".
3 0 vb4_1 was isolated from a human fetal brain cDNA library and was
identified as encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb4_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb4_1 protein").
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The nucleotide sequence of vb4_1 as presently determined is reported in SEQ ID
N0:5, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vb4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:6. Amino acids 2
to 14 of
SEQ ID N0:6 are a predicted leader/signal sequence, with the predicted mature
amino
acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the
predicted
leader/signal sequence, it is likely to act as a transmembrane domain should
the predicted
leader/signal sequence not be separated from the remainder of the vb4_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb4_1 should be approximately 2161 bp.
The nucleotide sequence disclosed herein for vb4_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb4_1 demonstrated at least some similarity with
sequences
identified as D88035 (Rat mRNA for glycoprotein specific UDP-
glucuronyltransferase,
complete cds), N49234 (yy83b10.s1 Homo Sapiens cDNA clone 280123 3'), and
Q59845
(Human brain Expressed Sequence Tag EST00765). Based upon sequence similarity,
vb4_1 proteins and each similar protein or peptide may share at least some
activity. The
TopPredlI computer program predicts two additional potential transmembrane
domains
within the vb4_1 protein sequence, one centered around amino acid 40 and
another
2 0 around amino acid 80 of SEQ ID N0:6.
Clone "vb5 1"
A polynucleotide of the present invention has been identified as clone
"vb5_1".
vb5_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
2 5 a secreted or transmembrane protein on the basis of computer analysis of
the amino acid
sequence of the encoded protein. vb5_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb5_1 protein").
The nucleotide sequence of vb5_1 as presently determined is reported in SEQ ID
N0:7, and includes a poly(A} tail. What applicants presently believe to be the
proper
3 0 reading frame and the predicted amino acid sequence of the vb5_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:8. Amino acids 7
to 19 of
SEQ ID N0:8 are a predicted leader/signal sequence, with the predicted mature
amino
acid sequence beginning at amino acid 20. Due to the hydrophobic nature of the
predicted
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leader/signal sequence, it is likely to act as a transmembrane domain should
the predicted
leader/signal sequence not be separated from the remainder of the vb5_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb5_1 should be approximately 724 bp.
The nucleotide sequence disclosed herein for vb5_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb5_7 demonstrated at least some similarity with
sequences
identified as AA835218 (ak65a05.s1 Barstead pancreas HPLRBI Homo sapiens cDNA
clone IMAGE:1412720 3', mRNA sequence). Based upon sequence similarity, vb5_1
proteins and each similar protein or peptide may share at least some activity.
Clone "vb6 1"
A polynucleotide of the present invention has been identified as clone
"vb6_1".
vb6_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb6_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb6_1 protein").
The nucleotide sequence of vb6_1 as presently determined is reported in SEQ ID
N0:9, and includes a poly(A) tail. What applicants presently believe to be the
proper
2 0 reading frame and the predicted amino acid sequence of the vb6_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:10. Amino acids
13 to 25
of SEQ ID NO:10 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 5 the predicted leader/signal sequence not be separated from the remainder
of the vb6_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb6_1 should be approximately 2685 bp.
The nucleotide sequence disclosed herein for vb6_1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb6_1 demonstrated at least some similarity with
sequences
identified as AA478801 (zv20fn5.s 1 Soares NhHMPu S 1 Homo sapiens cDNA clone
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754209 3', mRNA sequence). Based upon sequence similarity, vb6_1 proteins and
each
similar protein or peptide may share at least some activity.
done "vb7 1"
A polynucleotide of the present invention has been identified as clone "vb7
1".
vb7 1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb7 1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb7 1 protein').
The nucleotide sequence of vb7_1 as presently determined is reported in SEQ ID
N0:11, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vb7 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:12. Amino acids
35 to 47
of SEQ ID N0:12 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 48. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vb7 1
protein.
Another potential vb7 1 reading frame and predicted amino acid sequence that
2 0 could be encoded by basepairs 1093 to 1577 of SEQ ID N0:11 is reported in
SEQ ID
N0:98. Amino acids 11 to 23 of SEQ ID N0:98 are a predicted leader/signal
sequence,
with the predicted mature amino acid sequence beginning at amino acid 24 of
SEQ ID
N0:98, or are a transmembrane domain. The TapPredII computer program predicts
another potential transmembrane domain within the protein sequence of SEQ ID
N0:98
2 5 centered around amino acid 86 of SEQ ID N0:98. If a frameshift were
introduced into the
nucleotide sequence of SEQ ID N0:11 approximately between position 1090 and
position
1253, the open reading frame of SEQ ID N0:12 could be joined to the open
reading frame
of SEQ ID N0:98.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
3 0 vb7 1 should be approximately 1730 bp.
The nucleotide sequence disclosed herein for vb7 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb7 1 demonstrated at least some similarity with
sequences
identified as D 13748 {human eukaryotic initiation factor 4A)], M22873 (Mus
musculus
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protein synthesis initiation factor 4A (e1F-4A) gene, exon 1), and N36589
(yx86fO8.r1
Homo sapiens cDNA clone 268647 S'). The predicted amino acid sequence
disclosed
herein for vb7_1 was searched against the GenPept and GeneSeq amino acid
sequence
databases using the BLAST7C search protocol. The predicted vb7 1 protein
demonstrated
at least some similarity to the sequence identified as AL021839 (hypothetical
protein
[Schizosaccharomyces pombe]). Based upon sequence similarity, vb7 1 proteins
and each
similar protein or peptide may share at least some activity.
vb7_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 45 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone"vb8 1"
A polynucleotide of the present invention has been identified as clone
"vb8_1".
vb8_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb8_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb8_1 protein").
The nucleotide sequence of vb8_1 as presently determined is reported in SEQ ID
N0:13, and includes a poly(A) tail. What applicants presently believe to be
the proper
2 0 reading frame and the predicted amino acid sequence of the vb8_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:14.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb8_1 should be approximately 1363 bp.
The nucleotide sequence disclosed herein for vb8_1 was searched against the
2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb8_1 demonstrated at least some similarity with
sequences
identified as N57252 (yw93dll.rl Homo sapiens cDNA clone 259797 5'). The
predicted
amino acid sequence disclosed herein for vb8_1 was searched against the
GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The
3 0 predicted vb8_1 protein demonstrated at least some similarity to sequences
identified as
AF51239 (probable ubiquitin activating enzyme 2 [Picea mariana]). Based upon
sequence
similarity, vb8_1 proteins and each similar protein or peptide may share at
least some
activity. The TopPredII computer program predicts a potential transmembrane
domain
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within the vb8_1 protein sequence centered around amino acid 30 of SEQ ID
N0:14. Both
the CodonPreference and Testcode computer programs indicate that frameshifts
in the
nucleotide sequence of SEQ ID N0:13, resulting in the joining of the open
reading frame
of SEQ ID N0:14 with open reading frames that are more 5' to that of SEQ ID
N0:14, are
likely.
vb8_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 23 kDa was detected in conditioned medium using
SDS
polyacrylamide gel electrophoresis.
Clone "vb9 1"
A polynudeotide of the present invention has been identified as clone "vb9_1".
vb9_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vb9_1 is a full-length done, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb9_1 protein").
The nucleotide sequence of vb9_1 as presently determined is reported in SEQ ID
N0:15, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vb9_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:16. Amino acids
3 to 15
2 0 of SEQ ID N0:16 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 16. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vb9_1
protein.
2 5 The EcoRI/NotI restriction fragment obtainable from the deposit containing
done
vb9_1 should be approximately 2996 bp.
The nucleotide sequence disclosed herein for vb9_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
PASTA search protocols. vb9_1 demonstrated at least some similarity with
sequences
3 0 identified as AA446380 (zw58b09.r1 Soares total fetus Nb2HF8 9w Homo
sapiens cDNA
clone 774233 5', mRNA sequence) and L48440 (Rattus norvegicus collagen type II
mRNA,
complete cds). The predicted amino add sequence disclosed herein for vb9_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
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BLASTX search protocol. The predicted vb9_1 protein demonstrated at least some
similarity to the sequence identified as 278279 (Collagen alphal [Rattus
norvegicus]).
Based upon sequence similarity, vb9_1 proteins and each similar protein or
peptide may
share at least some activity.
vb9_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 58 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone"vc3 1"
A polynucleotide of the present invention has been identified as clone "v~ 1".
vc3_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vc3_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc3_1 protein").
The nucleotide sequence of vc3_1 as presently determined is reported in SEQ ID
N0:17, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc3_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:18. Amino acids
24 to 36
of SEQ ID N0:18 are a predicted leader/signal sequence, with the predicted
mature
2 0 amino acid sequence beginning at amino acid 37. Due to the hydrophobic
nature of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc3_1
protein.
Another potential vc3_1 reading frame and predicted amino acid sequence is
2 5 encoded by basepairs 227 to 703 of SEQ TD N0:17 and is reported in SEQ ID
N0:99.
Amino acids 83 to 95 of SEQ ID N0:99 are a predicted leader/signal sequence,
with the
predicted mature amino acid sequence beginning at amino acid 96, or are a
transmembrane domain, and the TopPredII computer program predicts two
additional
transmembrane domains within the SEQ ID N0:99 amino acid sequence. A
frameshift in
3 0 the nucleotide sequence of SEQ ID N0:17 between about nucleotide 109 to
about
nucleotide 417 could join together portions of the overlapping reading frames
of SEQ ID
N0:18 and SEQ ID N0:99.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc3_1 should be approximately 950 bp.
The nucleotide sequence disclosed herein for vc3_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc3_1 demonstrated at least some similarity with
sequences
identified as AA669665 (ac18h12.s1 Stratagene ovary (#937217) Homo sapiens
cDNA clone
856871 3'). Based upon sequence similarity, vc3_1 proteins and each similar
protein or
peptide may share at least some activity.
vc3_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 19 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone"vc4 1"
A polynucleotide of the present invention has been identified as clone
"vc4_1".
vc4_1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vc4_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc4_1 protein").
The nucleotide sequence of vc4 1 as presently determined is reported in SEQ ID
2 0 N0:19, and includes a poly(A) tail. What applicants presently believe to
be the proper
reading frame and the predicted amino acid sequence of the vc4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:20. Amino acids
2 to 14
of SEQ ID N0:20 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc4_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc4_1 should be approximately 1200 bp.
3 0 The nucleotide sequence disclosed herein for vc4_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc4_1 demonstrated at least some similarity with
sequences
identified as Q40970 (Human skeletal muscle ADP-ribosyltransferase gene),
U60881 (Mus
musculus Yac-2 NAD:arginine ADP-ribosyltransferase mRNA, complete cds), and
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W12489 (ma57b11.r1 Soares mouse p3NMF19.5 Mus musculus cDNA clone 314781 5'
similar to SW RT61_RAT P17982 ALLOANTIGEN RT6.1 PRECURSOR). The predicted
amino acid sequence disclosed herein for vc4_1 was searched against the
GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The
predicted vc4_1 protein demonstrated at least some similarity to sequences
identified as
837572 (Rabbit skeletal muscle ADP-ribosyltransferase) and U60881 (Yac-2 NAD
arginine
ADP-ribosyltransferase [Mus musculus]). ADP-ribosyltransferases are localized
to the
plasma membrane and are involved in "post-translational modification of
proteins in
which the ADP-ribose moiety of NAD is transferred to proteins", which is
"responsible
for the toxicity of some bacterial toxins (e.g. cholera toxin and pertussis
toxin)". Based
upon sequence similarity, vc4_1 proteins and each similar protein or peptide
may share
at least some activity.
vc4_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 26 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone "vc5 1"
A polynucleotide of the present invention has been identified as clone "v~ 1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as
encoding
2 0 a secreted or transmembrane protein on the basis of computer analysis of
the amino acid
sequence of the encoded protein. vc5_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc5_1 protein").
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:21, and includes a poly(A) tail. What applicants presently believe to be
the proper
2 5 reading frame and the predicted amino acid sequence of the v~ 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:22. Amino acids
63 to 75
of SEQ ID N0:22 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 76. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
3 0 the predicted leader/signal sequence not be separated from the remainder
of the vc5_1
protein.
Another potential vc5_1 reading frame and predicted amino acid sequence is
encoded by basepairs 215-376 of SEQ ID N0:21 and is reported in SEQ ID NO:100.
Amino
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acids 4 to 16 of SEQ ID NO:10(? are a predicted leader/signal sequence, with
the predicted
mature amino acid sequence beginning at amino acid 17 of SEQ ID N0:100.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
done
vc5_1 should be approximately 1650 bp.
The nucleotide sequence disclosed herein for vc5_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc5_1 demonstrated at least some similarity with
sequences
identified as AA002211 (zh81h07.s1 Soares fetal liver spleen 1NFLS S1 Homo
sapiens
cDNA clone 4277413'}. Based upon sequence similarity, vc5_1 proteins and each
similar
protein or peptide may share at least some activity.
vc5_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 28 kDa was detected in conditioned medium using
SDS
polyacrylamide gel electrophoresis.
Clone "vc7 1"
A polynucleotide of the present invention has been identified as clone "vc7
1".
vc7 1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vc7 1 is a full-length clone, including the
entire coding
2 0 sequence of a secreted protein (also referred to herein as "vc7 1
protein").
The nucleotide sequence of vc7_1 as presently determined is reported in SEQ ID
N0:23, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc7_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:24. Amino acids
11 to 23
2 5 of SEQ ID N0:24 are a possible leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 24.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc7 1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vc7 1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. No hits were found in the database.
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Clone"vc9 1"
A polynucleotide of the present invention has been identified as clone
"vc9_1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vc9_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "v~ 1 protein').
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:25, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the v~ 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:26. Amino acids
10 to 22
of SEQ ID N0:26 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the v~ 1
protein.
Another potential v~ 1 reading frame and predicted amino acid sequence is
encoded by basepairs 1981 to 2619 of SEQ ID N0:25 and is reported in SEQ ID
N0:101.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
v~ 1 should be approximately 4500 bp.
2 0 The nucleotide sequence disclosed herein for v~ 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using B1.,ASTN/BLASTX and
FASTA search protocols. vc9_1 demonstrated at least some similarity with
sequences
identified as N66453 (yz41a08.s1 Homo Sapiens cDNA clone 285590 3') and 275407
(Human DNA sequence from cosmid N128A12 on chromosome 22q12-qter contains
ESTs,
2 5 CpG island). Based upon sequence similarity, v~ 1 proteins and each
similar protein or
peptide may share at least some activity. The TopPredII computer program
predicts a
potential transmembrane domain within the v~ 1 protein sequence at the extreme
C-
terminus of SEQ ID N0:26.
3 0 Clone "vcl0 1"
A polynucleotide of the present invention has been identified as clone
"vcl0_1".
vcl0_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
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amino acid sequence of the encoded protein. vcl0_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vcl0_1 protein").
The nucleotide sequence of vcl0_1 as presently determined is reported in SEQ
ID
N0:27, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vcl0_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:28. Amino acids
21 to 33
of SEQ ID N0:28 are a possible leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 34.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vcl0_1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vcl0_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vcl0_1 demonstrated at least some similarity with
sequences
identified as AA398711 (zt75a05.s1 Soares testis NHT Homo sapiens cDNA clone
728144
3') and T24621 {Human gene signature HUMGS06681). Based upon sequence
similarity,
vcl0_1 proteins and each similar protein or peptide may share at least some
activity. The
TopPredII computer program predicts a potential transmembrane domain within
the
vcl0_1 protein sequence centered around amino acid 74 of SEQ ID N0:28.
Nuclotides
1103 to 1191 of SEQ ID N0:27 represent a possible intron in the predicted 3'
untranslated
2 0 region of the vcl0_1 mRNA molecule.
Clone"vcll 1"
A polynucleotide of the present invention has been identified as clone
"vcll_1".
vcll_1 was isolated from a human fetal brain cDNA library and was identified
as
2 5 encoding a secreted or transmembrane protein on the basis of computer
analysis of the
amino acid sequence of the encoded protein. vcl l 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vcll_1 protein').
The nucleotide sequence of vcll 1 as presently determined is reported in SEQ
ID
N0:29, and includes a poly(A) tail. What applicants presently believe to be
the proper
3 0 reading frame and the predicted amino acid sequence of the vcll 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:30. Amino acids
6 to 18
of SEQ ID N0:30 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 19. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
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the predicted leader/signal sequence not be separated from the remainder of
the vcll_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vcll_1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vcll 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vcll_1 demonstrated at Least some similarity with
sequences
identified as AA193348 (zr41c08.r1 Soares NhHMPu S1 Homo Sapiens cDNA clone
665966
5') and T23590 (Human gene signature HIJMGS05443). Based upon sequence
similarity,
vcll 1 proteins and each similar protein or peptide may share at least some
activity. The
TopPredII computer program predicts a potential transmembrane domain within
the
vcll 1 protein sequence centered around amino acid 32 of SEQ ID N0:30.
Clone"vcl4 1"
A polynucleotide of the present invention has been identified as clone
"vcl4_1".
vcl4_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vcl4_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vcl4_1 protein").
2 0 The nucleotide sequence of vcl4_1 as presently determined is reported in
SEQ ID
N0:31, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vcl4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:32. Amino acids
21 to 33
of SEQ ID N0:32 are a predicted leader/signal sequence, with the predicted
mature
2 5 amino acid sequence beginning at amino acid 34. Due to the hydrophobic
nature of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vcl4_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
3 0 vcl4_1 should be approximately 1300 bp.
The nucleotide sequence disclosed herein for vcl4_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vcl4_1 demonstrated at least some similarity with
sequences
identified as AA258182 (zs35f09.s1 NCI_CGAP_GCB1 Homo sapiens cDNA clone IMAGE
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687209 3'). The predicted amino acid sequence disclosed herein for vcl4_1 was
searched
against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vcl4 1 protein demonstrated at least some
similarity to
sequences identified as AC002339 (BAC T11A7 (Arabidopsis thaliana]) and 271266
(R06C7.6 [Caenorhabditis elegans]). Based upon sequence similarity, vcl4_1
proteins and
each similar protein or peptide may share at least some activity.
vcl4_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 22 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone"vcl6 1"
A polynucleotide of the present invention has been identified as clone
"vcl6_1".
vcl6_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vcl6_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vcl6_1 protein"}.
The nucleotide sequence of vcl6_1 as presently determined is reported in SEQ
ID
N0:33, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vcl6_1 protein
corresponding
2 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:34. Amino
acids 15 to 27
of SEQ ID N0:34 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vcl6_1
2 5 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vcl6_1 should be approximately 1256 bp.
The nucleotide sequence disclosed herein for vcl6_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
3 0 FASTA search protocols. vcl6_1 demonstrated at least some similarity with
sequences
identified as AA776882 (ac40a09.s1 Stratagene hNT neuron (#937233) Homo
sapiens
cDNA clone 858904 3' similar to SW XB3_XENLA Q09004 STATHMIN-LIKE
PROTEIN XB3, mRNA sequence), AF026528 (Rattus norvegicus stathmin-like-protein
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RB3 mRNA, complete cds), and AF026529 (Rattus norvegicus stathmin-like-protein
splice
variant RB3' mRNA, complete cds). The predicted amino acid sequence disclosed
herein
for vcl6_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vcl6_1 protein demonstrated at
least
some siirularity to sequences identified as AF026528 (stathmin-like-protein
RB3 [Rattus
norvegicus]). While stathmin itself is intracellular, stathmin-related protein
RB3 (as well
as related proteins SCG10 in rat and XB3 in Xenopus) is membrane-associated
and has
been isolated in the membrane fraction from cell cultures. RB3 is expressed in
neural
tissue and may be involved in the expression of differentiated neuronal
function. Based
upon sequence similarity, vcl6_1 proteins and each similar protein or peptide
may share
at least some activity.
vcl6_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 89 kDa was detected in conditioned medium using
SDS
polyacrylamide gel electrophoresis.
Clone "vcl7 1"
A polynucleotide of the present invention has been identified as clone "vcl7
1".
vcl7 1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
2 0 amino acid sequence of the encoded protein. vcl7 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vcl7
1 protein").
The nucleotide sequence of vcl7 1 as presently determined is reported in SEQ
ID
N0:35, and includes a poly{A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vcl7 1 protein
corresponding
2 5 to the foregoing nucleotide sequence is reported in SEQ ID N0:36. Amino
acids 30 to 42
of SEQ ID N0:36 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 43. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vcl7 1
3 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vcl7_1 should be approximately 1783 bp.
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The nucleotide sequence disclosed herein for vcl7_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vcl7_1 demonstrated at least some similarity with
sequences
identified as N73805 (yz80g02.s 1 Homo sapiens cDNA clone 289394 3'), and
T24437
(Human gene signature HLTMGS06471). Based upon sequence similarity, vcl7 1
proteins
and each similar protein or peptide may share at least some activity. The
TopPredII
computer program predicts an additional potential transmembrane domain within
the
vcl7 1 protein sequence centered around amino acid 60 of SEQ ID N0:36.
Clone "vc21 1"
A polynucleotide of the present invention has been identified as clone "vc21
1".
vc21 1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc21 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc21_1 protein").
The nucleotide sequence of vc21_1 as presently determined is reported in SEQ
ID
N0:37, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc21 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:38. Amino acids
11 to 23
2 0 of SEQ ID N0:38 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc21_1
protein.
2 5 Another potential vc21 1 reading frame and predicted amino acid sequence
is
encoded by basepairs 796 to 1014 of SEQ ID N0:37 and is reported in SEQ ID
N0:102.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc21 1 should be approximately 1773 bp.
The nucleotide sequence disclosed herein for vc21 1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc21 1 demonstrated at least some similarity with
sequences
identified as W85910 (zh52b10.s1 Soares fetal liver spleen 1NFLS S1 Homo
sapiens
cDNA clone 415675 3', mRNA sequence) and T24609 (Human gene signature
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HUMGS06668). Based upon sequence similarity, vc21 1 proteins and each similar
protein or peptide may share at least some activity.
Gone "vc23 1"
A polynucleotide of the present invention has been identified as clone
"vc23_1".
vc23_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc23_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc23_2 protein").
The nucleotide sequence of vc23_1 as presently determined is reported in SEQ
ID
N0:39, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the v~ 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:40. Amino acids
28 to 40
of SEQ ID N0:40 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 41. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc23_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
2 0 vc23_1 should be approximately 1998 bp.
The nucleotide sequence disclosed herein for vc23_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc23_1 demonstrated at least some similarity with
sequences
identified as AA580484 (nn22a05.s 1 NCI CGAP_Co 12 Homo sapiens cDNA clone
2 5 IMAGE:1084592 similar to TR:G 1209718 G 1209718 HYPOTHETICAL 50.1 KD
PROTEIN, mRNA sequence), T25530 (Human gene signature HUMGS07700), U41293
(Saccharomyces cerevisiae putative serine/threonine protein kinase gene,
putative
ribosomal protein L25 gene, and malate dehydrogenase (MDH2) gene, complete
cds), and
274866 (S.cerevisiae chromosome XV reading frame ORF YOL124c). The predicted
3 0 amino acid sequence disclosed herein for vc23_1 was searched against the
GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The
predicted vc23_1 protein demonstrated at least some similarity to sequences
identified as
U41293 (unknown [Saccharomyces cerevisiae]) and 274866 (ORF YOL124c [Saccharo-
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myces cerevisiae]). Based upon sequence similarity, vc23_1 proteins and each
similar
protein or peptide may share at least some activity. The vc23_1 protein
contains a "N-6
adenine-specific DNA methylases signature" motif. The TopPredII computer
program
predicts a potential transmembrane domain within the vc23_I protein sequence
centered
around amino acid 232 of SEQ ID N0:40.
vc23_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 51 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone "vc25 1"
A polynucleotide of the present invention has been identified as clone
"vc25_1".
vc25_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc25_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc25_1 protein").
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:41, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the v~ 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:42. Amino acids
25 to 37
2 0 of SEQ ID N0:42 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 38. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc25_1
protein.
2 5 The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc25_1 should be approximately 1653 bp.
The nucleotide sequence disclosed herein for v~ 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc25_1 demonstrated at least some similarity with
sequences
3 0 identified as N21690 (yx63h08.s1 Soares melanocyte 2NbHM Homo Sapiens cDNA
clone
266463 3', mRNA sequence) and T25257 (Human gene signature HUMGS07418). Based
upon sequence similarity, vc25_1 proteins and each similar protein or peptide
may share
at least some activity.
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vc25_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 15 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone "vc26 1"
A polynucleotide of the present invention has been identified as clone
"vc26_1".
vc26_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc26_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc26_1 protein").
The nucleotide sequence of vc26_1 as presently determined is reported in SEQ
ID
N0:43, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc26_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:44. Amino acids
11 to 23
of SEQ ID N0:44 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vc26_1
protein.
2 0 If the "G" residue at position 669 of SEQ ID N0:43 were deleted to create
a
frameshft, another potential vc26_1 reading frame and predicted amino acid
sequence
could be encoded by what would then be basepairs 87 to 992 of the deletion-
containing
version of SEQ ID N0:43. This potential vc26_1 reading frame and predicted
amino acid
sequence is reported in SEQ ID N0:103. Amino acids 11 to 23 of both SEQ ID
N0:44 and
2 5 SEQ ID N0:103 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 24, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc26_1 should be approximately 1982 bp.
The nucleotide sequence disclosed herein for vc26_1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc26_1 demonstrated at least some similarity with
sequences
identified as AA877534 (nrO1g08.s 1 NCI CGAP_Co 10 Homo sapiens cDNA clone
IMAGE:1160606 3', mRNA sequence) and T25645 (Human gene signature
HUMGS07835). The predicted vc26_1 protein of SEQ ID NO:10 contains an immuno-
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globulins and major histocompatibility complex proteins signature at amino
acid 131.
Based upon sequence similarity, vc26_1 proteins and each similar protein or
peptide may
share at least some activity. The TopPredlI computer program predicts seven
additional
potential transmembrane domains within the vc26_1 protein sequence, centered
around
amino acids 60,100,120,160, 210, 250, and 290 of SEQ ID N0:44, respectively.
Clone"vc30 1"
A polynucleotide of the present invention has been identified as clone
"vc30_1".
vc30_1 was isolated from a human fetal brain cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vc30_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vc30_1 protein").
The nucleotide sequence of vc30_l as presently determined is reported in SEQ
ID
N0:45, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vc30_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:46. Amino acids
19 to 31
of SEQ ID N0:46 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 0 the predicted leader/signal sequence not be separated from the remainder
of the vc30_1
protein.
If a frameshift were introduced in the nucleotide sequence of SEQ ID N0:45 by
deleting the cytosine residue at position 1393, another potential vc30_1
reading frame and
predicted amino acid sequence could be encoded by what would then be basepairs
1317
2 5 to 1659 of SEQ ID N0:45 and is reported in SEQ ID N0:104.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc30_1 should be approximately 1887 bp.
The nucleotide sequence disclosed herein for vc30_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
3 0 FASTA search protocols. vc30_1 demonstrated at least some similarity with
sequences
identified as AA496421 (zv37c04.r1 Soares ovary tumor NbHOT Homo sapiens cDNA
clone 755814 5', mRNA sequence). The predicted amino acid sequence disclosed
herein
for vc30_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vc30_l protein demonstrated at
least
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some similarity to sequences identified as AF047760 (phosphatidic acid
phosphohydrolase
type 2c [Homo sapiens]). Based upon sequence similarity, vc3a_1 proteins and
each
similar protein or peptide may share at least some activity. The TopPredII
computer
program predicts an additional potential transmembrane domain within the
vc30_1
protein sequence centered around amino acid 55 of SEQ ID N0:46.
Clone "vdl 1"
A polynucleotide of the present invention has been identified as clone "vd1
1".
vdl 1 was isolated from a human adult skin cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vdl_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vdl 1 protein").
The nucleotide sequence of vdl_1 as presently determined is reported in SEQ ID
N0:47, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vd1 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:48. Amino acids
8 to 20
of SEQ ID N0:48 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 0 the predicted leader/signal sequence not be separated from the remainder
of the vd1_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vd1 1 should be approximately 2000 bp.
The nucleotide sequence disclosed herein for vdl 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vdl_1 demonstrated at least some similarity with
sequences
identified as AA582963 (nn72e02.s1 NCI_CGAP_Larl Homo sapiens cDNA clone IMAGE
1089434) and AC002389 (Human DNA from chromosome 19 specific cosmid 828461,
genomic sequence, complete sequence). Based upon sequence similarity, vdl 1
proteins
3 0 and each similar protein or peptide may share at least some activity.
There is an 18-
residue amino acid stretch (with an approximate consensus sequence shown in
SEQ ID
N0:105 {HHAAGQAGNEAGRFGQG~) that is almost tandemly repeated 25 times in the
vd1 1 protein. Nucleotides 406-1668 of SEQ ID N0:47, which encode a region of
SEQ ID
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N0:48 that includes the 18-residue amino acid repeats, may represent an
alternatively
spliced region in mRNA molecules transcribed from the vdl 1 gene.
vdl_protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 55 kDa was detected in conditioned medium using
SDS
polyacrylamide gel electrophoresis.
Clone "vd2 1"
A polynucleotide of the present invention has been identified as clone
"vd2_1".
vd2_1 was isolated from a human adult skin cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vd2_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vd2_1 protein')
The nucleotide sequence of vd2_1 as presently determined is reported in SEQ ID
N0:49, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vd2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:50. Amino acids
2 to 14
of SEQ ID N0:50 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 0 the predicted leader/signal sequence not be separated from the remainder
of the vd2_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
done
vd2_1 should be approximately 900 bp.
The nucleotide sequence disclosed herein for vd2_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vd2_1 demonstrated at least some similarity with
sequences
identified as H03945 (yj44c02.s1 Homo sapiens cDNA clone 151586 3'). Based
upon
sequence similarity, vd2_1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts a potential
transmembrane
3 0 domain within the vd2_1 protein sequence centered around amino acid 115 of
SEQ ID
N0:50.
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Clone "vd3 1"
A polynudeotide of the present invention has been identified as clone "vd3_1".
vd3_1 was isolated from a human adult skin cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vd3_1 is a full-length done, including the
entire coding
sequence of a secreted protein (also referred to herein as "vd3_1 protein').
The nucleotide sequence of vd3_1 as presently determined is reported in SEQ ID
N0:51, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vd3_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:52. Amino acids
5 to 17
of SEQ ID N0:52 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vd3_1
protein.
If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:19
by
inserting an adenine or thymine residue at position 1132 or 1133, another
potential vd3_1
reading frame and predicted amino acid sequence could be encoded by basepairs
176 to
1281 of SEQ ID N0:51 and is reported in SEQ ID N0:106. Amino acids 5 to 17 of
SEQID
2 0 N0:106 are a predicted leader/signal sequence, with the predicted mature
amino acid
sequence beginning at amino acid 18 of SEQ ID N0:106, or are a transmembrane
domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
done
vd3_1 should be approximately 1537 bp.
The nucleotide sequence disclosed herein for vd3_1 was searched against the
2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vd3_1 demonstrated at least some similarity with
sequences
identified as AA873028 (ob11e05.s1 NCI CGAP_Kid3 Homo sapiens cDNA clone
IMAGE 1323392 3', mRNA sequence), AC002389 (Human DNA from chromosome 19
specific cosmid 828461, genomic sequence, complete sequence), and AD001502
(Homo
3 0 sapiens DNA from chromosome 19-cosmid (21246, genomic sequence). Based
upon
sequence similarity, vd3_1 proteins and each similar protein or peptide may
share at least
some activity. The TopPredII computer program predicts an additional possible
transmembrane domain within the vd3_1 protein sequence centered around amino
acid
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290 of SEQ ID N0:52. The vd3_1 protein is apparently a splice variant of the
vd4 1
protein described below.
vd3_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 42 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone "vd4 1"
A polynucleotide of the present invention has been identified as clone
"vd4_1".
vd4_1 was isolated from a human adult skin cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vd4_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vd4_1 protein").
The nucleotide sequence of vd4_1 as presently determined is reported in SEQ ID
N0:53, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vd4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:54. Amino acids
5 to 17
of SEQ ID N0:54 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 0 the predicted leader/signal sequence not be separated from the remainder
of the vd4_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vd4_1 should be approximately 1897 bp.
The nucleotide sequence disclosed herein for vd4 1 was searched against the
2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vd4_2 demonstrated at least some similarity with
sequences
identified as AA706316 (ah28e1l.sl Soares parathyroid tumor NbHPA Homo sapiens
cDNA clone 1240172 3', mRNA sequence), AC002389 (Human DNA from chromosome
19 specific cosmid 828461, genomic sequence, complete sequence), and AD001502
3 0 (Homo sapiens DNA from chromosome 19-cosmid f21246, genomic sequence).
Based
upon sequence similarity, vd4_1 proteins and each similar protein or peptide
may share
at least some activity. The TopPredII computer program predicts an additional
possible
transmembrane domain within the vd4_1 protein sequence centered around amino
acid
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290 of SEQ ID N0:54. The vd4_1 protein is apparently a splice variant of the
vd3_1
protein described above.
vd4_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 54 kDa was detected in conditioned medium using
SDS
polyacxylamide gel electrophoresis.
Clone "ve4 1"
A polynucleotide of the present invention has been identified as clone
"ve4_1".
ve4_1 was isolated from a human adult brain (Alzheimer s hippocampus level 7)
cDNA
library and was identified as encoding a secreted or transmembrane protein on
the basis
of computer analysis of the amino acid sequence of the encoded protein. ve4_1
is a full-
length clone, including the entire coding sequence of a secreted protein (also
referred to
herein as "ve4_1 protein").
The nucleotide sequence of ve4_1 as presently determined is reported in SEQ ID
N0:55, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the ve4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:56. Amino acids
25 to 37
of SEQ ID N0:56 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 38. Due to the hydrophobic nature
of the
2 0 predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the ve4_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
ve4_1 should be approximately 1578 bp.
2 5 The nucleotide sequence disclosed herein for ve4_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. ve4_1 demonstrated at least some similarity with
sequences
identified as AA707153 (zj33f10.s1 Soares fetal liver spleen 1NFT.S S1 Homo
sapiens
cDNA clone 452107 3' similar to TR P70295 P70295 AUP1 PRECURSOR, mRNA
3 0 sequence} and U41736 (Mus musculus ancient ubiquitous 46 kDa protein AUP1
precursor
(Aup 1 ) mRNA, complete cds). The predicted amino acid sequence disclosed
herein for
ve4_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted ve4_1 protein demonstrated at
least
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some similarity to the sequence identified as U41736 (ancient ubiquitous 46
kDa protein
AUP46 precursor [Mus musculus]). Based upon sequence similarity, ve4_1
proteins and
each similar protein or peptide may share at least some activity. The
TopPredII computer
program predicts two additional potential transmembrane domains within the
ve4_ 1
protein sequence, one centered around amino acid 110 and another around amino
acid 210
of SEQ m N0:56.
ve4_1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 41 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone "ve8 1"
A polynucleotide of the present invention has been identified as clone
"ve8_1".
ve8_1 was isolated from a human adult brain (Alzheimer's hippocampus level 7)
cDNA
library and was identified as encoding a secreted or transmembrane protein on
the basis
of computer analysis of the amino acid sequence of the encoded protein. ve8_1
is a full-
length clone, including the entire coding sequence of a secreted protein (also
referred to
herein as "ve8_1 protein").
The nucleoside sequence of ve8_i as presently determined is reported in SEQ ID
N0:57, and includes a poly(A) tail. What applicants presently believe to be
the proper
2 0 reading frame and the predicted amino acid sequence of the ve8_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:58. Amino acids
18 to 30
of SEQ ID N0:58 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 31. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
2 5 the predicted leader/signal sequence not be separated from the remainder
of the ve8_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
ve8_1 should be approximately 2093 bp.
The nucleotide sequence disclosed herein for ve8_1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. ve8_1 demonstrated at least some similarity with
sequences
identified as AC004126 (Homo Sapiens Chromosome l 1q12 pac pDJ606g6; HTGS
phase
1, 17 unordered pieces). Based upon sequence similarity, ve8_1 proteins and
each similar
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protein or peptide may share at least some activity. The TopPredII computer
program
predicts four additional potential transmembrane domains within the ve8_1
protein
sequence, centered around amino acids 94, 147, 150, and 193 of SEQ ID N0:58,
respectively.
Clone "vf1 1"
A polynucleotide of the present invention has been identified as clone
"vf1_1".
vfl 1 was isolated from a human adult heart cDNA library and was identified as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vfl 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vf1_1 protein").
The nucleotide sequence of vfl 1 as presently determined is reported in SEQ ID
N0:59, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vf1 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:60. Amino acids
13 to 25
of SEQ ID N0:60 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vf1_1
2 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vfl 1 should be approximately 1382 bp.
The nucleotide sequence disclosed herein for vfl_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
2 5 FASTA search protocols. vfl_1 demonstrated at least some similarity with
sequences
identified as AA349531 (EST56314 Infant brain Homo sapiens cDNA 5' end, mRNA
sequence) and AA532642 (nj17c07.s1 NCI_CGAP Pr22 Homo sapiens cDNA clone
IMAGE 986604, mRNA sequence). Based upon sequence similarity, vfl 1 proteins
and
each similar protein or peptide may share at least some activity. The
TopPredII computer
3 0 program predicts an additional potential transmembrane domain within the
vfl_1 protein
sequence centered around amino acid 138 of SEQ ID N0:60.
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vf1 1 protein was expressed in a COS cell expression system, and an expressed
protein band of approximately 40 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Clone "vhl 1"
A polynucleotide of the present invention has been identified as clone "vhl
1".
vhl_1 was isolated from a human adult thymus cDNA library and was identified
as
encoding a secreted or transmembrane protein on the basis of computer analysis
of the
amino acid sequence of the encoded protein. vhl 1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as "vhf
1 protein').
The nucleotide sequence of vh1_1 as presently determined is reported in SEQ ID
N0:61, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vhl_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:62. Amino acids
42 to 54
of SEQ ID N0:62 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 55. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vh1_1
protein.
2 0 Another potential vhl_1 reading frame and predicted amino acid sequence
that
could be encoded by basepairs 833 to 1054 of SEQ ID N0:61 is reported in SEQ
ID
N0:107. Amino aclds 22 to 34 of SEQ ID N0:107 are a predicted leader/signal
sequence,
with the predicted mature amino acid sequence beginning at amino acid 35 of
SEQ ID
N0:107, or are a transmembrane domain. If a frameshift were introduced into
the
2 5 nucleotide sequence of SEQ ID N0:61 approximately between position 830 and
position
998, the open reading frame of SEQ ID N0:62 could be joined to the open
reading frame
of SEQ ID N0:107.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vhl 1 should be approximately 1529 bp.
3 0 The nucleotide sequence disclosed herein for vhl 1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vhl_1 demonstrated at least some similarity with
sequences
identified as AA927736 (om72h10.s1 NCI CGAP_GC4 Homo sapiens cDNA clone
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IMAGE:1552771 3', mRNA sequence). Based upon sequence similarity, vhf 1
proteins
and each similar protein or peptide may share at least some activity.
Clone "vil 1"
A polynucleotide of the present invention has been identified as clone
"vi1_1".
vi1_1 was isolated from a human adult aorta cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
sequence of the encoded protein. vil 1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "viI 1 protein").
The nucleotide sequence of vi1_1 as presently determined is reported in SEQ ID
N0:63, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vi1 1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:64. Amino acids
13 to 25
of SEQ ID N0:64 are a predicted leader/signal sequence, with the predicted
mature
amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature
of the
predicted leader/signal sequence, it is likely to act as a transmembrane
domain should
the predicted leader/signal sequence not be separated from the remainder of
the vi1_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
2 0 vil 1 should be approximately 2348 bp.
The nucleotide sequence disclosed herein for vi1 1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vil_1 demonstrated at least some similarity with
sequences
identified as AA411541 (zv30a03.r1 Soares ovary tumor NbHOT Homo sapiens cDNA
2 5 clone 755116 S' similar to WP:F07H5.1 I CE03160) and T21484 (Human gene
signature
HUMGS02856). The predicted amino acid sequence disclosed herein for vil_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
BLASTX search protocol. The predicted viI_1 protein demonstrated at least some
similarity to the sequence identified as 268314 (F46C5.9 [Caenorhabditis
elegans]). The
3 0 amino acid sequence of the predicted vil_1 protein indicates that it may
contain a beta-
transducin family Trp-Asp repeat signature (WD-40} motif centered around
residue 300
of SEQ ID N0:28. The WD-40 motif is thought to be a widely distributed protein-
protein
interaction domain. Based upon sequence similarity, vil_1 proteins and each
similar
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protein or peptide may share at least some activity. The TopPredII computer
program
predicts two additional possible transmembrane domains within the vi 1_ 1
protein
sequence, one centered around amino acid 200 and another around amino acid 340
of SEQ
m N0:64.
vi 1 _ 1 protein was expressed in a COS cell expression system, and an
expressed
protein band of approximately 45 kDa was detected in membrane fractions using
SDS
polyacrylamide gel electrophoresis.
Deposit of Clones
Clones vc3_l, vc4_l, v~ 1, vc7 1, vc9_1, vcl0_1, vcll 1, vcl4_1, vd1_l, and
vd2_1 were deposited on April 24,1998 with the American Type Culture
Collection (10801
University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original
deposit under
the Budapest Treaty and were given the accession number ATCC 98748, from which
each
clone comprising a particular polynucleotide is obtainable.
Clone vc21_1 was deposited on June 10, 1998 with the American Type Culture
Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.)
as an
original deposit under the Budapest Treaty and was given the accession number
ATCC
98785, from which each clone comprising a particular polynucleotide is
obtainable.
Clones vcl6_1, vcl7 1, v~ 1, vc25_1, vc26_1, ve4_l, and vfl 1 were deposited
2 0 on June 10,1998 with the American Type Culture Collection (10801
University Boulevard,
Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the
Budapest Treaty
and were given the accession number ATCC 98784, from which each clone
comprising a
particular polynucleotide is obtainable.
Clones vb2_1, vb3_l, vb4_l, vb5_l, vb6_l, vb7_l, vb8_1, vb9_l, vc30_l, vd3_l,
2 5 vd4_l, ve8_l, vhl_l, and vil 1 were deposited on July 1,1998 with the
American Type
Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209
U.S.A.)
as an original deposit under the Budapest Treaty and were given the accession
number
ATCC 98804, from which each clone comprising a particular polynucleotide is
obtainable.
All restrictions on the availability to the public of the deposited material
will be
3 0 irrevocably removed upon the granting of the patent, except for the
requirements
specified in 37 C.F.R. ~ 1.808(b), and the term of the deposit will comply
with 37 C.F.R.
~ 1.806.
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Each clone has been transfected into separate bacterial cells (E. coli) in
these
composite deposits. Each clone can be removed from the vector in which it was
deposited
by performing an EcoRI/NotI digestion (5' site, EcoRI; 3' site, NotI) to
produce the
appropriate fragment for such clone. Each clone was deposited in either the
pED6 or
pNOTs vector depicted in Figures lA and 1B, respectively. The pED6dpc2 vector
("pED6") was derived from pED6dpc1 by insertion of a new polylinker to
facilitate
cDNA cloning (Kaufman et al.,1991, Nucleic Acids Res.19: 4485-4490); the pNOTs
vector
was derived from pMT2 (Kaufman et al.,1989, Mol. Cell. Biol. 9: 946-958) by
deletion of
the DHFR sequences, insertion of a new polylinker, and insertion of the M13
origin of
replication in the CIaI site. In some instances, the deposited clone can
become "flipped"
(i.e., in the reverse orientation) in the deposited isolate. In such
instances, the cDNA insert
can still be isolated by digestion with EcoRI and NotI. However, NotI will
then produce
the 5' site and EcoRI will produce the 3' site for placement of the cDNA in
proper
orientation for expression in a suitable vector. The cDNA may also be
expressed from the
vectors in which they were deposited.
Bacterial cells containing a particular clone can be obtained from the
composite
deposit as follows:
An oligonucleotide probe or probes should be designed to the sequence that is
known for that particular clone. This sequence can be derived from the
sequences
2 0 provided herein, or from a combination of those sequences. The sequence of
an
oligonucleotide probe that was used to isolate or to sequence each full-length
clone is
identified below, and should be most reliable in isolating the clone of
interest.
Clone Probe uence
2 5 vb2_1 SEQ ID N0:65
vb3_i SEQ ID N0:66
vb4_1 SEQ ID N0:67
vb5_1 SEQ ID N0:68
vb6_1 SEQ ID N0:69
3 0 vb7_1 SEQ ID N0:70
vb8 1 SEQ ID N0:71
vb9_1 SEQ ID N0:72
vc3_1 SEQ ID N0:73
vc4_1 SEQ ID N0:74
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vc5_1 SEQ ID N0:75
vc7 1 SEQ ID N0:76
vc9_1 SEQ ID N0:77
vcl0_1 SEQ ID N0:78
vcll_1 SEQ ID N0:79
vcl4_1 SEQ ID N0:80
vcl6_1 SEQ ID N0:81
vcl7_1 SEQ ID N0:82
vc21_1 SEQ ID N0:83
vc23_1 SEQ ID N0:84
vc25_1 SEQ ID N0:85
vc26_1 SEQ ID N0:86
vc30_1 SEQ ID N0:87
vd1 1 SEQ ID N0:88
vd2_1 SEQ ID N0:89
vd3_1 ~ SEQ ID N0:90
vd4_1 SEQ ID N0:91
ve4_1 SEQ ID N0:92
ve8_1 SEQ ID N0:93
2 0 vfl_1 SEQ ID N0:94
vhf 1 SEQ ID N0:95
vil_1 SEQ ID N0:96
In the sequences listed above which include an N at position 2, that position
is occupied
in preferred probes/primers by a biotinylated phosphoaramidite residue rather
than a
nucleotide (such as, for example, that produced by use of biotin
phosphoramidite (1-
dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-O-(2-cyanoethyl)-(N,N-
diisopropyl)-phosphoramadite) (Glen Research, cat. no.10-1953)).
The design of the oligonucleotide probe should preferably follow these
3 0 parameters:
(a) It should be designed to an area of the sequence which has the fewest
ambiguous bases ("N's"), if any;
(b) It should be designed to have a T," of approx. 80 ° C (assuming
2° for each
A or T and 4 degrees for each G or C).
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The oligonucleotide should preferably be labeled with y 32P ATP (specific
activity 6000
Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for
labeling oligonucleotides. Other labeling techniques can also be used.
Unincorporated
label should preferably be removed by gel filtration chromatography or other
established
methods. The amount of radioactivity incorporated into the probe should be
quantitated
by measurement in a scintillation counter. Preferably, specific activity of
the resulting
probe should be approximately 4e+6 dpm/pmole.
The bacterial culture containing the pool of full-length clones should
preferably
be thawed and 100 lxl of the stock used to inoculate a sterile culture flask
containing 25 ml
of sterile L-broth containing ampicillin at 100 pg/ml. The culture should
preferably be
grown to saturation at 37°C, and the saturated culture should
preferably be diluted in
fresh L broth. Aliquots of these dilutions should preferably be plated to
determine the
dilution and volume which will yield approximately 5000 distinct and well-
separated
colonies on solid bacteriological media containing L-broth containing
ampicillin at 100
ug/ml and agar at 1.5% in a 150 mm petri dish when grown overnight at
37°C. Other
known methods of obtaining distinct, well-separated colonies can also be
employed.
Standard colony hybridization procedures should then be used to transfer the
colonies to nitrocellulose filters and lyse, denature and bake them.
The filter is then preferably incubated at 65°C for 1 hour with gentle
agitation in
2 0 6X SSC (20X stock is 175.3 g NaCI/liter, 88.2 g Na citrate/liter, adjusted
to pH 7.0 with
NaOH) containing 0.5% SDS,100 pg/ml of yeast RNA, and 10 mM EDTA
(approximately
10 mL per 150 mm filter). Preferably, the probe is then added to the
hybridization mix at
a concentration greater than or equal to 1e+6 dpm/mL. The filter is then
preferably
incubated at 65°C with gentle agitation overnight. The filter is then
preferably washed in
2 5 500 mL of 2X SSC/0.5% SDS at room temperature without agitation,
preferably followed
by 500 mL of 2X SSC/0.1% SDS at room temperature with gentle shaking for 15
minutes.
A third wash with O.1X SSC/0.5% SDS at 65°C for 30 minutes to 1 hour is
optional. The
filter is then preferably dried and subjected to autoradiography for
sufficient time to
visualize the positives on the X-ray film. Other known hybridization methods
can also
3 0 be employed.
The positive colonies are picked, grown in culture, and plasmid DNA isolated
using standard procedures. The clones can then be verified by restriction
analysis,
hybridization analysis, or DNA sequencing.
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Fragments of the proteins of the present invention which are capable of
exhibiting
biological activity are also encompassed by the present invention. Fragments
of the
protein may be in linear form or they may be cyclized using known methods, for
example,
as described in H.U. Saragovi, et al., Bio/Technology 1~,0 773-778 (1992) and
in R.S.
McDowell, et al., J. Amer. Chem. Soc.114, 9245-9253 (1992), both of which are
incorporated
herein by reference. Such fragments may be fused to earner molecules such as
immunoglobulins for many purposes, including increasing the valency of protein
binding
sites. For example, fragments of the protein may be fused through "linker"
sequences to
the Fc portion of an immunoglobulin. For a bivalent form of the protein, such
a fusion
could be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes
may also
be used to generate such fusions. For example, a protein - IgM fusion would
generate a
decavalent form of the protein of the invention.
The present invention also provides both full-length and mature forms of the
disclosed proteins. The full-length form of the such proteins is identified in
the sequence
25 listing by translation of the nucleotide sequence of each disclosed clone.
The mature
forms) of such protein may be obtained by expression of the disclosed full-
length
polynucleotide (preferably those deposited with ATCC) in a suitable mammalian
cell or
other host cell. The sequences) of the mature forms) of the protein may also
be
determinable from the amino acid sequence of the full-length form.
2 0 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
2 5 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
3 0 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.
The chromosomal location corresponding to the polynucleotide sequences
disclosed herein may also be determined, for example by hybridizing
appropriately
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labeled polynucleotides of the present invention to chromosomes in situ. It
may also be
possible to determine the corresponding chromosomal location for a disclosed
polynucleotide by identifying significantly similar nucleotide sequences in
public
databases, such as expressed sequence tags (ESTs), that have already been
mapped to
particular chromosomal locations. For at least some of the polynucleotide
sequences
disclosed herein, public database sequences having at least some similarity to
the
polynucleotide of the present invention have been listed by database accession
number.
Searches using the GenBank accession numbers of these public database
sequences can
then be performed at an Internet site provided by the National Center for
Biotechnology
Information having the address http://www.ncbi.nlin.nih.gov/UruGene/, in order
to
identify "UniGene clusters" of overlapping sequences. Many of the "UniGene
clusters"
so identified will already have been mapped to particular chromosomal sites.
Organisms that have enhanced, reduced, or modified expression of the genes)
corresponding to the polynucleotide sequences disclosed herein are provided.
The
desired change in gene expression can be achieved through the use of antisense
polynucleotides or ribozymes that bind and/or cleave the mItNA 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
2 0 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
2 5 also provided (see European Patent No. 0 649 464 Bl, 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
3 0 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): 7431-79:35; Clark et aL,1994, Proc. Natl. Acad. Sci.
LISA 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,
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CA 02327551 2000-10-31
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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.
For
example, the TopPredII computer program can be used to predict the location of
transmembrane domains in an amino and sequence, domains which are described by
the
location of the center of the transmsmbrane domain, with at least ten
transmembrane
amino acids on each side of the reported central residue(s).
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
2 0 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
2 5 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.
In particular, sequence identity may be determined using WU-BLAST
3 0 (Washington University BLAST) version 2.0 software, which builds upon WU-
BLAST
version 1.4, which in turn is based on the public domain NCBI-BLAST version
1.4
(Altschul and Gish, 1996, Local alignment statistics, Doolittle ed., Methods
in Enzymology
266: 460-480; Altschul et al., 1990, Basic local alignment search tool,
Journal of
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CA 02327551 2000-10-31
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Molecular Biology 215: 403-410; Gish and States, 1993, Identification of
protein coding
regions by database similarity search, Nature Genetics 3: 266-272; Karlin and
Altschul,
1993, Applications and statistics for multiple high-scoring segments in
molecular
sequences, Proc. Natl. Acad. Sci. USA 90: 5873-5877; all of which are
incorporated by
reference herein). WU-BLAST version 2.0 executable programs for several UNIX
platforms can be downloaded from ftp://blast.wustl.edu/blasdexecutables. The
complete
suite of search programs (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) is
provided at that site, in addition to several support programs. WU-BLAST 2.0
is
copyrighted and may not be sold or redistributed in any form or manner without
the
express written consent of the author; but the posted executables may
otherwise be freely
used for commercial, nonprofit, or academic purposes. In all search programs
in the suite
-- BLASTP, BLASTN, BLASTX, TBLASTN and TBLASTX -- the gapped alignment
routines are integral to the database search itself, and thus yield much
better sensitivity and
selectivity while producing the more easily interpreted output. Gapping can
optionally be
turned off in all of these programs, if desired. The default penalty (Q) for a
gap of length
one is Q=9 for proteins and BLASTP, and Q=10 for BLASTN, but may be changed to
any
integer value including zero, one through eight, nine, ten, eleven, twelve
through twenty,
twenty-one through fifty, fifty-one through one hundred, etc. The default per-
residue
penalty for extending a gap (R) is R=2 for proteins and BLASTP, and R=10 for
BLASTN,
2 0 but may be changed to any integer value including zero, one, two, three,
four, five, six,
seven, eight, nine, ten, eleven, twelve through twenty, twenty-one through
fifty, fifty-one
through one hundred, etc. Any combination of values for Q and R can be used in
order to
align sequences so as to maximize overlap and identity while minimizing
sequence gaps.
The default amino acid comparison matrix is BLOSUM62, but other amino acid
2 5 comparison matrices such as PAM can be utilized.
Species homologues 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
3 0 polynucleotide. Preferably, polynucleotide species homologues have at
least 60% sequence
identity (more preferably, at least 75% identity; most preferably at least 90%
identity) with
the given polynucleotide, and protein species homologues have at least 30%
sequence
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CA 02327551 2000-10-31
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identity (more preferably, at least 45% identity; most preferably at least 60%
identity) with
the given protein, where sequence identity is determined by comparing the
nucleotide
sequences of the polynucleotides or the amino acid sequences of the proteins
when
aligned so as to maximize overlap and identity while minimizing sequence gaps.
Species
homologues 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. Preferably, species homologues are those isolated from
mammalian
species. Most preferably, species homologues are those isolated from certain
mammalian
species such as, for example, Pan troglodytes, Gorilla gorilla, Pongo
pygmaeus, HyIobates
concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus
aethiops, Cebus capucinus,
Aotus trivirgatus, Sanguinus Oedipus, Microcebus murinus, Mus musculus, Rattus
norvegicus,
Cricetulus griseus, Fells catus, Mustela vison, Canis familiaris, Oryctolagus
cuniculus, Bos taurus,
Ovis aries, Sus scrofa, and Eguus caballus, for which genetic maps have been
created
allowing the identification of syntenic relationships between the genomic
organization of
genes in one species and the genomic organization of the related genes in
another species
(O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al.,
1993, Nature
Genetics 3:103-112; Johansson et al.,1995, Genomics 25: 682-690; Lyons et
al.,1997, Nature
Genetics 15: 47 56; O'Brien et al.,1997, Trends in Genetics 13(10): 393-399;
Carver and Stubbs,
1997, Genome Research 7:1123-1137; all of which are incorporated by reference
herein).
2 0 The invention also encompasses allelic variants of the disclosed
polynucleotides
or proteins; that is, naturally-occurring alternative forms of the isolated
polynucleotides
which also encode proteins which are identical or have significantly similar
sequences to
those encoded by the disclosed polynucleotides. Preferably, allelic variants
have at least
60% sequence identity (more preferably, at least 75% identity; most preferably
at least 90%
2 5 identity) with the given polynucleotide, where sequence identity is
determined by
comparing the nucleotide sequences of the polynucleotides when aligned so as
to maximize
overlap and identity while minimizing sequence gaps. Allelic variants may be
isolated and
identified by making suitable probes or primers from the sequences provided
herein and
screening a suitable nucleic acid source from individuals of the appropriate
species.
3 0 The invention also includes polynucleotides with sequences complementary
to
those of the polynucleotides disclosed herein.
The present invention also includes polynucleotides that hybridize under
reduced
stringency conditions, more preferably stringent conditions, and most
preferably highly
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CA 02327551 2000-10-31
WO 99/55721 PGT/US99/08504
stringent conditions, to polynucleotides described herein. Examples of
stringency
conditions are shown in the table 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.
StringencyPolynucleotideHybrid Hybridization TemperatureWash
ConditionHybrid Length and Temperature
(bp)= Buffer' and Buffers
A DNA:DNA 2 50 65C; lxSSC -or- 65C; 0.3xSSC
42C; lxSSC, 50% formamide
B DNA:DNA <50 TB*; lxSSC TB*; lxSSC
C DNA:RNA 2 50 67C; lxSSC -or- 67C; 0.3xSSC
45C; lxSSC, 50% formamide
D DNA:RNA <50 Tp*; lxSSC Tp*; lxSSC
E RNA:RNA 2 50 70C; lxSSC -or- 70C; 0.3xSSC
50C; lxSSC, 50% formamide
F RNA:RNA <50 TF*; lxSSC TF*; lxSSC
G DNA:DNA 2 50 65C; 4xSSC -or- 65C; lxSSC
42C; 4xSSC, 50% formamide
H DNA:DNA <50 TH*; 4xSSC TH*; 4xSSC
I DNA:RNA x 50 67C; 4xSSC -or- 67C; lxSSC
45C; 4xSSC, 50% formamide
J DNA:RNA <50 TJ*; 4xSSC T~*; 4xSSC
K RNA:RNA 2 50 70C; 4xSSC -or- 67C; lxSSC
50C; 4xSSC, 50% formamide
L RNA:RNA <50 T,,*; 2xSSC T~*; 2xSSC
2 M DNA:DNA 2 50 SOC; 4xSSC -or- 50C; 2xSSC
0 40C; 6xSSC, 50% formamide
N DNA:DNA <50 TN*; 6xSSC T~,*; 6xSSC
O DNA:RNA 2 50 55C; 4xSSC -or- 55C; 2xSSC
42C; 6xSSC, 50% formamide
P DNA:RNA <50 TP*; 6xSSC Tp*; 6xSSC
Q RNA:RNA 2 50 60C; 4xSSC -or- 60C; 2xSSC
45C; 6xSSC, SO~o
formamide
2 R RNA:RNA <50 TR*; 4xSSC TR*; 4xSSC
5
t: 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
sequence are hybridized, the
3 0 hybrid length can be determined by aligning the sequences of the
polynudeotides and identifying the region
or regions of optimal sequence complementarity.
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t: SSPE (lxSSPE is 0.15M NaCI, lOmM NaHiPO,, and 1.25mM EDTA, pH 7.4) can be
substituted for SSC
(lxSSC is 0.15M NaCI and l5mM sodium citrate) in the hybridization and wash
buffers; washes are
performed for 15 minutes after hybridization is complete.
"TB - 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 (Tm) of the hybrid, where
Tm 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,
T,°(°C) = 81.5 + 16.6(log,o[Na*]) + 0.41(%G+C)
(600/N), 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 = 0.165 M).
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
2 0 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.
The isolated polynucleotide of the invention may be operably linked to an
2 5 expression control sequence such as the pMT2 or pED expression vectors
disclosed in
Kaufman et aL, Nucleic Acids Res. ~ 4485-4490 (1991), in order to produce the
protein
recombinantly. Many suitable expression control sequences are known in the
art. General
methods of expressing recombinant proteins are also known and are exemplified
in R.
Kaufman, Methods in Enzymology ~, 537-566 (1990). As defined herein "operably
3 0 linked" means that the isolated polynucleotide of the invention and an
expression control
sequence are situated within a vector or cell in such a way that the protein
is expressed
by a host cell which has been transformed (transfected) with the ligated
polynucleotide/expression control sequence.
A number of types of cells may act as suitable host cells for expression of
the
3 5 protein. Mammalian host cells include, for example, monkey COS cells,
Chinese Hamster
Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human
Co1o205
cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal
diploid cells, cell
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strains derived from in yitro culture of primary tissue, primary explants,
HeLa cells,
mouse L cells, BHK, HL-60, U937, HaK or jurkat cells.
Alternatively, it may be possible to produce the protein in lower eukaryotes
such
as yeast or in prokaryotes such as bacteria. Potentially suitable yeast
strains include
Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains,
Canriida, or any
yeast strain capable of expressing heterologous proteins. Potentially suitable
bacterial
strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium,
or any bacterial
strain capable of expressing heterologous proteins. If the protein is made in
yeast or
bacteria, it may be necessary to modify the protein produced therein, for
example by
phosphorylation or glycosylation of the appropriate sites, in order to obtain
the functional
protein. Such covalent attachments may be accomplished using known chemical or
enzymatic methods.
The protein may also be produced by operably linking the isolated
polynucleotide
of the invention to suitable control sequences in one or more insect
expression vectors,
and employing an insect expression system. Materials and methods for
baculovirus/insect cell expression systems are commercially available in kit
form from,
e.g., Invitrogen, San Diego, California, U.S.A. (the MaxBac~ kit), and such
methods are
well known in the art, as described in Summers and Smith, Texas Aericultural
Experiment
Station Bulletin No. 1555 (1987), incorporated herein by reference. As used
herein, an
2 0 insect cell capable of expressing a polynucleotide of the present
invention is
"transformed."
The protein of the invention may be prepared by culturing transformed host
cells
under culture conditions suitable to express the recombinant protein. The
resulting
expressed protein may then be purified from such culture (i.e., from culture
medium or
2 5 cell extracts) using known purification processes, such as gel filtration
and ion exchange
chromatography. The purification of the protein may also include an affinity
column
containing agents which will bind to the protein; one or more column steps
over such
affinity resins as concanavalin A-agarose, heparin-toyopearl~ or Cibacrom blue
3GA
Sepharose~; one or more steps involving hydrophobic interaction chromatography
using
3 0 such resins as phenyl ether, butyl ether, or propyl ether; or
immunoaffiruty
chromatography.
Alternatively, the protein of the invention may also be expressed in a form
which
will facilitate purification. For example, it may be expressed as a fusion
protein, such as
those of maltose binding protein (MBP), glutathione-S-transferase (GST) or
thioredoxin
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WO 99/55721 PCT/US99/08504
(TR7~. Kits for expression and purification of such fusion proteins are
commercially
available from New England BioLabs (Beverly, MA), Pharmacia (Piscataway, Nj)
and
Invitrogen Corporation (Carlsbad, CA), respectively. The protein can also be
tagged with
an epitope and subsequently purified by using a specific antibody directed to
such
epitope. One such epitope ("Flag") is commercially available from the Eastman
Kodak
Company (New Haven, CT).
Finally, one or more reverse-phase high performance liquid chromatography
(lZl'-
HPLC) steps employing hydrophobic 1ZP-HPLC media, e.g., silica gel having
pendant
methyl or other aliphatic groups, can be employed to further purify the
protein. Some or
all of the foregoing purification steps, in various combinations, can also be
employed to
provide a substantially homogeneous isolated recombinant protein. The protein
thus
purified is substantially free of other mammalian proteins and is defined in
accordance
with the present invention as an "isolated protein."
The protein of the invention may also be expressed as a product of transgeruc
animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or
sheep which
are characterized by somatic or germ cells containing a nucleotide sequence
encoding the
protein.
The protein may also be produced by known conventional chemical synthesis.
Methods for constructing the proteins of the present invention by synthetic
means are
2 0 known to those skilled in the art. The synthetically-constructed protein
sequences, by
virtue of sharing primary, secondary or tertiary structural and/or
conformational
characteristics with proteins may possess biological properties in common
therewith,
including protein activity. Thus, they may be employed as biologically active
or
immunological substitutes for natural, purified proteins in screening of
therapeutic
2 5 compounds and in immunological processes for the development of
antibodies.
The proteins provided herein also include proteins characterized by amino acid
sequences similar to those of purified proteins but into which modification
are naturally
provided or deliberately engineered. For example, modifications in the peptide
or DNA
sequences can be made by those skilled in the art using known techniques.
Modifications
3 0 of interest in the protein sequences may include the alteration,
substitution, replacement,
insertion or deletion of a selected amino acid residue in the coding sequence.
For
example, one or more of the cysteine residues may be deleted or replaced with
another
amino acid to alter the conformation of the molecule. Techniques for such
alteration,
substitution, replacement, insertion or deletion are well known to those
skilled in the art
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WO 99/55721 PCT/US99/08504
(see, e.g., U.S. Patent No. 4,518,584). Preferably, such alteration,
substitution, replacement,
insertion or deletion retains the desired activity of the protein.
Other fragments and derivatives of the sequences of proteins which would be
expected to retain protein activity in whole or in part and may thus be useful
for screening
or other immunological methodologies may also be easily made by those skilled
in the art
given the disclosures herein. Such modifications are believed to be
encompassed by the
presentinvention.
USES AND BIOLOGICAL ACTIVITY
The polynucleotides and proteins of the present invention are expected to
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 Uses and Utilities
The polynucleotides provided by the present invention can be used by the
research
community for various purposes. The polynucleotides can be used to express
2 0 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
2 5 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
3 0 examination of expression patterns; to raise anti-protein antibodies using
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, those
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described in Gyuris et al.,1993, Cell 75: 791-803 and in Rossi et al.,1997,
Proc. Natl. Acad.
Sci. USA 94: 8405-8410, all of which are incorporated by reference herein) 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.
2 0 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. ICimmel
eds.,1987.
Nutritional Uses
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
3 0 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.
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~,ytokine and Cell Proliferation/Differentiation 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, B9, B9/11,
BaF3,
MC9/G, M+ (preB M+), 2E8, RBS, DA1,123, T1165, HT2, CTLL2, TF 1, Mole 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 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;
Bertagnolli et al., J. Lmmunol.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.
2 0 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
2 5 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
lnterleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In
Current
3 0 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;
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Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of
human
Interleukin 11- Bennett, 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
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 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, 1986; Takai et al.,
J. Immunol.
140:508-5I2, 1988.
Immune Stimulating or Sup rn essin Activi ,
A protein of the present invention may also exhibit immune stimulating or
2 0 immune suppressing activity, including without limitation the activities
for which assays
are described herein. A protein may be useful in the treatment of various
immune
deficiencies and disorders (including severe combined immunodeficiency
(SCID)), e.g.,
in regulating (up or down) growth and proliferation of T and/or B lymphocytes,
as well
as effecting the cytolytic activity of NK cells and other cell populations.
These immune
2 5 deficiencies may be genetic or be caused by viral (e.g., HIV) as well as
bacterial or fungal
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
3 0 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
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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 regulate 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
2 0 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, B~), 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,
2 5 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,
3 0 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
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CA 02327551 2000-10-31
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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, marine models of GVI-iD {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
2 0 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
2 5 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
3 0 human autoimmune diseases. Examples include marine experimental autoimmune
encephalitis, systemic lupus erythmatosis in MRL/Ipr/lpr mice or NZB hybrid
mice,
marine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB
rats, and
marine experimental myasthenia gravis (see Paul ed., Fundamental Immunology,
Raven
Press, New York,1989, pp. 840-856).
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WO 99/55721 PCTNS99108504
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
common cold,
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
castimulatory signal to, and thereby activate, T cells in vivo.
In another application, up regulation or enhancement of antigen function
2 0 (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 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.
2 5 For example, tumor cells obtained from a patient can be transfected ex
vivo with an
expression vector directing the expression of a peptide having B7-2-like
activity alone, or
in conjunction with a peptide having B71-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. Alternatively, gene therapy techniques
can be used
3 0 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
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
MHC class II
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CA 02327551 2000-10-31
WO 99/SS721 PCT/US99/08504
molecules, or which fail to reexpress sufficient amounts of MHC class I or MHC
class II
molecules, can be transfected with nucleic acid encoding all or a portion of
(e.g., a
cytoplasmic-domain truncated portion) of an MHC class I a chain protein and
(32
microglobulin protein or an MHC class II a chain protein and an MHC class II
~i 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 B 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.
ICruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing
Associates
2 0 and Wiley-lnterscience (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,
2 5 1981; Herrmann et al., J. l:mmunol. 128:1968-1974, 1982; Handa et al., J.
l:mmunol.
235:1564-1572, 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
3 0 (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.
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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
2 0 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
2 5 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
85:2770-2778,1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551,1991.
Hematopoiesis Re atin A ' i ,
3 0 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,
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CA 02327551 2000-10-31
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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 proliferatian 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:
2 0 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,
2995; Kelley et
2 5 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 lympho-hematopoiesis) include, without
limitation, those
described in: Methylcellulose colony forming assays, Freshney, M.G. In Culture
of
3 0 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. USA 89:5907-5911, 1992;
Primitive
hematopoietic colony forming cells with high proliferative potential, McNiece,
LK. 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
22:353-359,
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1994; Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of
Hematopoietic
Cells. R.I. Freshney, et al. eds. Vol pp. l-21, Wiley-Liss, Inc.., New York,
NY.1994; Long
term bone marrow cultures in the presence of stromal cells, Spooncer, E.,
Dexter, M. and
Allen, T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol
pp. 163-179,
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.
Tissue Growth Activit3r
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 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
rcovo bone formation induced by an osteogenic agent contributes to the repair
of
2 0 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
2 5 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.
3 0 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
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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
tendirutis, 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
2 0 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
2 5 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
3 0 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)
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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);
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, epidermal Wound Healing, pps. 71-112 (Maibach, HI and Rovee, DT,
eds.), Year
Book Medical Publishers, lnc., Chicago, as modified by Eaglstein and Mertz, J.
Invest.
2 0 Dermatol 71:382-84 (1978).
~ctivin/Inhibin Activity
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
2 5 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 a family, may
be useful
as a contraceptive based on the ability of inhibins to decrease fertility in
female mammals
and decrease spermatogenesis in male mammals. Administration of sufficient
amounts
3 0 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-
~i 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
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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; 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 Activit<r
A protein of the present invention may have chemotactic 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
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
neutrophils to tumors or sites of infection may result in improved immune
responses
against the tumor or infecting agent.
2 0 A protein or peptide has chemotactic activity for a particular cell
population if it
can stimulate, directly or 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 such protein or peptide in any
known
2 5 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
3 0 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
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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 Thrombol3rtic Activ'~
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 (including hereditary 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.
Rece~tor/Lig~nd Activit3~
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
2 5 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
3 0 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.
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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:I145-1156, 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-Inflammatory Act
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 ?ctivities can be used to
treat
2 0 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
2 5 from over production of cytokines 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.
Cadherin/Tumor Invasion Suppressor Activit3r
Cadherins are calcium-dependent adhesion molecules that appear to play major
3 0 roles during development, particularly in defining specific cell types.
Loss or alteration
of normal cadherin expression can lead to changes in cell adhesion properties
linked to
tumor growth and metastasis. Cadherin malfunction is also implicated in other
human
diseases, such as pemphigus vulgaris and pemphigus foliaceus (auto-immune
blistering
skin diseases), Crohn's disease, and some developmental abnormalities.
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The cadherin superfamily includes well over forty members, each with a
distinct
pattern of expression. All members of the superfamily have in common conserved
extracellular repeats (cadherin domains), but structural differences are found
in other
parts of the molecule. The cadherin domains bind calcium to form their
tertiary structure
and thus calcium is required to mediate their adhesion. Only a few amino acids
in the
first cadherin domain provide the basis for homophilic adhesion; modification
of this
recognition site can change the specificity of a cadherin so that instead of
recognizing only
itself, the mutant molecule can now also bind to a different cadherin. In
addition, some
cadherins engage in heterophilic adhesion with other cadherins.
E-cadherin, one member of the cadherin superfamily, is expressed in epithelial
cell
types. Pathologically, if E-cadherin expression is lost in a tumor, the
malignant cells
become invasive and the cancer metastasizes. Transfection of cancer cell lines
with
polynucleotides expressing E-cadherin has reversed cancer-associated changes
by
returning altered cell shapes to normal, restoring cells' adhesiveness to each
other and to
their substrate, decreasing the cell growth rate, and drastically reducing
anchorage-
independent cell growth. Thus, reintroducing E-cadherin expression reverts
carcinomas
to a less advanced stage. It is likely that other cadherins have the same
invasion
suppressor role in carcinomas derived from other tissue types. Therefore,
proteins of the
present invention with cadherin activity, and polynucleotides of the present
invention
2 0 encoding such proteins, can be used to treat cancer. Introducing such
proteins or
polynucleotides into cancer cells can reduce or eliminate the cancerous
changes observed
in these cells by providing normal cadherin expression.
Cancer cells have also been shown to express cadherins of a different tissue
type
than their origin, thus allowing these cells to invade and metastasize in a
different tissue
2 5 in the body. Proteins of the present invention with cadherin activity, and
polynucleotides
of the present invention encoding such proteins, can be substituted in these
cells for the
inappropriately expressed cadherins, restoring normal cell adhesive properties
and
reducing or eliminating the tendency of the cells to metastasize.
Additionally, proteins of the present invention with cadherin activity, and
3 0 polynucleotides of the present invention encoding such proteins, can used
to generate
antibodies recognizing and binding to cadherins. Such antibodies can be used
to block
the adhesion of inappropriately expressed tumor-cell cadherins, preventing the
cells from
forming a tumor elsewhere. Such an anti-cadherin antibody can also be used as
a marker
for the grade, pathological type, and prognosis of a cancer, i.e. the more
progressed the
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cancer, the less cadherin expression there will be, and this decrease in
cadherin expression
can be detected by the use of a cadherin-binding antibody.
Fragments of proteins of the present invention with cadherin activity,
preferably
a polypeptide comprising a decapeptide of the cadherin recognition site, and
poly-
nucleotides of the present invention encoding such protein fragments, can also
be used
to block cadherin function by binding to cadherins and preventing them from
binding in
ways that produce undesirable effects. Additionally, fragments of proteins of
the present
invention with cadherin activity, preferably truncated soluble cadherin
fragments which
have been found to be stable in the circulation of cancer patients, and
polynucleotides
encoding such protein fragments, can be used to disturb proper cell-cell
adhesion.
Assays for cadherin adhesive and invasive suppressor activity include, without
limitation, those described in: Hortsch et al. J Biol Chem 270 (32): 18809-
18817, 1995;
Miyaki et al. Oncogene 11: 2547-2552,1995; Ozawa et al. Cell 63: 1033-
1038,1990.
Tumor Inhibition Activitar
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
antibody-dependent cell-mediated cytotoxicity (ADCC)). A protein may exhibit
its tumor
2 0 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.
Other Activities
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
3 0 (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,
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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
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 cross-reactive with such protein.
ADMINISTRATION AND DOSING
A protein of the present invention (from whatever source derived, including
without limitation from recombinant and non-recombinant sources) may be used
in a
pharmaceutical composition when combined with a pharmaceutically acceptable
carrier.
Such a composition may also contain (in addition to protein and a carrier)
diluents, fillers,
salts, buffers, stabilizers, solubilizers, and other materials well known in
the art. The term
2 0 "pharmaceutically acceptable" means a non toxic material that does not
interfere with the
effectiveness of the biological activity of the active ingredient(s). The
characteristics of the
carrier will depend on the route of administration. The pharmaceutical
composition of
the invention may also contain cytokines, lymphokines, or other hematopoietic
factors
such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, ILr6, ILr7, IIr8,
ILr9, ILrlO, ILrl l,
2 5 IL-12, IL-13, IL-14, IL-15,1FN, TNFO, TNFl, TNF2, G-CSF, Meg-CSF,
thrombopoietin, stem
cell factor, and erythropoietin. The pharmaceutical composition may further
contain other
agents which either enhance the activity of the protein or compliment its
activity or use
in treatment. Such additional factors and/or agents may be included in the
pharmaceutical composition to produce a synergistic effect with protein of the
invention,
3 0 or to minimize side effects. Conversely, protein of the present invention
may be included
in formulations of the particular cytokine, lymphokine, other hematopoietic
factor,
thrombolytic or anti-thrombotic factor, or anti-inflammatory agent to minimize
side effects
of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-
thrombotic
factor, or anti-inflammatory agent.
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A protein of the present invention may be active in multimers (e.g.,
heterodimers
or homodimers) or complexes with itself or other proteins. As a result,
pharmaceutical
compositions of the invention may comprise a protein of the invention in such
multimeric
or complexed form.
The pharmaceutical composition of the invention may be in the form of a
complex
of the proteins) of present invention along with protein or peptide antigens.
The protein
and/or peptide antigen will deliver a stimulatory signal to both B and T
lymphocytes. B
lymphocytes will respond to antigen through their surface immunoglobulin
receptor. T
lymphocytes will respond to antigen through the T cell receptor (TCR)
following
presentation of the antigen by MHC proteins. MI~iC and structurally related
proteins
including those encoded by class I and class II MHC genes on host cells will
serve to
present the peptide antigens) to T lymphocytes. The antigen components could
also be
supplied as purified MHC-peptide complexes alone or with co-stimulatory
molecules that
can directly signal T cells. Alternatively antibodies able to bind surface
immunolgobulin
and other molecules on B cells as well as antibodies able to bind the TCR and
other
molecules on T cells can be combined with the pharmaceutical composition of
the
invention.
The pharmaceutical composition of the invention may be in the form of a
liposome
in which protein of the present invention is combined, in addition to other
2 0 pharmaceutically acceptable earners, with amphipathic agents such as
lipids which exist
in aggregated form as micelles, insoluble monolayers, liquid crystals, or
lamellar layers
in aqueous solution. Suitable lipids for liposomal formulation include,
without limitation,
monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids,
saponin, bile acids,
and the like. Preparation of such liposomal formulations is within the level
of skill in the
2 5 art, as disclosed, for example, in U.S. Patent No. 4,235,871; U.S. Patent
No. 4,501,728; U.S.
Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are
incorporated herein
by reference.
As used herein, the term "therapeutically effective amount" means the total
amount of each active component of the pharmaceutical composition or method
that is
3 0 sufficient to show a meaningful patient benefit, i.e., treatment, healing,
prevention or
amelioration of the relevant medical condition, or an increase in rate of
treatment, healing,
prevention or amelioration of such conditions. When applied to an individual
active
ingredient, administered alone, the term refers to that ingredient alone. When
applied to
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a combination, the term refers to combined amounts of the active ingredients
that result
in the therapeutic effect, whether administered in combination, serially or
simultaneously.
In practicing the method of treatment or use of the present invention, a
therapeutically effective amount of protein of the present invention is
administered to a
mammal having a condition to be treated. Protein of the present invention may
be
administered in accordance with the method of the invention either alone or in
combination with other therapies such as treatments employing cytokines,
lymphokines
or other hematopoietic factors. When co-administered with one or more
cytokines,
lymphokines or other hematopoietic factors, protein of the present invention
may be
administered either simultaneously with the cytokine(s), lymphokine(s), other
hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or
sequentially. If
administered sequentially, the attending physician will decide on the
appropriate
sequence of administering protein of the present invention in combination with
cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or
anti-thrombotic
factors.
Administration of protein of the present invention used in the pharmaceutical
composition or to practice the method of the present invention can be carried
out in a
variety of conventional ways, such as oral ingestion, inhalation, topical
application or
cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection.
2 0 Intravenous administration to the patient is preferred.
When a therapeutically effective amount of protein of the present invention is
administered orally, protein of the present invention will be in the form of a
tablet,
capsule, powder, solution or elixir. When administered in tablet form, the
pharmaceutical
composition of the invention may additionally contain a solid carrier such as
a gelatin or
2 5 an adjuvant. The tablet, capsule, and powder contain from about 5 to 95%
protein of the
present invention, and preferably from about 25 to 90% protein of the present
invention.
When administered in liquid form, a liquid carrier such as water, petroleum,
oils of animal
or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil,
or synthetic ails
may be added. The liquid form of the pharmaceutical composition may further
contain
3 0 physiological saline solution, dextrose or other saccharide solution, or
glycols such as
ethylene glycol, propylene glycol or polyethylene glycol. When administered in
liquid
form, the pharmaceutical composition contains from about 0.5 to 90% by weight
of protein
of the present invention, and preferably from about 1 to 50% protein of the
present
invention.
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When a therapeutically effective amount of protein of the present invention is
administered by intravenous, cutaneous or subcutaneous injection; protein of
the present
invention will be in the form of a pyrogen-free, parenterally acceptable
aqueous solution.
The preparation of such parenterally acceptable protein solutions, having due
regard to
pH, isotonicity, stability, and the like, is within the skill in the art. A
preferred
pharmaceutical composition for intravenous, cutaneous, or subcutaneous
injection should
contain, in addition to protein of the present invention, an isotonic vehicle
such as Sodium
Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and
Sodium Chloride
Injection, Lactated Ringer's Injection, or other vehicle as known in the art.
The
pharmaceutical composition of the present invention may also contain
stabilizers,
preservatives, buffers, antioxidants, or other additives known to those of
skill in the art.
The amount of protein of the present invention in the pharmaceutical
composition
of the present invention will depend upon the nature and severity of the
condition being
treated, and on the nature of prior treatments which the patient has
undergone.
Ultimately, the attending physician will decide the amount of protein of the
present
invention with which to treat each individual patient. Initially, the
attending physician
will administer low doses of protein of the present invention and observe the
patient's
response. Larger doses of protein of the present invention may be administered
until the
optimal therapeutic effect is obtained for the patient, and at that point the
dosage is not
2 0 increased further. It is contemplated that the various pharmaceutical
compositions used
to practice the method of the present invention should contain about 0.01 pg
to about 100
mg (preferably about 0.lng to about 10 mg, more preferably about 0.1 ug to
about 1 mg)
of protein of the present invention per kg body weight.
The duration of intravenous therapy using the pharmaceutical composition of
the
2 5 present invention will vary, depending on the severity of the disease
being treated and
the condition and potential idiosyncratic response of each individual patient.
It is
contemplated that the duration of each application of the protein of the
present invention
will be in the range of 12 to 24 hours of continuous intravenous
administration.
Ultimately the attending physician will decide on the appropriate duration of
intravenous
3 0 therapy using the pharmaceutical composition of the present invention.
Protein of the invention may also be used to immunize animals to obtain
polyclonal and monoclonal antibodies which specifically react with the
protein. As used
herein, the term "antibody" includes without limitation a polyclonal antibody,
a
monoclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-
grafted
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antibody, a humanized antibody, or fragments thereof which bind to the
indicated protein.
Such term also includes any other species derived from an antibody or antibody
sequence
which is capable of binding the indicated protein.
Antibodies to a particular protein can be produced by methods well known to
those
skilled in the art. For example, monoclonal antibodies can be produced by
generation of
antibody-producing hybridomas in accordance with known methods (see for
example,
Goding, 1983, Monoclonal antibodies: principles and practice, Academic Press
Inc., New
York; and Yokoyama, 1992, "Production of Monoclonal Antibodies" in Current
Protocols
in Immunology, Unit 2.5, Greene Publishing Assoc. and John Wiley & Sons).
Polyclonal
sera and antibodies can be produced by inoculation of a mammalian subject with
the
relevant protein or fragments thereof in accordance with known methods.
Fragments of
antibodies, receptors, or other reactive peptides can be produced from the
corresponding
antibodies by cleavage of and collection of the desired fragments in
accordance with
known methods (see for example, Goding, supra; and Andrew et al., 1992,
"Fragmentation
of Immunoglobulins" in Current Protocols in Immunology, Unit 2.8, Greene
Publishing
Assoc. and John Wiley & Sons). Chimeric antibodies and single chain antibodies
can also
be produced in accordance with known recombinant methods (see for example,
5,169,939,
5,194,594, and 5,576,184). Humanized antibodies can also be made from
corresponding
marine antibodies in accordance with well known methods (see for example, U.S.
Patent
2 0 Nos. 5,530,101, 5,585,089, and 5,693,762). Additionally, human antibodies
may be
produced in non-human animals such as mice that have been genetically altered
to express
human antibody molecules (see for example Fishwild et al., 1996, Nature
Biotechnology
14: 845-851; Mendez et al., 1997, Nature Genetics 15: 146-156 (erratum Nature
Genetics
16: 410); and U.S. Patents 5,877,397 and 5,625,126). Such antibodies may be
obtained
2 5 using either the entire protein or fragments thereof as an immunogen. The
peptide
immunogens additionally may contain a cysteine residue at the carboxyl
terminus, and
are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods
for
synthesizing such peptides are known in the art, for example, as in R.P.
Merrifield, J.
Amer.Chem.Soc. $5, 2149-2154 (1963); J.L. ICrstenansky, et al., FEBS Lett.
211,10 (198.
3 0 Monoclonal antibodies binding to the protein of the invention may be
useful
diagnostic agents for the immunodetection of the protein. Neutralizing
monoclonal
antibodies binding to the protein may also be useful therapeutics for both
conditions
171

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WO 99/55721 PCTNS99/08504
associated with the protein and also in the treatment of some forms of cancer
where
abnormal expression of the protein is involved. In the case of cancerous cells
or leukemic
cells, neutralizing monoclonal antibodies against the protein may be useful in
detecting
and preventing the metastatic spread of the cancerous cells, which may be
mediated by
the protein.
For compositions of the present invention which are useful for bone,
cartilage,
tendon or ligament regeneration, the therapeutic method includes administering
the
composition topically, systematically, or locally as an implant or device.
When
administered, the therapeutic composition for use in this invention is, of
course, in a
pyrogen free, physiologically acceptable form. Further, the composition may
desirably
be encapsulated or injected in a viscous form for delivery to the site of
bone, cartilage or
tissue damage. Topical administration may be suitable for wound healing and
tissue
repair. Therapeutically useful agents other than a protein of the invention
which may also
optionally be included in the composition as described above, may
alternatively or
additionally, be administered simultaneously or sequentially with the
composition in the
methods of the invention. Preferably for bone and/or cartilage formation, the
composition would include a matrix capable of delivering the protein-
containing
composition to the site of bone and/or cartilage damage, providing a structure
for the
developing bone and cartilage and optimally capable of being resorbed into the
body.
2 0 Such matrices may be formed of materials presently in use for other
implanted medical
applications.
The choice of matrix material is based on biocompatibility, biodegradability,
mechanical properties, cosmetic appearance and interface properties. The
particular
application of the compositions will define the appropriate formulation.
Potential
2 5 matrices for the compositions may be biodegradable and chemically defined
calcium
sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid, polyglycolic
acid and
polyanhydrides. Other potential materials are biodegradable and biologically
well-
defined, such as bone or dermal collagen. Further matrices are comprised of
pure proteins
or extracellular matrix components. Other potential matrices are
nonbiodegradable and
3 0 chemically defined, such as sintered hydroxapatite, bioglass, aluminates,
or other
ceramics. Matrices may be comprised of combinations of any of the above
mentioned
types of material, such as polylactic acid and hydroxyapatite or collagen and
tricalciumphosphate. The bioceramics may be altered in composition, such as in
calcium-
172

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WO 99/55721 PCTNS99/08504
aluminate-phosphate and processing to alter pore size, particle size, particle
shape, and
biodegradability.
Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and
glycolic
acid in the form of porous particles having diameters ranging from 150 to 800
microns.
In some applications, it will be useful to utilize a sequestering agent, such
as
carboxymethyl cellulose or autologous blood clot, to prevent the protein
compositions
from disassociating from the matrix.
A preferred family of sequestering agents is cellulosic materials such as
alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose,
ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl
methylcellulose, and carboxymethylcellulose, the most preferred being cationic
salts of
carboxymethylcellulose (CMC). Other preferred sequestering agents include
hyaluronic
acid, sodium alginate, polyethylene glycol), polyoxyethylene oxide,
carboxyvinyl
polymer and polyvinyl alcohol). The amount of sequestering agent useful herein
is 0.5-20
wt%, preferably 1-10 wt% based on total formulation weight, which represents
the
amount necessary to prevent desorbtion of the protein from the polymer matrix
and to
provide appropriate handling of the composition, yet not so much that the
progenitor cells
are prevented from infiltrating the matrix, thereby providing the protein the
opportunity
to assist the osteogenic activity of the progenitor cells.
2 0 In further compositions, proteins of the invention may be combined with
other
agents beneficial to the treatment of the bone and/or cartilage defect, wound,
or tissue in
question. These agents include various growth factors such as epidermal growth
factor
(EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-
a and
TGR~3), and insulin-like growth factor (IGF).
2 5 The therapeutic compositions are also presently valuable for veterinary
applications. Particularly domestic animals and thoroughbred horses, in
addition to
humans, are desired patients for such treatment with proteins of the present
invention.
The dosage regimen of a protein-containing pharmaceutical composition to be
used in tissue regeneration will be determined by the attending physician
considering
3 0 various factors which modify the action of the proteins, e.g., amount of
tissue weight
desired to be formed, the site of damage, the condition of the damaged tissue,
the size of
a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and
diet, the severity
of any infection, time of administration and other clinical factors. The
dosage may vary
with the type of matrix used in the reconstitution and with inclusion of other
proteins in
173

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
the pharmaceutical composition. For example, the addition of other known
growth
factors, such as IGF I (insulin like growth factor I}, to the final
composition, may also effect
the dosage. Progress can be monitored by periodic assessment of tissue/bone
growth
and/or repair, for example, X-rays, histomorphometric determinations and
tetracycline
labeling.
Polynucleotides of the present invention can also be used for gene therapy.
Such
polynucleotides can be introduced either in vivo or ex vivo into cells for
expression in a
mammalian subject. Polynucleotides of the invention may also be administered
by other
known methods for introduction of nucleic acid into a cell or organism
(including, without
limitation, in the form of viral vectors or naked DNA).
Cells may also be cultured ex vivo in the presence of proteins of the present
invention in order to proliferate or to produce a desired effect on or
activity in such cells.
Treated cells can then be introduced in vivo for therapeutic purposes.
Patent and literature references cited herein are incorporated by reference as
if
fully set forth.
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SEQUENCE LISTING
<110> Valenzuela, Dario
Yuan, Olive
Hoffman, Heidi
Hall, Jeff
Rapiejko, Peter
AlphaGene, Inc.
<120> SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
<130> GI 6900X
<140>
<141>
<160> 107
<170> PatentIn Ver. 2.0
<210> 1
<211> 2201
<212> DNA
<213> Homo sapiens
<400> 1
tccttcgcct cctgcacctt gggagccctg ggctactctt tcacggcccc tgttgccctg 60
tgatctgtag gtccttgggg acgcacagtt aaggtgccag gacatcctgg aagctgggaa 120
atgatatgta ttcatttcct accaccgtag tggaagagat actatcccta tctttacaac 180
tgatagcatt tccaacagta agctgtgaga ttctgcttga aatcacctct caaacaaata 240
aaaaacagac ccgggagaca tgctacgctc attctgctga agaaataggc atcatagctg 300
ggaaacggat tcacaagacc caggctgttc cctacatatg tttcctcctc cgacatcagt 360
tcatcagtca atcaagccat gtgagagtgg aggccttgta ttccctatta ttcttgggca 420
ctctactcca agtaggaaaa ggccaggagg tcctgttaaa ggatgcactc agagcccggg 480
ctccctaaca tatgagagtg ctaaccagca ggtgtagact tttcaggagt gaagaatgag 540
gcaggcattc caaacctgga ccttcatcac cttttgtttc atctcaagac aattctgagg 600
gactgttttg gagcgtgtct ggaaggtgaa ccttgaagaa gagtgtgggc tttgatgtga 660
ctcagttgag atctttcatg gggaggcagg aattcaatgc ccagaatctg ggctggtgtc 720
tttgaggtca gtaggttgcg tctttgtatc caagtccatt gttactaggt tggaggctgg 780
agattctaaa tggcttccag accatctctc tgattctctt tgggagatgg ggtctgaaag 840
acaatatcag tagttttggg aaattctaga aagtgtgctt ggaaacgtgg gaagagctct 900
tgcctagtgc ctaaatgctc catttgcagc tctagccaag tagatacttg gtaggtatag 960
agccgggttt gcgtttatat cagcaaaacc tatatcagag ttgaagaagt agtcaggaaa 1020
aagcgtcttg gtcgcaggcc ggggaacatc ttaaaagcaa acttctagcc tgctgactct 1080
tggcaatgag tgttggatcc tggctaaagt gccttgaatg cagcatgagg ccaatccatg 1140
aatccaactt ctcatggaga aatgttaata ttttttcagt ttgaatcaat cagggtgaaa 1200
ctaccatgct attggtttgc ttacttttta ttatttcatg taaaatctaa gacaaaatac 1260
attaaatgct tattgacata tgtatttatt cttcaccagg ctgataatat ctgcctaatt 1320
ttaaactttc ttccattttg taggtttcaa cttattctat tgtaagatac tgttaaatct 1380
aatagaggca ttgtcacttt tacgtataat tttattttat ttcatatatt tcctattggc 1440
tttttacatt taaattatgg agcacttcat catataaaaa acttcaatta tatttaaaca 1500
gtaagtcttt ggattttttt gccttgtaat ttccatatta cataataatg agataaacat 1560
taatgttttc agggtacttt aaattttaga taattactca ttgtattcat gtgaaatttg 1620
ttttactgc atgtgtgggt tggaggactg ttttcacttc tgattcatct ttactcttat 1680
~ctcatcagag ctcatacctc ttgtagttgg gggattgcag tttataattc caataaatgg 1740
'ggcaaattca ataataacat aatacaaatg agtttgaatg caggacaggt cttcaaagca 1800
tacacaacat gggcctacat atgtacaaca ataataattt ataagttact gtttggatgg 1860
aaagtaaaag tacagaaaat ttgttaaagg aaattaaaat ggagatcatg tctcaataat 1920
ctctgagcag acaaaattag ttaggtctca taagtgatct caacctcgct tgatttgcaa 1980
atacaaacaa aacttacatt atttcttgta gctgcatatt gaaaaaagag aaatgaagct 2040
1

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caaccagtca gaagtagcca acaaccttat ataaatagaa actgtccaac aaggtaaaca 2100
gacaaacaaa aaacaataaa aaaagttgtg ctaccaccaa aaaaaaaaaa aaaaaaaaaa 2160
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 2201
<210> 2
<211> 120
<212> PRT
<213> Homo sapiens
<400> 2
Met Tyr Ser Phe Pro Thr Thr Val Val Glu Glu Ile Leu Ser Leu Ser
1 5 10 15
Leu Gln Leu Ile Ala Phe Pro Thr Val Ser Cys Glu Ile Leu Leu Glu
20 25 30
Ile Thr Ser Gln Thr Asn Lys Lys Gln Thr Arg Glu Thr Cys Tyr Ala
35 40 45
His Ser Ala Glu Glu Ile Gly Ile Ile Ala Gly Lys Arg Ile His Lys
50 55 60
Thr Gln Ala Val Pro Tyr Ile Cys Phe Leu Leu Arg His Gln Phe Ile
65 70 75 80
Ser Gln Ser Ser His Val Arg Val Glu Ala Leu Tyr Ser Leu Leu Phe
85 90 95
Leu Gly Thr Leu Leu Gln Val Gly Lys Gly Gln Glu Val Leu Leu Lys
100 105 110
Asp Ala Leu Arg Ala Arg Ala Pro
115 120
<210> 3
<211> 2498
<212> DNA
<213> Homo sapiens
<400> 3
ggtcgtttgg atagtgatga acagaaaatt cagaatgata tcattgatat tttactgact 60
tttacacaag gagttaatga aaaactcaca atctcagaag agactctggc caataatact 120
tggtctttaa tgttaaaaga agttctttct tcaatcttga aggttcctga aggatttttt 180
tctggactca tactcctttc agagctgctg cctcttccat tgcccatgca aacaactcag 240
gttattgagc cacatgatat atcagtggca ctcaacaccc gaaaattgtg gagcatgcac 300
cttcatgttc aagcaaagtt gctccaagaa atagttcgct ctttctctgg cacaacctgc 360
cagcccattc aacatatgtt acggcgtatt tgtgttcaat tgtgtgacct tgcctcacca 420
actgcacttc tgattatgag aactgtgttg gatttgattg tagaagactt gcaaagcact 480
tcagaagata aagaaaaaca gtatactagc caaaccacca ggttgcttgc tcttcttgat 540
gctctggctt cacacaaagc ttgtaaatta gctattttgc atctaattaa tggaactatt 600
aaaggtgatg aaagatatgc agagatattc caggatcttt tagctttggt gcggtctcct 660
ggagacagtg ttattcgcca acagtgtgtt gaatatgtca catccatttt gcagtctctc 720
tgtgatcagg acattgcact tatcttacca agctcttctg aaggttctat ttctgaactg 780
gagcagctct ccaattctct accaaataaa gaattgatga cctcaatctg tgactgtctg 840
ttggctacgc tagctaactc tgagagcagt tacaactgtt tactgacatg tgtcagaaca 900
atgatgtttc ttgcagagca tgattatgga ttatttcatt taaaaagttc tttaaggaaa 960
aacagtagtg ctctgcatag tttactgaaa cgagtggtca gcacatttag taaggacaca 1020
ggagagcttg catcttcatt tttagaattt atgagacaaa ttcttaactc tgacacaatt 1080
ggatgctgtg gagatgataa tggtctcatg gaagtagagg gagctcatac atcacggacg 1140
2

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atgagtatta atgctgcaga gttaaaacag cttctacaaa gcaaagaaga aagtccagaa 1200
aatttgttcc ttgaactaga gaagcttgtt ttggaacatt caaaagatga tgacaatctg 1260
gattctttgt tggacagtgt agttggactt aagcagatgc tggagtcatc aggtgaccct 1320
ttacctctca gtgaccagga tgtagaacca gtactttcag ctccagaatc tcttcagaat 1380
ctgtttaaca ataggactgc ctatgtgctt gctgatgtca tggatgatca gttgaaatct 1440
atgtggttca ctccatttca ggctgaagag atagatacag atctggattt ggtaaaggtt 1500
gacttaattg aactctctga aaaatgctgt agtgactttg atttgcactc agaattagag 1560
cgctcatttt tgtcagaacc atcatctcca ggaagaacca agactactaa aggattcaaa 1620
cttgggaagc acaagcatga gacctttata acgtcaagtg gaaaatctga atacattgaa 1680
cctgccaaaa gagctcatgt tgtgccacca ccaagaggaa ggggcagggg aggatttgga 1740
cagggtatac gacctcatga tatttttcgt cagagaaaac agaacacaag tagaccacca 1800
tctatgcatg tggatgactt tgttgctgct gaaagtaaag aagtggttcc tcaagatgga 1860
atacctccac caaaacggcc actcaaagca tcacagaaga tttcttcccg tggtgggttt 1920
tcaggcaata gaggaggacg gggtgctttc cacagtcaga ataggttttt cacaccacct 1980
gcttcaaaag gaaactacag tcgtcgggaa ggaacaagag gctccagttg gagtgctcag 2040
aatactcctc gaggaaatta caatgaaagt cgtggaggcc agagcaattt taacagaggc 2100
cctcttccac cattacgacc ccttagttct acaggttacc gcccaagtcc tcgggaccgt 2160
gcttctagag gtcgtggggg acttggacct tcctgggcta gtgcaaatag cggcagtgga 2220
ggctcaagag gaaagtttgt tagtggaggc agtggtagag gtcgtcatgt acgctccttt 2280
acacgataaa aatccttttg ggaacatctt aactgtatat gaacatttca cgaggacaat 2340
aaaaataaga cattgaagga ccaatttaga cttagcagtt atctggagac atctgagaga 2400
atatttttat ctgaagaaag cagaatttgt ttgataccta acaagatttc aataaaaatc 2460
caaactttgt atgtaaaaaa aaaaaaaaaa aaaaaaaa 2498
<210> 4
<211> 719
<212> PRT
<213> Homo sapiens
<400> 4
Met Leu Lys Glu Val Leu Ser Ser Ile Leu Lys Val Pro Glu Gly Phe
1 5 10 15
Phe Ser Gly Leu Ile Leu Leu Ser Glu Leu Leu Pro Leu Pro Leu Pro
20 25 30
Met Gln Thr Thr Gln Val Ile Glu Pro His Asp Ile Ser Val Ala Leu
35 40 45
Asn Thr Arg Lys Leu Trp Ser Met His Leu His Val Gln Ala Lys Leu
50 55 60
Leu Gln Glu Ile Val Arg Ser Phe Ser Gly Thr Thr Cys Gln Pro Ile
65 70 75 80
Gln His Met Leu Arg Arg Ile Cys Val Gln Leu Cys Asp Leu Ala Ser
85 90 95
Pro Thr Ala Leu Leu Ile Met Arg Thr Val Leu Asp Leu Ile Val Glu
100 105 110
Asp Leu Gln Ser Thr Ser Glu Asp Lys Glu Lys Gln Tyr Thr Ser Gln
115 120 125
Thr Thr Arg Leu Leu Ala Leu Leu Asp Ala Leu Ala Ser His Lys Ala
130 135 140
Cys Lys Leu Ala Ile Leu His Leu Ile Asn Gly Thr Ile Lys Gly Asp
145 150 155 160
3

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Glu Arg Tyr Ala Glu Ile Phe Gln Asp Leu Leu Ala Leu Val Arg Ser
165 170 175
Pro Gly Asp Ser Val Ile Arg Gln Gln Cys Val Glu Tyr Val Thr Ser
180 185 190
Ile Leu Gln Ser Leu Cys Asp Gln Asp Ile Ala Leu Ile Leu Pro Ser
195 200 205
Ser Ser Glu Gly Ser Ile Ser Glu Leu Glu Gln Leu Ser Asn Ser Leu
210 215 220
Pro Asn Lys Glu Leu Met Thr Ser Ile Cys Asp Cys Leu Leu Ala Thr
225 230 235 240
Leu Ala Asn Ser Glu Ser Ser Tyr Asn Cys Leu Leu Thr Cys Val Arg
245 250 255
Thr Met Met Phe Leu Ala Glu His Asp Tyr Gly Leu Phe His Leu Lys
260 265 270
Ser Ser Leu Arg Lys Asn Ser Ser Ala Leu His Ser Leu Leu Lys Arg
275 280 285
Val Val Ser Thr Phe Ser Lys Asp Thr Gly Glu Leu Ala Ser Ser Phe
290 295 300
Leu Glu Phe Met Arg Gln Ile Leu Asn Ser Asp Thr Ile Gly Cys Cys
305 310 315 320
Gly Asp Asp Asn Gly Leu Met Glu Val Glu Gly Ala His Thr Ser Arg
325 330 335
Thr Met Ser Ile Asn Ala Ala Glu Leu Lys Gln Leu Leu Gln Ser Lys
340 345 350
Glu Glu Ser Pro Glu Asn Leu Phe Leu Glu Leu Glu Lys Leu Val Leu
355 360 365
Glu His Ser Lys Asp Asp Asp Asn Leu Asp Ser Leu Leu Asp Ser Val
370 375 380
Val Gly Leu Lys Gln Met Leu Glu Ser Ser Gly Asp Pro Leu Pro Leu
385 390 395 400
Ser Asp Gln Asp Val Glu Pro Val Leu Ser Ala Pro Glu Ser Leu Gln
405 410 415
Asn Leu Phe Asn Asn Arg Thr Ala Tyr Val Leu Ala Asp Val Met Asp
420 425 430
Asp Gln Leu Lys Ser Met Trp Phe Thr Pro Phe Gln Ala Glu Glu Ile
435 440 445
Asp Thr Asp Leu Asp Leu Val Lys Val Asp Leu Ile Glu Leu Ser Glu
450 455 460
Lys Cys Cys Ser Asp Phe Asp Leu His Ser Glu Leu Glu Arg Ser Phe
465 470 475 480
4

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Leu Ser Glu Pro Ser Ser Pro Gly Arg Thr Lys Thr Thr Lys Gly Phe
485 490 495
Lys Leu Gly Lys His Lys His Glu Thr Phe Ile Thr Ser Ser Gly Lys
500 505 510
Ser Glu Tyr Ile Glu Pro Ala Lys Arg Ala His Val Val Pro Pro Pro
515 520 525
Arg Gly Arg Gly Arg Gly Gly Phe Gly Gln Gly Ile Arg Pro His Asp
530 535 540
Ile Phe Arg Gln Arg Lys Gln Asn Thr Ser Arg Pro Pro Ser Met His
545 550 555 560
Val Asp Asp Phe Val Ala Ala Glu Ser Lys Glu Val Val Pro Gln Asp
565 570 575
Gly Ile Pro Pro Pro Lys Arg Pro Leu Lys Ala Ser Gln Lys Ile Ser
580 585 590
Ser Arg Gly Gly Phe Ser Gly Asn Arg Gly Gly Arg Gly Ala Phe His
595 600 605
Ser Gln Asn Arg Phe Phe Thr Pro Pro Ala Ser Lys Gly Asn Tyr Ser
610 615 620
Arg Arg Glu Gly Thr Arg Gly Ser Ser Trp Ser Ala Gln Asn Thr Pro
625 630 635 640
Arg Gly Asn Tyr Asn Glu Ser Arg Gly Gly Gln Ser Asn Phe Asn Arg
645 650 655
Gly Pro Leu Pro Pro Leu Arg Pro Leu Ser Ser Thr Gly Tyr Arg Pro
660 665 670
Ser Pro Arg Asp Arg Ala Ser Arg Gly Arg Gly Gly Leu Gly Pro Ser
675 680 685
Trp Ala Ser Ala Asn Ser Gly Ser Gly Gly Ser Arg Gly Lys Phe Val
690 695 700
Ser Gly Gly Ser Gly Arg Gly Arg His Val Arg Ser Phe Thr Arg
705 710 715
<210> 5
<211> 2054
<212> DNA
<213> Homo sapiens
<400> 5
tgcagggcca gggtggggtg tccagcacca gccaagctgg tgctccagcg cacctcccca 60
gagctccccg cactgacggg gctgcaggag caggtgcagt gggcgcccac actggccctg 120
cagtgatgca gggcgggagg gagataagaa gaccccgcag tcaagtggag catggccctc 180
cctggctccc tgtccctggg ctcagcacga ccacacagga cacccagcca gggaattctg 240
aagaccagag agcagcccac gggcatcacg agcgctctgc tcctctcctg ggcccctgct 300
cttcccgaga gctgccccca aatcagacat acctctgtgg ctctcctctg gttcacgttt 360
acagagcata aggctgtctt ggatcccaac aggcacccag ccctgcatgg ggggagcctg 420
ggcctaatag gcaccccctg tacctcaggc tgtggcggga gcagagtccc cccctccggc 480

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ccctcttcct ttaccccttc tcctccagca gtggcaaagg ggtaggctct agagccagca 540
caggtcactg cctgacctgg actaagaacc ccacggcccc actgtccaca cactgcctcc 600
ccaccgccca cctcggctgc taggcccctc gcctggactg gactggggag ggaaagcgcc 660
ttttcctgca gctcttcaga gccacagacc tcagggtgga gtgagcccat ggtgggcagt 720
gggcaaggcg gtgggtggtg ggcaaggtgg gacctcctgc agcctggaaa gaggagggag 780
gccaaggcca ttccctaact ccctcctgcc cctggtctga ggaggaggga ctctggagta 840
gcagaggggc tgggaaagag ggggcagggg ctgctgggac actgagcagg agggaggcct 900
gagcacactg ctttggaaat tattctaaac acaaaaaagg gaaagaaaat gttatttctc 960
cctaagtcag gagcatgcag agctagccca cctcatgtcc agctgtccac tttccatcct 1020
ggagaaagaa cagtgtgcct caaactcctg ccctccccag gcctctgggg cccgctggaa 1080
agggctctga ccccctggcc cggccgggct ctctagtggt gatccggctc attctcctgc 1140
aagttggaag cacaattttc cccccaagtg gaggaaaagg aaagggcccc agcctactga 1200
agaggtgttt attttttaac taacagcctc ccaccccatt aagactcacc aggagaggtc 1260
tgagggccat tcagaaccca ctcctgagtg ggtgggtggg tgggactcag tccagagacc 1320
taacattcag aatatagcat tggttgccta ttttgagatg gatttaatct cccacagtat 1380
tcatgagacc atctgatgga atcagatccc tgagccacct tgcaggacgt tttccccaac 1440
ctcttacacc ctggatgtca ctttggaaac caagcccttg gaagcaagtg gggtggcatg 1500
ggagagaagg gaggaggtgg gcacaggtgg tgagcttatg tgtgggcact ctactgcctc 1560
acagaagcca gccaagtgcc aaggtcagct tggctggtct gaggccacct tcttagccaa 1620
aaacctaggg ttcattttca ggactttgat aatgaacaac aaaatgggga cttctttggg 1680
cagatgctag gtcagttgtt ttcacctaat atcctctttt agctgcatgt atatttattt 1740
ataattataa ccctggtgga ctgcagcctt catctttatt gggaatgagt ttgttataaa 1800
tcagaaatgg gtccatgatg accactgttt tccaaaccca gtctgttccc tgctccctcg 1860
ctggcaagcc ccaccacaca ggagtgaggc caggggctag gagttctaag aacagaggct 1920
ggggtgaggg tggcacccag gcagctgcat ctggtctgtt ttaatttaac tgtatttaat 1980
ttgctttcaa aattaaaagt caaatacagt ttttaacagt ectaaaaaaa aaaaaaaaaa 2040
aaaaaaaaaa aaaa 2054
<210> 6
<211> 117
<212> PRT
<213> Homo Sapiens
<400> 6
Met Ala Leu Pro Gly Ser Leu Ser Leu Gly Ser Ala Arg Pro His Arg
1 5 10 15
Thr Pro Ser Gln Gly Ile Leu Lys Thr Arg Glu Gln Pro Thr Gly Ile
20 25 30
Thr Ser Ala Leu Leu Leu Ser Trp Ala Pro Ala Leu Pro Glu Ser Cys
35 40 45
Pro Gln Ile Arg His Thr Ser Val Ala Leu Leu Trp Phe Thr Phe Thr
50 55 60
Glu His Lys Ala Val Leu Asp Pro Asn Arg His Pro Ala Leu His Gly
65 70 75 80
Gly Ser Leu Gly Leu Ile Gly Thr Pro Cys Thr Ser Gly Cys Gly Gly
85 90 95
Ser Arg Val Pro Pro Ser Gly Pro Ser Ser Phe Thr Pro Ser Pro Pro
100 105 110
Ala Val Ala Lys Gly
115
<210> 7
6

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
<211> 724
<212> DNA
<213> Homo Sapiens
<400> 7
gtggacctgt gctgtctcag tttgctctgg ggtctgggca gtcctgtggt ttgggcagag 60
gcctcagagg gccctaggga cagactgacc caggtctgag cctcttggga gcgtgcggat 120
ggccggcctc agacaggcct ggttgtgggt ttgtcttcca aggggcacac gcgcactctg 180
gtgcttcctg gcattcagaa gagaatgggg aatccagaca tcaggccttc cttctccctg 240
ggaaggatgg caggtgcttg gagccaggcc tgtcttgaga gccagggctc tgggtcttcc 300
tcctccagtg ccctgttcca cgccttcagt gcacaaagca ctcccctcct gggatctctt 360
cagggatccc cgggatgcaa actggccagg gattagaatt ccacatttga gcaaacagac 420
tgagagtgga gaagcaccca gctggacatc ctctaggtgt tcctggcaga ggcccttgct 480
acttgtctgt gcccaaaggc cctagagggt cctagatgtg ggacaaggtc tcagcagggc 540
tccagtccca ggcctggaaa cagctggggg tgggggaagc tggctgggtg ggtgtggtta 600
tcttttccca gcttgtggct ccgaggtgac agaaccaatc tcaggaggct ttgtttggtt 660
aataaaatct actgaatggt ttaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720
aaaa 724
<210> B
<211> 128
<212> PRT
<213> Homo Sapiens
<400> 8
Met Ala Gly Leu Arg Gln Ala Trp Leu Trp Val Cys Leu Pro Arg Gly
1 5 10 15
Thr Arg Ala Leu Trp Cys Phe Leu Ala Phe Arg Arg Glu Trp Gly Ile
20 25 30
Gln Thr Ser Gly Leu Pro Ser Pro Trp Glu Gly Trp Gln Val Leu Gly
35 40 45
Ala Arg Pro Val Leu Arg Ala Arg Ala Leu Gly Leu Pro Pro Pro Val
50 55 60
Pro Cys Ser Thr Pro Ser Val His Lys Ala Leu Pro Ser Trp Asp Leu
65 70 75 80
Phe Arg Asp Pro Arg Asp Ala Asn Trp Pro Gly Ile Arg Ile Pro His
85 90 95
Leu Ser Lys Gln Thr Glu Ser Gly Glu Ala Pro Ser Trp Thr Ser Ser
100 105 110
Arg Cys Ser Trp Gln Arg Pro Leu Leu Leu Val Cys Ala Gln Arg Pro
115 120 125
<210> 9
<211> 2685
<212> DNA
<213> Homo sapiens
<400> 9
acaccagctg ccacttcttt tgcctcatga agaactcttg ggccagccaa actgggaacc 60
taggtgtctg ggtcttgtga caaccaaagc actttgacac taccccctgc cgagagaaga 120
ggagtggatg agcctgcggg tttgcctcaa gaaacttcat gagggtctct tactaactcc 180
attacactct ctctcctgga gcctcatctc catgtcaagc aggagggtaa agaagggaac 240
7

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
taagagcagg tctttcaagc cacaccccca cctgcggatg gatgggtttc tctgtaggcc 300
atgcaggcct ttgtcgcagc aaaccttccc agcagccctt gagccaagta aaaccagcac 360
aaccagccac cagtggttgg tgaggcagtg cccacaaggc tcatgttgta tgcctttgat 420
aaggccatct tggctttgag tagcagtgtt cctcgtcacc catttccccc tcaggattac 480
aacacctgct atcaaatcat ctaagctgaa aacatgagat gcgcttggaa aggcctagtc 540
agaagccatt tcctcttatc atttccctct cctatgcacc agtaaggccc gtccagagcc 600
ccagcaggga gtgggccctg agtccacact gtccctgagt gatccaggag gctgcccaca 660
tccccacatg tgcactgtgg ttccagtgta gctgctgtga gcccactgcc actgcctcag 720
aagggagcca ctgtgaacct ctcgagtggc tccaaagagc agtggctttt tgagaatggc 780
ccatacttct ggcccggctg gatgaaggga atgccgaccc tttggcctct ccccctcctt 840
ccatctcttc tctctcttgc cctatctctc tttctacttc agaaaaaaaa aaaaaaaaaa 900
agcctgtcat tcacttttta acactttatc ccaaataaga tccctgtgta attctgaagc 960
tggtgatcca cttggaattg tagatagttt caggaagctc ctgcagggct gtccaccgtt 1020
ggtgtgtgcc tcagtatttg gacttccgaa actgaaagtg aasgtgtctt tataggagag 1080
aaacgcatgc tgctctttgg ctctttctgt ccaacttttc tagaaatgac tcaaagtcca 1140
ttaagatttg tgaatattgt ataaattagc tatggaaagt agcaggtcag atggaaaatt 1200
cttttccaca gccctgctct ccgcctccct ccatcttagg agcgcctgcc tcaattcctc 1260
gtcaactgct ttgctccact ccatcccaca ggtgtgagtg ggggaagttt ttcattagga 1320
atacagtctg cgtgacatgg agaatggatg gagggagctt tgctactctg ctcttggcat 1380
gactccagga tttttttctg gaatccaacc tctgtcctct taggagaagg aacctgtcct 1940
tggttcagat ggctgggcat gaggaggaaa atttccatta gtgtagaaaa gtgctggaca 1500
gaatccggtt tggaaaatta caaatccagt tggtcasaat aggccatttc ctatgtgtga 1560
cctattcgtg gtatgccaac tggactgctt cctaaacagg acgaggaaag tgaggaatat 1620
ttttatatga aagccttagc ctgtctggca cccatgaaaa aaactattta tgcactccta 1680
ctttcaccgt ctttttgcat tctctatttg tagcacaaca gagttgaatg ccacaaaaca 1740
ccccgtttat agtgagctgt tttcagtgac caatatcaga aggaggcttg cttctggact 1800
agcctcacta attgccagca gccaccattt tccatggaat ggccttggga cagatgtcac 1860
ctctgttatg gggctctaat aggaaagaga atgttttttc ccttcctatg atcaatactg 1920
caaattattg ctgctcacag cttttatagg attctcccaa ctgaaagttg cagcattttt 1980
ctgtccctgt gcatcagtac taacaaaaga cagcctcacc aagtctgtat atttgaacag 2040
aggcaagtta attcatcccc ccgtgtcaga gccacaggca tgttgagggg gttgatacgt 2100
agcactggac cagggcgcaa agcccagata gttccagcca tgagaggaga gcacaagaat 2160
gctctgcact ctgcactcag caccatcttg ggtctgcttt gcccagatga gggaccacta 2220
acaaccttct cagcacatgt gaatgtggac tgattttaaa atgcattcat tctgctagga 2280
ttgggctgga agctggaaca gtgagagtac tttttctgct cctagtcatc tccctttctc 2340
agcgtgacat cctcctgcag caagcctagt atcactagca gtagttcctg cgactcttag 2400
caacacaacc cgaatatttg ctccctgcat ctgggtcctc caccaggatg ggcctgcgca 2460
tctgcattgc tgtacagaca ascaggcctt ttaatttaca tcctccttta attctcatta 2520
aaatcgcagg gtttttgttt gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2580
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2685
<210> 10
<211> 103
<212> PRT
<213> Homo Sapiens
<400> 10
Met Ser Leu Arg Val Cys Leu Lys Lys Leu His Glu Gly Leu Leu Leu
1 5 10 15
Thr Pro Leu His Ser Leu Ser Trp Ser Leu Ile Ser Met Ser Ser Arg
20 25 30
Arg Val Lys Lys Gly Thr Lys Ser Arg Ser Phe Lys Pro His Pro His
35 40 45
Leu Arg Met Asp Gly Phe Leu Cys Arg Pro Cys Arg Pro Leu Ser Gln
50 55 60
g

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
Gln Thr Phe Pro Ala Ala Leu Glu Pro Ser Lys Thr Ser Thr Thr Ser
65 70 75 80
His Gln Trp Leu Val Arg Gln Cys Pro Gln Gly Ser Cys Cys Met Pro
85 90 95
Leu Ile Arg Pro Ser Trp Leu
100
<210> 11
<211> 1760
<212> DNA
<213> Homo sapiens
<400> 11
ggcggggcct cgcacacccc aagaaccatc tttcacccca gcaagggggt gcgacgccac 60
aggtgccatc cccctgttgt cgttttgact ccccccgggg gccacctcca ccccggctgg 120
gtctgctagg tgctctcatg gctgaggatg gggtgagagg gtctccacca gtgccctctg 180
ggccccccat ggaggaagat ggactcaggt ggactccaaa gtctcctctg gaccctgact 240
cgggcctcct ttcatgtact ctgcccaacg gttttggggg acaatctggg ccagaagggg 300
agcgcagctt ggcaccccct gatgccagca tcctcatcag caatgtgtgc agcatcgggg 360
accatgtggc ccaggagctt tttcagggct cagatttggg catggcagaa gaggcagaga 420
ggcctgggga gaaagccggc cagcacagcc ccctgcgaga ggagcatgtg acctgcgtac 480
agagcatctt ggacgaattc cttcaaacgt atggcagcct catacccctc agcactgatg 540
aggtagtaga gaagctggag gacattttcc agcaggagtt ttccacccct tccaggaagg 600
gcctggtgtt gcagctgatc cagtcttacc agcggatgcc aggcaatgcc atggtgaggg 660
gcttccgagt ggcttataag cggcacgtgc tgaccatgga tgacttgggg accttgtatg 720
gacagaactg gctcaatgac caggtgatga acatgtatgg agacctggtc atggacacag 780
tccctgaaaa ggtgcatttc ttcaatagtt tcttctatga taaactccgt accsagggtt 840
atgatggggt gaaaaggtgg accaaaaacg tggacatctt caataaggag ctactgctaa 900
tccccatcca cctggaggtg cattggtccc tcatctctgt tgatgtgagg cgacgcacca 960
tcacctattt tgactcgcag cgtaccctaa accgccgctg ccctaagcat attgccaagt 1020
atctacaggc agaggcggta aagaaagacc gactggattt ccaccagggc tggaaaggtt 1080
acttcaaaat gaatgtggcc aggcagaata atgacagtga ctgtggtgct tttgtgttgc 1140
agtactgcaa gcatctggcc ctgtctcagc cattcagctt cacccagcag gacatgccca 1200
aacttcgtcg gcagatctac aaggagctgt gtcactgcaa actcactgtg tgagcctcgt 1260
accccagacc ccaagcccat aaatgggaag ggagacatgg gagtcccttc ccaagaaact 1320
ccagttcctt tcctctcttg cctcttccca ctcacttccc tttggttttt catatttaaa 1380
tgtttcaatt tctgtatttt tttttctttg agagaatact tgttgatttc tgatgtgcag 1440
ggggtggcta cagaaaagcc cctttcttcc tctgtttgca ggggagtgtg gccctgtggc 1500
ctgggtggag cagtcatcct cccccttccc cgtgcaggga gcaggaaatc agtgctgggg 1560
gtggtgggcg gacaatagga tcactgcctg ccagatcttc aaacttttat atatatatat 1620
atatatatat atatatatat atatatatat atatatatat ataaaaatgc cacggtcctg 1680
ctctggtcaa taaaggatcc tttgttgata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1740
aaaaaaaaaa aaaaaaaaaa 1760
<210> 12
<211> 371
<212> PRT
<213> Homo Sapiens
<400> 12
Met Ala Glu Asp Gly Val Arg Gly Ser Pro Pro Val Pro Ser Gly Pro
1 5 10 15
Pro Met Glu Glu Asp Gly Leu Arg Trp Thr Pro Lys Ser Pro Leu Asp
20 25 30
Pro Asp Ser Gly Leu Leu Ser Cys Thr Leu Pro Asn Gly Phe Gly Gly
9

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
35 40 45
Gln Ser Gly Pro Glu Gly Glu Arg Ser Leu Ala Pro Pro Asp Ala Ser
50 55 60
Ile Leu Ile 5er Asn Val Cys Ser Ile Gly Asp His Val Ala Gln Glu
65 70 75 80
Leu Phe Gln Gly Ser Asp Leu Gly Met Ala Glu Glu Ala Glu Arg Pro
B5 90 95
Gly Glu Lys Ala Gly Gln His Ser Pro Leu Arg Glu Glu His Val Thr
100 105 110
Cys Val Gln Ser Ile Leu Asp Glu Phe Leu Gln Thr Tyr Gly Ser Leu
115 120 125
Ile Pro Leu Ser Thr Asp Glu Val Val Glu Lys Leu Glu Asp Ile Phe
130 135 140
Gln Gln Glu Phe Ser Thr Pro Ser Arg Lys Gly Leu Val Leu Gln Leu
145 150 155 160
Ile Gln Ser Tyr Gln Arg Met Pro Gly Asn Ala Met Val Arg Gly Phe
165 170 175
Arg Val Ala Tyr Lys Arg His Val Leu Thr Met Asp Asp Leu Gly Thr
180 185 190
Leu Tyr Gly Gln Asn Trp Leu Asn Asp Gln Val Met Asn Met Tyr Gly
195 200 205
Asp Leu Val Met Asp Thr Val Pro Glu Lys Val His Phe Phe Asn Ser
210 215 220
Phe Phe Tyr Asp Lys Leu Arg Thr Lys Gly Tyr Asp Gly Val Lys Arg
225 230 235 240
Trp Thr Lys Asn Val Asp Ile Phe Asn Lys Glu Leu Leu Leu Ile Pro
245 250 255
Ile His Leu Glu Val His Trp Ser Leu Ile Ser Val Asp Val Arg Arg
260 265 270
Arg Thr Ile Thr Tyr Phe Asp Ser Gln Arg Thr Leu Asn Arg Arg Cys
275 280 285
Pro Lys His Ile Ala Lys Tyr Leu Gln Ala Glu Ala Val Lys Lys Asp
290 295 300
Arg Leu Asp Phe His Gln Gly Trp Lys Gly Tyr Phe Lys Met Asn Val
305 310 315 320
Ala Arg Gln Asn Asn Asp Ser Asp Cys Gly Ala Phe Val Leu Gln Tyr
325 330 335
Cys Lys His Leu Ala Leu Ser Gln Pro Phe Ser Phe Thr Gln Gln Asp
340 345 350
Met Pro Lys Leu Arg Arg Gln Ile Tyr Lys Glu Leu Cys His Cys Lys
1~

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
355 360 365
Leu Thr Val
370
<210> 13
<211> 1299
<212> DNA
<213> Homo Sapiens
<400> 13
agtgctctta aagttccgta cagataaagg aagagatccc agttctgata catatgagga 60
agattctgag ttgttgctcc agatacgaaa tgatgtgctt gactcactgg gtattagtcc 120
tgacctgctt cctgaggact ttgtcaggta ctgcttctcc gagatggccc cagtgtgtgc 180
ggtggttgga gggattttgg cacaggaaat tgtgaaggcc ctgtctcagc gggaccctcc 240
tcacaacaac ttcttcttct tcgatggcat gaaggggaat gggattgtgg agtgccttgg 300
ccccaagtga actcaagatt tggcagcccc agagatgcca actgcagcat gcccacctgt 360
attccctgtc cccttccttc atgaaggcat ctccaggcaa ggaaaactga agtcattggc 420
ccgatacaaa acatttcctg caacgaagga ggtggtgccg acgtgctgct tcccatcacc 480
agcagctgct cgacaagggg cgcagggtgg ctgtctttgt tccagcactg ttcaggctgc 540
ctgtcatccc gggcctgcca gctcccctga gtgatgagca cttccaagca cccctctgcc 600
ctttctctgt ccttatgctg tcccggctcg ccagccctct ggggcattgt gggagatgcc 660
tgccaggaat gagcaagctc tgttgctcgg gagcctcttg tcaccttctt ggacttattc 720
cccacctgat accttataga gaaaagtgtg aattcaggtg gagagtaggc ccaggcccca 780
tgaggcacca gtggaagcac agctccaagt tcagacaggt gcccttagag aggaaaacca 840
tgacaggcaa atgcatttcc tctggagttt gagaccctga caaacaacag gtggcatctg 900
gtgtgctgtt cttgagtttt cgtttaggat tagttgagtt ccagctgggt tttgggagaa 960
aggagatgct accaagtctt ggatgttagg gcgagaccct gcaagttgag tattagagag 1020
cttgtctttc aaggcaggtt cctggggctC cagggctagg agggaggagc ctgccctttt 1080
aacagaaccc cagtcacatg cggctcaagt cactcagagg ctgttgcatt tcagggctat 1140
gttggtcctt tgtttacctc ctaaaccaca gctgtttgtg tttcacatat gttgtgaatt 1200
ttccttggtt ctttttaaag gaatgataat aaagttactt gctttaggaa aaaaaaaaaa 1260
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1299
<210> 14
<211> 85
<212> PRT
<213> Homo Sapiens
<400> 14
Met Leu Ser Arg Leu Ala Ser Pro Leu Gly His Cys Gly Arg Cys Leu
1 5 10 15
Pro Gly Met Ser Lys Leu Cys Cys Ser Gly Ala Ser Cys His Leu Leu
20 25 30
Gly Leu Ile Pro His Leu Ile Pro Tyr Arg Glu Lys Cys Glu Phe Arg
35 40 45
Trp Arg Val Gly Pro Gly Pro Met Arg His Gln Trp Lys His Ser Ser
50 55 60
Lys Phe Arg Gln Val Pro Leu Glu Arg Lys Thr Met Thr Gly Lys Cys
65 70 75 80
Ile Ser Ser Gly Val
11

CA 02327551 2000-10-31
WO 99ISS7Z1 PCT/US99/08504
<210> 15
<211> 2996
<212> DNA
<213> Homo Sapiens
<400> 15
atttccagct cgcacccggg ctccgatcgc tcgccccgct cctctcgctc tgctcctggc 60
cggggctgcg ggttcggtcc gggcgccggt gcgctcctgc cggtcctcgt gcccgggact 120
ccgggtcccc gcgggctgct gcgcacgatg aagctggccc tgctcctgcc ctgggcgtgt 180
tgctgcctct gcgggtcggc gctggccact ggctttctct atcccttctc ggccgcagct 240
ctgcagcagc acggctaccc cgagcccggc gccggctccc ctggcagcgg ctacgcgagc 300
cgccggcact ggtgccatca cacagtgaca cggacggtgt cctgccaggt gcagaatggc 360
tcggagacgg tggtccagcg cgtgtaccag agctgccggt ggccggggcc ctgcgccaac 420
ctcgtaagtt acaggactct gatcagaccc acctacagag tgtcctaccg cacggtgacg 480
gtgctggagt ggagatgctg ccctggcttc accgggagca actgtgatga ggaatgcatg 540
aactgcaccc ggctcagtga catgagtgag cgactgacca cactggaggc caaggtcctc 600
ctgctagaag cagcagaacg gccctccagc ccggacaacg acctgccagc ccccgagagc 660
actccgccga cctggaatga ggacttcctc cccgacgcca tccctcttgc tcaccctgtg 720
ccacgacaga gaaggcccac gggcccagcc gggcccccgg ggcagacagg accaccaggg 780
cctgcaggcc cccccgggtc tasaggtgac cgaggccaga caggagagaa gggtccagcg 840
gggccgcctg ggctcctggg gcctccaggg ccccgtgggc ttcctggaga gatggggcgc 900
cccggccccc caggaccacc cggcccagca ggcaacccag gcccctcacc aaacagcccc 960
cagggcgccc tctactccct gcagccgcct acagacaaag acaatggaga ctcaaggctg 1020
gcctctgcca tcgtggacac agtgctggca ggtgtcccag gaccccgggg tccccctggt 1080
ccaccaggtc cccctgggcc tcgaggtccc ccaggacccc caggaacacc tggatcccag 1140
ggcctggctg gagagcgagg cacagtgggg ccgtctggtg aacctggcgt gaagggggaa 1200
gaaggagaga sagccgccac tgcagagggc gagggggtgc agcagctgag agaggccctg 1260
aagatcctgg cagsgcgagt cctcatcctg gagcacatga ttgggatcca cgatcccctg 1320
gcctccccag agggaggttc tggccaggat gctgccctga gagccaacct caagatgaag 1380
aggggtggcg cccaacccga tggggtcctt gctgccctgc ttgggcccga ccctggacag 1440
aagagcgtgg accaggccag cagcaggaag tgagagccca ctgctccagg acaccctgtc 1500
ctggctagag acccagcccc agaggcctga gccgccgctg tttcctaaag atgcccccag 1560
gggaactggg ctccaggcgt ggatgattgt gaggacatgg ggggctttgg ggacagataa 1620
tgtctccagg ggcagggtct ggaggggcca acaccctcat cagagccctc ctctggcctg 1680
tcccctcccc tacccccact cccggctgga gacggggtct gggtgggctg ggtgctggga 1740
atgagaataa tcctaatacc catcatttat tgagtccctg ctgtaactgg ccctgtccag 1800
ggaactttcg ttacgttgtc tcattattta acccttagga ggtaagctta ttatccccac 1860
ttcacaaggg gaccgaggct cagacggtag aaataaccct ctcttggcca ccagatcacg 1920
ggtggcaggg gcaggatttg aacccaggac cctcagttcc tgaagccatg ttctcttgac 1980
cctgccagct tcccctcttc gagagaaaac tcagacaggg agggcgcagg gccagaacgg 2040
ctccttaagg caggcagggc tgcggggagg ctgggccagc cagcctgagg gggtaggcag 2100
ggtcctgcag ggcctggggc ttcccttcct catccccctt ccccactggc tcggggagca 2160
gcctggactg cagctctcag aggccaggga gaccctgaat aaatcactgc cagccatacg 2220
gacttgagga ccttgagaga gaagcattgg gggtgcaagg gtcccccaaa ccagataggc 2280
atccctggcc actgcctccc agtcttgctg agcccacccg ctctctctgg gtccatccca 2340
tccctgagcc aggggaggca gcatttcatg ggcatgtcta tcagaggtgg gacttgcagc 2400
ctctgcccca cgagtttgtc tctcagtgga ctctataggt ttgctacttt tgcatgacac 2460
agcaagccca gtgtcccctt tgcaagctgc agagagggaa acagagtccc aggcctgctg 2520
ggaagagatg ctcctgcctc ccaccttcca gagttggggg cctggcaggc tccatggcag 2580
gcaccaggtc cctagcagcc cagaacagct ctgactggag ccctcaaggc ctctggggcc 2640
agggtctccg tgatcagctc agccctggtg ttcctctctt gctgggctgg gacctgggac 2700
acagccacgg cagcaaactc agagaattga aggtgctggc gccaccctgg ggcactctgt 2760
cttcacagca ggagtgactg tctccagtgc tcttggtact cctgtttggc tgtggcctgg 2820
tccctctggg ccctgggatc ttcttctggc ccttgaggca ggtctggaga ggcagtctct 2880
gtcttcatgg aggggtggtc agaggcgggc gggaccacca gcctgtagcg ttattattat 2940
atgtgacaat aaaggtgctc tccccacaaa aaaaaaaaaa aaaaasaaaa aaaaaa 2996
<210> 16
<211> 441
<212> PRT
12

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
<213> Homo Sapiens
<400> 16
Met Lys Leu Ala Leu Leu Leu Pro Trp Ala Cys Cys Cys Leu Cys Gly
1 5 10 15
Ser Ala Leu Ala Thr Gly Phe Leu Tyr Pro Phe Ser Ala Ala Ala Leu
20 25 30
Gln Gln His Gly Tyr Pro Glu Pro Gly Ala Gly Ser Pro Gly Ser Gly
35 40 45
Tyr Ala Ser Arg Arg His Trp Cys His His Thr Val Thr Arg Thr Val
50 55 60
Ser Cys Gln Val Gln Asn Gly Ser Glu Thr Val Val Gln Arg Val Tyr
65 70 75 80
Gln Ser Cys Arg Trp Pro Gly Pro Cys Ala Asn Leu Val Ser Tyr Arg
85 90 95
Thr Leu Ile Arg Pro Thr Tyr Arg Val Ser Tyr Arg Thr Val Thr Val
100 105 110
Leu Glu Trp Arg Cys Cys Pro Gly Phe Thr Gly Ser Asn Cys Asp Glu
115 120 125
Glu Cys Met Asn Cys Thr Arg Leu Ser Asp Met Ser Glu Arg Leu Thr
130 135 140
Thr Leu Glu Ala Lys Val Leu Leu Leu Glu Ala Ala Glu Arg Pro Ser
145 150 155 160
Ser Pro Asp Asn Asp Leu Pro Ala Pro Glu Ser Thr Pro Pro Thr Trp
165 170 175
Asn Glu Asp Phe Leu Pro Asp Ala Ile Pro Leu Ala His Pro Val Pro
180 185 190
Arg Gln Arg Arg Pro Thr Gly Pro Ala Gly Pro Pro Gly Gln Thr Gly
195 200 205
Pro Pro Gly Pro Ala Gly Pro Pro Gly Ser Lys Gly Asp Arg Gly Gln
210 215 220
Thr Gly Glu Lys Gly Pro Ala Gly Pro Pro Gly Leu Leu Gly Pro Pro
225 230 235 240
Gly Pro Arg Gly Leu Pro Gly Glu Met Gly Arg Pro Gly Pro Pro Gly
245 250 255
Pro Pro Gly Pro Ala Gly Asn Pro Gly Pro Ser Pro Asn Ser Pro Gln
260 265 270
Gly Ala Leu Tyr Ser Leu Gln Pro Pro Thr Asp Lys Asp Asn Gly Asp
275 280 285
Ser Arg Leu Ala Ser Ala Ile Val Asp Thr Val Leu Ala Gly Val Pro
290 295 300
13

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
Gly Pro Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Arg Gly
305 310 315 320
Pro Pro Gly Pro Pro Gly Thr Pro Gly Ser Gln Gly Leu Ala Gly Glu
325 330 335
Arg Gly Thr Val Gly Pro Ser Gly Glu Pro Gly Val Lys Gly Glu Glu
340 345 350
Gly Glu Lys Ala Ala Thr Ala Glu Gly Glu Gly Val Gln Gln Leu Arg
355 360 365
Glu Ala Leu Lys Ile Leu Ala Glu Arg Val Leu Ile Leu Glu His Met
370 375 380
Ile Gly Ile His Asp Pro Leu Ala Ser Pro Glu Gly Gly Ser Gly Gln
385 390 395 400
Asp Ala Ala Leu Arg Ala Asn Leu Lys Met Lys Arg Gly Gly Ala Gln
405 410 415
Pro Asp Gly Val Leu Ala Ala Leu Leu Gly Pro Asp Pro Gly Gln Lys
420 425 430
Ser Val Asp Gln Ala Ser Ser Arg Lys
435 440
<210> 17
<211> 850
<212> DNA
<213> Homo sapiens
<400> 17
cgagggcgtt cctgtcgggg ctgcagcggc gggagggagc ccagtggagg cgccctcccg 60
aagcgccact gcccatgctg accacccagc cctccggctg ctgatgtcat gagtaacacc 120
actgtgccca atgcccccca ggccaacagc gactccatgg tgggctatgt gttggggccc 180
ttcttcctca tcaccctggt cggggtggtg gtggctgtgg taatgtatgt acagaagaaa 240
aagcgggtgg accggctgcg ccatcacctg ctccccatgt acagctatga cccagctgag 300
gaactgcatg aggctgagca ggagctgctc tctgacatgg gagaccccaa ggtggtacat 360
ggctggcaga gtggctacca gcacaagcgg atgccactgc tggatgtcaa gacgtgacct 420
gacccccttg ccccaccctt cagagcctgg ggtcctggac tgcctggggc cctgccatct 480
gcttcccctg ctgtcacctg gctccccctg ctgggtgctg ggtctccatt tctccctcca 540
cccaccctca gcagcatctg cttcccatgc cctcaccatc acctcactgc ccccaggcct 600
tctgcccttt gtgggtgttg agctcaccgc ccacccacag gcactcatgg gaagaggctt 660
tccttctggg atggcggcgg ctggtagaca cctttgcttt ctctagccct cctgggctgg 720
gcttgggcac aaatccccag gcaggctttg gagttgtttc catggtgatg gggccagatg 780
tatagtattc agtatatatt ttgtaaataa aatgttttgt ggctaaaaaa aaaaaaaaaa 840
saaaaaaaaa 850
<210> 1B
<211> 102
<212> PRT
<213> Homo sapiens
<400> 18
Met Ser Asn Thr Thr Val Pro Asn Ala Pro Gln Ala Asn Ser Asp Ser
1 5 10 15
Met Val Gly Tyr Val Leu Gly Pro Phe Phe Leu Ile Thr Leu Val Gly
14

CA 02327551 2000-10-31
WO 99/55721 PGT/US99/08504
20 25 30
Val Val Val Ala Val Val Met Tyr Val Gln Lys Lys Lys Arg Val Asp
35 40 45
Arg Leu Arg His His Leu Leu Pro Met Tyr Ser Tyr Asp Pro Ala Glu
50 55 60
Glu Leu His Glu Ala Glu Gln Glu Leu Leu Ser Asp Met Gly Asp Pro
65 70 75 80
Lys Val Val His Gly Trp Gln Ser Gly Tyr Gln His Lys Arg Met Pro
85 90 95
Leu Leu Asp Val Lys Thr
100
<210> 19
<211> 1108
<212> DNA
<213> Homo sapiens
<400> 19
ataaactccc aggccccgcc cacgccccgc cggggcctta tcctggaccc gggatcccgc 60
gcgcctggag acagggtcca gatctgcctc gagcccctcg aaaccaggac tccagcacct 120
ctggtcccgc cctcacccgg acccctggcc ctcacgtctc ctccagggat ggcgctggcg 180
gctttgatga tcgccctcgg cagcctcggc ctccacacct ggcaggccca ggctgttccc 240
accatcctgc ccctgggcct ggctccagac acctttgacg atacctatgt gggttgtgca 300
gaggagatgg aggagaaggc agcccccctg ctaaaggagg aaatggccca ccatgccctg 360
ctgcgggaat cctgggaggc agcccaggag acctgggagg acaagcgtcg agggcttacc 420
ttgccccctg gcttcaaagc ccagaatgga atagccatta tggtctacac caactcatcg 480
aacaccttgt actgggagtt gaatcaggcc gtgcggacgg gcggaggctc ccgggagctc 540
tacatgaggc actttccctt caaggccctg catttctacc tgatccgggc cctgcagctg 600
ctgcgaggca gtgggggctg cagcagggga cctggggagg tggtgttccg aggtgtgggc 660
agccttcgct ttgaacccaa gaggctgggg gactctgtcc gcttgggcca gtttgcctcc 720
agctccctgg ataaggcagt ggcccacaga tttggggaga agaggcgggg ctgtgtgtct 780
gcgccaggag ccctgggaac gggtgacctt catatgacga agaggcacct ccagcagcct B40
tgagaagcaa gaacatggtt ccggacccag ccctagcagc cttctcccca accaggatgt 900
tggcctgggg aggccacagc agggctgagg gaactctgct atgtgatggg gacttcctgg 960
gacaagcaag gaaagtactg aggcagccac ttgattgaac ggtgttgcaa tgtggagaca 1020
tggagtttta ttgaggtagc tacgtgatta aatggtattg cagtgtggaa aaaaaaaaaa 1080
aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1108
<210> 20
<211> 224
<212> PRT
<213> Homo sapiens
<400> 20
Met Ala Leu Ala Ala Leu Met Ile Ala Leu Gly Ser Leu Gly Leu His
1 5 10 15
Thr Trp Gln Ala Gln Ala Val Pro Thr Ile Leu Pro Leu Gly Leu Ala
20 25 30
Pro Asp Thr Phe Asp Asp Thr Tyr Val Gly Cys Ala Glu Glu Met Glu
35 40 45
Glu Lys Ala Ala Pro Leu Leu Lys Glu Glu Met Ala His His Ala Leu

CA 02327551 2000-10-31
WO 99/55721 PCTN599/08504
50 55 60
Leu Arg Glu Ser Trp Glu Ala Ala Gln Glu Thr Trp Glu Asp Lys Arg
65 70 75 80
Arg Gly Leu Thr Leu Pro Pro Gly Phe Lys Ala Gln Asn Gly Ile Ala
85 90 95
Ile Met Val Tyr Thr Asn Ser Ser Asn Thr Leu Tyr Trp Glu Leu Asn
100 105 110
Gln Ala Val Arg Thr Gly Gly Gly Ser Arg Glu Leu Tyr Met Arg His
115 120 125
Phe Pro Phe Lys Ala Leu His Phe Tyr Leu Ile Arg Ala Leu Gln Leu
130 135 190
Leu Arg Gly Ser Gly Gly Cys Ser Arg Gly Pro Gly Glu Val Val Phe
145 150 155 160
Arg Gly Val Gly Ser Leu Arg Phe Glu Pro Lys Arg Leu Gly Asp Ser
165 170 175
Val Arg Leu Gly Gln Phe Ala Ser Ser Ser Leu Asp Lys Ala Val Ala
180 185 190
His Arg Phe Gly Glu Lys Arg Arg Gly Cys Val Ser Ala Pro Gly Ala
195 200 205
Leu Gly Thr Gly Asp Leu His Met Thr Lys Arg His Leu Gln Gln Pro
210 215 220
<210> 21
<211> 1589
<212> DNA
<213> Homo sapiens
<400> 21
tctgaacctg tcttgtcctg ggtcctccag ttgttggaag ccactctttt ccccaaccat 60
gctgaaatgc cacctttacc acacactgat gtcttacata gacttagatc tatttctgga 120
acttctcttc tcttcgctta cttgggtgtc tcatctggca ccagccatac aattttaact 180
attgtcaatt tctaatgtct tattatgtgg tgggatgagt cccttcactc ttcttttaca 240
aaatttccta gttattctct cacatctatt cttccacata aactttaaat tgtgcccagt 300
cctccacccc ctgtcccatt cccaccccca aattctgggc tctgtcattc cctgtgccat 360
catcttcccc ccattgtaat tactgtccac tcagggctgt gaaatagact atgttctata 420
aagagggaca aaaagggcat cctgatcttg agagaagcct gctgttcctc ccatcatttc 480
acctgccccc taagcccagg agttgtcatg agaggtcacc aggcccccac tcaatctcag 540
cttgggaacc aaagtcaccc accttggttg tgttggggtg gacccgccat ctgtccctgg 600
tccagacgag aaagaggagt ctctcctagg cctggagctg ggaaagaatg tgtggcccag 660
ttgtctgcac ttctaattct catcatggag aaacctttat tcctatctcc ctttcctgaa 720
ctggtttttt gttgtttttg tttcattttg ttttgggggg atagtttctt gctctttaat 780
ttggagtctc cagtaccttt gggatgcagg cagttcttgc ctgggccttc tcggaaccct 840
cactccccta gcccactctt gcgctacctg caggaggctg ccaacctggt gcattctgac 900
aagcctccca cccaaatctc tctcctgcca ttgtgtccaa aatcccacca ttagaggctc 960
ttgtagggaa gagcgtttct tgaaggcttt taggccttcc agagccagga gggaagtcag 1020
acaatagcag gaagtcccca ggccttttca aagttccaaa ccaagctctc ctgattttaa 1080
tgtagagatc ataccaaccc aggtggggga ggagggtccc cagccccagg cagcagccat 1140
caccccctcc actgaaaaca atattggagg ctgctttggg actgcccttc tcagccccct 1200
aagtctgttt tgtaatgcct gtggtgctct ccctcctgga cctttcctct cgggggtcac 1260
16

CA 02327551 2000-10-31
WO 99I557Z1 PCT/US99/08504
cacactttgc taactcttgt gtgcacatat tttataatag agtagcgagg gaatggtgcc 1320
gcctccagct tccgtaagct gcccgggctc tggggggctc tgggacaatc ggggctggga 1380
agtgactgtg ctcttattgt acactcttta tttctgtgta tctttggctt gtgctctttg 1440
taattaatgg gatttgtctg ccttttcaac actatactga gcaataacaa taaatgcaca 1500
cgtggaaatg cagacacggt acacatcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1560
aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1589
<210> 22
<211> 148
<212> PRT
<213> Homo sapiens
<400> 22
Met Arg Gly His Gln Ala Pro Thr Gln Ser Gln Leu Gly Asn Gln Ser
1 5 10 15
His Pro Pro Trp Leu Cys Trp Gly Gly Pro Ala Ile Cys Pro Trp Ser
20 25 30
Arg Arg Glu Arg Gly Val Ser Pro Arg Pro Gly Ala Gly Lys Glu Cys
35 40 45
Val Ala Gln Leu Ser Ala Leu Leu Ile Leu Ile Met Glu Lys Pro Leu
50 55 60
Phe Leu Ser Pro Phe Pro Glu Leu Val Phe Cys Cys Phe Cys Phe Ile
65 70 75 BO
Leu Phe Trp Gly Asp Ser Phe Leu Leu Phe Asn Leu Glu Ser Pro Val
85 90 95
Pro Leu Gly Cys Arg Gln Phe Leu Pro Gly Pro Ser Arg Asn Pro His
100 105 110
Ser Pro Ser Pro Leu Leu Arg Tyr Leu Gln Glu Ala Ala Asn Leu Val
115 120 125
His Ser Asp Lys Pro Pro Thr Gln Ile Ser Leu Leu Pro Leu Cys Pro
130 135 140
Lys Ser His His
145
<210> 23
<211> 2538
<212> DNA
<213> Homo Sapiens
<400> 23
aaaggttgta taccctgaaa taccatctga taaaacctgc agaaaggata attttagttc 60
ataaatgtga ccctcattgt tggcgcatca gtgagatggg agagaacagg ctgagtcaaa 120
ggagatgatc ctcccagctg cccccaccca actgttactt ctctgtagat caagaagtga 180
tgtggcacag gctctgggtt cagattctag cttctccact cacttgttgc atggctacat 240
caagttactt actgtctcta cgctttcatg ttatcttcaa aattgggata atatgattcc 300
atcagtggct atcgtttttt taatatggcc cagagacctc ctgaaattag acatgggtgg 360
caatttattt tgttttggga ttcagaaagg aaacatttgt aaaactgtgc tcaaggatca 420
aaaatcctgc agttattttg actgttacaa cctccttatt aatgctacca aggcatttca 480
gagagttgct tcctgaagtg actccattca tctgagctct gtggtgttcc gtcataatat 540
gtggtgagct ttaatcttcc ctttcagctc aggaagctgt gagtcattta tctacttgtg 600
17

CA 02327551 2000-10-31
WO 99/55721 PGT/US99/08504
caaagaggac agagacatcc tatctcttat gttcatcagt ttgttcagat ctatagtggt 660
tgtattggag aaacctggct gttatccaaa agggtaggtt ggaagaggct taccacacac 720
attgaatata tttcttaaag ctgctatgga aataaagtga tgtcaccttc tacccctaat 780
ttgcatgtgg ctggaatctc tgaggcatgg gtttgccctt cccaccctcc tgtgcgttgg 840
tgtctcagac ttgtaatctt gcttggtgaa gaagtcattc tttgtttttt tgggtagatg 900
gaaatgggtg gcccaaagtg tacctctaaa ctcatatctg cttgctccca ctgttaggga 960
gatgtctaga cacggagaaa agggcttggt aattaattga ctttgggaaa ttccacttaa 1020
aagtagagat acaatttttt ttattttata aaatatttca aacaaagagg aaattggaag 1080
agtaatataa cacacacatg tatatgtaaa agttactgac tatatatgcc aagggccatt 1140
ttgagtttct aagagggtga atatagattg tgatatttac atatttgttg gacttttttc 1200
tagagcatct ttcctttggg atacattttg ggaaatattg gtttataatt tattttcttg 1260
gtgggaaaga catggataag tatctatacc ttgagataaa taactaaaac tgcataatta 1320
aagaaataag ttgtcaagtg aatttcacaa gcacaaggga gagttaaagt gttgtagtgg 1380
gtcatataag ctttgacata tttttcctca taaagctgat aactcttcag tattgagttt 1440
ctaaaaaagg aagtatttcc tgtggtaaat tttcacttgt gtatctgtga ataccattat 1500
tgtgtgtgaa acttaaaaac tggtagagaa cactaccttt ctcaataaat cagtacccac 1560
gatgggtcta gtgtggaaga caggagggtg tgggaagtgt tgttgtaaca gaatttaaaa 1620
gtgccaaggg agaagaaatt cacaaggtgt ttatatccag gaaagtgtat ttaataatgt 1680
tttttacatt ctctaagaaa aaaagattga aaatatcagg agagtctcaa tgaaaagaac 1?40
atacaaaaag aacataccag gattctagga ctgatacatt ttctgtcaac gctattgcta 1800
ttacaagtaa agggattaag cacttgtgaa tgttgatacc atgtataata actctaattg 1860
gatattgttc aacgtttatt tccatattac ccaatattta gtgcattgta actaatagaa 1920
ggccctcata gccaacctta cttgatcttc ttgataacct tgagaggtgg atattattat 1980
ccccatttta tagatgtgta aaataagcct cagagaagaa tagaagtttc tgttgaaaaa 2040
tatatatgaa gaattttata ccaaatgaca gatatttgtc aaacatttca gaaaacattt 2100
ggagaccggc agagtttttt aaataattga aataattgga attggtacct aagcagcaaa 2160
ggaaatttaa ggagaaagaa tattttgaag taaattataa attaaacaat gtgaaataca 2220
gttttcatag gttgtcataa atgctttcat gtagtttgtg catgctttgc aactcagctg 2280
caagtgctta cagaaactaa ttttttattt ttaacaattt tttgcaagtt tttgaaaatg 2340
ttttgattgt caggttcata gacttctaac tcaaaactaa tgtaacaaaa tattagaaaa 2400
agtggaaata ttagaaaggg gatcttagaa tttataaaaa taaatatctg aagagtacct 2460
atttgaaaaa atgtagtctt gttttatcat atattagtta cagtaaaaat tatcaaaaaa 2520
aaaaaaaaaa aaaaaaaa 2538
<210> 24
<211> 123
<212> PRT
<213> Homo sapiens
<400> 24
Met Ile Leu Pro Ala Ala Pro Thr Gln Leu Leu Leu Leu Cys Arg Ser
1 5 10 15
Arg Ser Asp Val Ala Gln Ala Leu Gly Ser Asp Ser Ser Phe Ser Thr
20 25 30
His Leu Leu His Gly Tyr Ile Lys Leu Leu Thr Val Ser Thr Leu Ser
35 40 45
Cys Tyr Leu Gln Asn Trp Asp Asn Met Ile Pro Ser Val Ala Ile Val
50 55 60
Phe Leu Ile Trp Pro Arg Asp Leu Leu Lys Leu Asp Met Gly Gly Asn
65 70 75 80
Leu Phe Cys Phe Gly Ile Gln Lys Gly Asn Ile Cys Lys Thr Val Leu
85 90 95
Lys Asp Gln Lys Ser Cys Ser Tyr Phe Asp Cys Tyr Asn Leu Leu Ile
100 105 110
1g

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
Asn Ala Thr Lys Ala Phe Gln Arg Val Ala Ser
115 120
<210> 25
<211> 4466
<212> DNA
<213> Homo Sapiens
<400> 25
gttgcggaga acctacaagt ctccgctccg gcatgcgcgg cgcgcccaaa tcaggaagac 60
ttctgcctct aatagggctg tgcgagagag gcagatgctc tgccgccagc tggcctctgc 120
gggcacgggg ccttgcccag tgcatccagc ttccaacggg actagtccag cgccagccct 180
gcctgcccga gcacggaatc tttaagaatc cgccagcact tggtagcgtc tgcagccacc 240
caggtagcat acgctctttg ctgtgtagaa gaaatgccca tacgacagct ttgcccctgt 300
ttgaagacct cccttcttgc ctctccagac gtgttccccg aggagatctt ccttccgtcc 360
ttcctggcgc cctggttgcc caccttgccg tgcttcctct tacgtgctag ctttgtacct 420
atcgctcact gcatgctcgc ctccctcttg ctggcatccc ggcctgtttc aatgactacc 480
gctctgctac ttaggcacag ggactccgcc gcacgctgac ggaccacgag ggctgacccc 540
ttccagcctg acttggttca tggaggctcc tactctgccc tctccaagct cccctggcgg 600
ctccccacct ggttgcccag ttcctattga tgagctctgg acagaaagat gcccgtttgg 660
ccaggctggt ggcttgatgg gtgtacctgg agagggggtc tggcttcctg cccaagatgc 720
ctcccagccc tgccagggcc cggtgcagcg ggcagggcct catctgtgct gtagtggtcg 780
agtggtcgct gcaaggagcg tagttctgcc atgtctgggg gccaggttcc actctgcaca 840
tgaatatgca gtctgggagg ccctactgct catactggga aggaccaatg ttgcacctct 900
gttaatgcct gacttcagct gctggtgttc tgatggagcc agaggcttgg ggaatctgga 960
acttgcctgc taaataaggt catggtggac tctcagccat tgggcaggtc tatcaggctg 1020
caggttccta cacacccacg cctgagggcc atagcaggct aagggtggat accagcgact 1080
ccctttgctg cccaggatct ccatgggcag tgccacagcg gctgatgctc agtcactcct 1140
gcttctaccc cctgtcactg atggcgagcc ttgcccagct tgagacctgt tcccatctcc 1200
attcaggtgc catgtggcct tcactgcagc cctgcagcca cccacgcacc atctgtgggt 1260
ctccaaaggc accttgtagc atgtactccc cgtgcctggg caatcagatg ggctgccttt 1320
gtccaaggga aaacagactc ccttcgggaa acatccttaa gcacttaagg ccgggggggg 1380
gtgtctgcct ctggcaaccc agccagggtc ttggtggcat ttgtaaaagc aaagagctgt 1440
ggactgccgt ggtcctagtg tggtgacaat gcagcactgg catgcatgtc cttctgaagg 1500
acctcatcct tcctcacagg cggatgacca agaaatcatt ttgtggctgg gtttggccac 1560
gccctttgga ctgtgctgtt ccgccatatt tcaatgccaa atgaaccaca ttgacatgac 1620
ctggaccata gggcttccta tcctgggctc agctgcccct gtctgaaggg tcctggcttg 1680
attgcagaag gacaacctcc gcacccacct aaagacatgt atatgtcttg ggatcccaga 1740
gattgggtcc ttgggcctgg cttcttaaga gttttgatga tgctgggaaa agtgactgcg 1800
attctgaaga accgctgcct tgcaaggtca aggacattca gtggttgctg gggtccgcag 1860
actactgcca cccactcacc atcaactctg ttagcccaat tgccctgctg aacaactgcc 1920
tgaatacagg ctttaggttc ccctggactc cagccaaggc tgttcaggtg ggaccatggt 1980
gctctttaag cgtgatcgga gggaagacac acagcagggc caccattcca tgaatgggag 2040
gtgtacagat cactttctct ttgtgctcag ttctcttctg tctccagcag ctatattggt 2100
aagactagta cctgccaggg agaggtgccc ccaagtgaag gggtacagtg gcacctggga 2160
aaaggcacct ggaaggtttc catgtggccc agcccagcat ggaagcaggg tgggaactct 2220
gctgtgtcgc cagccctcac tctactcaag tggctttttg agagccctgc catgtctgtg 2280
tcaggcctgt gctgcttcac accctacagc tgcctgggaa aggccggcca cgctccctgt 2340
ccacacactc cctgtccaca cactccctgt ccacaactgc agccgggccc tctgcctatg 2400
ggcacccaat ccaagcagct gctccacctt tgtttggcat ggtgatttgt gttttttctc 2460
ttggtgctta tgtgtgtggg cttgggacga gtgctggtat gcacttagga ccttcttgat 2520
agctccctgc actttggaac acggagcaga tgagagaggg tcaggggctt gccctccacc 2580
ttggacttgg aagaagccca cattggagag gtgaggaccc catggtggct ctagtggaag 2640
atacgttagt ctccagctaa ggaggatgag gcgcagcccc agagggagac ctcagtgata 2700
ggggatcagg ctacgaaagt gggggaaggg agatgctttg tacatatttt ggggttataa 2760
tttctctaaa ttttaggaga acgggtattg attgataaaa gggacaggca gtagtgttca 2820
acagtgcatg tgaaggaaag ttctgttttc catggttttg acattctttg gactgtattg 2880
tgactgctgt ctggtccaca tggtaccctt ttggtaagta ggcttcagtg cataccaggg 2940
19

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
tatcactgga gatgggagtt agtgaagggg tgactccctg gcctagtata gtgtgaccct 3000
gggacaactt aatgtcctaa agcattttgg tgacttctag ggaatagcaa agacctattt 3060
cattgtcccc aggtaagtat gtgatgagca atgaggagga gtggaaaaca aaacccagaa 3120
agtgcggcag gaccagcctg acgcacacgc tcctgttgtc atggcagaca gccgccttgg 3180
gtgggcacca ccctggcagt tccagcctgt aggggagtga agggacatgg ctgagctggg 3240
catgtgctga ggttgactta gggaacaagc cctgggattg gacaaaaggg cccatgctgc 3300
agccactgac tgggggcaga gctctgggtg gaagagggaa gagatcctaa tggaggcgcc 3360
tccatctgca accacagttg taaggctcat ggcacctctg cttggaaagc actggtttag 3420
ggacttagag aggtaggcac aaggtgggtc tcctgggtag ggaagcaaga gcagactgtt 3480
gggccaacag gagaagctcc ccagagtagg ggagaaggtt ggggtgtagg gccttccacg 3540
tggaacagac agcccctgtg tctctgtctc ttggggacct gagtttgggt ggggtggcag 3600
ttggcacagc gcagatgcgg tagagatggg aggaaaccca gctcctcact tccgtgtgcc 3660
tcatgccttt gcatacacaa gcaccaaacc tactaggtct tctcattacc catgtaaacc 3720
acatgttaga taaatttttg caagtagagg aaagaaggaa ataaaacatc acattttggt 3780
gtctctcagg ctttcccccc caactatggt ttctttgctt tttgttttaa catagttttg 3840
ttgctgtctt ctgtaatgat acagttttgt gcagctgttt tcacttagca tatcgtgggc 3900
atctcccctt atgattacta aatattttat tttggagtgg ctgtgtactc tcccattgac 3960
tagatggacc attgtgccag ttgccaatca ctaatgctgt tactaacttt tcagttataa 4020
attgatgaat atctttgtgc acaggctgtt tcccaatgtc aagttattag ggtagactcc 4080
aggaggtggg attcttcaac taaagaatat gaaaaccttt gaggctttta ctacatattg 4140
acaaaatggt ttccggaaat atttgtatcc ccttacactg ccaccagcaa ggataaacat 4200
gtccatcttg cccgtattgg~gaattatcat ctggctaaat atttgctaat ttgataatga 4260
aaaaatagca tcgtgtttca gttggcattt cactgacttc tagcacggtt gaacatcttt 4320
catgtggagc gattgtattt cctcctttgt ggattgtcag tgtcctttgc tctatcttct 4380
ggggtcagat aaatttgtat gagctcggta tatattaaag atattaacct ggtgtgtgtc 4440
ataaaaaaaa aaaaaaaaaa aaaaaa 4466
<210> 26
<211> 125
<212> PRT
<213> Homo sapiens
<400> 26
Met Arg Gly Ala Pro Lys Ser Gly Arg Leu Leu Pro Leu Ile Gly Leu
1 5 10 15
Cys Glu Arg Gly Arg Cys Ser Ala Ala Ser Trp Pro Leu Arg Ala Arg
20 25 30
Gly Leu Ala Gln Cys Ile Gln Leu Pro Thr Gly Leu Val Gln Arg Gln
35 40 45
Pro Cys Leu Pro Glu His Gly Ile Phe Lys Asn Pro Pro Ala Leu Gly
50 55 60
Ser Val Cys Ser His Pro Gly Ser Ile Arg Ser Leu Leu Cys Arg Arg
65 70 75 80
Asn Ala His Thr Thr Ala Leu Pro Leu Phe Glu Asp Leu Pro Ser Cys
85 90 95
Leu Ser Arg Arg Val Pro Arg Gly Asp Leu Pro Ser Val Leu Pro Gly
100 105 110
Ala Leu Val Ala His Leu Ala Val Leu Pro Leu Thr Cys
115 120 125
<210> 27
<211> 2667

CA 02327551 2000-10-31
WO 99/55721 PC'T/US99/08504
<212> DNA
<213> Homo Sapiens
<400> 27
gtcccctggg acccatgggc cttctgggtg tgtgtagggg acagcgcctg gattaagcca 60
gggaagtaag gacttggatt gttaagaaac agccctctgg ctgctgtggg gaacccagga 120
aggcagcttg gagccttctc cagggccctg gctggcggca cagggggctg ctcacatgtc 180
caggacccgt gaaggaccca ggaggtggtg gacagggccg gtagcccgag gtgcactggg 240
atgggggctc tgcatgtgtc tgaaggtggc agccgtcagg cacagcttct cgccccctcc 300
tcaccccaca ggaagagcag cgaggaggcc atgcgggagc gacagcaggt ggtgtccctg 360
gccgccatgc gggagcccag cctgctgcgg ttctacgtgt cccgcgagtg gctcaacaag 420
ttcaacacct tcgcagagcc aggccccatc accaaccaga ccttcctctg ctcccacgga 480
ggtgaggcgc cccctgtggt gggagagcag ggtgggcagc tgggccgagc cacagcttcg 540
ctccctgtac cttcttccca ggcatcccgc cccacaaata ccactacatc gacgacctgg 600
tggtcatcct gccccagaac gtctgggagc acctgtacaa cagattcggg ggtggccccg 660
ccgtgaacca cctgtacgtg tgctccatct gccaggtgga gatcgaggca ctggccaagc 720
gcaggaggat cgagatcgac accttcatca agttgaacaa ggccttccag gccgaggagt 780
cgccgggcgt catctactgc atcagcatgc agtggttccg ggagtgggag gcgttcgtca 840
aggggaagga caacgagccc cccgggccca ttgacaacag caggattgca caggtcaaag 900
gaagcggcca tgtccagctg aagcagggag ctgactacgg gcagatttcg gaggagacct 960
ggacctacct gaacagcctg tatggaggtg gccccgagat tgccatccgc cagagtgtgg 1020
cgcagccgct gggcccagag aacctgcacg gggagcagaa gatcgaagcc gagacgcggg 1080
ccgtgtgatc tgctgggcta gtctgtaagt cgccccggct ggtccctcca tggcactctg 1140
ggtcctctcc tcactctcca gagaccctca catgtccttt tgaacatcca aagagcaggt 1200
ccctgaaagc accttcctgg aggatgtggg agggccctgg acatggcccg gccccactgc 1260
tgagtgcccg tgtccccaca gccccatgtg ccccaccccg cggaaggcgt gtttgtgccc 1320
agaagagagg ccgggctgct gcagaacccc gccgtgtaaa gaggcagaaa agttggtttg 1380
gtttgcagta acgctgcaac tagaaaatat atgcacttca ggcttgttga aacgaccaag 1440
actctgtgac gttaatttgg gtctttgtcc tggcagtgcc tctgccagtc actgtcatcg 1500
ttgtgtcccc cacaactgtc ctcttgctag ctcggcccag ctttgtccct ggagcccgat 1560
gctacccctg tcagacagag gctgcggcct gggccagagt cagggagtag ctgctgcttc 1620
acggcgtctc cactgtgcga ttggcccgga gccccgaaga ctcggaggga gctgctcagg 1680
gccggtgagc gcagccagaa gccctggcca gtgaggagct cacaggtcct ccctggtggt 1740
cccgccgcac ctctgcatct cctgggcgtc accaggaagg ctctgaagtc ccgggctgct 1800
ctcagcactt ctcctgcaga ctgaagactc tggactcatt gctgattgga acaccaggag 1860
gaggttggat ttctgccagt gggggatgtt tctggaggca gctggtcccc cacaccgcgt 1920
cctgctgagc ctgccccctg gattggctgt aatttgcctc gaagttcagc agttcatctt 1980
catgggaaat ttgctgagcc cccaccaggg aaccggatga tgaaacaggg atacctcaca 2040
gcttggccat ttgaggcaaa ggcagcttcc cgagctgatg ctaaagaaga cagactttcc 2100
cttcctccca gcagcagcag tgcagagccc gcctggaggg atgtgggggc tgtgcagggt 2160
gcagcgctca ggtggatcct gggaagcagc ctctggatgc tgagtggagg gagccactga 2220
gcacagcaag gcaccaaagc ccctggagaa accgccaggg cgaggtgcga ccatcatcag 2280
gatcaaagca gacggggcgt gggtggggaa ggggctctgg gaccagaccc cccacactac 2340
tgcgtctttg tttctatcag tctttgtaga agcaggtggt ggtggaaatt ccagcaggtg 2400
ggtcccgcag aggccctgag gcctcacttt tcggatcttc tgtcccagat cctgctccct 2460
ccctgctgag cctggggttc ccctggcatt ggccccagcc ttctgaaagc cggcgctgca 2520
gccagaggcc gcacgctgca ctgtcgcgac gcagagaggc ttctgtgcag gctgggatcg 2580
ggccccatgt ctgtgctgtc tagtttgtgt tcaaaatgtc agaataaaca cagaataaat 2640
gttaaaaaaa aaaaaaaaaa aaasaaa 2667
<210> 28
<211> 232
<212> PRT
<213> Homo Sapiens
<400> 2B
Met Ser Arg Thr Arg Glu Gly Pro Arg Arg Trp Trp Thr Gly Pro Val
1 5 10 15
Ala Arg Gly Ala Leu Gly Trp Gly Leu Cys Met Cys Leu Lys Val Ala
21

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
20 25 30
Ala Val Arg His Ser Phe Ser Pro Pro Pro His Pro Thr Gly Arg Ala
35 40 45
Ala Arg Arg Pro Cys Gly Ser Asp Ser Arg Trp Cys Pro Trp Pro Pro
50 55 60
Cys Gly Ser Pro Ala Cys Cys Gly Ser Thr Cys Pro AIa Ser Gly Ser
65 70 75 80
Thr Ser Ser Thr Pro Ser Gln Ser Gln Ala Pro Ser Pro Thr Arg Pro
85 90 95
Ser Ser Ala Pro Thr Glu Val Arg Arg Pro Leu Trp Trp Glu Ser Arg
100 105 110
Val Gly Ser Trp Ala Glu Pro Gln Leu Arg Ser Leu Tyr Leu Leu Pro
115 120 125
Arg His Pro Ala Pro Gln Ile Pro Leu His Arg Arg Pro Gly Gly His
130 135 140
Pro Ala Pro Glu Arg Leu Gly Ala Pro Val Gln Gln Ile Arg Gly Trp
145 150 155 160
Pro Arg Arg Glu Pro Pro Val Arg Val Leu His Leu Pro Gly Gly Asp
165 170 175
Arg Gly Thr Gly Gln Ala Gln Glu Asp Arg Asp Arg His Leu His Gln
180 185 190
Val Glu Gln Gly Leu Pro Gly Arg Gly Val Ala Gly Arg His Leu Leu
195 200 205
His Gln His Ala Val Val Pro Gly Val Gly Gly Val Arg Gln Gly Glu
210 215 220
Gly Gln Arg Ala Pro Arg Ala His
225 230
<210> 29
<211> 2699
<212> DNA
<213> Homo sapiens
<400> 29
agaaattgcc gtggatattg taaaacatgc ctttattact aaatccatga cattactgca 60
gatgtctaca gtgaatatag agccagtctt gcttttgacc ttgttagcag ccgacagaaa 120
aatgcataca ctgattacag tgactctgta gcacggagga tgggctttat tcctctccca 180
ctagctgttt tactcatcag agttgtaaca agctcaatta aagtgcaagg aatcctgtct 240
tatgcctgtg tcatactctt ctattttggg ttgatatccc tgaaagtact taatagcatc 300
gtgctgttgg ggaaatcgtg ccagtatgtg aaggaagcca aaatggaaga gaagctgtcg 360
aatcctcccg caacctgcac tccaggcaag ccgtccagta aatcacagaa caaatgtaaa 420
ccctctcaag gcctttccac agaagaaaac ctgtctgcct ccatcaccaa acaacctatt 480
catcaaaagg aaaatatcat accattactt gtgacaagca attctgatca gtttttgaca 540
actccagatg gtgacgagaa ggacataacg caggacaatt ctgaattaaa acacagatcc 600
tcaaagaaag atttgttaga gatagacagg ttcacaattt gtggaaaccg aattgactga 660
atctgtggct tcatgcgctg aagaagctgg gtcctggggc aacaagtgct gtgttgccag 720
22

CA 02327551 2000-10-31
WO 99/55721 PCTNS99I08504
gacaaataga tgctaaacat ggcacttaaa tatttattta aaaacttaaa ttattattgg 780
caagcaaatc ttagtatctt tcttccagta atatggcctg gctgagggtc agaccacagg 840
acaggagcga cctccggcct tgactgtctg ggaagcttga tggattataa aacttcctcc 900
tgcctggcca agcagcagca tcatttccag gacccaacaa aggcaacatc aaaatctgtt 960
ttgctttgtc agtctgggct tccagaatgt tgaatttgcc tcaaggcctc ttcagtataa 1020
ggaaatacct ggaaaactgt gaaactttta ccacgacgta atctttccag tctcatacta 1080
ttttcacaaa cagttttcaa acgttacttc atctgccaaa gcattaaaaa aattaaacat 1140
aagtcaagat aaatgttctt accaccagaa taacccttaa agatgtatct taattaatca 1200
gaataaaagg ctaccttaaa taagacatga tgaatagtag cattttgtag ggttaaaaaa 1260
aaatgctaaa ctagtttatt tattaaaaaa ataattaatg aaggctatgc attactggga 1320
aaaatccttc ataatttttc agtttactct ttaaagcaaa atgtgagctg tatgtcattt 1380
aattggtgga taaaacaaat ttccttacaa aagggcactt tttacaccaa ggaagcagag 1440
cagtgttaac tttaaggtat acttaactga ttttgcttta aaactaatta cttcataaat 1500
tattacagct aaaaggattc gatgttgaac aggctgaaaa attgtcaatg tacaaaattc 1560
aaaactgtca actttaactg taaagtaaat gctccaagtg tgttagacag catcatcttg 1620
cttgggctta ccaaatgcat tagtctttgt gtttgggtcg acagcgagtg tgcctgtgct 1680
ggggcagggt gtgtgttctg tgggagggtg tctgtgggga tgtgactatc agggtgggcc 1740
tgtgctgggg atggggcagg cctgggtctg gagaggattt tgtgtgaaag taaatggggt 1800
gtttgaggcg tatgggtggc tgttggtgtg gggaggcatc tgtgtatggc tgttgggaac 1860
agcaaccaaa aggtgctttt tggttttatt tgagatgaag attgtgtttc cgcttaatta 1920
ctagtttgtg gtctatatca tagaagttat ttcccacccc attttatctt gacaaccgtg 1980
tttgcatttc tgtaaaactt ctacaacttc tggtgtcaga actgtccaga agatggtact 2040
gttaactgtt atttcctttg atgttttgat tttgaagttt agctctcatg caaatgtttc 2100
aggcgtacat acataggcag aaagcaattt ttaggtgatt tgtctgtttc ttggatgaaa 2160
tataaagcaa gctttaatgt tctgacttgt tcatttgaaa tacaaaaaag taagtgaatt 2220
ttaatgtttt gcattaacta aagaaatctg aagattaatg ttgaggaaat tgtatggaca 2280
tgcctttgtg aaaccaggaa gtattttaag ttaaaaatga aaaaggtttt aattgctttg 2340
tgtgtgtttt aatggagccc cattttagaa ttattttttc catctccctt taccaacsaa 2400
aggaacaatg ccaccgtgaa tggaatagtt tggggaaagc tttgccaaac acaaccctga 2460
tttcagagca ggaacatggt ttggatagat cttcagttcc gcttgaatta ttctgttact 2520
gcgctgtcat tttcagaaga tttccattcc tttgcagatg ctgttgggag ttcgggatta 2580
tgttcatttc ttctgtttta atggcattca gtactaattt tataagtgca tcttgtgtga 2640
atctcaataa attcagtttt gtaatcttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2699
<210> 30
<211> 166
<212> PRT
<213> Homo sapiens
<400> 30
Met Gly Phe Ile Pro Leu Pro Leu Ala Val Leu Leu Ile Arg Val Val
1 5 10 15
Thr Ser Ser Ile Lys Val Gln Gly Ile Leu Ser Tyr Ala Cys Val Ile
20 25 30
Leu Phe Tyr Phe Gly Leu Ile Ser Leu Lys Val Leu Asn Ser Ile Val
35 40 45
Leu Leu Gly Lys Ser Cys Gln Tyr Val Lys Glu Ala Lys Met Glu Glu
50 55 60
Lys Leu Ser Asn Pro Pro Ala Thr Cys Thr Pro Gly Lys Pro Ser Ser
65 70 75 80
Lys Ser Gln Asn Lys Cys Lys Pro Ser Gln Gly Leu Ser Thr Glu Glu
85 90 95
Asn Leu Ser Ala Ser Ile Thr Lys Gln Pro Ile His Gln Lys Glu Asn
100 105 110
23

CA 02327551 2000-10-31
WO 99/55721 PCT/US99108504
Ile Ile Pro Leu Leu Val Thr Ser Asn Ser Asp Gln Phe Leu Thr Thr
115 120 125
Pro Asp Gly Asp Glu Lys Asp Ile Thr Gln Asp Asn Ser Glu Leu Lys
130 135 140
His Arg Ser Ser Lys Lys Asp Leu Leu Glu Ile Asp Arg Phe Thr Ile
145 150 155 160
Cys Gly Asn Arg Ile Asp
165
<210> 31
<211> 1300
<212> DNA
<213> Homo sapiens
<400> 31
tctccccccg ggctccgccc accccacgcc gggaacccac gcgggccact acaagcccgc 60
cctttcctac gtctggtcca gtcggtcttc ctccggcccg ggccctggcc cagctagccg 120
gccatggaag tgaagaaaat gtttggaagc tctgtgaata catcaaaaac catgaccagt 180
atcctttaga agaatgttat gctgtcttca tatctaatga gaggaagatg atacctatct 240
ggaaacaaca ggcgagacct ggagatggac ctgtgatctg ggattaccat gttgttttgc 300
ttcatgtttc aagtggagga cagagcttca tttatgatct cgatactgtc ttgccatttc 360
cctgcctctt tgacacttat gtagaagatg ccattaagtc tgatgatgac attcacccac 420
agtttaggag gaaatttaga gtgatctgtg cagattcata tttgaagaac tttgcttctg 480
accgatctca catgaaagac tccagtggga attggagaga gcctccgccg ccatatccct 540
gcattgagac tggagattcc aaaatgaacc tgaacgattt catcagtatg gatcccaagg 600
taggatgggg cgccgtctac acactatccg aatttacaca tcggtttggc agtaaaaact 660
gctgaacttg gcctcaagat gtggaactgt ggagaaattc taggacatga acaagctatc 720
ctttcatcga ggacagcaaa cattatggta cagttggctt ggaattatgt ctttctcttt 780
taatttgatt gagtggaaat ctgagtgagt acaaatataa atgaacaaca taaaaacttt 840
tgttttgaca tgtcaaattg aaacttgata aagtgcgtac ttgctaagat attcctgtgg 900
ctcatgcgtt acaacacgag gacttaagcc agtaatcgtt tttgttcaga tagaggtgtg 960
gaggtagagc cagcccctca tgtctgttct ggatgttttg tgtctctcca gctacactgt 1020
aagttccttg agggcagggc catggcccat tgctctgtga atctcaaatg cccataaaag 1080
gtgcccataa aatgttttct tgaacatttg aatgtgctgt tgtctggaaa ggggtaatat 1140
tgtgagctga atcagcaata agtattagtc tttttggact atggtattgt taasaagact 1200
gcagccctct cagacttgag cgttaattgg cttatttatt tatggcttta aataaaatcg 1260
atttaacgtt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1300
<210> 32
<211> 145
<212> PRT
<213> Homo sapiens
<400> 32
Met Ile Pro Ile Trp Lys Gln Gln Ala Arg Pro Gly Asp Gly Pro Val
1 5 10 15
Ile Trp Asp Tyr His Val Val Leu Leu His Val Ser Ser Gly Gly Gln
20 25 30
Ser Phe Ile Tyr Asp Leu Asp Thr Val Leu Pro Phe Pro Cys Leu Phe
35 40 45
Asp Thr Tyr Val Glu Asp Ala Ile Lys Ser Asp Asp Asp Ile His Pro
50 55 60
24

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
Gln Phe Arg Arg Lys Phe Arg Val Ile Cys Ala Asp Ser Tyr Leu Lys
65 70 75 80
Asn Phe Ala Ser Asp Arg Ser His Met Lys Asp Ser Ser Gly Asn Trp
85 90 95
Arg Glu Pro Pro Pro Pro Tyr Pro Cys Ile Glu Thr Gly Asp Ser Lys
100 105 110
Met Asn Leu Asn Asp Phe Ile Ser Met Asp Pro Lys Val Gly Trp Gly
115 120 125
Ala Val Tyr Thr Leu Ser Glu Phe Thr His Arg Phe Gly Ser Lys Asn
130 135 140
Cys
145
<210> 33
<211> 1256
<212> DNA
<213> Homo Sapiens
<400> 33
ctcgcttcta actggactgc acgttggtga cagcgtccca agctggtgac agacccactc 60
tgtaactttc agctagattc agccaccaga tcccagaaac atgacccttg ctgcctacaa 120
agagsagatg aaggagctcc cgctggtgtc cttgttctgc tcctgcttcc tggccgatcc 180
cctgaataag tcgtcctaca aatatgaagc agacacggtg gacctgaatt ggtgcgtcat 240
ttccgacatg gaagtcatcg agctgascaa atgcacctcg ggccaatcct ttgaagtcat 300
cctgaagcca ccctcctttg atggggttcc cgagttcaac gcctccctgc caaggcggcg 360
agacccatcc ctggaagaga tccagasgaa actagaagcg gctgaggagc gaaggaagta 420
ccaggasgcg gagctcctga aacacctagc agagaaacgg gaacatgaga gagaggtgat 480
ccaaaaggcc attgaggaaa acaacaactt catcaagatg gctaaggaaa aactggccca 540
gaagatggaa tccaacaagg agaacaggga ggcccacctc gccgccatgt tggaacggct 600
gcaagagaag gacaagcacg ccgaggaggt gcggaaaaac aaggagctga aggaagaggc 660
ctccaggtaa agcctagagg ccaaagaact ttccaggtca gccggacagc tccagcagct 720
ccacgttcca ggcagcctcg cccgccggct gcgctcccag cactggggtt tggggggagg 780
ggggtggcca aggggcgttt cctctgcttt tggtgtttgt acatgttaag aattgaccag 840
tgaagccatc ctatttgttt ccggggaaca atgaccgggt gggagagggg agaggagaga 900
gtttgggaaa gggagatgga gaagaactca aggacattgc aaccctgccc ggcgcagatc 960
tgattttcac atctctacct ggacattgag cctccaggca ccatgttgag gagagatgaa 1020
aaccagggcg gtagaacttc agggtgaagg acagagtcct gggtggggca gcggctgcag 1080
ggcgcaccag agaacccagc cagagggggt gtgagtacca gtggtgttgc ttccaccctg 1140
cagcaggtgg gatgaggtct gtgtgtgtgt gtgaaccatc attttttgat catcatgacc 1200
aatgaaacat tgaaaaaaaa aaaaaasaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 1256
<210> 34
<211> 189
<212> PRT
<213> Homo Sapiens
<400> 34
Met Thr Leu Ala Ala Tyr Lys Glu Lys Met Lys Glu Leu Pro Leu Val
1 5 10 15
Ser Leu Phe Cys Ser Cys Phe Leu Ala Asp Pro Leu Asn Lys Ser Ser
20 25 30

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
Tyr Lys Tyr Glu Ala Asp Thr Val Asp Leu Asn Trp Cys Val Ile Ser
35 40 45
Asp Met Glu Val Ile Glu Leu Asn Lys Cys Thr Ser Gly Gln Ser Phe
50 55 60
Glu Val Ile Leu Lys Pro Pro Ser Phe Asp Gly Val Pro Glu Phe Asn
65 70 75 80
Ala Ser Leu Pro Arg Arg Arg Asp Pro Ser Leu Glu Glu Ile Gln Lys
85 90 95
Lys Leu Glu Ala Ala Glu Glu Arg Arg Lys Tyr Gln Glu Ala Glu Leu
100 105 110
Leu Lys His Leu Ala Glu Lys Arg Glu His Glu Arg Glu Val Ile Gln
115 120 125
Lys Ala Ile Glu Glu Asn Asn Asn Phe Ile Lys Met Ala Lys Glu Lys
130 135 140
Leu Ala Gln Lys Met Glu Ser Asn Lys Glu Asn Arg Glu Ala His Leu
145 150 155 160
Ala Ala Met Leu Glu Arg Leu Gln Glu Lys Asp Lys His Ala Glu Glu
165 170 175
Val Arg Lys Asn Lys Glu Leu Lys Glu Glu Ala Ser Arg
180 185
<210> 35
<211> 1783
<212> DNA
<213> Homo sapiens
<400> 35
aaggataatg gcctccagct cagatggaat atctctatca tatagacctg ttgttacagg 60
gcaggatcgg atgatggaca ctgaagtcct cagcttgcta agttcagttg ctctccctag 120
cctccttttg gcttcagagt cttttgattc catctatcct ggtatttttt gtgtgctgat 180
gtttagttct ggattggttt cagctgtgct aataggsagg gcgttgtctt ttcaagcaat 240
cttaaaaggt ggtcaatcaa aaggccagag tctgastccc ttctgtggct taaataattt 300
gaggatcaag tccagtgtct tgttaatccc tgttctactg tgccagacac tatcttgaat 360
gcttttatat gttcaggttc aaaatcgctc tttcatacca ggggatgata gtaacgtgta 420
acttgcaata gattccttca tcttagtaat aagatgatca gtctagttag gacaaaatag 480
agattgaata aattaacttt tccaagttta cagagtaaaa atgagcagat ctctgcctgg 540
ttttgtgsaa aagagttagc actggtaaat agaatatttc tactcctaca ccattctttc 600
agtatatcat cactgaagac aggaagatag gcacacagat tcttcctcgt agtaattcat 660
agtgcactag gtgaaagaga tgaagtatgt attaaaagta caatgtgatg gcatttatta 720
ttcagataat cccaggattc tagaagaaaa taaagaagag tgacagttca gttagggtgt 780
gaacttccag aggagcactg cttaagctga acttgagagc attgtgcaaa agcacagtag 840
tctgttaaga actagaaata acctagcttg tgccacttcg ggagtattaa gacataagcc 900
tagaaaggta ggcaaaggtt agatcttaga ctgtcttgta tttttctcat tcctgttgat 960
tacctacctc aaaattgaat atgtttttcc tcctgcctaa cacaaaacta cccaagggca 1020
gaaatttaaa ttcttccttg gtgtatgtgc aaagaaggtt gaatatattc atgcctacct 1080
tattttggac taggaataca gtagtatact ttccgaagac ttgcctgaat agtatataag 1140
gtggaggcaa ctgactagtt aggtcagtat ttttagaaac tcttaatagc tcatactctt 1200
gataccaaaa gcagccctga ttgttaaagc acacacctgc acaagaagca gtgatggttg 1260
catttacatt tcctgggtgc acaaaaaaaa attctcaaaa agcaaggact tacgcttttt 1320
gcaaagcctt tgagaagtta ctggatcata ggaagcttat aacaagaatg gaagattctt 1380
26

CA 02327551 2000-10-31
WO 99/55721 PC'C/US99/08504
aaataactca ctttctttgg tatccagtaa cagtagatgt tcaaaatatg tagctgatta 1440
ataccagcat tgtgaacgct gtacaacctt gtggttatta ctaagcaagt tactactagc 1500
ttctgaaaag tagcttcata attaatgtta tttatacact gccttccatg acttttactt 1560
tgccctaagc taatctccaa aatctgaaat gctactccaa tatcagaaaa aaagggggag 1620
gtggaattat atttcctgtg attttaagag tacagagaat catgcacatc tctgattagt 1680
tcatatatgt ctagtgtgta ataaaagtca agatgaactc tcaaaaaaaa aaaaaaaaaa 1740
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1783
<210> 36
<211> 116
<212> PRT
<213> Homo Sapiens
<400> 36
Met Ala Ser Ser Ser Asp Gly Ile Ser Leu Ser Tyr Arg Pro Val Val
1 5 10 15
Thr Gly Gln Asp Arg Met Met Asp Thr Glu Val Leu Ser Leu Leu Ser
20 25 30
Ser Val Ala Leu Pro Ser Leu Leu Leu Ala Ser Glu Ser Phe Asp Ser
35 40 45
Ile Tyr Pro Gly Ile Phe Cys Val Leu Met Phe Ser Ser Gly Leu Val
50 55 60
Ser Ala Val Leu Ile Gly Arg Ala Leu Ser Phe Gln Ala Ile Leu Lys
65 70 75 80
Gly Gly Gln Ser Lys Gly Gln Ser Leu Asn Pro Phe Cys Gly Leu Asn
85 90 95
Asn Leu Arg Ile Lys Ser Ser Val Leu Leu Ile Pro Val Leu Leu Cys
100 105 110
Gln Thr Leu Ser
115
<210> 37
<211> 1725
<212> DNA
<213> Homo Sapiens
<400> 37
ggttggtaat aggaaatgga ggggctgctg aggtcctgtg aatgtttctg tcattgtact 60
ttcttccaga agcctgcaga gaatggaagc atcttcttta ttgtcctttc ctggcatgtc 120
catccttatt gtcactacgt tgcaactgga gtttgatttg gatctggttt taaaattctt 180
ctgtgcaata gatgggtttg aggatttagc ggccctgatg tcttggtcat agcctggtaa 240
gaatgtccat gctgaggagc cagatgttgt atttctaact gcctgagtca cacagaatag 300
ggtaagagcc tgaccccatt ctgtaaatca gaaagcaagg atggagaccc tttcctgctg 360
ctattattgg ctctctttga ggaagttgga ggttaaggaa ggaacttgtt tgtttccgta 420
tacgactcct tcttctctct agttcagtct tcagccagtc cagcgctctc ttccacactt 480
cagagcccct tcagagaaag cattagcagg aatgagacaa ggcagagctg cagtgccccc 540
tgaggcttcc acacatcttt ctgaatatta tttttcaagt aacaagggca gggacagcgg 600
aaacagctgc ccaccccccc catcccagca gctcagctaa gccctgatga gaatgaagcc 660
acaggagttg tctgaggtga acccagccgc tcagccacac atggaagcca ttgcctttgc 720
acatagttct tgggttcttt ttcctaaaaa ggtaaggagc tgaggtgtgt ggttttttaa 780
tattaagaat atataatgga aaacacacga ctgacgctca ggcatcttcc cctactcccc 840
aacagatccc cagaagacag cgtggaaggc agtgtagaca gtaaatcggg cttcagttct 900
27

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
atagccaaga agagatcagc tgctgaaacc accagtgggt accccaggcc acctgccttt 960
gaacttgggg atttgccatg tctgatcttg tcacatactt gcttttttac aagatgaact 1020
ctttgtattt atgatttggg gggcaatgaa aggtgcaatg caggaactgc tgctgccgag 1080
ctcgctggtc acatgggggt gccaggcggg attctggaaa accagtgcac ttaaactgat 1140
cctgaagaga gctgtcccag cactctggcc accaggaggg ccagattccc cagaaactac 1200
cttttgccca aagaacatgc tcagtatttg gggcatttcc tcccacaaac cctgactgct 1260
tctgttacct cagggccttg gtacctggat actgccacag aattggggcg ggtgggggag 1320
gggcctattt ttaaataaaa taactgttca aagttggggg ttttttaaaa aattaagaaa 1380
aaggaaagct attctgtatt gcaccttttc acaatttaat acattttctt acattttcct 1440
gtgattttcg aaactaaacc attgtgtgtc ctgtagtgtc ctggttgagc tgccgctcag 1500
cagcttcctc ggggggattt ggaacacctg tgtctgtcgc cgcactgcct gtgggagggg 1560
cccagagggc tgctgggact ggcgtctgta cacacttgtt tggccttttc tgtagttgat 1620
gctgtaaact ctatggcttt ttaaaaacga tttcatgttt ttatttagta ttggaaatcc 1680
aatacacttt tttaatccaa tcaaaaaaaa aaaaaaaaaa aaaaa 1725
<210> 38
<211> 74
<212> PRT
<213> Homo Sapiens
<400> 38
Met Ile Trp Gly Ala Met Lys Gly Ala Met Gln Glu Leu Leu Leu Pro
1 5 10 15
Ser Ser Leu Val Thr Trp Gly Cys Gln Ala Gly Phe Trp Lys Thr Ser
20 25 30
Ala Leu Lys Leu Ile Leu Lys Arg Ala Val Pro Ala Leu Trp Pro Pro
35 40 45
Gly Gly Pro Asp Ser Pro Glu Thr Thr Phe Cys Pro Lys Asn Met Leu
50 55 60
Ser Ile Trp Gly Ile Ser Ser His Lys Pro
65 70
<210> 39
<211> 1953
<212> DNA
<213> Homo sapiens
<400> 39
gcccttcagg ctctgtctct gtggagactg ggctttggga gggagaaaga gggacctagc 60
gcgggccgcg caggcgcacg gtgggcagct gcaatggcgc tgtcgtgtac ccttaacagg 120
tatctgctcc tcatggcgca ggagcatctg gagttccgcc tgccggaaat aaagtctttg 180
cttttgcttt ttggaggtca gtttgccagc agtcaagaaa cttatggaaa gtcaccattt 240
tggattctta gcattccctc tgaagatatt gcaagaaatt tgatgaaacg gacagtgtgt 300
gccaagtcta tatttgaact atggggtcat ggacaatctc ctgaggagct gtacagttct 360
cttaaaaact accctgtgga gaagatggtt ccatttctac attcggactc tacatataaa 420
ataaagattc acacttttaa taagacattg acacaagaag agaaaatcaa gcgaatagat 480
gcacttgaat ttctgccatt tgaaggaaaa gtgaatttaa agaaaccgca acatgtattt 540
tctgttttgg aggattatgg tttagaccca aactgcatcc ctgagaatcc acataatatt 600
tattttggta gatggattgc agatggacag agagagctta ttgagtcata cagtgtcaaa 660
aagagacact ttattggaaa tacaagtatg gatgctggtt tgtcattcat tatggctaac 720
catggaaaag tgaaagaaaa tgatattgtc tttgatccat ttgttggaac aggtggcctg 780
ctgatagcat gtgctcattt tggtgcatat gtgtatggga cagacataga ctacaacaca 840
gttcatggct tgggaaaggc tactaggaaa aaccagaagt ggagaggacc agatgaaaac 900
attagggcca atcttcgtca atatggttta gagaagtatt accttgatgt cctggtttca 960
gatgcatcta aaccttcctg gaggaagggc acatattttg atgcaatcat tactgatcct 1020
28

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
ccatatggta tcagagaatc tacaagaaga acaggttcac agaaggagat accaaagggg 1080
atagaaaaat gggaaaaatg tccagaaagc catgttcctg tttccttgag ttatcatctg 1140
agtgatatgt ttcttgacct gttaaacttc gcagctgaga ccctcgtttt aggtggaaga 1240
ctagtctatt ggttaccggt gtatacgcca gaatacactg aagagatggt gccttggcac 1260
ccttgcctgg aactcgttag caactgcgag cagaagcttt ccagtcacac atcaaggcgc 1320
ttgatcacaa tggaaaaggt gaagaaattt gagaatcggg accagtattc acatctgcta 1380
agtgatcatt ttctgccata ccaaggtcat aattccttcc gtgagaaata ttttagtggg 1440
gtaacaaaaa gaattgccaa ggaagaaaaa tccacccagg aatgaaaatt aagattttga 1500
caatgaagaa agaataagaa tttgatttaa aaagacatct ggatgtgaac tttcatgtat 1560
gatccagaaa ataggtacgg ttttaaaata ttttatatag aaaagctaca aagtaaattg 1620
agcaatgctt ttaaagttat ctttgtttta tagacttttt tgttgtatgt attacagtct 1680
ttataatctt atttaatgta tatttgtact ttcaagtact gatggagata gactcaaaac 1740
agttattttt ttacaattaa tctacaaagg gaattaatat tgttgacttt taaaacatct 1800
gctggatata ttatatgcaa ttaatagtag ttaagaattt attcatttgg tagatatgtt 1860
tatttggttt ttggttgtca tcgatttaca ttgccactaa taaaccatat tgagaatttc 1920
taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1953
<210> 40
<211> 463
<212> PRT
<213> Homo Sapiens
<400> 40
Met Ala Leu Ser Cys Thr Leu Asn Arg Tyr Leu Leu Leu Met Ala Gln
1 5 10 15
Glu His Leu Glu Phe Arg Leu Pro Glu Ile Lys Ser Leu Leu Leu Leu
20 25 30
Phe Gly Gly Gln Phe Ala Ser Ser Gln Glu Thr Tyr Gly Lys Ser Pro
35 40 45
Phe Trp Ile Leu Ser Ile Pro Ser Glu Asp Ile Ala Arg Asn Leu Met
50 55 60
Lys Arg Thr Val Cys Ala Lys Ser Ile Phe Glu Leu Trp Gly His Gly
65 70 75 8~
Gln Ser Pro Glu Glu Leu Tyr Ser Ser Leu Lys Asn Tyr Pro Val Glu
85 90 95
Lys Met Val Pro Phe Leu His Ser Asp Ser Thr Tyr Lys Ile Lys Ile
100 105 110
His Thr Phe Asn Lys Thr Leu Thr Gln Glu Glu Lys Ile Lys Arg Ile
115 120 125
Asp Ala Leu Glu Phe Leu Pro Phe Glu Gly Lys Val Asn Leu Lys Lys
130 135 140
Pro Gln His Val Phe Ser Val Leu Glu Asp Tyr Gly Leu Asp Pro Asn
145 150 155 160
Cys Ile Pro Glu Asn Pro His Asn Ile Tyr Phe Gly Arg Trp Ile Ala
165 170 175
Asp Gly Gln Arg Glu Leu Ile Glu Ser Tyr Ser Val Lys Lys Arg His
180 185 190
Phe Ile Gly Asn Thr Ser Met Asp Ala Gly Leu Ser Phe Ile Met Ala
29

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
195 200 205
Asn His GIy Lys Val Lys Glu Asn Asp Ile Val Phe Asp Pro Phe Val
220 215 220
Gly Thr Gly Gly Leu Leu Ile Ala Cys Ala His Phe Gly Ala Tyr Val
225 230 235 240
Tyr Gly Thr Asp Ile Asp Tyr Asn Thr Val His Gly Leu Gly Lys Ala
245 250 255
Thr Arg Lys Asn Gln Lys Trp Arg Gly Pro Asp Glu Asn Ile Arg Ala
260 265 270
Asn Leu Arg Gln Tyr Gly Leu Glu Lys Tyr Tyr Leu Asp Val Leu Val
275 280 285
Ser Asp Ala Ser Lys Pro Ser Trp Arg Lys Gly Thr Tyr Phe Asp Ala
290 295 300
Ile Ile Thr Asp Pro Pro Tyr Gly Ile Arg Glu Ser Thr Arg Arg Thr
305 310 315 320
Gly Ser Gln Lys Glu Ile Pro Lys Gly Ile Glu Lys Trp Glu Lys Cys
325 330 335
Pro Glu Ser His Val Pro Val Ser Leu Ser Tyr His Leu Ser Asp Met
340 345 350
Phe Leu Asp Leu Leu Asn Phe Ala Ala Glu Thr Leu Val Leu Gly Gly
355 360 365
Arg Leu Val Tyr Trp Leu Pro Val Tyr Thr Pro Glu Tyr Thr Glu Glu
370 375 380
Met Val Pro Trp His Pro Cys Leu Glu Leu Val Ser Asn Cys Glu Gln
385 390 395 400
Lys Leu Ser Ser His Thr Ser Arg Arg Leu Ile Thr Met Glu Lys Val
405 410 415
Lys Lys Phe Glu Asn Arg Asp Gln Tyr Ser His Leu Leu Ser Asp His
420 425 430
Phe Leu Pro Tyr Gln Gly His Asn Ser Phe Arg Glu Lys Tyr Phe Ser
435 440 445
Gly Val Thr Lys Arg Ile Ala Lys Glu Glu Lys Ser Thr Gln Glu
450 455 460
<210> 41
<211> 1605
<212> DNA
<213> Homo Sapiens
<400> 41
agggagattc ctcgaaacta gtgtgtgttt attaaaagga gaaaggataa caatagaatg 60
ttctaaaacc agaagtccaa gtgcgtgtct acttatggga ccaataaata aagaacagac 120
atttgatttg aggtgaggta aaagcctgaa acatggaatg gcattctgtt ttgatggatt 180

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
ttcatttctt cgcacttctg agacggcaaa gccaaccact tagaagcctt ccacatcttt 240
gtcacctgcc tggctcctgc tctctgatgt acctctgggt agtgagatgg aaatggtgcc 300
tgcagaagtt ggggagaagg atacttttgc acagcctcca tgatgtcttt attgcaaata 360
tggatgacaa gggtctctgt tacaggggcc tcagagcacc ttcgtttctc ctctagacca 420
gggacaggtg tagagataag gactggcaac cagagcctca gcatccaaag atggactgaa 480
gtgggatggc tgacaggcac ataacttacg ggaaagggaa tttcatacat acgatttttg 540
ttttgtgggt aggagggctt atcatcaaca ctgattttat aatctgacaa taaatgtctt 600
tcattaaaga gtttacctaa atgatgttcg attatatgta taatttataa aatatttatg 660
tatagtttgt ttattcaggt atatgtataa tttattgaac acctactatg tcccagcata 720
tctacaaaac tgggtacata catactgtct aactgctaat ccacatttcc agtcttacaa 780
aggacataat gattagttaa gccctaattt agatttgagg aaactgaagc tgagagaggg 840
ttaagtaaat tacccaaagt acagctaata agacccagaa tctcagtctc actccttggg 900
atcctgtgta tttccctgag tcttctaaca tatgaaaatt catatctaaa tcaacaagtg 960
actgtaatct ggtactataa atactaaata aacacttctt cataacactg taccaattca 1020
gcttttaaat tttattactt tgctttcctg tcctttgcca actcttaacc tagttaatcc 1080
tagttctgtt gacattggac caggctcagt aaataaacga atggatttcc agcctttttt 1140
tcccatctgt tcctgctttt agtcctctga atctgcttct tttcttactg ctgctttatt 1200
ttacagtgat tttgtcaaac atagaataca ggactaaaaa tgcaaagaaa ttgggtctgt 2260
gtttaatttt gatgtttcaa attttgagct tccaagtctt tgtggccacc caatgaagtt 1320
tgagtctgcc tgttcagatg tgaaaggtaa gggctgcagc aggtttaagg gtggcccttc 1380
accaccctgt tgtcacctgc acaggcactc ccccatttgc agatgaagaa atgttcagag 1440
aagaaaaatg atggaccaaa cgtctgtttg cacaattgaa actctaccag tggactattc 1500
tattttcaca gctacctagt ttctgccgat gattttttta aatgtgaaat aaacagtgat 1560
actttaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 1605
<210> 42
<211> 87
<212> PRT
<213> Homo sapiens
<400> 42
Met Glu Trp His Ser Val Leu Met Asp Phe His Phe Phe Ala Leu Leu
1 5 10 15
Arg Arg Gln Ser Gln Pro Leu Arg Ser Leu Pro His Leu Cys His Leu
20 25 30
Pro Gly Ser Cys Ser Leu Met Tyr Leu Trp Val Val Arg Trp Lys Trp
35 40 45
Cys Leu Gln Lys Leu Gly Arg Arg Ile Leu Leu His Ser Leu His Asp
50 55 60
Val Phe Ile Ala Asn Met Asp Asp Lys Gly Leu Cys Tyr Arg Gly Leu
65 70 75 80
Arg Ala Pro Ser Phe Leu Leu
<210> 43
<211> 1936
<212> DNA
<213> Homo sapiens
<400> 43
agaaactccc atctccctca ccagccggaa agtacgagtc ggctcagcct ggagggaccc 60
aaccagagcc tggcctggga gccaggatgg ccatccacaa agccttggtg atgtgcctgg 120
gactgcctct cttcctgttc ccaggggcct gggcccaggg ccatgtccca cccggctgca 180
gccaaggcct caaccccctg tactacaacc tgtgtgaccg ctctggggcg tggggcatcg 240
3I

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
tcctggaggc cgtggctggg gcgggcattg tcaccacgtt tgtgctcacc atcatcctgg 300
tggccagcct cccctttgtg caggacacca agaaacggag cctgctgggg acccaggtat 360
tcttccttct ggggaccctg ggcctcttct gcctcgtgtt tgcctgtgtg gtgaagcccg 420
acttctccac ctgtgcctct cggcgcttcc tctttggggt tctgttcgcc atctgcttct 480
cttgtctggc ggctcacgtc tttgccctca acttcctggc ccggaagaac cacgggcccc 540
ggggctgggt gatcttcact gtggctctgc tgctgaccct ggtagaggtc atcatcaata 600
cagagtggct gatcatcacc ctggttcggg gcagtggcga gggcggccct cagggcaaca 660
gcagcgcagg ctgggccgtg gcctccccct gtgccatcgc caacatggac tttgtcatgg 720
cactcatcta cgtcatgctg ctgctgctgg gtgccttcct gggggcctgg cccgccctgt 780
gtggccgcta caagcgctgg cgtaagcatg gggtctttgt gctcctcacc acagccacct 840
ccgttgccat atgggtggtg tggatcgtca tgtatactta cggcaacaag cagcacaaca 900
gtcccacctg ggatgacccc acgctggcca tcgccctcgc cgccaatgcc tgggccttcg 960
tcctcttcta cgtcatcccc gaggtctccc aggtgaccaa gtccagccca gagcaaagct 1020
accaggggga catgtacccc acccggggcg tgggctatga gaccatcctg aaagagcaga 1080
agggtcagag catgttcgtg gagaacaagg ccttttccat ggatgagccg gttgcagcta 1140
agaggccggt gtcaccatac agcgggtaca atgggcagct gctgaccagt gtgtaccagc 1200
ccactgagat ggccctgatg cacaaagttc cgtccgaagg agcttacgac atcatcctcc 1260
cacgggccac cgccaacagc caggtgatgg gcagtgccaa ctcgaccctg cgggctgaag 1320
acatgtactc ggcccagagc caccaggcgg ccacaccgcc gaaagacggc aagaactctc 1380
aggtctttag aaacccctac gtgtgggact gagtcagcgg tggcgaggag aggcggtcgg 1440
atttggggag ggccctgagg acctggcccc gggcaaggga ctctccaggc tcctcctccc 1500
cctggcaggc ccagcaacat gtgccccaga tgtggaaggg cctccctctc tgccagtgtt 1560
tgggtgggtg tcatgggtgt ccccacccac tcctcagtgt ttgtggagtc gaggagccaa 1620
ccccagcctc ctgccaggat cacctcggcg gtcacactcc agccasatag tgttctcggg 1680
gtggtggctg ggcagcgcct atgtttctct ggagattcct gcaacctcaa gagacttccc 1740
aggcgctcag gcctggatct tgctcctctg tgaggaacaa gggtgcctaa taaatacatt 1800
tctgctttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1860
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1920
aaaaaaaaaa aaaaaa 1936
<210> 44
<211> 441
<212> PRT
<213> Homo sapiens
<400> 44
Met Ala Ile His Lys Ala Leu Val Met Cys Leu Gly Leu Pro Leu Phe
1 5 10 15
Leu Phe Pro Gly Ala Trp Ala Gln Gly His Val Pro Pro Gly Cys Ser
20 25 30
Gln Gly Leu Asn Pro Leu Tyr Tyr Asn Leu Cys Asp Arg Ser Gly Ala
35 40 45
Trp Gly Ile Val Leu Glu Ala Val Ala Gly Ala Gly Ile Val Thr Thr
50 55 60
Phe Val Leu Thr Ile Ile Leu Val Ala Ser Leu Pro Phe Val Gln Asp
65 70 75 80
Thr Lys Lys Arg Ser Leu Leu Gly Thr Gln Val Phe Phe Leu Leu Gly
85 90 95
Thr Leu Gly Leu Phe Cys Leu Val Phe Ala Cys Val Val Lys Pro Asp
100 105 110
Phe Ser Thr Cys Ala Ser Arg Arg Phe Leu Phe Gly Val Leu Phe Ala
115 120 125
32

CA 02327551 2000-10-31
WO 99/55721 PC'T/US99/08504
Ile Cys Phe Ser Cys Leu Ala Ala His Val Phe Ala Leu Asn Phe Leu
130 135 140
Ala Arg Lys Asn His Gly Pro Arg Gly Trp Val Ile Phe Thr Val Ala
145 150 155 160
Leu Leu Leu Thr Leu Val Glu Val Ile Ile Asn Thr Glu Trp Leu Ile
165 170 175
Ile Thr Leu Val Arg Gly Ser Gly Glu Gly Gly Pro Gln Gly Asn Ser
180 185 190
Ser Ala Gly Trp Ala Val Ala Ser Pro Cys Ala Ile Ala Asn Met Asp
195 200 205
Phe Val Met Ala Leu Ile Tyr Val Met Leu Leu Leu Leu Gly Ala Phe
210 215 220
Leu Gly Ala Trp Pro Ala Leu Cys Gly Arg Tyr Lys Arg Trp Arg Lys
225 230 235 240
His Gly Val Phe Val Leu Leu Thr Thr Ala Thr Ser Val Ala Ile Trp
245 250 255
Val Val Trp Ile Val Met Tyr Thr Tyr Gly Asn Lys Gln His Asn Ser
260 265 270
Pro Thr Trp Asp Asp Pro Thr Leu Ala Ile Ala Leu Ala Ala Asn Ala
275 280 285
Trp Ala Phe Val Leu Phe Tyr Val Ile Pro Glu Val Ser Gln Val Thr
290 295 300
Lys Ser Ser Pro Glu Gln Ser Tyr Gln Gly Asp Met Tyr Pro Thr Arg
305 310 315 320
Gly Val Gly Tyr Glu Thr Ile Leu Lys Glu Gln Lys Gly Gln Ser Met
325 330 335
Phe Val Glu Asn Lys Ala Phe Ser Met Asp Glu Pro Val Ala Ala Lys
340 345 350
Arg Pro Val Ser Pro Tyr Ser Gly Tyr Asn Gly Gln Leu Leu Thr Ser
355 360 365
Val Tyr Gln Pro Thr Glu Met Ala Leu Met His Lys Val Pro Ser Glu
370 375 380
Gly Ala Tyr Asp Ile Ile Leu Pro Arg Ala Thr Ala Asn Ser GIn Val
385 390 395 400
Met Gly Ser Ala Asn Ser Thr Leu Arg Ala Glu Asp Met Tyr Ser Ala
405 410 415
Gln Ser His Gln Ala Ala Thr Pro Pro Lys Asp Gly Lys Asn Ser Gln
420 425 430
Val Phe Arg Asn Pro Tyr Val Trp Asp
435 440
33

CA 02327551 2000-10-31
WO 99/55721 PCT/US99I08504
<210> 45
<211> 1773
<212> DNA
<213> Homo Sapiens
<400> 45
cgcgccgcgc cttcccctgc aaggatgcgg ccctctgcgc ctacgcggtc acctacacag 60
cgatgtacgt gactctcgtg ttccgcgtga agggctcccg cctggtcaaa ccctcgctct 120
gcctggcctt gctgtgcccg gccttcctgg tgggcgtggt ccgcgtggcc gagtaccgaa 180
accactggtc ggacgtgctg gctggcttcc tgacaggggc ggccatcgcc acctttttgg 240
tcacctgcgt tgtgcataac tttcagagcc ggccaccctc tggccgaagg ctctctccct 300
gggaggacct gggccaagcc cccaccatgg atagccccct cgaaaagaac ccgaggtctg 360
caggccgcat tcgacaccgg cacggctcac cccatccaag tcgcagaact gcgcccgccg 420
tggccacctg atccccagct gtgtctcctc cagggcccca gccatgtgtt cgtcgccccg 480
tgtgccccgt cctcgattga ggtctgagcc gacgcccttg cccctgcccc tacccctgcc 540
agcgcccacc cccagccagg gcccctcgcc ttcctcccct ggacctgggg ggccaggcgg 600
gggtggtgga cgtggccgga agctgctgct gcccacgccc ctgctgcggg acctgtacac 660
cctgagtgga ctctatccct cccccttcca ccgggacaac ttcagccctt acctgtttgc 720
cagccgtgac cacctgctgt gaggcccgac cacccaccca gaatctgccc agtccccact 780
tcttccctgc cacgcgtgtg tgtgcgtgtg ccacgtgagt gccaaagtcc cctgcccccc 840
aagccagcca gacccagaca ttagtaagat ggctagaagg acatttagga gacatctgcc 900
tctctggccc tctgagatat cccgatgggc acaaatggaa ggtgcgcact tgcccctact 960
attgcccttt taagggccaa agcttgaccc cattggccat tgcctggcta atgagaaccc 1020
ctggttctca gaattttaac caaaaggagt tggctccaac caatgggagc cttcccctca 1080
cttcttagaa tcctcctgca agagggcaac tccagccagt gttcagcgac tgaacagcca 1140
ataggagccc ttggtttcca gaatttctag agtgggtggg catgattcca gtcaatgggg 1200
gaccgcccgt gtctaagcat gtgcaaagga gaggagggag atgaggtcat tgtttgtcat 1260
tgagtcttct ctcagaatca gcgagcccag ctgtagggtg gggggcaggc tcccccatgg 1320
cagggtcctt ggggtacccc ttttcctctc agcccctccc tgtgtgcggc ctctccacct 1380
ctcacccact ctctcctaat cccctactta agtagggctt gccccacttc agaggttttg 1440
gggttcaggg tgctgtgtct ccccttgcct gtgcccaggt catcccaaac ccttctgtta 1500
tttattaggg ctgtgggaag ggtttttctt ctttttcttg gaacctgccc ctgttcttca 1560
cactgccccc catgcctcag cctcatacag atgtgccatc atggggggca tgggtggagc 1620
agaggggctc cctcaccccg ggcaggcaas ggcagtgggt agaggaggca ctgcccccct 1680
ttcctgcccc ctcctcatct ttaataaaga cctggcttct catctttaat aaagacctgt 1740
ttgtaacaga aaaaaaaaaa aaaaaaaaaa aaa 1773
<210> 46
<211> 122
<212> PRT
<213> Homo Sapiens
<400> 46
Met Tyr Val Thr Leu Val Phe Arg Val Lys Gly Ser Arg Leu Val Lys
1 5 10 15
Pro Ser Leu Cys Leu Ala Leu Leu Cys Pro Ala Phe Leu Val Gly Val
20 25 30
Val Arg Val Ala Glu Tyr Arg Asn His Trp Ser Asp Val Leu Ala Gly
35 40 45
Phe Leu Thr Gly Ala Ala Ile Ala Thr Phe Leu Val Thr Cys Val Val
50 55 60
His Asn Phe Gln Ser Arg Pro Pro Ser Gly Arg Arg Leu Ser Pro Trp
65 70 75 80
Glu Asp Leu Gly Gln Ala Pro Thr Met Asp Ser Pro Leu Glu Lys Asn
34

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
85 90 95
Pro Arg Ser Ala Gly Arg Ile Arg His Arg His Gly Ser Pro His Pro
100 105 110
Ser Arg Arg Thr Ala Pro Ala Val Ala Thr
115 120
<210> 47
<211> 1974
<212> DNA
<213> Homo sapiens
<400> 47
tctgcatcct tcccgacctt cccagcaata tgcatcttgc acgtctggtc ggctcctgct 60
ccctccttct gctactgggg gccctgtctg gatgggcggc cagcgatgac cccattgaga 120
aggtcattga agggatcaac cgagggctga gcaatgcaga gagagaggtg ggcaaggccc 180
tggatggcat caacagtgga atcacgcatg ccggaaggga agtggagasg gttttcaacg 240
gacttagcaa catggggagc cacaccggca aggagttgga caaaggcgtc caggggctca 300
accacggcat ggacaaggtt gcccatgaga tcaaccatgg tattggacaa gcaggaaagg 360
aagcagagaa gcttggccat ggggtcaaca acgctgctgg acaggttggg aaggaggcag 420
acaaactgat ccatcatggg gtccatcacg gggccaacca ggcgggaagt gaggcaggga 480
agtttggcca gggagtcgac aatgctgcag ggcaggctgg aaatgaggct gggaggtttg 540
gccagggagt ccaccatgct gcagggcagg ccggaaatga ggctgggagg tttggccagg 600
gagtccacca tgctgcaggg caggccggaa atgaggctgg gagatttggc cagggggccc 660
accatggtct cagtgagggc tggaaggaga cagagaagtt tggccagggg atccaccatg 720
ctgccggtca ggttgggaag gaggcagaga agtttggcca gggggcccac catgctgcgg 780
ggcaggccgg aaatgaggca gggagatttg gccagggggt ccaccatggt ctcagtgagg 840
gctggaagga gacagagaag tttggccagg gggtccacca tactgctggt caggttggga 900
aggaggcaga gaagtttggc cagggggccc accatgctgc ggggcaggcc ggaaatgagg 960
cagggagatt tggccagggg gcccaccatg ctgcggggca ggccggaaat gaggctggga 1020
ggtttggcca gggggtccac catggtctca gtgagggctg gaaggagaca gagaagtttg 1080
gccagggggt ccaccatgct gccagtcagt ttgggaagga aacagagaag ctcggccatg 1140
gggtccacca tggggttaat gaggcctgga aggaagcaga gaagtttggc cagggtgtcc 1200
accatgctgc ctcgcaggtg gggaaggagg aagacagagt ggtccaaggc ctccatcatg 1260
gcgttagtca ggctggaagg gagggggggc agtttggcca cgacattcac cacacagcag 1320
ggcaggctgg gaaagaggga gacatagcag ttcatggtgt ccaacctggg gtccacgagg 1380
ccgggaagga ggcagggcag tttggccagg gagttcacca tacccttgaa caggccggga 1440
aggaagcaga caaagcggtc caagggttcc acactggggt ccaccaggct gggaaggaag 1500
cagagaaact tggccaaggg gtcaaccatg ctgctgacca ggctggaaag gaagtggaga 1560
agcttggcca aggtgcccac catgctgctg gccaggccgg gaaggagctg cagaatgctc 1620
ataatggggt caaccaagcc agcaaggagg ccaaccagct gctgaatggc aaccatcaaa 1680
gcggatcttc cagccatcaa ggaggggcca caaccacgcc gttagcctct ggggcctcag 1740
tcaacacgcc tttcatcaac cttcccgccc tgtggaggag cgtcgccaac atcatgccct 1800
aaactggcat ccggccttgc tgggagaata atgtcgccgt tgtcacatca gctgacatga 1860
cctggagggg ttgggggtgg gggacaggtt tctgaaatcc ctgaaggggg ttgtactggg 1920
atttgtgaat aaacttgata cactatgctg tcaaaaaaaa aaaaaaaaaa aaaa 1974
<210> 48
<211> 590
<212> PRT
<213> Homo sapiens
<400> 4B
Met His Leu Ala Arg Leu Val Gly Ser Cys Ser Leu Leu Leu Leu Leu
1 5 10 15
Gly Ala Leu Ser Gly Trp Ala Ala Ser Asp Asp Pro Ile Glu Lys Val
20 25 30

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
Ile Glu Gly Ile Asn Arg Gly Leu Ser Asn Ala Glu Arg Glu Val Gly
35 90 45
Lys Ala Leu Asp Gly Ile Asn Ser Gly Ile Thr His Ala Gly Arg Glu
50 55 60
Val Glu Lys Val Phe Asn Gly Leu Ser Asn Met Gly Ser His Thr Gly
65 70 75 80
Lys Glu Leu Asp Lys Gly Val Gln Gly Leu Asn His Gly Met Asp Lys
85 90 95
Val Ala His Glu Ile Asn His Gly Ile Gly GIn Ala Gly Lys Glu Ala
100 105 110
Glu Lys Leu Gly His Gly Val Asn Asn Ala Ala Gly Gln Val Gly Lys
115 120 125
Glu Ala Asp Lys Leu Ile His His Gly Val His His Gly Ala Asn Gln
130 135 140
Ala Gly Ser Glu Ala Gly Lys Phe Gly Gln Gly Val Asp Asn Ala Ala
145 150 155 160
Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His
165 170 175
Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val
180 185 190
His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln
195 200 205
Gly Ala His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe
210 215 220
Gly Gln Gly Ile His His Ala Ala Gly Gln Val Gly Lys Glu Ala Glu
225 230 235 240
Lys Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu
245 250 255
Ala Gly Arg Phe Gly Gln Gly Val His His Gly Leu Ser Glu Gly Trp
260 265 270
Lys Glu Thr Glu Lys Phe Gly Gln Gly Val His His Thr Ala Gly Gln
275 280 285
Val Gly Lys Glu Ala Glu Lys Phe Gly Gln Gly Ala His His Ala Ala
290 295 300
Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Ala His His
305 310 315 320
Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val
325 330 335
His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln
340 345 350
36

CA 02327551 2000-10-31
WO 99/55721 1'CTIUS99/0$504
Gly Val His His Ala Ala Ser Gln Phe Gly Lys Glu Thr Glu Lys Leu
355 360 365
Gly His Gly Val His His Gly Val Asn Glu Ala Trp Lys Glu Ala Glu
370 375 380
Lys Phe Gly Gln Gly Val His His Ala Ala Ser Gln Val Gly Lys Glu
385 390 395 400
Glu Asp Arg Val Val Gln Gly Leu His His Gly Val Ser Gln Ala Gly
405 410 415
Arg Glu Gly Gly Gln Phe Gly His Asp Ile His His Thr Ala Gly Gln
420 425 430
Ala Gly Lys Glu Gly Asp Ile Ala Val His Gly Val Gln Pro Gly Val
435 440 445
His Glu Ala Gly Lys Glu Ala Gly Gln Phe Gly Gln Gly Val His His
450 455 460
Thr Leu Glu Gln Ala Gly Lys Glu Ala Asp Lys Ala Val Gln Gly Phe
465 470 475 480
His Thr Gly Val His Gln Ala Gly Lys Glu Ala Glu Lys Leu Gly Gln
485 490 495
Gly Val Asn His Ala Ala Asp Gln Ala Gly Lys Glu Val Glu Lys Leu
500 505 510
Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Lys Glu Leu Gln
515 520 525
Asn Ala His Asn Gly Val Asn Gln Ala Ser Lys Glu Ala Asn Gln Leu
530 535 540
Leu Asn Gly Asn His Gln Ser Gly Ser Ser Ser His Gln Gly Gly Ala
545 550 555 560
Thr Thr Thr Pro Leu Ala Ser Gly Ala Ser Val Asn Thr Pro Phe Ile
565 570 575
Asn Leu Pro Ala Leu Trp Arg Ser Val Ala Asn Ile Met Pro
580 585 590
<210> 49
<211> 923
<212> DNA
<213> Homo sapiens
<400> 49
gagagctgga tccttgaaaa tctactctat cagctgctgt ggttgccacc attctcagga 60
ccctcgccat gaaagccctt atgctgctca ccctgtctgt tctgctctgc tgggtctcag 120
ctgacattcg ctgtcactcc tgctacaagg tccctgtgct gggctgtgtg gaccggcagt 180
cctgccgcct ggagccagga cagcaatgcc tgacaacaca tgcatacctt ggtaagatgt 240
gggttttctc caatctgcgc tgtggcacac cagaagagcc ctgtcaggag gccttcaacc 300
aaaccaaccg taagctgggt ctgacatata acaccacctg ctgcaacaag gacaactgca 360
acagcgcagg accccggccc actccagccc tgggccttgt cttccttacc tccttggctg 420
37

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
gccttggcct ctggctgctg cactgagact cattccattg gctgcccctc ctcccacctg 480
ccttggcctg agcctctctc cctgtgtctc tgtatcccct ggctttacag aatcgtctct 540
ccctagctcc catttcttta attaaacact gttccgagtg gtctcctcat ccgtccttcc 600
cacctcacac ccttcactct cctttttctg ggtcccttcc cacttccttc caggacctcc 660
attggctcct agaagggctc cccactttgc ttcctatact ctgctgtccc ctacttgagg 720
agggattggg atctggggcc tgaaatgggg cttctgtgtt gtccccagtg aaggctccca 780
caaggacctg atgacctcac tgtacagagc tgactcccca aatccaggct cccatatgta 840
ccccatcccc catactcacc tctttccatt ttgagtaata aatgtctgag tctgaaaaaa 900
aaaaaaaaaa aaaaaaaaaa aaa 923
<210> 50
<211> 125
<212> PRT
<213> Homo Sapiens
<400> 50
Met Lys Ala Leu Met Leu Leu Thr Leu Ser Val Leu Leu Cys Trp Val
1 5 10 15
Ser Ala Asp Ile Arg Cys His Ser Cys Tyr Lys Val Pro Val Leu Gly
20 25 30
Cys Val Asp Arg Gln Ser Cys Arg Leu Glu Pro Gly Gln Gln Cys Leu
35 40 45
Thr Thr His Ala Tyr Leu Gly Lys Met Trp Val Phe Ser Asn Leu Arg
50 55 60
Cys Gly Thr Pro Glu Glu Pro Cys Gln Glu Ala Phe Asn Gln Thr Asn
65 70 75 80
Arg Lys Leu Gly Leu Thr Tyr Asn Thr Thr Cys Cys Asn Lys Asp Asn
85 90 95
Cys Asn Ser Ala Gly Pro Arg Pro Thr Pro Ala Leu Gly Leu Val Phe
100 105 110
Leu Thr Ser Leu Ala Gly Leu Gly Leu Trp Leu Leu His
115 120 125
<210> 51
<211> 1493
<212> D13A
<213> Homo Sapiens
<400> 51
ggagaagccc aggcagttga ggacaggaga gagaaggctg cagacccaga gggagggagg 60
acagggagtc ggaaggagga ggacagagga gggcacagag acgcagagca agggcggcaa 120
ggaggagacc ctggtgggag gaagacactc tggagagaga gggggctggg cagagatgaa 180
gttccagggg cccctggcct gcctcctgct ggccctctgc ctgggcagtg gggaggctgg 240
ccccctgcag agcggagagg aaagcactgg gacaaatatt ggggaggccc ttggacatgg 300
cctgggagac gccctgagcg aaggggtggg aaaggccatt ggcaaagagg ccggaggggc 360
agctggctct aaagtcagtg aggcccttgg ccaagggacc agagaagcag ttggcactgg 420
agtcaggcag gttccaggct ttggcgtagc agatgctttg ggcaacaggg tcggggaagc 480
agcccatgct ctgggaaaca ctgggcacga gattggcaga caggcagaag atgtcattcg 540
acacggagca gatgctgtcc gcggctcctg gcagggggtg cctggccaca atggtgcttg 600
ggaaacttct ggaggccatg gcatctttgg ctctcaaggt ggccttggag gccagggcca 660
gggcaatcct ggaggtctgg ggactccgtg ggtccacgga taccccggaa actcagcagg 720
cagctttgga atgaatcctc agggagctcc ctggggtcaa ggaggcaatg gagggccacc 780
38

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
aaactttggg accaacactc agggagctgt ggcccagcct ggctatggtt cagtgagagc 840
cagcaaccag aatgaagggt gcacgaatcc cccaccatct ggctcaggtg gaggctccag 900
caactctggg ggaggcagcg gctcacagtc gggcagcagt ggcagtggca gcaatggtga 960
caacaacaat ggcagcagca gtggtggcag cagcagtggc agcagcagtg gcggcagcag 1020
tggcggcagc agtggtggca gcagtggcaa cagtggtggc agcagaggtg acagcggcag 1080
tgagtcctcc tggggatcca gcaccggctc ctcctccggc aaccacggtg gagcggcgga 1140
ggaaatggac ataaacccgg gaactctgag acgtctcctg ggatgtttaa ctttgacact 1200
ttctggaaga attttaaatc caagctgggt ttcatcaact gggatgccat aaacaaggac 1260
cagagaagct ctcgcatccc gtgacctcca gacaaggagc caccagattg gatgggagcc 1320
cccacactcc ctccttaaaa caccaccctc tcatcactaa tctcagccct tgcccttgaa 1380
ataaacctta gctgccccac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1440
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1493
<210> 52
<211> 358
<212> PRT
<213> Homo sapiens
<400> 52
Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu
1 5 10 15
Gly Ser Gly Glu Ala Gly Pro Leu Gln Ser Gly Glu Glu Ser Thr Gly
20 25 30
Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp Ala Leu Ser
35 40 45
Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly Gly Ala Ala Gly
50 55 60
Ser Lys Val Ser Glu Ala Leu Gly Gln Gly Thr Arg Glu Ala Val Gly
65 70 75 80
Thr Gly Val Arg Gln Val Pro Gly Phe Gly Val Ala Asp Ala Leu Gly
85 90 95
Asn Arg Val Gly Glu Ala Ala His Ala Leu GIy Asn Thr Gly His Glu
100 105 110
Ile Gly Arg Gln Ala Glu Asp Val Ile Arg His Gly Ala Asp Ala Val
115 120 125
Arg Gly Ser Trp Gln Gly Val Pro Gly His Asn Gly Ala Trp Glu Thr
130 135 140
Ser Gly Gly His Gly Ile Phe Gly Ser Gln Gly Gly Leu Gly Gly Gln
145 150 155 160
Gly Gln Gly Asn Pro Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr
165 170 175
Pro Gly Asn Ser Ala Gly Ser Phe Gly Met Asn Pro Gln Gly Ala Pro
180 185 190
Trp Gly Gln Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr
195 200 205
Gln Gly Ala Val Ala Gln Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn
210 215 220
39

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
Gln Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly
225 230 235 240
Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gln Ser Gly Ser Ser Gly
245 250 255
Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser
260 265 270
Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly
275 280 285
Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser
290 295 300
Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ala
305 310 315 320
Ala Glu Glu Met Asp Ile Asn Pro Gly Thr Leu Arg Arg Leu Leu Gly
325 330 335
Cys Leu Thr Leu Thr Leu Ser Gly Arg Ile Leu Asn Pro Ser Trp Val
340 345 350
Ser Ser Thr Gly Met Pro
355
<210> 53
<211> 1897
<212> DNA
<213> Homo sapiens
<400> 53
acagaggagg gcacagagac gcagagcaag ggcggcaagg aggagaccct ggtgggagga 60
agacactctg gagagagagg gggctgggca gagatgaagt tccaggggcc cctggcctgc 120
ctcctgctgg ccctctgcct gggcagtggg gaggctggcc ccctgcagag cggagaggaa 180
agcactggga caaatattgg ggaggccctt ggacatggcc tgggagacgc cctgagcgaa 240
ggggtgggaa aggccattgg caaagaggcc ggaggggcag ctggctctaa agtcagtgag 300
gcccttggcc aagggaccag agaagcagtt ggcactggag tcaggcaggt tccaggcttt 360
ggcgtagcag atgctttggg caacagggtc ggggaagcag cccatgctct gggaaacact 420
gggcacgaga ttggcagaca ggcagaagat gtcattcgac acggagcaga tgctgtccgc 480
ggctcctggc agggggtgcc tggccacaat ggtgcttggg aaacttctgg aggccatggc 540
atctttggct ctcaaggtgg ccttggaggc cagggccagg gcaatcctgg aggtctgggg 600
actccgtggg tccacggata ccccggaaac tcagcaggca gctttggaat gaatcctcag 660
ggagctccct ggggtcaagg aggcaatgga gggccaccaa actttgggac caacactcag 720
ggagctgtgg cccagcctgg ctatggttca gtgagagcca gcaaccagaa tgaagggtgc 780
acgaatcccc caccatctgg ctcaggtgga ggctccagca actctggggg aggcagcggc 840
tcacagtcgg gcagcagtgg cagtggcagc aatggtgaca acaacaatgg cagcagcagt 900
ggtggcagca gcagtggcag cagcagtggc ggcagcagtg gcggcagcag tggtggcagc 960
agtggcaaca gtggtggcag cagaggtgac agcggcagtg agtcctcctg gggatccagc 1020
accggctcct cctccggcaa ccacggtggg agcggcggag gaaatggaca taaacccggg 1080
gggcaagggt cgagctgggg cagtggagga ggtgacgctg ttggtggagt caatactgtg 1140
aactctgaga cgtctcctgg gatgtttaac tttgacactt tctggaagaa ttttaaatcc 1200
aagctgggtt tcatcaactg ggatgccata aacaagaacc aggtcccgcc ccccagcacc 1260
cgagccctcc tctacttcag ccgactctgg gaggatttca aacagaacac tcctttcctc 1320
aactggaaag caattattga gggtgcggac gcgtcatcac tgcagaaacg tgcaggcaga 1380
gccgatcaga actacaatta caaccagcat gcgtatccca ctgcctatgg tgggaagtac 1440
tcagtcaaga cccctgcaaa ggggggagtc tcaccttctt cctcggcttc ccgggtgcaa 1500

CA 02327551 2000-10-31
WO 99/SS721 PCT/US99/08504
cctggcctgc taggcaattt cttgcaacca 1560
tgcagtgggt ccaccgaggc
gaagttttgg
cccgaaaagc tcccctt ggcccccagcctg 1620
actggtcgtc tgccagccct
agggagctcc
ggcccggctg ctggggaccc agcttgtctc 1680
ccacacctct tccttgtttc
gtttcctagg
ttcccactgc accagcc tcgtcacatacac 1740
actgtggtgc cagcatcttt
ttcagtggcc
ctgtacctcc cactgtgaca gttctccagg 1800
tccctttggt aaggaggagc
gacctgaagt
ttcctacttt aaacatgaat cttgtttccc 1860
tgagtttctc taaaaaaaaa
tgtggaaata
aaaaaaaaaa aaaaaaa 1897
aaaaaaaaaa
aaaaaaaaaa
<210> 54
<211> 479
<212> PRT
<2I3> Homo
sapiens
<400> 54
Met Lys Phe Pro Ala CysLeu LeuLeu LeuCys Leu
Gln Gly Leu Ala
1 5 10 15
Gly Ser Gly Gly Leu GlnSer GlyGlu SerThr Gly
Glu Ala Pro Glu
20 25 30
Thr Asn Ile Ala Gly HisGly LeuGly AlaLeu Ser
Gly Glu Leu Asp
35 40 45
Glu Gly Val Ala Gly LysGlu AlaGly AlaAla Gly
Gly Lys Ile Gly
50 55 60
Ser Lys Val Ala Gly GlnGly ThrArg AlaVal Gly
Ser Glu Leu Glu
65 70 75 80
Thr Gly Val Val Gly PheGly ValAla AlaLeu Gly
Arg Gln Pro Asp
85 90 95
Asn Arg Val Ala His AlaLeu GlyAsn GlyHis Glu
Gly Glu Ala Thr
100 105 110
Ile Gly Arg Glu Val IleArg HisGly AspAla Val
Gln Ala Asp Ala
115 120 125
Arg Gly Ser Gly Pro GlyHis AsnGly TrpGlu Thr
Trp Gln Val Ala
130 135 140
Ser Gly Gly Ile Gly SerGln GlyGly GlyGly Gln
His Gly Phe Leu
145 150 155 160
Gly Gln Gly Gly Leu GlyThr ProTrp HisGly Tyr
Asn Pro Gly Val
165 170 175
Pro Gly Asn Gly Phe GlyMet AsnPro GlyAla Pro
Ser Ala Ser Gln
180 185 190
Trp Gly Gln Asn Gly ProPro AsnPhe ThrAsn Thr
Gly Gly Gly Gly
195 200 205
Gln Gly Ala Gln Gly TyrGly SerVal AlaSer Asn
Val Ala Pro Arg
210 215 220
Gln Asn Glu Thr Pro ProPro SerGly GlyGly Gly
Gly Cys Asn Ser
225 230 235 240
Ser Ser Asn Gly Ser GlySer GlnSer SerSer Gly
Ser Gly Gly Gly
41

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
245 250 255
Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser
260 265 270
Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly
275 280 285
Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser
290 295 300
Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ser
305 310 315 320
Gly Gly Gly Asn Gly His Lys Pro Gly Gly Gln Gly Ser Ser Trp Gly
325 330 335
Ser Gly Gly Gly Asp Ala Val Gly Gly Val Asn Thr Val Asn Ser Glu
340 345 350
Thr Ser Pro Gly Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys
355 360 365
Ser Lys Leu Gly Phe Ile Asn Trp Asp Ala Ile Asn Lys Asn Gln Val
370 375 380
Pro Pro Pro Ser Thr Arg Ala Leu Leu Tyr Phe Ser Arg Leu Trp Glu
385 390 395 400
Asp Phe Lys Gln Asn Thr Pro Phe Leu Asn Trp Lys Ala Ile Ile Glu
405 410 415
Gly Ala Asp Ala Ser Ser Leu Gln Lys Arg Ala Gly Arg Ala Asp Gln
420 425 430
Asn Tyr Asn Tyr Asn Gln His Ala Tyr Pro Thr Ala Tyr Gly Gly Lys
435 440 445
Tyr Ser Val Lys Thr Pro Ala Lys Gly Gly Val Ser Pro Ser Ser Ser
450 455 460
Ala Ser Arg Val Gln Pro Gly Leu Leu Gln Trp Val Lys Phe Trp
465 470 475
<210> 55
<211> 1532
<212> DNA
<213> Homo sapiens
<400> 55
gaagagcccc tgcggccggg cgcgaaaatg gcggcggcgg cgacggccgg gcgctcctga 60
agcagcagtt atggagcttc cctcagggcc ggggccggag cggctctttg actcgcaccg 120
gcttccgggt gactgcttcc tactgctcgt gctgctgctc tacgcgccag tcgggttctg 180
cctcctcgtc ctgcgcctgt ttctcgggat ccacgtcttc ctggtcagct gcgcgctgcc 240
agacagcgtc cttcgcagat tcgtagtgcg gaccatgtgt gcggtgctag ggctcgtggc 300
ccggcaggag gactccggac tccgggatca cagtgtcagg gtcctcattt ccaaccatgt 360
gacacctttc gaccacaaca tagtcaattt gcttaccacc tgtagcaccc ctctactcaa 420
tagtcccccc agctttgtgt gctggtctcg gggcttcatg gagatgaatg ggcgggggga 480
gttggtggag tcactcaaga gattctgtgc ttccacgagg cttcccccca ctcctctgct 540
42

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
gctattccct gaggaagagg ccaccaatgg ccgggagggg ctcctgcgct tcagttcctg 600
gccattttct atccaagatg tggtacaacc tcttaccctg caagttcaga gacccctggt 660
ctctgtgacg gtgtcagatg cctcctgggt ctcagaactg ctgtggtcac ttttcgtccc 720
tttcacggtg tatcaagtaa ggtggcttcg tcctgttcat cgccaactag gggaagcgaa 780
tgaggagttt gcactccgtg tacaacagct ggtggccaag gaattgggcc agacagggac 840
acggctcact ccagctgaca aagcagagca catgaagcga caaagacacc ccagattgcg 900
cccccagtca gcccagtctt ctttccctcc ctcccctggt ccttctcctg atgtgcaact 960
ggcaactctg gctcagagag tcaaggaagt tttgccccat gtgccattgg gtgtcatcca 1020
gagagacctg gccaagactg gctgtgtaga cttgactatc actaatctgc ttgagggggc 1080
cgtagctttc atgcctgaag acatcaccaa gggaactcag tccctaccca cagcctctgc 1140
ctccaagttt cccagctctg gcccggtgac ccctcagcca acagccctaa catttgccaa 1200
gtcttcctgg gcccggcagg agagcctgca ggagcgcaag caagcactat atgaatacgc 1260
aagaaggaga ttcacagaga gacgagccca ggaggctgac tgagctcaaa ggaacaggat 1320
ggcacccaga gccgcaggac ggagactggg ggcagccctc acccaactca caacaggctg 1380
gatgggtggg tggtaaaaag ggaaggatga ggctccccca atgtcacatt aaattcatgg 1440
ttttcattca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1532
<210> 56
<211> 410
<212> PRT
<213> Homo sapiens
<400> 56
Met Glu Leu Pro Ser Gly Pro Gly Pro Glu Arg Leu Phe Asp Ser His
1 5 10 15
Arg Leu Pro Gly Asp Cys Phe Leu Leu Leu Val Leu Leu Leu Tyr Ala
20 25 30
Pro Val Gly Phe Cys Leu Leu Val Leu Arg Leu Phe Leu Gly Ile His
35 40 45
Val Phe Leu Val Ser Cys Ala Leu Pro Asp Ser Val Leu Arg Arg Phe
50 55 60
Val Val Arg Thr Met Cys Ala Val Leu Gly Leu Val Ala Arg Gln Glu
65 70 75 80
Asp Ser Gly Leu Arg Asp His Ser Val Arg Val Leu Ile Ser Asn His
85 90 95
Val Thr Pro Phe Asp His Asn Ile Val Asn Leu Leu Thr Thr Cys Ser
100 105 110
Thr Pro Leu Leu Asn Ser Pro Pro Ser Phe Val Cys Trp Ser Arg Gly
115 120 125
Phe Met Glu Met Asn Gly Arg Gly Glu Leu Val Glu Ser Leu Lys Arg
130 135 140
Phe Cys Ala Ser Thr Arg Leu Pro Pro Thr Pro Leu Leu Leu Phe Pro
145 150 155 160
Glu Glu Glu Ala Thr Asn Gly Arg Glu Gly Leu Leu Arg Phe Ser Ser
165 170 175
Trp Pro Phe Ser Ile Gln Asp Val Val Gln Pro Leu Thr Leu Gln Val
180 185 190
43

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
Gln Arg Pro Leu Val Ser Val Thr Val Ser Asp Ala Ser Trp Val Ser
195 200 205
Glu Leu Leu Trp Ser Leu Phe Val Pro Phe Thr Val Tyr Gln Val Arg
210 215 220
Trp Leu Arg Pro Val His Arg Gln Leu Gly Glu Ala Asn Glu Glu Phe
225 230 235 240
Ala Leu Arg Val Gln Gln Leu Val Ala Lys Glu Leu Gly Gln Thr Gly
245 250 255
Thr Arg Leu Thr Pro Ala Asp Lys Ala Glu His Met Lys Arg Gln Arg
260 265 270
His Pro Arg Leu Arg Pro Gln Ser Ala Gln Ser Ser Phe Pro Pro Ser
275 280 285
Pro Gly Pro Ser Pro Asp Val Gln Leu Ala Thr Leu Ala Gln Arg Val
290 295 300
Lys Glu Val Leu Pro His Val Pro Leu Gly Val Ile Gln Arg Asp Leu
305 310 315 320
Ala Lys Thr Gly Cys Val Asp Leu Thr Ile Thr Asn Leu Leu Glu Gly
325 330 335
Ala Val Ala Phe Met Pro Glu Asp Ile Thr Lys Gly Thr Gln Ser Leu
340 345 350
Pro Thr Ala Ser Ala Ser Lys Phe Pro Ser Ser Gly Pro Val Thr Pro
355 360 365
Gln Pro Thr Ala Leu Thr Phe Ala Lys Ser Ser Trp Ala Arg Gln Glu
370 375 380
Ser Leu Gln Glu Arg Lys Gln Ala Leu Tyr Glu Tyr Ala Arg Arg Arg
385 390 395 400
Phe Thr Glu Arg Arg Ala Gln Glu Ala Asp
405 410
<210> 57
<211> 2093
<212> DNA
<213> Homo sapiens
<400> 57
cgcgtttcag cgaagtcgca cgtgaaggat agcagtggcc tgagaaagac ccagtcatgg 60
cagcctccag catcagttca ccatggggaa agcatgtgtt caaagccatt ctgatggtcc 120
tagtggccct tatcctcctc cactcagcat tggcccagtc ccgtcgagac tttgcaccac 180
caggccaaca gaagagagaa gccccagttg atgtcttgac ccagataggt cgatctgtgc 240
gagggacact ggatgcctgg attgggccag agaccatgca cctggtgtca gagtcttcgt 300
cccaagtgtt gtgggccatc tcatcagcca tttctgtggc cttctttgct ctgtctggga 360
tcgccgcaca gctgctgaat gccttgggac tagctggtga ttacctcgcc cagggcctga 420
agctcagccc tggccaggtc cagaccttcc tgctgtgggg agcaggggcc ctggtcgtct 480
actggctgct gtctctgctc ctcggcttgg tcttggcctt gctggggcgg atcctgtggg 540
gcctgaagct tgtcatcttc ctggccggct tcgtggccct gatgaggtcg gtgcccgacc 600
cttccacccg ggccctgcta ctcctggcct tgctgatcct ctacgccctg ctgagccggc 660

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
tcactggctc ccgagcctct ggggcccaac tcgaggccaa ggtgcgaggg ctggaacgcc 720
aggtggagga gctgcgctgg cgccagaggc gagcggccaa gggggcccgc agtgtggagg 780
aggagtgagc cggatgcccc acacaccgcc agtgtcatac caaagagctg agctgcttcg 840
gggccatgca gccctcctgc cagccccctg cccttttctt gccctgtctc tgaaccttca 900
gaacattgat ccttgccgca gccccactag ccaagagaaa cagagaaaga ccattccccc 960
tgcctgtcct tgcggccctg tcttctgagg ttctctgtct ggggttggct ctcttaaccc 1020
tttctctgct cccagcctgc ctcaccaggg aaggttggag gggcctccct ctggcttctg 1080
catctgcgcc agcaaacatc actgccgttg gtctctcatg acttaactgg cttccctctg 1140
ctgctgcctt ggcttcctcc taatgctcgt gctctcctgt ccttctgaag ttgctccttg 1200
gccaaatctc cagctccctt cttgttttcc tcatcctcct accctgtact cccaccaaac 1260
catggtcctt taaggcacgc tcctgtcctc ctcattgccc agcagtaggg aggggcaggg 1320
gtaaggggac ctgaggataa agggtgggga aacagggtcc cctgaggcct gtgggggctg 1380
caggggagga ggatgtacct tgtgtctctt tcaagtgcct taatccgagc cagcagggcc 1440
ttctgcttgc ctgctgccat actgtatgta ggaaagtgtt ctgtggctgc tttgtgtcaa 1500
gaaaagagca gtcactctca gaatcttgat tccccatcag ccaaagcaaa agatggctgc 1560
tgctttgtag gcatgtgcct gcaagtggga ccttgctggg cattatatgc cctgtggggg 1620
tttcagagac cctgaaagag gagggaggac ccgcctcctt gtctgcacaa ctgcatgcac 1680
ttctctcccc atcgctccac aacctgaaac cgagaaggag ttgctgacca gtgcccaccc 1740
cggcagcccg ggaggaacac aggcagctcc tttcccttca cgtggtctgc agagagcagg 1800
gtgagctgcc agctgcccct ctccaccagg gtaccctgtc ttggtggtta ggggccactt 1860
ttcctttgag gctctagtgg aggtggatgt ccttctctgc caggcttggc acatgatgtg 1920
aagaataaat gcccaattct tactgttcag gtttgatgtg gaatcacagc tgcagtgata 1980
tatatttttt atcagtgctt ggttggtttt aaataaagtg cacgctattt tattatcttg 2040
ttctgaataa aatgtattta ctccaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 2093
<210> 58
<211> 243
<212> PRT
<213> Homo Sapiens
<400> 58
Met Ala Ala Ser Ser Ile Ser Ser Pro Trp Gly Lys His Val Phe Lys
1 5 10 15
Ala Ile Leu Met Val Leu Val Ala Leu Ile Leu Leu His Ser Ala Leu
20 25 30
Ala Gln Ser Arg Arg Asp Phe Ala Pro Pro Gly Gln Gln Lys Arg Glu
35 40 45
Ala Pro Val Asp Val Leu Thr Gln Ile Gly Arg Ser Val Arg Gly Thr
50 55 60
Leu Asp Ala Trp Ile Gly Pro Glu Thr Met His Leu Val Ser Glu Ser
65 70 75 80
Ser Ser Gln Val Leu Trp Ala Ile Ser Ser Ala Ile Ser Val Ala Phe
85 90 95
Phe Ala Leu Ser Gly Ile Ala Ala Gln Leu Leu Asn Ala Leu Gly Leu
100 105 110
Ala Gly Asp Tyr Leu Ala Gln Gly Leu Lys Leu Ser Pro Gly Gln Val
115 120 125
Gln Thr Phe Leu Leu Trp Gly Ala Gly Ala Leu Val Val Tyr Trp Leu
130 135 140
Leu Ser Leu Leu Leu Gly Leu Val Leu Ala Leu Leu Gly Arg Ile Leu
145 150 155 160

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
Trp Gly Leu Lys Leu Val Ile Phe Leu Ala Gly Phe Val Ala Leu Met
165 170 175
Arg Ser Val Pro Asp Pro Ser Thr Arg Ala Leu Leu Leu Leu Ala Leu
180 185 190
Leu Ile Leu Tyr Ala Leu Leu Ser Arg Leu Thr Gly Ser Arg Ala Ser
195 200 205
Gly Ala Gln Leu Glu Ala Lys Val Arg Gly Leu Glu Arg Gln Val Glu
210 215 220
Glu Leu Arg Trp Arg Gln Arg Arg Ala Ala Lys Gly Ala Arg Ser Val
225 230 235 240
Glu Glu Glu
<210> 59
<211> 1372
<212> DNA
<213> Homo sapiens
<400> 59
atcggcgtcc gcagcgggcg gctgctgagc tgccttgagg tgcagtgttg gggatccaga 60
gccatgtcgg acctgctact actgggcctg attgggggcc tgactctctt actgctgctg 120
acgctgctgg cctttgccgg gtactcaggg ctactggctg gggtggaagt gagtgctggg 180
tcacccccca tccgcaacgt cactgtggcc tacaagttcc acatggggct ctatggtgag 240
actgggcggc ttttcactga gagctgcagc atctctccca agctccgctc catcgctgtc 300
tactatgaca acccccacat ggtgccccct gataagtgcc gatgtgccgt gggcagcatc 360
ctgagtgaag gtgaggaatc gccctcccct gagctcatcg acctctacca gasatttggc 420
ttcaaggtgt tctccttccc ggcacccagc catgtggtga cagccacctt cccctacacc 480
accattctgt ccatctggct ggctacccgc cgtgtccatc ctgccttgga cacctacatc 540
aaggagcgga agctgtgtgc ctatcctcgg ctggagatct accaggaaga ccagatccat 600
ttcatgtgcc cactggcacg gcagggagac ttctatgtgc ctgagatgaa ggagacagag 660
tggaaatggc gggggcttgt ggaggccatt gacacccagg tggatggcac aggagctgac 720
acaatgagtg acacgagttc tgtaagcttg gaagtgagcc ctggcagccg ggagacttca 780
gctgccacac tgtcacctgg ggcgagcagc cgtggctggg atgacggtga cacccgcagc 840
gagcacagct acagcgagtc aggtgccagc ggctcctctt ttgaggagct ggacttggag 900
ggcgaggggc ccttagggga gtcacggctg gaccctggga ctgagcccct ggggactacc 960
sagtggctct gggagcccac tgcccctgag aagggcaagg agtaacccat ggcctgcacc 1020
ctcctgcagt gcagttgctg aggaactgag cagactctcc agcagactct ccagccctct 1080
tcctccttcc tctgggggag gaggggttcc tgagggacct gacttcccct gctccaggcc 1140
tcttgctaag ccttctcctc actgcccttt aggctcccag ggccagagga gccagggact 1200
attttctgca ccagccccca gggctgccgc ccctgttgtg tctttttttc agactcacag 1260
tggagcttcc aggacccaga ataaagccaa tgatttactt gtttcacctg gaaaaaaaaa 1320
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1372
<210> 60
<211> 313
<212> PRT
<213> Homo sapiens
<400> 60
Met Ser Asp Leu Leu Leu Leu Gly Leu Ile Gly Gly Leu Thr Leu Leu
1 5 10 15
Leu Leu Leu Thr Leu Leu Ala Phe Ala Gly Tyr Ser Gly Leu Leu Ala
46

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
20 25 30
Gly Val Glu Val Ser Ala Gly Ser Pro Pro Ile Arg Asn Val Thr Val
35 40 45
Ala Tyr Lys Phe His Met Gly Leu Tyr Gly Glu Thr Gly Arg Leu Phe
50 55 60
Thr Glu Ser Cys Ser Ile Ser Pro Lys Leu Arg Ser Ile Ala Val Tyr
65 70 75 80
Tyr Asp Asn Pro His Met Val Pro Pro Asp Lys Cys Arg Cys Ala Val
85 90 95
Gly Ser Ile Leu Ser Glu Gly Glu Glu Ser Pro Ser Pro Glu Leu Ile
100 105 110
Asp Leu Tyr Gln Lys Phe Gly Phe Lys Val Phe Ser Phe Pro Ala Pro
115 120 125
Ser His Val Val Thr Ala Thr Phe Pro Tyr Thr Thr Ile Leu Ser Ile
130 135 140
Trp Leu Ala Thr Arg Arg Val His Pro Ala Leu Asp Thr Tyr Ile Lys
145 150 155 160
Glu Arg Lys Leu Cys Ala Tyr Pro Arg Leu Glu Ile Tyr Gln Glu Asp
165 1?0 175
Gln Ile His Phe Met Cys Pro Leu Ala Arg Gln Gly Asp Phe Tyr Val
180 185 190
Pro Glu Met Lys Glu Thr Glu Trp Lys Trp Arg Gly Leu Val Glu Ala
195 200 205
Ile Asp Thr Gln Val Asp Gly Thr Gly Ala Asp Thr Met Ser Asp Thr
210 215 220
Ser Ser Val Ser Leu Glu Val Ser Pro Gly Ser Arg Glu Thr Ser Ala
225 230 235 240
Ala Thr Leu Ser Pro Gly Ala Ser Ser Arg Gly Trp Asp Asp Gly Asp
245 250 255
Thr Arg Ser Glu His Ser Tyr Ser Glu Ser Gly Ala Ser Gly Ser Ser
260 265 270
Phe Glu Glu Leu Asp Leu Glu Gly Glu Gly Pro Leu Gly Glu Ser Arg
275 280 285
Leu Asp Pro Gly Thr Glu Pro Leu Gly Thr Thr Lys Trp Leu Trp Glu
290 295 300
Pro Thr Ala Pro Glu Lys Gly Lys Glu
305 3I0
<210> 61
<211> 1529
<212> DNA
47

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
<213> Homo sapiens
<400> 61
gggctgcctg gtccaggaag ggggtgcggc tctgtcagga aacctggact ctcaaggccc 60
accagcctct ccgtgagtgt tagaaatcac agatacagta tatacttaat tacactaaat 120
tattgctggg attccttata agcactaatt atacctgatt ataggttaaa atatttattt 180
tgtcaaaata ttttcttggg aatgtgttta accctttctg cgttcattgt tgctgagatg 240
tgaaaactaa ccattccctc ctgcctacct ttttggccac tgggcggcag agaatggcgc 300
tatgtgcagt tgggcccctg gcaccatggg cctttggcct gcctgctgca gagtagccct 360
gcctgggcag tctccaggca ctgagcaggc catctgtggc caggctgaga gaatgactgg 420
ctcgcttacc agcgtgcatg ggacaaggag ctttggagcc tcaaggggtt gttgctggcc 480
tgggctagag ggaaaggtga ccatccgtct gtcctcctgt ctttctatta gcgcctccat 540
gtgagtgatg gtgccttggt tcactagcct tcccccacca ccccaccatg ccacctggtg 600
gtcttggggc ctgtgctgtc actccagccc ctggggagga gaggacccag cccggagagt 660
tggggcaagg gctccacatg gcccaagggc aacagatgct cgcagggcag ctgctgccga 720
tgctcacgct cctgcccccc tccttcccgc tgccacaccc caccctgggc ccccgcagac 780
acgcatctct aactcagttg ggcccagcct tctggatggc ttggggtagg ccatgggccc 840
acctggggcc aggccagccc ctggggcagc tctggaagag cagtgtggag gagcacttgc 900
ttgcagcctg gcttcagcct ctggcactgc tggagtggtc cctgggagct tctgcactgt 960
cggctttggg gacgtctcac ccacttgggt tacagtaggc cttccccacc cagagagaag 1020
tgtttccacc ccagagacat tgtctgtcag cccctgaagt gctcgcctcc cccagtgccc 1080
gtcaccagcc cttcctatct gtggggtcca agtcaggctt cccctgcggc caccagccat 1140
agggagcagc catcagcccc cgagtcagaa ctgcttctgt ctgtccatac ctccaggctc 1200
tcccggagag ggggacggat atttatttcc taaagtttgc acttaattgt gaggattctc 1260
aggattgttg ggggctactg aaaagaggaa tgtgttgaat gtcgcgtttg ctgtccactc 1320
gtcctagaag tttagtgttt ttgtcactgt catgtgtttc tgtgggcaga gctggttctg 1380
gagggtgggt cagtgcaccc gaggctcaga gcatccatcc accccactgg ccctccttcc 1440
agataccctc tctctaattg ggttcttgca tgtaaaatac tccacaataa ataaataatt 1500
gaacaaaaaa aaaaaaaaaa aaaaaaaaa 1529
<210> 62
<211> 136
<212> PRT
<213> Homo sapiens
<400> 62
Met Pro Pro Gly Gly Leu Gly Ala Cys Ala Val Thr Pro Ala Pro Gly
1 5 10 15
Glu Glu Arg Thr Gln Pro Gly Glu Leu Gly Gln Gly Leu His Met Ala
20 25 30
Gln Gly Gln Gln Met Leu Ala Gly Gln Leu Leu Pro Met Leu Thr Leu
35 40 45
Leu Pro Pro Ser Phe Pro Leu Pro His Pro Thr Leu Gly Pro Arg Arg
50 55 60
His Ala Ser Leu Thr Gln Leu Gly Pro Ala Phe Trp Met Ala Trp Gly
65 70 75 80
Arg Pro Trp Ala His Leu Gly Pro Gly Gln Pro Leu Gly Gln Leu Trp
85 90 95
Lys Ser Ser Val Glu Glu His Leu Leu Ala Ala Trp Leu Gln Pro Leu
100 105 110
Ala Leu Leu Glu Trp Ser Leu Gly Ala Ser Ala Leu Ser Ala Leu Gly
115 120 125
48

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
Thr Ser His Pro Leu Gly Leu Gln
130 135
<210> 63
<211> 2242
<212> DNA
<213> Homo Sapiens
<400> 63
gagctgaggt ggcagtggtt ccaccaacat ggagctctcg cagatgtcgg agctcatggg 60
gctgtcggtg ttgcttgggc tgctggccct gatggcgacg gcggcggtag cgcgggggtg 120
gctgcgcgcg ggggaggaga ggagcggccg gcccgcctgc caaaaagcaa atggatttcc 180
acctgacaaa tcttcgggat ccaagaagca gaaacaatat cagcggattc ggaaggagaa 240
gcctcaacaa cacaacttca cccaccgcct cctggctgca gctctgaaga gccacagcgg 300
gaacatatct tgcatggact ttagcagcaa tggcaaatac ctggctacct gtgcagatga 360
tcgcaccatc cgcatctgga gcaccaagga cttcctgcag cgagagcacc gcagcatgag 420
agccaacgtg gagctggacc acgccaccct ggtgcgcttc agccctgact gcagagcctt 480
catcgtctgg ctggccaacg gggacaccct ccgtgtcttc aagatgacca agcgggagga 540
tgggggctac accttcacag ccaccccaga ggacttccct aaaaagcaca aggcgcctgt 600
catcgacatt ggcattgcta acacagggaa gtttatcatg actgcctcca gtgacaccac 660
tgtcctcatc tggagcctga agggtcaagt gctgtctacc atcaacacca accagatgaa 720
caacacacac gctgctgtat ctccctgtgg cagatttgta gcctcgtgtg gcttcacccc 780
agatgtgaag gtttgggaag tctgctttgg aaagaagggg gagttccagg aggtggtgcg 840
agccttcgaa ctaaagggcc actccgcggc tgtgcactcg tttgctttct ccaacgactc 900
acggaggatg gcttctgtct ccaaggatgg tacatggaaa ctgtgggaca cagatgtgga 960
atacaagaag aagcaggacc cctacttgct gaagacaggc cgctttgaag aggcggcggg 1020
tgccgcgccg tgccgcctgg ccctctcccc caacgcccag gtcttggcct tggccagtgg 1080
cagtagtatt catctctaca atacccggcg gggcgagaag gaggagtgct ttgagcgggt 1140
ccatggcgag tgtatcgcca acttgtcctt tgacatcact ggccgctttc tggcctcctg 1200
tggggaccgg gcggtgcggc tgtttcacaa cactcctggc caccgagcca tggtggagga 1260
gatgcagggc cacctgaagc gggcctccaa cgagagcacc cgccagaggc tgcagcagca 1320
gctgacccag gcccaagaga ccctgaagag cctgggtgcc ctgaagaagt gactctggga 1380
gggcccggcg cagaggattg aggaggaggg atctggcctc ctcatggcac tgctgccatc 1440
tttcctccca ggtggaagcc tttcagaagg agtctcctgg ttttcttact ggtggccctg 1500
cttcttccca ttgaaactac tcttgtctac ttaggtctct ctcttcttgc tggctgtgac 1560
tcctccctga ctagtggcca aggtgctttt cttcctccca ggcccagtgg gtggaatctg 1620
tccccacctg gcactgagga gaatggtaga gaggagagga gagagagaga gaatgtgatt 1680
tttggccttg tggcagcaca tcctcacacc caaagaagtt tgtaaatgtt ccagaacaac 1740
ctagagaaca cctgagtact aagcagcagt tttgcaagga tgggagactg ggatagcttc 1800
ccatcacaga actgtgttcc atcaaaaaga cactaaggga tttccttctg ggcctcagtt 1860
ctatttgtaa gatggagaat aatcctctct gtgaactcct tgcaaagatg atatgaggct 1920
aagagaatat caagtcccca ggtctggaag aaaagtagaa aagagtagta ctattgtcca 1980
atgtcatgaa agtggtaaaa gtgggaacca gtgtgctttg aaaccaaatt agaaacacat 2040
tccttgggaa ggcaaagttt tctgggactt gatcatacat tttatatggt tgggacttct 2100
ctcttcggga gatgatatct tgtttaagga gacctctttt cagttcatca agttcatcag 2160
atatttgagt gcccactctg tgcccaaata aatatgagct ggggattaaa tacgaaaaaa 2220
aaaaaaaaaa aaaaaaaaaa as 2242
<210> 64
<211> 447
<212> PRT
<213> Homo sapiens
<400> 64
Met Glu Leu Ser Gln Met Ser Glu Leu Met Gly Leu Ser Val Leu Leu
1 5 10 15
Gly Leu Leu Ala Leu Met Ala Thr Ala Ala Val Ala Arg Gly Trp Leu
20 25 30
49

CA 02327551 2000-10-31
WO 99/55721 PCTNS99108504
Arg Ala Gly Glu Glu Arg Ser Gly Arg Pro Ala Cys Gln Lys Ala Asn
35 40 45
Gly Phe Pro Pro Asp Lys Ser Ser Gly Ser Lys Lys Gln Lys Gln Tyr
50 55 60
Gln Arg Ile Arg Lys Glu Lys Pro Gln Gln His Asn Phe Thr His Arg
65 70 75 80
Leu Leu Ala AIa Ala Leu Lys Ser His Ser Gly Asn Ile Ser Cys Met
85 90 95
Asp Phe Ser Ser Asn Gly Lys Tyr Leu Ala Thr Cys Ala Asp Asp Arg
100 105 110
Thr Ile Arg Ile Trp Ser Thr Lys Asp Phe Leu Gln Arg Glu His Arg
115 120 125
Ser Met Arg Ala Asn Val Glu Leu Asp His Ala Thr Leu Val Arg Phe
130 135 140
Ser Pro Asp Cys Arg Ala Phe Ile Val Trp Leu Ala Asn Gly Asp Thr
145 ' 150 155 160
Leu Arg Val Phe Lys Met Thr Lys Arg Glu Asp Gly Gly Tyr Thr Phe
165 170 175
Thr Ala Thr Pro Glu Asp Phe Pro Lys Lys His Lys Ala Pro Val Ile
180 185 190
Asp Ile Gly Ile Ala Asn Thr Gly Lys Phe Ile Met Thr Ala Ser S'er
195 200 205
Asp Thr Thr Val Leu Ile Trp Ser Leu Lys Gly Gln Val Leu Ser Thr
210 215 220
Ile Asn Thr Asn Gln Met Asn Asn Thr His Ala Ala Val Ser Pro Cys
225 230 235 240
Gly Arg Phe Val Ala Ser Cys Gly Phe Thr Pro Asp Val Lys Val Trp
245 250 255
Glu Val Cys Phe Gly Lys Lys Gly Glu Phe Gln Glu Val Val Arg Ala
260 265 270
Phe Glu Leu Lys Gly His Ser Ala Ala Val His Ser Phe Ala Phe Ser
275 280 285
Asn Asp Ser Arg Arg Met Ala Ser Val Ser Lys Asp Gly Thr Trp Lys
290 295 300
Leu Trp Asp Thr Asp Val Glu Tyr Lys Lys Lys Gln Asp Pro Tyr Leu
305 310 315 320
Leu Lys Thr Gly Arg Phe Glu Glu Ala Ala Gly Ala Ala Pro Cys Arg
325 330 335
Leu Ala Leu Ser Pro Asn Ala Gln Val Leu Ala Leu Ala Ser Gly Ser
340 345 350

CA 02327551 2000-10-31
WO 99/55721 PCTNS99/08504
Ser Ile His Leu Tyr Asn Thr Arg Arg Gly Glu Lys Glu Glu Cys Phe
355 360 365
Glu Arg Val His Gly Glu Cys Ile Ala Asn Leu Ser Phe Asp Ile Thr
370 375 380
Gly Arg Phe Leu Ala Ser Cys Gly Asp Arg Ala Val Arg Leu Phe His
385 390 395 400
Asn Thr Pro Gly His Arg Ala Met Val Glu Glu Met Gln Gly His Leu
405 410 415
Lys Arg Ala Ser Asn Glu Ser Thr Arg Gln Arg Leu Gln Gln Gln Leu
420 425 430
Thr Gln Ala Gln Glu Thr Leu Lys Ser Leu Gly Ala Leu Lys Lys
435 440 445
<210> 65
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 65
aagtgatctc aacctcgctt g 21
<210> 66
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 66
gtcagaacca tcatctccag g 21
<210> 67
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 67
cagtccagtc caggcgag 18
<210> 68
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
51

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
<400> ss
aggaagcacc agagtgcg le
<210> 69
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 69
ccatctgacc tgctactttc c 21
<210> 70
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 70
gctgatgagg atgctggc 18
<210> 71
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 71
ctcaggaagc aggtcaggac 20
<210> 72
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 72
ctctgatgag ggtgttggc 19
<210> 73
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 73
cacaggcact catgggaag i9
<210> 74
52

CA 02327551 2000-10-31
WO 99/55721 PC'T/US99/08504
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 74
ctggagacag ggtccagatc 20
<210> 75
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 75
tggaagaata gatgtgagag 20
<210> 76
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 76
tcagagagtt gcttcctgaa g 21
<210> 77
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 77
gctcctactc tgccctctcc 20
<210> 7B
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 78
gaaggtctgg ttggtgatgg 20
<210> 79
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
53

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
<223> oligonucleotide
<400> 79
cagttctgac accagaagtt g 21
<210> 80
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 80
tttcatcgag gacagcaaac 20
<210> 81
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 81
aggacagagt cctgggtgg 19
<210> 82
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 82
cagagatgtg catgattccc 20
<210> 83
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 83
agcgtggaag gcagtgtag 19
<210> 84
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 84
ccaaggcacc atctcttcag 20
54

CA 02327551 2000-10-31
WO 99/55721 PGT/US99/08504
<210> 85
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 85
aatcagtgtt gatgataagc c 21
<210> 86
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 86
tggactttgt catggcactc 20
<210> 87
<211> 18
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 87
ttctgcgact tggatggg 18
<210> 88
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 88
ggaaggaggc agagaagttt g 21
<210> 89
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 89
gctcaccctg tctgttctgc 20
<210> 90
<211> 18
<212> DNA
<213> Artificial Sequence

CA 02327551 2000-10-31
WO 99/55721 PCT/US99/08504
<220>
<223> oligonucleotide
<400> 90
ccagggtctc ctccttgc 18
<210> 91
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 91
ggaacttcat ctctgcccag 20
<210> 92
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 92
ccagctttgt gtgctggtc 19
<210> 93
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 93
gccaacagaa gagagaagcc 20
<210> 94
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 94
tcctggaagc tccactgtg 19
<210> 95
<211> 19
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 95
aggtaggcag gagggaatg 19
56

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<210> 96
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 96
tcctctctgt gaactccttg c 21
<210> 97
<211> 85
<212> PRT
<213> Homo Sapiens
<400> 97
Met Tyr Ser Phe Pro Thr Thr Val Val Glu Glu Ile Leu Ser Leu Ser
1 5 10 15
Leu Gln Leu Ile Ala Phe Pro Thr Val Ser Cys Glu Ile Leu Leu Glu
20 25 30
Ile Thr Ser Gln Thr Asn Lys Lys Gln Thr Arg Glu Thr Cys Tyr Ala
35 40 45
His Ser Ala Glu Glu Ile Gly Ile Ile Ala Gly Lys Arg Ile His Arg
5p 55 60
Pro Arg Leu Phe Pro Thr Tyr Val Ser Ser Ser Asp Ile Ser Ser Ser
65 70 75 80
Val Asn Gln Ala Met
<210> 9B
<211> 161
<212> PRT
<213> Homo Sapiens
<400> 98
Met Trp Pro Gly Arg Ile Met Thr Val Thr Val Val Leu Leu Cys Cys
1 5 10 15
Ser Thr Ala Ser Ile Trp Pro Cys Leu Ser His Ser Ala Ser Pro Ser
20 25 30
Arg Thr Cys Pro Asn Phe Val Gly Arg Ser Thr Arg Ser Cys Val Thr
35 40 45
Ala Asn Ser Leu Cys Glu Pro Arg Thr Pro Asp Pro Lys Pro Ile Asn
50 55 60
Gly Lys Gly Asp Met Gly Val Pro Ser Gln Glu Thr Pro Val Pro Phe
65 70 75 80
Leu Ser Cys Leu Phe Pro Leu Thr Ser Leu Trp Phe Phe Ile Phe Lys
85 90 95
57

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Cys Phe Asn Phe Cys Ile Phe Phe Ser Leu Arg Glu Tyr Leu Leu Ile
100 105 110
Ser Asp Val Gln Gly Val Ala Thr Glu Lys Pro Leu Ser Ser Ser Val
115 120 125
Cys Arg Gly Val Trp Pro Cys Gly Leu Gly Gly Ala Val Ile Leu Pro
130 135 140
Leu Pro Arg Ala Gly Ser Arg Lys Ser Val Leu Gly Val Val Gly Gly
145 150 155 160
Gln
<210> 99
<211> 159
<212> PRT
<213> Homo Sapiens
<400> 99
Met Tyr Arg Arg Lys Ser Gly Trp Thr Gly Cys Ala Ile Thr Cys Ser
1 5 10 15
Pro Cys Thr Ala Met Thr Gln Leu Arg Asn Cys Met Arg Leu Ser Arg
20 25 30
Ser Cys Ser Leu Thr Trp Glu Thr Pro Arg Trp Tyr Met Ala Gly Arg
35 40 45
Val Ala Thr Ser Thr Ser Gly Cys His Cys Trp Met Ser Arg Arg Asp
50 55 60
Leu Thr Pro Leu Pro His Pro Ser Glu Pro Gly Val Leu Asp Cys Leu
65 70 75 80
Gly Pro Cys His Leu Leu Pro Leu Leu Ser Pro Gly Ser Pro Cys Trp
85 90 95
Val Leu Gly Leu His Phe Ser Leu His Pro Pro Ser Ala Ala Ser Ala
100 105 110
Ser His Ala Leu Thr Ile Thr Ser Leu Pro Pro Gly Leu Leu Pro Phe
115 120 125
Val Gly Val Glu Leu Thr Ala His Pro Gln Ala Leu Met Gly Arg Gly
130 135 140
Phe Pro Ser Gly Met Ala Ala Ala Gly Arg His Leu Cys Phe Leu
145 150 155
<210> 100
<211> 54
<212> PRT
<213> Homo Sapiens
<400> 100
58

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Met Ser Pro Phe Thr Leu Leu Leu Gln Asn Phe Leu Val Ile Leu Ser
1 5 10 15
His Leu Phe Phe His Ile Asn Phe Lys Leu Cys Pro Val Leu His Pro
20 25 30
Leu Ser His Ser His Pro Gln Ile Leu Gly Ser Val Ile Pro Cys Ala
35 40 45
Ile Ile Phe Pro Pro Leu
<210> 101
<211> 212
<212> PRT
<213> Homo sapiens
<400> 101
Met Val Leu Phe Lys Arg Asp Arg Arg Glu Asp Thr Gln Gln Gly His
1 5 10 15
His Ser Met Asn Gly Arg Cys Thr Asp His Phe Leu Phe Val Leu Ser
20 25 30
Ser Leu Leu Ser Pro Ala Ala Ile Leu Val Arg Leu Val Pro Ala Arg
35 40 45
Glu Arg Cys Pro Gln Val Lys Gly Tyr Ser Gly Thr Trp Glu Lys Ala
50 55 60
Pro Gly Arg Phe Pro Cys Gly Pro Ala Gln His Gly Ser Arg Val Gly
65 70 75 80
Thr Leu Leu Cys Arg Gln Pro Ser Leu Tyr Ser Ser Gly Phe Leu Arg
85 90 95
Ala Leu Pro Cys Leu Cys Gln Ala Cys Ala Ala Ser His Pro Thr Ala
100 105 110
Ala Trp Glu Arg Pro Ala Thr Leu Pro Val His Thr Leu Pro Val His
115 120 125
Thr Leu Pro Val His Asn Cys Ser Arg Ala Leu Cys Leu Trp Ala Pro
130 135 140
Asn Pro Ser Ser Cys Ser Thr Phe Val Trp His Gly Asp Leu Cys Phe
145 150 155 160
Phe Ser Trp Cys Leu Cys Val Trp Ala Trp Asp Glu Cys Trp Tyr Ala
165 170 175
Leu Arg Thr Phe Leu Ile Ala Pro Cys Thr Leu Glu His Gly Ala Asp
180 185 190
Glu Arg Gly Ser Gly Ala Cys Pro Pro Pro Trp Thr Trp Lys Lys Pro
195 200 205
Thr Leu Glu Arg
210
59

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<210> 102
<211> 73
<212> PRT
<213> Homo Sapiens
<400> 202
Met Glu Asn Thr Arg Leu Thr Leu Arg His Leu Pro Leu Leu Pro Asn
1 5 10 15
Arg Ser Pro Glu Asp Ser Val Glu Gly Ser Val Asp Ser Lys Ser Gly
20 25 30
Phe Ser Ser Ile Ala Lys Lys Arg Ser Ala Ala Glu Thr Thr Ser Gly
35 40 45
Tyr Pro Arg Pro Pro Ala Phe Glu Leu Gly Asp Leu Pro Cys Leu Ile
50 55 60
Leu Ser His Thr Cys Phe Phe Thr Arg
65 70
<210> 103
<211> 302
<212> PRT
<213> Homo Sapiens
<400> 103
Met Ala Ile His Lys Ala Leu Val Met Cys Leu Gly Leu Pro Leu Phe
1 5 10 15
Leu Phe Pro Gly Ala Trp Ala Gln Gly His Val Pro Pro Gly Cys Ser
20 25 30
Gln Gly Leu Asn Pro Leu Tyr Tyr Asn Leu Cys Asp Arg Ser Gly Ala
35 40 45
Trp Gly Ile Val Leu Glu Ala Val Ala Gly Ala Gly Ile Val Thr Thr
50 55 60
Phe Val Leu Thr Ile Ile Leu Val Ala Ser Leu Pro Phe Val Gln Asp
65 70 75 80
Thr Lys Lys Arg Ser Leu Leu Gly Thr Gln Val Phe Phe Leu Leu Gly
85 90 95
Thr Leu Gly Leu Phe Cys Leu Val Phe Ala Cys Val Val Lys Pro Asp
100 105 I10
Phe Ser Thr Cys Ala Ser Arg Arg Phe Leu Phe Gly Val Leu Phe Ala
115 120 125
Ile Cys Phe Ser Cys Leu Ala Ala His Val Phe Ala Leu Asn Phe Leu
130 135 140
Ala Arg Lys Asn His Gly Pro Arg Gly Trp Val Ile Phe Thr Val Ala
145 150 155 160

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Leu Leu Leu Thr Leu Val Glu Val Ile Ile Asn Thr Glu Trp Leu Ile
165 170 175
Ile Thr Leu Val Arg Gly Ser Gly Glu Gly Gly Pro Gln Gly Asn Ser
180 185 190
Ser Ala Ala Gly Pro Trp Pro Pro Pro Val Pro Ser Pro Thr Trp Thr
195 200 205
Leu Ser Trp His Ser Ser Thr Ser Cys Cys Cys Cys Trp Val Pro Ser
210 215 220
Trp Gly Pro Gly Pro Pro Cys Val Ala Ala Thr Ser Ala Gly Val Ser
225 230 235 240
Met Gly Ser Leu Cys Ser Ser Pro Gln Pro Pro Pro Leu Pro Tyr Gly
245 250 255
Trp Cys Gly Ser Ser Cys Ile Leu Thr Ala Thr Ser Ser Thr Thr Val
260 265 270
Pro Pro Gly Met Thr Pro Arg Trp Pro Ser Pro Ser Pro Pro Met Pro
275 280 285
Gly Pro Ser Ser Ser Ser Thr Ser Ser Pro Arg Ser Pro Arg
290 295 300
<210> 104
<211> 114
<212> PRT
<213> Homo sapiens
<400> 104
Met Ala Gly Ser Leu Gly Tyr Pro Phe Ser Ser Gln Pro Leu Pro Val
1 5 10 15
Cys Gly Leu Ser Thr Ser His Pro Leu Phe Leu Ile Pro Tyr Leu Ser
20 25 30
Arg Ala Cys Pro Thr Ser Glu Val Leu Gly Phe Arg Val Leu Cys Leu
35 40 45
Pro Leu Pro Val Pro Arg Ser Ser Gln Thr Leu Leu Leu Phe Ile Arg
50 55 60
Ala Val Gly Arg Val Phe Leu Leu Phe Leu Gly Thr Cys Pro Cys Ser
65 70 75 80
Ser His Cys Pro Pro Cys Leu Ser Leu Ile Gln Met Cys His His Gly
85 90 95
Gly His Gly Trp Ser Arg Gly Ala Pro Ser Pro Arg Ala Gly Lys Gly
100 105 110
Ser Gly
<210> 105
61

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<211> 18
<212> PRT
<213> Homo sapiens
<400> 105
His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln
1 5 10 15
Gly Val
<210> 106
<211> 369
<212> PRT
<213> Homo Sapiens
<400> 106
Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu
1 5 10 15
Gly Ser Gly Glu Ala Gly Pro Leu Gln Ser Gly Glu Glu Ser Thr Gly
20 25 30
Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp Ala Leu Ser
35 40 45
Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly Gly Ala Ala Gly
50 55 60
Ser Lys Val Ser Glu Ala Leu Gly Gln Gly Thr Arg Glu Ala Val Gly
65 70 ?5 80
Thr Gly Val Arg Gln Val Pro Gly Phe Gly Val Ala Asp Ala Leu Gly
85 90 95
Asn Arg Val Gly Glu Ala Ala His Ala Leu Gly Asn Thr Gly His Glu
100 105 110
Ile Gly Arg Gln Ala Glu Asp Val Ile Arg His Gly Ala Asp Ala Val
115 220 125
Arg Gly Ser Trp Gln Gly Val Pro Gly His Asn Gly Ala Trp Glu Thr
130 135 140
Ser Gly Gly His Gly Ile Phe Gly Ser Gln Gly Gly Leu Gly Gly Gln
145 150 155 160
Gly Gln Gly Asn Pro Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr
165 170 175
Pro Gly Asn Ser Ala Gly Ser Phe Gly Met Asn Pro Gln Gly Ala Pro
180 185 190
Trp Gly Gln Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr
195 200 205
Gln Gly Ala Val Ala Gln Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn
210 215 220
62
59

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Gln Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly
225 230 235 240
Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gln Ser Gly Ser Ser Gly
245 250 255
Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser
260 265 270
Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly
275 280 285
Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser
290 295 300
Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ser
305 310 315 320
Gly Gly Gly Asn Gly His Lys Pro Gly Asn Ser Glu Thr Ser Pro Gly
325 330 335
Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys Ser Lys Leu Gly
340 345 350
Phe Ile Asn Trp Asp Ala Ile Asn Lys Asp Gln Arg Ser Ser Arg Ile
355 360 365
Pro
<210> 107
<211> 74
<212> PRT
<213> Homo Sapiens
<400> 107
Met Gly Pro Pro Gly Ala Arg Pro Ala Pro Gly Ala Ala Leu Glu Glu
1 5 10 15
Gln Cys Gly Gly Ala Leu Ala Cys Ser Leu Ala Ser Ala Ser Gly Thr
20 25 30
Ala Gly Val Val Pro Gly Ser Phe Cys Thr Val Gly Phe Gly Asp Val
35 40 45
Ser Pro Thr Trp Val Thr Val Gly Leu Pro His Pro Glu Arg Ser Val
50 55 60
Ser Thr Pro Glu Thr Leu Ser Val Ser Pro
65 70
63