SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM

PROTEINES SECRETEES ET POLYNUCLEOTIDES LES CODANT

English Abstract

The present invention provides secreted proteins and polynucleotides encoding
them, along with therapeutic, diagnostic and research utilities for these
polynucleotides and proteins.

French Abstract

L'invention concerne des protéines secrétées et des polynucléotides codant pour ces protéines, ainsi que l'utilisation de ces protéines et de ces polynucléotides à des fins thérapeutiques, diagnostiques et de recherche.

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 737 to
nucleotide 5302;

(c) the nucleotide sequence of SEQ ID NO:1 from nucleotide 782 to
nucleotide 5302;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vb24_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb24_1 deposited with the ATCC under accession
number 361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vb24_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb24_1 deposited with the ATCC under accession number
361;

(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.
188




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.

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 in a suitable culture medium,
wherein the host cell has been transformed with the polynucleotide of claim 2;
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 vb24_1 deposited with the ATCC under accession number
361.

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
vb24_1 deposited with the ATCC under accession number 361;
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.

189




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;

(b) the nucleotide sequence of SEQ ID NO:3 from nucleotide 60 to
nucleotide 1130;

(c) the nucleotide sequence of SEQ ID NO:3 from nucleotide 156 to
nucleotide 1130;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc64_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc64_1 deposited with the ATCC under accession number
361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vc64_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc64_1 deposited with the ATCC under accession number
361;

(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 anyone 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.

190




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
vc64_1 deposited with the ATCC under accession number 361;
the protein being substantially free from other mammalian proteins.

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 195 to
nucleotide 1298;

(c) the nucleotide sequence of SEQ ID NO:5 from nucleotide 333 to
nucleotide 1298;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vp20_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vp20_1 deposited with the ATCC under accession
number 361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vp20_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vp20_1 deposited with the ATCC under accession number
361;

(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;
191




(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

(c) the amino acid sequence encoded by the cDNA insert of clone
vp20_1 deposited with the ATCC under accession number 361;
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 129 to
nucleotide 731;

(c) the nucleotide sequence of SEQ ID NO:7 from nucleotide 186 to
nucleotide 731;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq4_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq4_1 deposited with the ATCC under accession number
361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vq4_1 deposited with the ATCC under accession number 361;
192




(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq4_1 deposited with the ATCC under accession number
361;

(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:

(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 vq4_1
deposited with the ATCC under accession number 361;
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 143 to
nucleotide 571;

(c) the nucleotide sequence of SEQ ID NO:9 from nucleotide 221 to
nucleotide 571;

193



(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo7_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo7_1 deposited with the ATCC under accession number
361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vo7_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
eDNA insert of clone vo7_1 deposited with the ATCC under accession number
361;

(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.

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 vo7_1
deposited with the ATCC under accession number 361;
the protein being substantially free from other mammalian proteins.

194




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 112 to
nucleotide 570;

(c) the nucleotide sequence of SEQ ID NO:11 from nucleotide 190 to
nucleotide 570;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc65_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc65_1 deposited with the ATCC under accession number
361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vc65_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc65_1 deposited with the ATCC under accession number
361;

(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
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:

195




(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
vc65_1 deposited with the ATCC under accession number 361;
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 4 to
nucleotide 261;

(c) the nucleotide sequence of SEQ ID NO:13 from nucleotide 124 to
nucleotide 261;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc66_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc66_1 deposited with the ATCC under accession number
361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vc66_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc66_1 deposited with the ATCC under accession number
361;

(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:14;

(i) 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;

(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
196



(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:13.

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
vc66_1 deposited with the ATCC under accession number 361;
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 135 to
nucleotide 1227;

(c) the nucleotide sequence of SEQ ID NO:15 from nucleotide 216 to
nucleotide 1227;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc68_1 deposited with the ATCC under accession number 361;

(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc68_1 deposited with the ATCC under accession number
361;

(f) the nucleotide sequence of a mature protein coding sequence of
clone vc68_1 deposited with the ATCC under accession number 361;

(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc68_1 deposited with the ATCC under accession number
361;

197




(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
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
vc68_1 deposited with the ATCC under accession number 361;
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 79 to
nucleotide 2424;

(c) the nucleotide sequence of SEQ ID NO:17 from nucleotide 145 to
nucleotide 2424;

(d) the nucleotide sequence of the full-length protein coding sequence
of clone vk6_1 deposited with the ATCC under accession number 361;

198




(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vk6_1 deposited with the ATCC under accession number
361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vk6_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vk6_1 deposited with the ATCC under accession number
361;
(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;
(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 vk6_1
deposited with the ATCC under accession number 361;
the protein being substantially free from other mammalian proteins.
28. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
199




(a) the nucleotide sequence of SEQ ID NO:19;
(b) the nucleotide sequence of SEQ ID NO:19 from nucleotide 2 to
nucleotide 733;
(c) the nucleotide sequence of SEQ ID NO:19 from nucleotide 71 to
nucleotide 733;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo4_1 deposited with the ATCC under accession number 361;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo4_1 deposited with the ATCC under accession number
361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo4_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo4_1 deposited with the ATCC under accession number
361;
(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:20;
(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;
200




(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 vo4_1
deposited with the ATCC under accession number 361;
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 151 to
nucleotide 1323;
(c) the nucleotide sequence of SEQ ID NO:21 from nucleotide 217 to
nucleotide 1323;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo8_1 deposited with the ATCC under accession number 361;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo8_1 deposited with the ATCC under accession number
361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo8_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo8_1 deposited with the ATCC under accession number
361;
(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
201




(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 vo8_1
deposited with the ATCC under accession number 361;
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 134 to
nucleotide 613;
(c) the nucleotide sequence of SEQ ID NO:23 from nucleotide 215 to
nucleotide 613;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo10_1 deposited with the ATCC under accession number 361;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo10_1 deposited with the ATCC under accession
number 361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo10_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo10_1 deposited with the ATCC under accession number
361;
202




(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:24;
(i) 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;
(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: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
vo10_1 deposited with the ATCC under accession number 361;
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 102 to
nucleotide 1163;
(c) the nucleotide sequence of SEQ ID NO:25 from nucleotide 156 to
nucleotide 1163;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo20_1 deposited with the ATCC under accession number 361;
203




(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo20_1 deposited with the ATCC under accession
number 361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo20_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo20_1 deposited with the ATCC under accession number
361;
(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:26;
(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
vo20_1 deposited with the ATCC under accession number 361;
the protein being substantially free from other mammalian proteins.
36. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
204




(a) the nucleotide sequence of SEQ ID NO:27;
(b) the nucleotide sequence of SEQ ID NO:27 from nucleotide 67 to
nucleotide 702;
(c) the nucleotide sequence of SEQ ID NO:27 from nucleotide 157 to
nucleotide 702;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo21_1 deposited with the ATCC under accession number 361;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo21_1 deposited with the ATCC under accession
number 361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo21_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo21_1 deposited with the ATCC under accession number
361;
(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:28;
(i) 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;
(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: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;
205




(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
vo21_1 deposited with the ATCC under accession number 361;
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 57 to
nucleotide 272;
(c) the nucleotide sequence of SEQ ID NO:29 from nucleotide 114 to
nucleotide 272;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vp24_1 deposited with the ATCC under accession number 361;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vp24_1 deposited with the ATCC under accession
number 361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vp24_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vp24_1 deposited with the ATCC under accession number
361;
(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
206




(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
vp24_1 deposited with the ATCC under accession number 361;
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 38 to
nucleotide 757;
(c) the nucleotide sequence of SEQ ID NO:31 from nucleotide 137 to
nucleotide 757;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo17_1 deposited with the ATCC under accession number 361;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo17_1 deposited with the ATCC under accession
number 361;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo17_1 deposited with the ATCC under accession number 361;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo17_1 deposited with the ATCC under accession number
361;
207




(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
vo17_1 deposited with the ATCC under accession number 361;
the protein being substantially free from other mammalian proteins.
42. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:33;
(b) the nucleotide sequence of SEQ ID NO:33 from nucleotide 93 to
nucleotide 263;
(c) the nucleotide sequence of SEQ ID NO:33 from nucleotide 174 to
nucleotide 263;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq11_1 deposited with the ATCC under accession number PTA-367;
208




(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq11_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq11_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq11_1 deposited with the ATCC under accession number
PTA-367;
(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
vq11_1 deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins.
44. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
209




(a) the nucleotide sequence of SEQ ID NO:35;
(b) the nucleotide sequence of SEQ ID NO:35 from nucleotide 43 to
nucleotide 1125;
(c) the nucleotide sequence of SEQ ID NO:35 from nucleotide 85 to
nucleotide 1125;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq12_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq12_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq12_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq12_1 deposited with the ATCC under accession number
PTA-367;
(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO0:36;
(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;
210




(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
(c) the amino acid sequence encoded by the cDNA insert of clone
vq12_1 deposited with the ATCC under accession number PTA-367;
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 32 to
nucleotide 904;
(c) the nucleotide sequence of SEQ ID NO:37 from nucleotide 77 to
nucleotide 904;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq14_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq14_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq14_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq14_1 deposited with the ATCC under accession number
PTA-367;
(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
211




(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:
(a) the amino acid sequence of SEQ ID NO:38;
(b) 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
(c) the amino acid sequence encoded by the cDNA insert of clone
vq14_1 deposited with the ATCC under accession number PTA-367;
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 384 to
nucleotide 1193;
(c) the nucleotide sequence of SEQ ID NO:39 from nucleotide 642 to
nucleotide 1193;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq15_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq15_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq15_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq15_1 deposited with the ATCC under accession number
PTA-367;
212




(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
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
vq15_1 deposited with the ATCC under accession number PTA-367;
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 132 to
nucleotide 503;
(c) the nucleotide sequence of SEQ ID NO:41 from nucleotide 189 to
nucleotide 503;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq17_1 deposited with the ATCC under accession number PTA-367;
213




(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq17_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq17_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq17_1 deposited with the ATCC under accession number
PTA-367;
(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;
(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
vq17_1 deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins.
52. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
214




(a) the nucleotide sequence of SEQ ID NO:43;
(b) the nucleotide sequence of SEQ ID NO:43 from nucleotide 69 to
nucleotide 401;
(c) the nucleotide sequence of SEQ ID NO:43 from nucleotide 138 to
nucleotide 401;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq18_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq18_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq18_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq18_1 deposited with the ATCC under accession number
PTA-367;
(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:44;
(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;
215




(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
vq18_1 deposited with the ATCC under accession number PTA-367;
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 65 to
nucleotide 1180;
(c) the nucleotide sequence of SEQ ID NO:45 from nucleotide 149 to
nucleotide 1180;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq22_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq22_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq22_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq22_1 deposited with the ATCC under accession number
PTA-367;
(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:46;
(i) 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;
(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
216




(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: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) 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
(c) the amino acid sequence encoded by the cDNA insert of clone
vq22_1 deposited with the ATCC under accession number PTA-367;
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 18 to
nucleotide 1409;
(c) the nucleotide sequence of SEQ ID NO:47 from nucleotide 60 to
nucleotide 1409;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vr3_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vr3_1 deposited with the ATCC under accession number
PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vr3_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vr3_1 deposited with the ATCC under accession number
PTA-367;
217




(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 vr3_1
deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins.
58. An isolated polynucleotide comprising a nucleotide sequence selected from
the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:49;
(b) the nucleotide sequence of SEQ ID NO:49 from nucleotide 690 to
nucleotide 2570;
(c) the nucleotide sequence of SEQ ID NO:49 from nucleotide 765 to
nucleotide 2570;
(d) the nucleotide sequence of SEQ ID NO:49 from nucleotide 1286 to
nucleotide 2895;
218




(e) the nucleotide sequence of the full-length protein coding sequence
of clone vb26_1 deposited with the ATCC under accession number PTA-367;
(f) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vb26_1 deposited with the ATCC under accession
number PTA-367;
(g) the nucleotide sequence of a mature protein coding sequence of
clone vb26_1 deposited with the ATCC under accession number PTA-367;
(h) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vb26_1 deposited with the ATCC under accession number
PTA-367;
(i) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:50;
(j) 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;
(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
(1) 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: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) the amino acid sequence of SEQ ID NO:50 from amino acid 200 to
amino acid 627;
(c) 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
(d) the amino acid sequence encoded by the cDNA insert of clone
vb26_1 deposited with the ATCC under accession number PTA-367;
219




the protein being substantially free from other mammalian proteins.
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 105 to
nucleotide 1724;
(c) the nucleotide sequence of SEQ ID NO:51 from nucleotide 186 to
nucleotide 1724;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vc70_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vc70_1 deposited with the ATCC under accession number
PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vc70_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vc70_1 deposited with the ATCC under accession number
PTA-367;
(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°lo 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:51.
220


31. 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
(c) the amino acid sequence encoded by the cDNA insert of clone
vc70_1 deposited with the ATCC under accession number PTA-367;
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 3 to
nucleotide 239;
(c) the nucleotide sequence of the full-length protein coding sequence
of clone vo28_1 deposited with the ATCC under accession number PTA-367;
(d) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo28_1 deposited with the ATCC under accession
number PTA-367;
(e) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:54;
(f) 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;
(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:53.
221


63. A protein comprising an amino acid sequence selected from the group
consisting of:
(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
vo28_1 deposited with the ATCC under accession number PTA-367;
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 49 to
nucleotide 1452;
(c) the nucleotide sequence of SEQ ID NO:55 from nucleotide 109 to
nucleotide 1452;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo29_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo29_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo29_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo29_1 deposited with the ATCC under accession number
PTA-367;
(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;
222


(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.
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
vo29_1 deposited with the ATCC under accession number PTA-367;
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 48 to
nucleotide 866;
(c) the nucleotide sequence of SEQ ID NO:57 from nucleotide 114 to
nucleotide 866;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vo30_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vo30_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vo30_1 deposited with the ATCC under accession number PTA-367;
223


(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vo30_1 deposited with the ATCC under accession number
PTA-367;
(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
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
vo30_1 deposited with the ATCC under accession number PTA-367;
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 235 to
nucleotide 510;
(c) the nucleotide sequence of SEQ ID NO:59 from nucleotide 316 to
nucleotide 510;
224


(d) the nucleotide sequence of the full-length protein coding sequence
of clone vp25_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vp25_1 deposited with the ATCC under accession
number PTA-367;
the nucleotide sequence of a mature protein coding sequence of
clone vp25_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vp25_1 deposited with the ATCC under accession number
PTA-367;
(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;
(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
vp25_1 deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins.
225



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 177 to
nucleotide 1626;
(c) the nucleotide sequence of SEQ ID NO:61 from nucleotide 219 to
nucleotide 1626;
(d) the nucleotide sequence of the full-length protein coding sequence
of clone vq25_1 deposited with the ATCC under accession number PTA-367;
(e) a nucleotide sequence encoding the full-length protein encoded by
the cDNA insert of clone vq25_1 deposited with the ATCC under accession
number PTA-367;
(f) the nucleotide sequence of a mature protein coding sequence of
clone vq25_1 deposited with the ATCC under accession number PTA-367;
(g) a nucleotide sequence encoding a mature protein encoded by the
cDNA insert of clone vq25_1 deposited with the ATCC under accession number
PTA-367;
(h) a nucleotide sequence encoding a protein comprising the amino acid
sequence of SEQ ID NO:62;
(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:
226



(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
vq25_1 deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins.
227

Description

CA 02362538 2001-08-16
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SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
This application is a continuation-in-part of the following applications:
(1) application Ser. No. 09/298,733, filed April 23, 1999; which claims the
benefit of
provisional application Ser. No. 60/082,961, filed April 24, 1998, now
abandoned;
(2) provisional application Ser. No. 60/120,680, filed February 19, 1999;
(3) provisional application Ser. No. 60/149,639, filed August 17, 1999;
(4) provisional application Ser. No. 60/155,686, filed September 23, 1999;
(5) provisional application Ser. No. 60/157,247, filed October 1, 1999;
(6) provisional application Ser. No. 60/167,823, filed November 29, 1999;
(7) provisional application Ser. No. 60/167,822, filed November 29, 1999;
2 0 (8) provisional application Ser. No. 60/XXX,XXX, filed February 15, 2000;
all of which are incorporated by reference herein.
2 5 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.



CA 02362538 2001-08-16
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BACKGROUND OF 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 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
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 polynucleotides
encoding
them that the present invention is directed.
2



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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
NO: l from nucleotide 737 to nucleotide 5302;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO: l from nucleotide 782 to nucleotide 5302;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb24_1 deposited with the ATCC under
accession number 207113;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb24_1 deposited with the ATCC under accession number
207113;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb24_1 deposited with the ATCC under
accession
number 207113;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone vb24_1 deposited with the ATCC under accession number
207113;
(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
2 5 comprising eight contiguous amino acids of SEQ ID N0:2;
(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
3



CA 02362538 2001-08-16
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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 NO:l.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:1
from nucleotide 737 to nucleotide 5302; the nucleotide sequence of SEQ ID NO:l
from
nucleotide 782 to nucleotide 5302; the nucleotide sequence of the full-length
protein
coding sequence of clone vb24_1 deposited with the ATCC under accession number
207113; or the nucleotide sequence of a mature protein coding sequence of
clone vb24_1
deposited with the ATCC under accession number 207113. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vb24_1 deposited with the ATCC under accession number
207113. 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 756 to amino acid 765 of SEQ ID N0:2.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID NO:1.
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 NO: l, but excluding the poly(A) tail at the
3' end of SEQ ID NO:1; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vb24_1 deposited with the ATCC under accession number 207113;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
4



CA 02362538 2001-08-16
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(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 NO:1, but excluding the poly(A) tail at the
3' end of SEQ ID NO:l; and
(bb) the nucleotide sequence of the cDNA insert of clone
vb24_1 deposited with the ATCC under accession number 207113;
(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 NO:1, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
NO:l to
a nucleotide sequence corresponding to the 3' end of SEQ ID NO:1 , but
excluding the
2 0 poly(A) tail at the 3' end of SEQ ID NO:1. 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 737 to nucleotide 5302, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID NO:l from nucleotide 737 to nucleotide 5302, to a nucleotide sequence
2 5 corresponding to the 3' end of said sequence of SEQ ID NO:1 from
nucleotide 737 to
nucleotide 5302. 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 782 to nucleotide 5302, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
NO:1 from
3 0 nucleotide 782 to nucleotide 5302, to a nucleotide sequence corresponding
to the 3' end of
said sequence of SEQ ID NO: l from nucleotide 782 to nucleotide 5302.
5



CA 02362538 2001-08-16
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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 N0:2;
(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
(c) the amino acid sequence encoded by the cDNA insert of clone
vb24_1 deposited with the ATCC under accession number 207113;
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 756 to amino acid 765 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
2 0 N0:3;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 60 to nucleotide 1130;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 156 to nucleotide 1130;
2 5 (d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc64_ 1 deposited with the ATCC under
accession number 207113;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc64_1 deposited with the ATCC under accession number
30 207113;
6



CA 02362538 2001-08-16
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(fj a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc64_1 deposited with the ATCC under
accession
number 207113;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc64_1 deposited with the ATCC under accession number 207113;
(h) a polynucleotide encoding a protein comprising the amino acid
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;
(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 ;
(I) 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.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID N0:3
from nucleotide 60 to nucleotide 1130; the nucleotide sequence of SEQ ID N0:3
from
nucleotide 156 to nucleotide 1130; the nucleotide sequence of the full-length
protein
coding sequence of clone vc64_1 deposited with the ATCC under accession number
207113; or the nucleotide sequence of a mature protein coding sequence of
clone vc64_1
2 5 deposited with the ATCC under accession number 207113. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc64_1 deposited with the ATCC under accession number
207113. In further preferred embodiments, the present invention provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
3 0 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
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
7



CA 02362538 2001-08-16
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SEQ ID N0:4 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 173 to amino acid 182 of SEQ ID N0:4.
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:
(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
(ab) the nucleotide sequence of the cDNA insert of clone
vc64_1 deposited with the ATCC under accession number 207113;
(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 N0:3, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:3; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc64_1 deposited with the ATCC under accession number 207113;
(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).
8



CA 02362538 2001-08-16
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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 N0:3, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:3 to
a nucleotide sequence corresponding 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 polynucleotide
isolated
according to the above process comprises a nucleotide sequence corresponding
to the
cDNA sequence of SEQ ID N0:3 from nucleotide 60 to nucleotide 1130, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:3 from nucleotide 60 to nucleotide 1130, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide 60
to
nucleotide 1130. Also preferably the polynucleotide isolated according to the
above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:3 from nucleotide 156 to nucleotide 1130, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:3 from
nucleotide 156 to nucleotide 1130, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:3 from nucleotide 156 to nucleotide 1130.
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 N0:4;
(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
vc64_1 deposited with the ATCC under accession number 207113;
2 5 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
3 0 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 173 to amino acid 182 of SEQ ID N0:4.
9



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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
N0:5;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 195 to nucleotide 1298;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 333 to nucleotide 1298;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vp20_1 deposited with the ATCC under
accession number 207113;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vp20_1 deposited with the ATCC under accession number
207113;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vp20_1 deposited with the ATCC under
accession
number 207113;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vp20_1 deposited with the ATCC under accession number 207113;
2 0 (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;
2 5 (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
3 0 one of the polynucleotides specified in (a)-(i); and



CA 02362538 2001-08-16
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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 NO:S.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:S
from nucleotide 195 to nucleotide 1298; the nucleotide sequence of SEQ ID NO:S
from
nucleotide 333 to nucleotide 1298; the nucleotide sequence of the full-length
protein
coding sequence of clone vp20_1 deposited with the ATCC under accession number
207113; or the nucleotide sequence of a mature protein coding sequence of
clone vp20_1
deposited with the ATCC under accession number 207113. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vp20_1 deposited with the ATCC under accession number
207113. In further preferred embodiments, the present invention provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of
SEQ ID N0:6 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 >D N0:6 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 179 to amino acid 188 of SEQ ID N0:6.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID NO:S.
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 NO:S, but excluding the poly(A) tail at the
3' end of SEQ ID NO:S; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vp20_1 deposited with the ATCC under accession number 207113;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
11



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(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 N0:5, 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
vp20_1 deposited with the ATCC under accession number 207113;
(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 N0:5, and
extending
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
2 0 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 195 to nucleotide 1298, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:5 from nucleotide 195 to nucleotide 1298, to a nucleotide sequence
2 5 corresponding to the 3' end of said sequence of SEQ ID N0:5 from
nucleotide 195 to
nucleotide 1298. 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 333 to nucleotide 1298, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:5 from
3 0 nucleotide 333 to nucleotide 1298, to a nucleotide sequence corresponding
to the 3' end of
said sequence of SEQ ID N0:5 from nucleotide 333 to nucleotide 1298.
12



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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
vp20_1 deposited with the ATCC under accession number 207113;
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
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
amino acid 179 to amino acid 188 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
2 0 N0:7;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 129 to nucleotide 731;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 186 to nucleotide 731;
2 5 (d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vq4_1 deposited with the ATCC under
accession number 207113;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vq4_1 deposited with the ATCC under accession number
30 207113;
13



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(fj a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vq4_1 deposited with the ATCC under accession
number 207113;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vq4_1 deposited with the ATCC under accession number 207113;
(h) a polynucleotide 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 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 N0:7.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID N0:7
from nucleotide 129 to nucleotide 731; the nucleotide sequence of SEQ ID N0:7
from
nucleotide 186 to nucleotide 731; the nucleotide sequence of the full-length
protein coding
sequence of clone vq4_1 deposited with the ATCC under accession number 207113;
or the
nucleotide sequence of a mature protein coding sequence of clone vq4_1
deposited with
2 5 the ATCC under accession number 207113. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of
clone vq4_1 deposited with the ATCC under accession number 207113. 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
3 0 activity, the fragment 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
14



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activity, the fragment comprising the amino acid sequence from amino acid 95
to amino
acid 104 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
vq4_1 deposited with the ATCC under accession number 207113;
(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 N0:7, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:7; and
(bb) the nucleotide sequence of the cDNA insert of clone
vq4_1 deposited with the ATCC under accession number 207113;
(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).



CA 02362538 2001-08-16
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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 129 to nucleotide 731, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:7 from nucleotide 129 to nucleotide 731, to a nucleotide sequence
corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide
129 to
nucleotide 731. 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 186 to nucleotide 731, and extending contiguously from a
nucleotide
sequence corresponding to the 5' end of said sequence of SEQ ID N0:7 from
nucleotide
186 to nucleotide 731, to a nucleotide sequence corresponding to the 3' end of
said
sequence of SEQ ID N0:7 from nucleotide 186 to nucleotide 731.
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 vq4_1
deposited with the ATCC under accession number 207113;
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 acids
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 95 to amino acid 104 of SEQ ID N0:8.
16



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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
N0:9;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 143 to nucleotide 571;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 221 to nucleotide 571;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vo7_1 deposited with the ATCC under
accession number PTA-362;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo7_1 deposited with the ATCC under accession number
PTA-362;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo7_1 deposited with the ATCC under accession
number PTA-362;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo7_1 deposited with the ATCC under accession number PTA-362;
2 0 (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
amino acid sequence of SEQ ID NO:10 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID NO:10;
2 5 (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
3 0 one of the polynucleotides specified in (a)-(i); and
17



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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 N0:9.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:9
from nucleotide 143 to nucleotide 571; the nucleotide sequence of SEQ ID N0:9
from
nucleotide 221 to nucleotide 571; the nucleotide sequence of the full-length
protein coding
sequence of clone vo7_1 deposited with the ATCC under accession number PTA-
362; or
the nucleotide sequence of a mature protein coding sequence of clone vo7_1
deposited with
the ATCC under accession number PTA-362. In other preferred embodiments, the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of
clone vo7_1 deposited with the ATCC under accession number PTA-362. In further
preferred embodiments, the present invention provides a polynucleotide
encoding a protein
comprising a fragment of the amino acid sequence of SEQ ID NO: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 66
to amino
acid 75 of SEQ ID NO:10.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 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
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(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
3 0 vo7_1 deposited with the ATCC under accession number PTA-362;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
18



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(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 N0:9, but excluding the poly(A) tail at the
3' end of SEQ ID N0:9; and
(bb) the nucleotide sequence of the cDNA insert of clone
vo7_1 deposited with the ATCC under accession number PTA-362;
(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
2 0 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 143 to nucleotide 571, and
extending
contiguously from a nucleotide sequence corresponding to the 5' end of said
sequence of
SEQ ID N0:9 from nucleotide 143 to nucleotide 571, to a nucleotide sequence
2 5 corresponding to the 3' end of said sequence of SEQ ID N0:9 from
nucleotide 143 to
nucleotide 571. 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 221 to nucleotide 571, and extending contiguously from a
nucleotide
sequence corresponding to the 5' end of said sequence of SEQ ID N0:9 from
nucleotide
3 0 221 to nucleotide 571, to a nucleotide sequence corresponding to the 3'
end of said
sequence of SEQ ID N0:9 from nucleotide 221 to nucleotide 571.
19



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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: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 vo7_1
deposited with the ATCC under accession number PTA-362;
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 NO: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 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 66 to amino acid 75 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
2 0 NO:11;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:11 from nucleotide 112 to nucleotide 570;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:11 from nucleotide 190 to nucleotide 570;
2 5 (d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc65_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc65_1 deposited with the ATCC under accession number
3 0 PTA-361;



CA 02362538 2001-08-16
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(f) a polynucleotide comprising the nucleotide sequence of a mature '
protein coding sequence of clone vc65_1 deposited with the ATCC under
accession
number PTA-361;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc65_1 deposited with the ATCC under accession number PTA-361;
(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;
(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 NO:11.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
NO:11 from nucleotide 112 to nucleotide 570; the nucleotide sequence of SEQ ID
NO:11
from nucleotide 190 to nucleotide 570; the nucleotide sequence of the full-
length protein
coding sequence of clone vc65_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vc65_1
2 5 deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc65_1 deposited with the ATCC under accession number
PTA-
361. 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
3 0 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
21



CA 02362538 2001-08-16
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SEQ ID N0:12 having biological activity, the fragment comprising the amino
acid '
sequence from amino acid 71 to amino acid 80 of SEQ ID N0:12.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID NO: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
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID NO:11, but excluding the poly(A) tail at the
3' end of SEQ ID NO:11; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc65_1 deposited with the ATCC under accession number PTA-
361;
(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);
2 0 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 NO:11, but excluding the poly(A) tail at the
3' end of SEQ ID NO:11; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc65_1 deposited with the ATCC under accession number PTA-
361;
3 0 (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
22



CA 02362538 2001-08-16
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(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 NO:11, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ ID
NO: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 NO:11. Also preferably the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID NO:11 from nucleotide 112 to
nucleotide
570, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID NO:11 from nucleotide 112 to nucleotide 570, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID NO:11 from
nucleotide
112 to nucleotide 570. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
NO:11 from nucleotide 190 to nucleotide 570, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
NO:11 from
nucleotide 190 to nucleotide 570, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID NO:11 from nucleotide 190 to nucleotide 570.
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 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:12;
(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
vc65_1 deposited with the ATCC under accession number PTA-361;
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
3 0 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
23



CA 02362538 2001-08-16
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ID N0:12 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 71 to amino acid 80 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 4 to nucleotide 261;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13 from nucleotide 124 to nucleotide 261;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc66_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc66_1 deposited with the ATCC under accession number
PTA-361;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc66_1 deposited with the ATCC under
accession
number PTA-361;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc66_1 deposited with the ATCC under accession number PTA-361;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:14;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:14 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:14;
(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
3 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
24



CA 02362538 2001-08-16
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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 N0:13.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:13 from nucleotide 4 to nucleotide 261; the nucleotide sequence of SEQ ID
N0:13
from nucleotide 124 to nucleotide 261; the nucleotide sequence of the full-
length protein
coding sequence of clone vc66_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vc66_1
deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc66_1 deposited with the ATCC under accession number
PTA-
361. 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 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 38 to amino acid 47 of SEQ ID N0:14.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
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
2 5 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
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vc66_1 deposited with the ATCC under accession number PTA-
361;



CA 02362538 2001-08-16
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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 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
vc66_1 deposited with the ATCC under accession number PTA-
361;
(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
2 0 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
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 5 corresponding to the cDNA sequence of SEQ ID N0:13 from nucleotide 4 to
nucleotide
261, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:13 from nucleotide 4 to nucleotide 261, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:13 from
nucleotide
4 to nucleotide 261. Also preferably the polynucleotide isolated according to
the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:13 from nucleotide 124 to nucleotide 261, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:13 from
26



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nucleotide 124 to nucleotide 261, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:13 from nucleotide 124 to nucleotide 261.
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;
(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
vc66_1 deposited with the ATCC under accession number PTA-361;
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 38 to amino acid 47 of SEQ ID N0:14.
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
N0:15;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 135 to nucleotide 1227;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 216 to nucleotide 1227;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc68_1 deposited with the ATCC under
accession number PTA-361;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc68_1 deposited with the ATCC under accession number
PTA-361;
27



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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc68_1 deposited with the ATCC under
accession
number PTA-361;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc68_1 deposited with the ATCC under accession number PTA-361;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:16;
(i) a polynucleotide 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°Io of the length of SEQ ID NO:15.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
NO:15 from nucleotide 135 to nucleotide 1227; the nucleotide sequence of SEQ
ID NO:15
from nucleotide 216 to nucleotide 1227; the nucleotide sequence of the full-
length protein
coding sequence of clone vc68_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vc68_1
2 5 deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc68_1 deposited with the ATCC under accession number
PTA-
361. 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
3 0 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 fragment of the amino acid
sequence of
28



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SEQ ID N0:16 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 160 to amino acid 169 of SEQ ID N0:16.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID NO:15.
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 NO:15, but excluding the poly(A) tail at the
3' end of SEQ ID NO:15; and
(ab) the nucleotide sequence of the cDNA insert of clone
vc68_1 deposited with the ATCC under accession number PTA-
361;
(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);
2 0 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 5 (ba) SEQ ID NO:15, but excluding the poly(A) tail at the
3' end of SEQ ID NO:15; and
(bb) the nucleotide sequence of the cDNA insert of clone
vc68_1 deposited with the ATCC under accession number PTA-
361;
3 0 (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
29



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(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 N0:15, 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
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:15 from nucleotide 135 to
nucleotide
1227, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:15 from nucleotide 135 to nucleotide 1227, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from
nucleotide
135 to nucleotide 1227. 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 216 to nucleotide 1227, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
NO:1 S from
nucleotide 216 to nucleotide 1227, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:15 from nucleotide 216 to nucleotide 1227.
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 0 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
vc68_1 deposited with the ATCC under accession number PTA-361;
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
3 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ ID N0:16, or a protein comprising a fragment of the amino acid sequence
of SEQ



CA 02362538 2001-08-16
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ID N0:16 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 160 to amino acid 169 of SEQ ID N0:16.
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
N0:17;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 79 to nucleotide 2424;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 145 to nucleotide 2424;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vk6_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vk6_1 deposited with the ATCC under accession number
PTA-361;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vk6_1 deposited with the ATCC under accession
number PTA-361;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vk6_1 deposited with the ATCC under accession number PTA-361;
(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
2 5 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
3 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and
31



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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 N0:17.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:17 from nucleotide 79 to nucleotide 2424; the nucleotide sequence of SEQ ID
N0:17
from nucleotide 145 to nucleotide 2424; the nucleotide sequence of the full-
length protein
coding sequence of clone vk6_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vk6_1
deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vk6_1 deposited with the ATCC under accession number
PTA-
361. In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:18
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 fragment comprising the amino
acid
sequence from amino acid 386 to amino acid 395 of SEQ ID N0:18.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 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
2 5 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
3 0 vk6_1 deposited with the ATCC under accession number PTA-361;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
32



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(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 N0:17, but excluding the poly(A) tail at the
3' end of SEQ ID N0:17; and
(bb) the nucleotide sequence of the cDNA insert of clone
vk6_1 deposited with the ATCC under accession number PTA-361;
(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 N0:17, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ ID
N0:17 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:17 ,
but
2 0 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 79 to
nucleotide
2424, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ >D N0:17 from nucleotide 79 to nucleotide 2424, to a
nucleotide
2 5 sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from
nucleotide
79 to nucleotide 2424. 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 145 to nucleotide 2424, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:17 from
3 0 nucleotide 145 to nucleotide 2424, to a nucleotide sequence corresponding
to the 3' end of
said sequence of SEQ ID N0:17 from nucleotide 145 to nucleotide 2424.
33



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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 N0:18, the
fragment comprising eight contiguous amino acids of SEQ ID N0:18; and
(c) the amino acid sequence encoded by the cDNA insert of clone vk6_1
deposited with the ATCC under accession number PTA-361;
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 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 LD 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 386 to amino acid 395 of SEQ ID N0:18.
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
2 0 N0:19;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 2 to nucleotide 733;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 71 to nucleotide 733;
2 5 (d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vo4_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo4_1 deposited with the ATCC under accession number
3 0 PTA-361;
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CA 02362538 2001-08-16
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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo4_1 deposited with the ATCC under accession
number PTA-361;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo4_1 deposited with the ATCC under accession number PTA-361;
(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;
(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 N0:19.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:19 from nucleotide 2 to nucleotide 733; the nucleotide sequence of SEQ ID
N0:19
from nucleotide 71 to nucleotide 733; the nucleotide sequence of the full-
length protein
coding sequence of clone vo4_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vo4_ 1
2 5 deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vo4_1 deposited with the ATCC under accession number
PTA-
361. 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
3 0 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



CA 02362538 2001-08-16
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SEQ ID N0:20 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 117 to amino acid 126 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
(ab) the nucleotide sequence of the cDNA insert of clone
vo4_1 deposited with the ATCC under accession number PTA-361;
(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 N0:19, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:19; and
(bb) the nucleotide sequence of the cDNA insert of clone
vo4_1 deposited with the ATCC under accession number PTA-361;
(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).
36



CA 02362538 2001-08-16
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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 N0:19, 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 2 to
nucleotide
733, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:19 from nucleotide 2 to nucleotide 733, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:19 from
nucleotide
2 to nucleotide 733. 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 71 to nucleotide 733, and extending contiguously from a
nucleotide
sequence corresponding to the 5' end of said sequence of SEQ ID N0:19 from
nucleotide
71 to nucleotide 733, to a nucleotide sequence corresponding to the 3' end of
said sequence
of SEQ ID N0:19 from nucleotide 71 to nucleotide 733.
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 N0:20;
(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 acid sequence encoded by the cDNA insert of clone vo4_ 1
deposited with the ATCC under accession number PTA-361;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such
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 acids
3 0 of SEQ ID N0:20, or 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 117 to amino acid 126 of SEQ ID N0:20.
37



CA 02362538 2001-08-16
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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 151 to nucleotide 1323;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 217 to nucleotide 1323;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vo8_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo8_1 deposited with the ATCC under accession number
PTA-361;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo8_1 deposited with the ATCC under accession
number PTA-361;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo8_1 deposited with the ATCC under accession number PTA-361;
2 0 (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
comprising eight contiguous amino acids of SEQ ID N0:22;
2 5 (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
3 0 one of the polynucleotides specified in (a)-(i); and
38



CA 02362538 2001-08-16
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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 N0:21.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:21 from nucleotide 151 to nucleotide 1323; the nucleotide sequence of SEQ
ID N0:21
from nucleotide 217 to nucleotide 1323; the nucleotide sequence of the full-
length protein
coding sequence of clone vo8_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vo8_1
deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vo8_1 deposited with the ATCC under accession number
PTA-
361. 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 190 to amino acid 199 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:
(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 N0:21, but excluding the poly(A) tail at the
3' end of SEQ ID N0:21; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vo8_1 deposited with the ATCC under accession number PTA-361;
(ii) hybridizing said probes) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C; and
39



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(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 N0:21, 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
vo8_1 deposited with the ATCC under accession number PTA-361;
(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
NO:21 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:21 ,
but
2 0 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 151 to
nucleotide
1323, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:21 from nucleotide 151 to nucleotide 1323, to a
nucleotide
2 5 sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from
nucleotide
151 to nucleotide 1323. 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 217 to nucleotide 1323, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:21 from
3 0 nucleotide 217 to nucleotide 1323, to a nucleotide sequence corresponding
to the 3' end of
said sequence of SEQ ID N0:21 from nucleotide 217 to nucleotide 1323.



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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 N0:22;
(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
(c) the amino acid sequence encoded by the cDNA insert of clone vo8_ 1
deposited with the ATCC under accession number PTA-361;
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 190 to amino acid 199 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
2 0 N0:23;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23 from nucleotide 134 to nucleotide 613;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23 from nucleotide 215 to nucleotide 613;
2 5 (d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vol0_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vol0_1 deposited with the ATCC under accession number
3 0 PTA-361;
41



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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vol0_1 deposited with the ATCC under
accession
number PTA-361;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vol0_1 deposited with the ATCC under accession number PTA-361;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:24;
(i) a polynucleotide encoding a protein comprising a fragment of the
amino acid sequence of SEQ ID N0:24 having biological activity, the fragment
comprising eight contiguous amino acids of SEQ ID N0:24;
(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 N0:23.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:23 from nucleotide 134 to nucleotide 613; the nucleotide sequence of SEQ ID
N0:23
from nucleotide 215 to nucleotide 613; the nucleotide sequence of the full-
length protein
coding sequence of clone vol0_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vol0_1
2 5 deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vol0_1 deposited with the ATCC under accession number
PTA-
361. 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
3 0 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
42



CA 02362538 2001-08-16
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SEQ ID N0:24 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 75 to amino acid 84 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
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 N0:23, 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
vol0_1 deposited with the ATCC under accession number PTA-
361;
(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);
2 0 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 5 (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 clone
vo 10_ 1 deposited with the ATCC under accession number PTA-
361;
3 0 (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
43



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(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 N0:23, and
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 134 to
nucleotide
613, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:23 from nucleotide 134 to nucleotide 613, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:23 from
nucleotide
134 to nucleotide 613. 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 215 to nucleotide 613, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:23 from
nucleotide 215 to nucleotide 613, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:23 from nucleotide 215 to nucleotide 613.
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 0 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
(c) the amino acid sequence encoded by the cDNA insert of clone
vol0_1 deposited with the ATCC under accession number PTA-361;
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
3 0 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
44



CA 02362538 2001-08-16
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ID N0:24 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 75 to amino acid 84 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 102 to nucleotide 1163;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 156 to nucleotide 1163;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vo20_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo20_1 deposited with the ATCC under accession number
PTA-361;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo20_1 deposited with the ATCC under
accession
number PTA-361;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo20_1 deposited with the ATCC under accession number PTA-361;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:26;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:26 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:26;
(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
3 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and



CA 02362538 2001-08-16
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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 N0:25.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:25 from nucleotide 102 to nucleotide 1163; the nucleotide sequence of SEQ
ID N0:25
from nucleotide 156 to nucleotide 1163; the nucleotide sequence of the full-
length protein
coding sequence of clone vo20_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vo20_1
deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vo20_1 deposited with the ATCC under accession number
PTA-
361. In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:26
having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:26, or a
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 172 to amino acid 181 of SEQ ID N0:26.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 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:
(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 N0:25, but excluding the poly(A) tail at the
3' end of SEQ ID N0:25; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vo20_1 deposited with the ATCC under accession number PTA-
361;
46



CA 02362538 2001-08-16
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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 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
vo20_1 deposited with the ATCC under accession number PTA-
361;
(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
2 0 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
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 5 corresponding to the cDNA sequence of SEQ ID N0:25 from nucleotide 102 to
nucleotide
1163, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:25 from nucleotide 102 to nucleotide 1163, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from
nucleotide
102 to nucleotide 1163. Also preferably the polynucleotide isolated according
to the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:25 from nucleotide 156 to nucleotide 1163, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:25 from
47



CA 02362538 2001-08-16
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nucleotide 156 to nucleotide 1163, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:25 from nucleotide 156 to nucleotide 1163.
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
vo20_1 deposited with the ATCC under accession number PTA-361;
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 1D 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 172 to amino acid 181 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 67 to nucleotide 702;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27 from nucleotide 157 to nucleotide 702;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vo21_1 deposited with the ATCC under
accession number PTA-361;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo21_1 deposited with the ATCC under accession number
PTA-361;
48



CA 02362538 2001-08-16
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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo21_1 deposited with the ATCC under
accession
number PTA-361;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo21_1 deposited with the ATCC under accession number PTA-361;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:28;
(i) 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;
(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 N0:27.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:27 from nucleotide 67 to nucleotide 702; the nucleotide sequence of SEQ ID
N0:27
from nucleotide 157 to nucleotide 702; the nucleotide sequence of the full-
length protein
coding sequence of clone vo21_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vo21_1
2 5 deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vo21_1 deposited with the ATCC under accession number
PTA-
361. 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
3 0 having biological activity, the fragment preferably comprising eight (more
preferably
twenty, most 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
49



CA 02362538 2001-08-16
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SEQ ID N0:28 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 101 to amino acid 110 of SEQ ID N0:28.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
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:
(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
vo21_1 deposited with the ATCC under accession number PTA-
361;
(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);
2 0 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 5 (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
vo21_1 deposited with the ATCC under accession number PTA-
361;
3 0 (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



CA 02362538 2001-08-16
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(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 N0:27, 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
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:27 from nucleotide 67 to
nucleotide
702, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:27 from nucleotide 67 to nucleotide 702, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:27 from
nucleotide
67 to nucleotide 702. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:27 from nucleotide 157 to nucleotide 702, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:27 from
nucleotide 1~7 to nucleotide 702, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:27 from nucleotide 157 to nucleotide 702.
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 0 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
vo21_1 deposited with the ATCC under accession number PTA-361;
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
3 0 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
51



CA 02362538 2001-08-16
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ID N0:28 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 101 to amino acid 110 of SEQ ID N0:28.
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
N0:29;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 57 to nucleotide 272;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 114 to nucleotide 272;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vp24_1 deposited with the ATCC under
accession number PTA-361;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vp24_1 deposited with the ATCC under accession number
PTA-361;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vp24_1 deposited with the ATCC under
accession
number PTA-361;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vp24_1 deposited with the ATCC under accession number PTA-361;
(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
2 5 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
3 0 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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CA 02362538 2001-08-16
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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 N0:29.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:29 from nucleotide 57 to nucleotide 272; the nucleotide sequence of SEQ ID
N0:29
from nucleotide 114 to nucleotide 272; the nucleotide sequence of the full-
length protein
coding sequence of clone vp24_1 deposited with the ATCC under accession number
PTA-
361; or the nucleotide sequence of a mature protein coding sequence of clone
vp24_1
deposited with the ATCC under accession number PTA-361. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vp24_1 deposited with the ATCC under accession number
PTA-
361. In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:30
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 fragment comprising the amino
acid
sequence from amino acid 31 to amino acid 40 of SEQ ID N0:30.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:29.
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 N0:29, but excluding the poly(A) tail at the
3' end of SEQ ID N0:29; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vp24_1 deposited with the ATCC under accession number PTA-
361;
53



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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 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 N0:29, 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
vp24_1 deposited with the ATCC under accession number PTA-
361;
(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
2 0 nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29,
and
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
2 5 corresponding to the cDNA sequence of SEQ ID N0:29 from nucleotide 57 to
nucleotide
272, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:29 from nucleotide 57 to nucleotide 272, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from
nucleotide
57 to nucleotide 272. Also preferably the polynucleotide isolated according to
the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:29 from nucleotide 114 to nucleotide 272, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:29 from
54



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nucleotide 114 to nucleotide 272, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:29 from nucleotide 114 to nucleotide 272.
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
vp24_1 deposited with the ATCC under accession number PTA-361;
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
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
from amino acid 31 to amino acid 40 of SEQ ID N0:30.
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
N0:31;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 38 to nucleotide 757;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 137 to nucleotide 757;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vol7_1 deposited with the ATCC under
accession number PTA-366;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vol7_1 deposited with the ATCC under accession number
PTA-366;



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(fj a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vol7_1 deposited with the ATCC under
accession
number PTA-366;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vol7_1 deposited with the ATCC under accession number PTA-366;
(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 ;
(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 N0:31.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:31 from nucleotide 38 to nucleotide 757; the nucleotide sequence of SEQ ID
N0:31
from nucleotide 137 to nucleotide 757; the nucleotide sequence of the full-
length protein
coding sequence of clone vol7_1 deposited with the ATCC under accession number
PTA-
366; or the nucleotide sequence of a mature protein coding sequence of clone
vol7_1
2 5 deposited with the ATCC under accession number PTA-366. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vol7_1 deposited with the ATCC under accession number
PTA-
366. 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
3 0 having biological activity, the fragment 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
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SEQ ID N0:32 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 115 to amino acid 124 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
vol7_1 deposited with the ATCC under accession number PTA-
366;
(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);
2 0 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 5 (ba) SEQ ID N0:3 l, 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
vol7_1 deposited with the ATCC under accession number PTA-
366;
3 0 (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
57



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(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 N0:31, 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 38 to
nucleotide
757, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:31 from nucleotide 38 to nucleotide 757, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from
nucleotide
38 to nucleotide 757. 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 137 to nucleotide 757, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:31 from
nucleotide 137 to nucleotide 757, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:31 from nucleotide 137 to nucleotide 757.
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 0 consisting of:
(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
vol7_1 deposited with the ATCC under accession number PTA-366;
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
3 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ ID N0:32, or a protein comprising a fragment of the amino acid sequence
of SEQ
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ID N0:32 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 115 to amino acid 124 of SEQ ID N0:32.
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
N0:33;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 93 to nucleotide 263;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 174 to nucleotide 263;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vq 11 _ 1 deposited with the ATCC
under
accession number PTA-367;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql l_1 deposited with the ATCC under accession number
PTA-367;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vql 1_1 deposited with the ATCC under
accession
number PTA-367;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vql l_1 deposited with the ATCC under accession number PTA-
367;
(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 5 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
3 0 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 N0:33.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:33 from nucleotide 93 to nucleotide 263; the nucleotide sequence of SEQ ID
N0:33
from nucleotide 174 to nucleotide 263; the nucleotide sequence of the full-
length protein
coding sequence of clone vql 1_1 deposited with the ATCC under accession
number PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vqll_1
deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vql 1_1 deposited with the ATCC under accession
number PTA-
367. 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 23 to amino acid 32 of SEQ ID N0:34.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 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
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(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
30 vql l_1 deposited with the ATCC under accession number PTA-
367;



CA 02362538 2001-08-16
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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 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 N0:33, but excluding the poly(A) tail at the
3' end of SEQ ID N0:33; and
(bb) the nucleotide sequence of the cDNA insert of clone
vql l_1 deposited with the ATCC under accession number PTA-
367;
(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
2 0 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
2 5 corresponding to the cDNA sequence of SEQ ID N0:33 from nucleotide 93 to
nucleotide
263, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:33 from nucleotide 93 to nucleotide 263, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from
nucleotide
93 to nucleotide 263. Also preferably the polynucleotide isolated according to
the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:33 from nucleotide 174 to nucleotide 263, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:33 from
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nucleotide 174 to nucleotide 263, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:33 from nucleotide 174 to nucleotide 263.
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 N0:34;
(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
vql l_1 deposited with the ATCC under accession number PTA-367;
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
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
of SEQ ID N0:34, or a protein comprising a fragment of the amino acid sequence
of 5EQ
ID N0:34 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 23 to amino acid 32 of SEQ ID N0:34.
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
N0:35;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 43 to nucleotide 1125;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 85 to nucleotide 1125;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vq 12_ 1 deposited with the ATCC under
accession number PTA-367;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql2_1 deposited with the ATCC under accession number
PTA-367;
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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vql2_1 deposited with the ATCC under
accession
number PTA-367;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vq 12_ 1 deposited with the ATCC under accession number PTA-
367;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:36;
(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;
(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 N0:35.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:35 from nucleotide 43 to nucleotide 1125; the nucleotide sequence of SEQ ID
N0:35
from nucleotide 85 to nucleotide 1125; the nucleotide sequence of the full-
length protein
coding sequence of clone vql2_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vql2_1
2 5 deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vql2_1 deposited with the ATCC under accession number
PTA-
367. 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
3 0 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
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SEQ ID N0:36 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 175 to amino acid 184 of SEQ ID N0:36.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
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
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
vql2_1 deposited with the ATCC under accession number PTA
367;
(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);
2 0 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 5 (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
vql2_1 deposited with the ATCC under accession number PTA-
367;
3 0 (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
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(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
corresponding to the cDNA sequence of SEQ ID N0:35 from nucleotide 43 to
nucleotide
1125, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:35 from nucleotide 43 to nucleotide 1125, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from
nucleotide
43 to nucleotide 1125. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:35 from nucleotide 85 to nucleotide 1125, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:35 from
nucleotide 85 to nucleotide 1125, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:35 from nucleotide 85 to nucleotide 1125.
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 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:36;
(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
2 5 vq 12_1 deposited with the ATCC under accession number PTA-367;
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
3 0 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



CA 02362538 2001-08-16
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ID N0:36 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 175 to amino acid 184 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 32 to nucleotide 904;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37 from nucleotide 77 to nucleotide 904;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vql4_1 deposited with the ATCC under
accession number PTA-367;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql4_1 deposited with the ATCC under accession number
PTA-367;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vql4_1 deposited with the ATCC under
accession
number PTA-367;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vq 14_1 deposited with the ATCC under accession number PTA-
367;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:38;
(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
3 0 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 N0:37.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:37 from nucleotide 32 to nucleotide 904; the nucleotide sequence of SEQ ID
N0:37
from nucleotide 77 to nucleotide 904; the nucleotide sequence of the full-
length protein
coding sequence of clone vql4_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vql4_1
deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vql4_1 deposited with the ATCC under accession number
PTA-
367. 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
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 140 to amino acid 149 of SEQ ID N0:38.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 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:
(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 N0:37, 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 clone
30 vql4_1 deposited with the ATCC under accession number PTA-
367;
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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 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
vql4_1 deposited with the ATCC under accession number PTA-
367;
(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
2 0 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
polynucleotide isolated according to the above process comprises a nucleotide
sequence
2 5 corresponding to the cDNA sequence of SEQ ID N0:37 from nucleotide 32 to
nucleotide
904, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:37 from nucleotide 32 to nucleotide 904, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from
nucleotide
32 to nucleotide 904. Also preferably the polynucleotide isolated according to
the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:37 from nucleotide 77 to nucleotide 904, and extending contiguously from a
nucleotide
sequence corresponding to the 5' end of said sequence of SEQ ID N0:37 from
nucleotide
68



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77 to nucleotide 904, to a nucleotide sequence corresponding to the 3' end of
said sequence
of SEQ ID N0:37 from nucleotide 77 to nucleotide 904.
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) 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
(c) the amino acid sequence encoded by the cDNA insert of clone
vql4_1 deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:38. In further
preferred
embodiments, 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 acid 140 to amino acid 149 of SEQ ID N0:38.
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
N0:39;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 384 to nucleotide 1193;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 642 to nucleotide 1193;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vql5_1 deposited with the ATCC under
accession number PTA-367;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql5_1 deposited with the ATCC under accession number
PTA-367;
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(fj a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vql5_1 deposited with the ATCC under
accession
number PTA-367;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vql5_1 deposited with the ATCC under accession number PTA-367;
(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 ;
(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 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:39 from nucleotide 384 to nucleotide 1193; the nucleotide sequence of SEQ
ID N0:39
from nucleotide 642 to nucleotide 1193; the nucleotide sequence of the full-
length protein
coding sequence of clone vql5_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vql5_1
2 5 deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vql5_1 deposited with the ATCC under accession number
PTA-
367. 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
3 0 having biological activity, the fragment 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



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SEQ ID N0:40 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 130 to amino acid 139 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
vql5_1 deposited with the ATCC under accession number PTA
367;
(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);
2 0 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 5 (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
vql5_1 deposited with the ATCC under accession number PTA-
367;
3 0 (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
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(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 N0:39, 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 384 to
nucleotide
1193, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:39 from nucleotide 384 to nucleotide 1193, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from
nucleotide
384 to nucleotide 1193. 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 642 to nucleotide 1193, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:39 from
nucleotide 642 to nucleotide 1193, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:39 from nucleotide 642 to nucleotide 1193.
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 0 consisting of:
(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
vql5_1 deposited with the ATCC under accession number PTA-367;
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
3 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ ID N0:40, or a protein comprising a fragment of the amino acid sequence
of SEQ
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ID N0:40 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 130 to amino acid 139 of SEQ ID N0:40.
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
N0:41;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 132 to nucleotide 503;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 189 to nucleotide 503;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vq 17_ 1 deposited with the ATCC under
accession number PTA-367;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql7_1 deposited with the ATCC under accession number
PTA-367;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vql7_1 deposited with the ATCC under
accession
number PTA-367;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vql7_1 deposited with the ATCC under accession number PTA-367;
(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 5 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
3 0 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°l0 of the length of SEQ ID N0:41.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:41 from nucleotide 132 to nucleotide 503; the nucleotide sequence of SEQ ID
N0:41
from nucleotide 189 to nucleotide 503; the nucleotide sequence of the full-
length protein
coding sequence of clone vql7_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vql7_1
deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vql7_1 deposited with the ATCC under accession number
PTA-
367. 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 57 to amino acid 66 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
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ )D 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
vql7_1 deposited with the ATCC under accession number PTA-
367;
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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 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 N0:41, but excluding the poly(A) tail at the
3' end of SEQ ID N0:41; and
(bb) the nucleotide sequence of the cDNA insert of clone
vql7_1 deposited with the ATCC under accession number PTA-
367;
(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
2 0 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 ID
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
2 5 corresponding to the cDNA sequence of SEQ ID N0:41 from nucleotide 132 to
nucleotide
503, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:41 from nucleotide 132 to nucleotide 503, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from
nucleotide
132 to nucleotide 503. Also preferably the polynucleotide isolated according
to the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:41 from nucleotide 189 to nucleotide 503, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:41 from



CA 02362538 2001-08-16
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nucleotide 189 to nucleotide 503, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:41 from nucleotide 189 to nucleotide 503.
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 N0:42;
(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
vql7_1 deposited with the ATCC under accession number PTA-367;
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
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 57 to amino acid 66 of SEQ ID N0:42.
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
N0:43;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 69 to nucleotide 401;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 138 to nucleotide 401;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vql8_1 deposited with the ATCC under
accession number PTA-367;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vql8_1 deposited with the ATCC under accession number
PTA-367;
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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vq 18_1 deposited with the ATCC under
accession
number PTA-367;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vq 18_1 deposited with the ATCC under accession number PTA-
367;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:44;
(i) a polynucleotide 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 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 N0:43.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:43 from nucleotide 69 to nucleotide 401; the nucleotide sequence of SEQ ID
N0:43
from nucleotide 138 to nucleotide 401; the nucleotide sequence of the full-
length protein
coding sequence of clone vql8_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vq 18_ 1
2 5 deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vql8_1 deposited with the ATCC under accession number
PTA-
367. 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
3 0 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
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SEQ ID N0:44 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 50 to amino acid 59 of SEQ ID N0:44.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
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
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
vql8_1 deposited with the ATCC under accession number PTA
367;
(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);
2 0 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 5 (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
vql8_1 deposited with the ATCC under accession number PTA-
367;
3 0 (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
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(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
corresponding to the cDNA sequence of SEQ ID N0:43 from nucleotide 69 to
nucleotide
401, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:43 from nucleotide 69 to nucleotide 401, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from
nucleotide
69 to nucleotide 401. Also preferably the polynucleotide isolated according to
the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:43 from nucleotide 138 to nucleotide 401, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:43 from
nucleotide 138 to nucleotide 401, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:43 from nucleotide 138 to nucleotide 401.
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 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:44;
(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
2 5 vq 18_1 deposited with the ATCC under accession number PTA-367;
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
3 0 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
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ID N0:44 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 50 to amino acid 59 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 65 to nucleotide 1180;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 149 to nucleotide 1180;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vq22_1 deposited with the ATCC under
accession number PTA-367;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vq22_1 deposited with the ATCC under accession number
PTA-367;
(fj a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vq22_1 deposited with the ATCC under
accession
number PTA-367;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vq22_1 deposited with the ATCC under accession number PTA-367;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:46;
(i) a polynucleotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:46 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:46;
(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
3 0 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(i); and



CA 02362538 2001-08-16
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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 N0:45.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:45 from nucleotide 65 to nucleotide 1180; the nucleotide sequence of SEQ ID
N0:45
from nucleotide 149 to nucleotide 1180; the nucleotide sequence of the full-
length protein
coding sequence of clone vq22_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vq22_1
deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vq22_1 deposited with the ATCC under accession number
PTA-
367. In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:46
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 181 to amino acid 190 of SEQ ID N0:46.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:45.
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 >D 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
3 0 vq22_1 deposited with the ATCC under accession number PTA-
367;
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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 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
(bb) the nucleotide sequence of the cDNA insert of clone
vq22_1 deposited with the ATCC under accession number PTA-
367;
25 (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
2 0 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
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
2 5 corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 65 to
nucleotide
1180, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:45 from nucleotide 65 to nucleotide 1180, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from
nucleotide
65 to nucleotide 1180. Also preferably the polynucleotide isolated according
to the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:45 from nucleotide 149 to nucleotide 1180, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:45 from
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nucleotide 149 to nucleotide 1180, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:45 from nucleotide 149 to nucleotide 1180.
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) 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
(c) the amino acid sequence encoded by the cDNA insert of clone
vq22_1 deposited with the ATCC under accession number PTA-367;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:46. 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 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 181 to amino acid 190 of SEQ ID N0:46.
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
N0:47;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 18 to nucleotide 1409;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 60 to nucleotide 1409;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vr3_1 deposited with the ATCC under
accession number PTA-367;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vr3_1 deposited with the ATCC under accession number
PTA-367;
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(fj a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vr3_1 deposited with the ATCC under accession
number PTA-367;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vr3_1 deposited with the ATCC under accession number PTA-367;
(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
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
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 N0:47.
2 0 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:47 from nucleotide 18 to nucleotide 1409; the nucleotide sequence of SEQ ID
N0:47
from nucleotide 60 to nucleotide 1409; the nucleotide sequence of the full-
length protein
coding sequence of clone vr3_1 deposited with the ATCC under accession number
PTA-
367; or the nucleotide sequence of a mature protein coding sequence of clone
vr3_1
2 5 deposited with the ATCC under accession number PTA-367. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vr3_1 deposited with the ATCC under accession number
PTA-
367. 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
3 0 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
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SEQ ID N0:48 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 227 to amino acid 236 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:
(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
vr3_1 deposited with the ATCC under accession number PTA-367;
(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 N0:47, but excluding the poly(A) tail at the
2 5 3' end of SEQ ID N0:47; and
(bb) the nucleotide sequence of the cDNA insert of clone
vr3_1 deposited with the ATCC under accession number PTA-367;
(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).



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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 N0:47, 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 18 to
nucleotide
1409, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:47 from nucleotide 18 to nucleotide 1409, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from
nucleotide
18 to nucleotide 1409. 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 60 to nucleotide 1409, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:47 from
nucleotide 60 to nucleotide 1409, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:47 from nucleotide 60 to nucleotide 1409.
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 N0:48;
(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 vr3_1
deposited with the ATCC under accession number PTA-367;
2 5 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
comprising eight (more preferably twenty, most preferably thirty) contiguous
amino acids
3 0 of SEQ ID N0:48, 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 227 to amino acid 236 of SEQ ID N0:48.
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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 690 to nucleotide 2570;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 765 to nucleotide 2570;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 1286 to nucleotide 2895;
(e) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vb26_1 deposited with the ATCC under
accession number PTA-501;
(f) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vb26_1 deposited with the ATCC under accession number
PTA-501;
(g) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vb26_1 deposited with the ATCC under
accession
number PTA-501;
2 0 (h) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb26_1 deposited with the ATCC under accession number PTA-501;
(i) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:50;
(j) a polynucleotide encoding a protein comprising a fragment of the
2 5 amino acid sequence of SEQ ID N0:50 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:50;
(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
3 0 of (i) or (j) above ;
(m) a polynucleotide that hybridizes under stringent conditions to any
one of the polynucleotides specified in (a)-(j); and
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(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 N0:49.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:49 from nucleotide 690 to nucleotide 2570; the nucleotide sequence of SEQ
ID N0:49
from nucleotide 765 to nucleotide 2570; the nucleotide sequence of SEQ ID
N0:49 from
nucleotide 1286 to nucleotide 2895; the nucleotide sequence of SEQ ID N0:49
from
nucleotide 1286 to nucleotide 2570; the nucleotide sequence of SEQ ID N0:49
from
nucleotide 981 to nucleotide 1282; the nucleotide sequence of the full-length
protein coding
sequence of clone vb26_1 deposited with the ATCC under accession number PTA-
501; or
the nucleotide sequence of a mature protein coding sequence of clone vb26_1
deposited
with the ATCC under accession number PTA-501. In other preferred embodiments,
the
polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of
clone vb26_1 deposited with the ATCC under accession number PTA-501. In yet
other
preferred embodiments, the present invention provides a polynucleotide
encoding a protein
comprising the amino acid sequence of SEQ ID N0:50 from amino acid 112 to
amino acid
197. In further preferred embodiments, the present invention provides a
polynucleotide
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
NO:50
having biological activity, the fragment preferably comprising eight (more
preferably
2 0 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 >D N0:50 having biological activity, the fragment comprising an amino acid
sequence
selected from the group comprising the sequence from amino acid 308 to amino
acid 317
of SEQ ID NO:50, the sequence from amino acid 112 to amino acid 197 of SEQ ID
2 5 N0:50, the sequence from amino acid 200 to amino acid 627 of SEQ ID N0:50,
and the
sequence from amino acid 364 to amino acid 373 of SEQ ID N0:50.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:49.
Further embodiments of the invention provide isolated polynucleotides produced
3 0 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 N0:49, 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
vb26_1 deposited with the ATCC under accession number
PTA-501;
(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 N0:49, but excluding the poly(A) tail at the
3' end of SEQ ID N0:49; and
2 0 (bb) the nucleotide sequence of the cDNA insert of clone
vb26_1 deposited with the ATCC under accession number
PTA-501;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
2 5 (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
3 0 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
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corresponding to the cDNA sequence of SEQ ID N0:49 from nucleotide 690 to
nucleotide
2570, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:49 from nucleotide 690 to nucleotide 2570, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from
nucleotide
690 to nucleotide 2570. Also preferably the polynucleotide isolated according
to the above
process comprises a nuc,~eotide sequence corresponding to the cDNA sequence of
SEQ ID
N0:49 from nucleotide 765 to nucleotide 2570, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:49 from
nucleotide 765 to nucleotide 2570, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:49 from nucleotide 765 to nucleotide 2570. Also
preferably
the polynucleotide isolated according to the above process comprises a
nucleotide sequence
corresponding to the cDNA sequence of SEQ ID N0:49 from nucleotide 1286 to
nucleotide
2895, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:49 from nucleotide 1286 to nucleotide 2895, to a
nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID
N0:49 from
nucleotide 1286 to nucleotide 2895.
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 N0:50;
(b) the amino acid sequence of SEQ ID N0:50 from amino acid 112 to
amino acid 197;
(c) 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
2 5 (d) the amino acid sequence encoded by the cDNA insert of clone
vb26_1 deposited with the ATCC under accession number PTA-501;
the protein being substantially free from other mammalian proteins. Preferably
such
protein comprises the amino acid sequence of SEQ ID N0:50 or the amino acid
sequence
of SEQ ID N0:50 from amino acid 112 to amino acid 197. In further preferred
3 0 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



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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 an amino acid
sequence
selected from the group comprising the sequence from amino acid 308 to amino
acid 317
of SEQ ID N0:50, the sequence from amino acid 112 to amino acid 197 of SEQ ID
N0:50, the sequence from amino acid 200 to amino acid 627 of SEQ ID N0:50, and
the
sequence from amino acid 364 to amino acid 373 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 105 to nucleotide 1724;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51 from nucleotide 186 to nucleotide 1724;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vc70_1 deposited with the ATCC under
accession number PTA-1074;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vc70_1 deposited with the ATCC under accession number
2 0 PTA-1074;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vc70_1 deposited with the ATCC under
accession
number PTA-1074;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc70_1 deposited with the ATCC under accession number PTA-
1074;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:52;
(i) a polynucleotide encoding a protein comprising a fragment of the
3 0 amino acid sequence of SEQ ID N0:52 having biological activity, the
fragment
comprising eight contiguous amino acids of SEQ ID N0:52;
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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 NO:51.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:51 from nucleotide 105 to nucleotide 1724; the nucleotide sequence of SEQ
ID NO:51
from nucleotide 186 to nucleotide 1724; the nucleotide sequence of the full-
length protein
coding sequence of clone vc70_1 deposited with the ATCC under accession number
PTA-
1074; or the nucleotide sequence of a mature protein coding sequence of clone
vc70_1
deposited with the ATCC under accession number PTA-1074. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vc70_1 deposited with the ATCC under accession number
PTA-
1074. 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
2 0 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 fragment of the amino acid
sequence of
SEQ ID N0:52 having biological activity, the fragment comprising the amino
acid
sequence from amino acid 265 to amino acid 274 of SEQ ID N0:52.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of
SEQ
ID NO:51.
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:
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(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
vc70_1 deposited with the ATCC under accession number PTA-
1074;
(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
vc70_1 deposited with the ATCC under accession number PTA-
1074;
2 0 (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
2 5 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
polynucleotide isolated according to the above process comprises a nucleotide
sequence
3 0 corresponding to the cDNA sequence of SEQ ID N0:51 from nucleotide 105 to
nucleotide
1724, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:51 from nucleotide 105 to nucleotide 1724, to a
nucleotide
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sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from
nucleotide
105 to nucleotide 1724. 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 186 to nucleotide 1724, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:51 from
nucleotide 186 to nucleotide 1724, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:51 from nucleotide 186 to nucleotide 1724.
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 acid 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
vc70_1 deposited with the ATCC under accession number PTA-1074;
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
2 0 comprising eight (more preferably twenty, most preferably thirty)
contiguous amino acids
of SEQ >D 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 265 to amino acid 274 of SEQ ID N0:52.
In one embodiment, the present invention provides a composition comprising an
2 5 isolated polynucleotide selected from the group consisting of:
(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 3 to nucleotide 239;
3 0 (c) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vo28_1 deposited with the ATCC under
accession number PTA-1074;
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(d) a polynucleotide encoding the full-length protein encoded by the '
cDNA insert of clone vo28_1 deposited with the ATCC under accession number
PTA-1074;
(e) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo28_1 deposited with the ATCC under
accession
number PTA-1074;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo28_1 deposited with the ATCC under accession number PTA-
1074;
(g) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:54;
(h) 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;
(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
2 0 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 N0:53.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
2 5 N0:53 from nucleotide 3 to nucleotide 239; the nucleotide sequence of the
full-length
protein coding sequence of clone vo28_1 deposited with the ATCC under
accession
number PTA-1074; or the nucleotide sequence of a mature protein coding
sequence of
clone vo28_1 deposited with the ATCC under accession number PTA-1074. In other
preferred embodiments, the polynucleotide encodes the full-length or a mature
protein
3 0 encoded by the cDNA insert of clone vo28_1 deposited with the ATCC under
accession
number PTA-1074. In further preferred embodiments, the present invention
provides a
polynucleotide encoding a protein comprising a fragment of the amino acid
sequence of



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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 fragment comprising the amino
acid
sequence from amino acid 34 to amino acid 43 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 polynucleotide probes that hybridize
in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ID N0:53, 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
vo28_1 deposited with the ATCC under accession number PTA-
1074;
(ii) hybridizing said probes) to human genomic DNA in
2 0 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:
2 5 (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 N0:53, but excluding the poly(A) tail at the
3' end of SEQ ID N0:53; and
3 0 (bb) the nucleotide sequence of the cDNA insert of clone
vo28_1 deposited with the ATCC under accession number PTA-
1074;
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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 N0:53, and
extending contiguously from a nucleotide sequence corresponding to the 5' end
of SEQ 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 3 to
nucleotide
239, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:53 from nucleotide 3 to nucleotide 239, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from
nucleotide
3 to nucleotide 239.
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;
2 0 (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
(c) the amino acid sequence encoded by the cDNA insert of clone
vo28_1 deposited with the ATCC under accession number PTA-1074;
the protein being substantially free from other mammalian proteins. Preferably
such
2 5 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 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
3 0 ID N0:54 having biological activity, the fragment comprising the amino
acid sequence
from amino acid 34 to amino acid 43 of SEQ ID N0:54.
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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;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 49 to nucleotide 1452;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 109 to nucleotide 1452;
(d) a polynucleotide comprising the nucleotide sequence of the full
length protein coding sequence of clone vo29_1 deposited with the ATCC under
accession number PTA-1074;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo29_1 deposited with the ATCC under accession number
PTA-1074;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo29_ 1 deposited with the ATCC under
accession
number PTA-1074;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo29_1 deposited with the ATCC under accession number PTA-
2 0 1074;
(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
2 5 comprising eight contiguous amino acids of SEQ ID N0:56;
(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
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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 NO:55.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:55 from nucleotide 49 to nucleotide 1452; the nucleotide sequence of SEQ ID
NO:55
from nucleotide 109 to nucleotide 1452; the nucleotide sequence of the full-
length protein
coding sequence of clone vo29_1 deposited with the ATCC under accession number
PTA-
1074; or the nucleotide sequence of a mature protein coding sequence of clone
vo29_1
deposited with the ATCC under accession number PTA-1074. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vo29_1 deposited with the ATCC under accession number
PTA-
1074. 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 229 to amino acid 238 of SEQ ID N0:56.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID NO: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
2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group
consisting of:
(aa) SEQ ff~ NO:55, but excluding the poly(A) tail at the
3' end of SEQ ID NO:55; and
(ab) the nucleotide sequence of the cDNA insert of clone
3 0 vo29_1 deposited with the ATCC under accession number PTA-
1074;
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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 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 N0:55, 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
vo29_1 deposited with the ATCC under accession number PTA-
1074;
(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
2 0 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
2 5 corresponding to the cDNA sequence of SEQ ID N0:55 from nucleotide 49 to
nucleotide
1452, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:55 from nucleotide 49 to nucleotide 1452, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:55 from
nucleotide
49 to nucleotide 1452. Also preferably the polynucleotide isolated according
to the above
3 0 process comprises a nucleotide sequence corresponding to the cDNA sequence
of SEQ ID
N0:55 from nucleotide 109 to nucleotide 1452, and extending contiguously from
a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:55 from
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nucleotide 109 to nucleotide 1452, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:55 from nucleotide 109 to nucleotide 1452.
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 N0:56;
(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
vo29_1 deposited with the ATCC under accession number PTA-1074;
the protein being substantially free from other mammalian proteins. Preferably
such
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
ID N0:56 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 229 to amino acid 238 of SEQ ID N0:56.
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
N0:57;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 48 to nucleotide 866;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 114 to nucleotide 866;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vo30_1 deposited with the ATCC under
accession number PTA-1074;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vo30_1 deposited with the ATCC under accession number
PTA-1074;
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(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vo30_1 deposited with the ATCC under
accession
number PTA-1074;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vo30_1 deposited with the ATCC under accession number PTA-
1074;
(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
comprising eight contiguous amino acids of SEQ ID N0:58;
(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
2 0 25% of the length of SEQ ID N0:57.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:57 from nucleotide 48 to nucleotide 866; the nucleotide sequence of SEQ ID
N0:57
from nucleotide 114 to nucleotide 866; the nucleotide sequence of the full-
length protein
coding sequence of clone vo30_1 deposited with the ATCC under accession
number.PTA-
1074; or the nucleotide sequence of a mature protein coding sequence of clone
vo30_1
deposited with the ATCC under accession number PTA-1074. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vo30_1 deposited with the ATCC under accession number
PTA-
1074. In further preferred embodiments, the present invention provides a
polynucleotide
3 0 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
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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 131 to amino acid 140 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:
(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
3' end of SEQ ID N0:57; and
(ab) the nucleotide sequence of the cDNA insert of clone
vo30_1 deposited with the ATCC under accession number PTA-
1074;
(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 0 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
2 5 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 clone
vo30_1 deposited with the ATCC under accession number PTA-
3 0 1074;
(ii) hybridizing said primers) to human genomic DNA in
conditions at least as stringent as 4X SSC at 50 degrees C;
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(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 48 to
nucleotide
866, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:57 from nucleotide 48 to nucleotide 866, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from
nucleotide
48 to nucleotide 866. 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 114 to nucleotide 866, and extending contiguously from a
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:57 from
nucleotide 114 to nucleotide 866, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:57 from nucleotide 114 to nucleotide 866.
In other embodiments, the present invention provides a composition comprising
a
2 0 protein, wherein said protein comprises an amino acid sequence selected
from the group
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
2 5 (c) the amino acid sequence encoded by the cDNA insert of clone
vo30_1 deposited with the ATCC under accession number PTA-1074;
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
3 0 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
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ID N0:58 having biological activity, the fragment comprising the amino acid
sequence
from amino acid 131 to amino acid 140 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 235 to nucleotide 510;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 316 to nucleotide 510;
(d) a polynucleotide comprising the nucleotide sequence of the full-
length protein coding sequence of clone vp25_1 deposited with the ATCC under
accession number PTA-1074;
(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vp25_1 deposited with the ATCC under accession number
PTA-1074;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vp25_1 deposited with the ATCC under
accession
number PTA-1074;
2 0 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vp25_1 deposited with the ATCC under accession number PTA-
1074;
(h) a polynucleotide encoding a protein comprising the amino acid
sequence of SEQ ID N0:60;
2 5 (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;
(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 ;
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(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 235 to nucleotide 510; the nucleotide sequence of SEQ ID
N0:59
from nucleotide 316 to nucleotide 510; the nucleotide sequence of the full-
length protein
coding sequence of clone vp25_1 deposited with the ATCC under accession number
PTA-
1074; or the nucleotide sequence of a mature protein coding sequence of clone
vp25_1
deposited with the ATCC under accession number PTA-1074. In other preferred
embodiments, the polynucleotide encodes the full-length or a mature protein
encoded by
the cDNA insert of clone vp25_1 deposited with the ATCC under accession number
PTA-
1074. 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 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
2 0 sequence from amino acid 41 to amino acid 50 of SEQ ID N0:60.
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:
2 5 (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 N0:59, but excluding the poly(A) tail at the
3 0 3' end of SEQ ID N0:59; and
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(ab) the nucleotide sequence of the cDNA insert of clone
vp25_1 deposited with the ATCC under accession number PTA-1074;
(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 >D 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 clone
vp25_1 deposited with the ATCC under accession number PTA
1074;
(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 0 (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 N0:59, 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
2 5 excluding the poly(A) tail at the 3' end of SEQ ID N0:59. Also preferably
the
polynucleotide isolated according to the above process comprises a nucleotide
sequence
corresponding to the cDNA sequence of SEQ ID N0:59 from nucleotide 235 to
nucleotide
510, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:59 from nucleotide 235 to nucleotide 510, to a
nucleotide
3 0 sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from
nucleotide
235 to nucleotide 510. Also preferably the polynucleotide isolated according
to the above
process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID
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N0:59 from nucleotide 316 to nucleotide 510, and extending contiguously from a
'
nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:59 from
nucleotide 316 to nucleotide 510, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:59 from nucleotide 316 to nucleotide 510.
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 N0:60;
(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
vp25_1 deposited with the ATCC under accession number PTA-1074;
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
2 0 from amino acid 41 to amino acid 50 of SEQ ID N0:60.
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
N0:61;
2 5 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 177 to nucleotide 1626;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 219 to nucleotide 1626;
(d) a polynucleotide comprising the nucleotide sequence of the full-
3 0 length protein coding sequence of clone vq25_1 deposited with the ATCC
under
accession number PTA-1074;
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(e) a polynucleotide encoding the full-length protein encoded by the
cDNA insert of clone vq25_1 deposited with the ATCC under accession number
PTA-1074;
(f) a polynucleotide comprising the nucleotide sequence of a mature
protein coding sequence of clone vq25_1 deposited with the ATCC under
accession
number PTA-1074;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vq25_1 deposited with the ATCC under accession number PTA-
1074;
(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 protein
of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any
2 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°10 of the length of SEQ ID N0:61.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
2 5 N0:61 from nucleotide 177 to nucleotide 1626; the nucleotide sequence of
SEQ ID N0:61
from nucleotide 219 to nucleotide 1626; the nucleotide sequence of the full-
length protein
coding sequence of clone vq25_1 deposited with the ATCC under accession number
PTA-
1074; or the nucleotide sequence of a mature protein coding sequence of clone
vq25_1
deposited with the ATCC under accession number PTA-1074. In other preferred
3 0 embodiments, the polynucleotide encodes the full-length or a mature
protein encoded by
the cDNA insert of clone vq25_1 deposited with the ATCC under accession number
PTA-
1074. In further preferred embodiments, the present invention provides a
polynucleotide
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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 fragment comprising the amino
acid
sequence from amino acid 236 to amino acid 245 of SEQ ID N0:62.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:61.
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
vq25_1 deposited with the ATCC under accession number PTA-
1074;
2 0 (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 5 (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 N0:61, but excluding the poly(A) tail at the
3 0 3' end of SEQ ID N0:61; and
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(bb) the nucleotide sequence of the cDNA insert of clone
vq25_1 deposited with the ATCC under accession number PTA-1074;
(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 N0:61, and
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 177 to
nucleotide
1626, and extending contiguously from a nucleotide sequence corresponding to
the 5' end
of said sequence of SEQ ID N0:61 from nucleotide 177 to nucleotide 1626, to a
nucleotide
sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from
nucleotide
177 to nucleotide 1626. 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 219 to nucleotide 1626, and extending contiguously from
a
2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:61 from
nucleotide 219 to nucleotide 1626, to a nucleotide sequence corresponding to
the 3' end of
said sequence of SEQ ID N0:61 from nucleotide 219 to nucleotide 1626.
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 N0:62;
(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
3 0 vq25_1 deposited with the ATCC under accession number PTA-1074;
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
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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
from amino acid 236 to amino acid 245 of SEQ ID N0:62.
In certain preferred embodiments, the polynucleotide is operably linked to an
expression control sequence. The invention also provides a host cell,
including bacterial,
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 carrier. Compositions comprising an antibody which
2 0 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
Figures lA and 1B are schematic representations of the pED6 and pNOTs vectors,
respectively, used for deposit of clones disclosed herein.
3 0 DETAILED DESCRIPTION
ISOLATED PROTEINS AND POLYNUCLEOTIDES
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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 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.
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"vb24 1"
A polynucleotide of the present invention has been identified as clone "vb24 1
".
vb24_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. vb24_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb24_1 protein").
The nucleotide sequence of vb24_1 as presently determined is reported in SEQ
ID
NO:l, 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 vb24_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ )D N0:2. Amino acids 3
to 15 of
SEQ ID N0:2 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
3 0 leader/signal sequence not be separated from the remainder of the vb24_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vb24_1 should be approximately 6033 bp.
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The nucleotide sequence disclosed herein for vb24_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vb24_1 demonstrated at least some similarity with
sequences
identified as AB005299 (Homo sapiens BAI 3 mRNA, complete cds), ABO11122 (Homo
sapiens mRNA for KIAA0550 protein, complete cds), N50991 (yy94e07.s1 Homo
sapiens
cDNA clone 281220 3'), and Q77404 (Human genome fragment (Preferred);
standard;
DNA). The predicted amino acid sequence disclosed herein for vb24_1 was
searched
against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vb24_1 protein demonstrated at least some
similarity to
sequences identified as AB005299 (BAI 3 [Homo sapiens]) and W37412 (Human
G-protein coupled receptor HIBCD07). Based upon sequence similarity, vb24_1
proteins
and each similar protein or peptide may share at least some activity. The
TopPredII
computer program predicts eight potential transmembrane domains within the
vb24 1
protein sequence, centered around amino acids 16, 888, 923, 952, 993, 1030,
1100, and
1138 of SEQ ID N0:2, respectively. The vb24_1 protein shares significant amino
acid
sequence similarity with GenBank Accession Number AB005299 (BAI 3 [Homo
sapiens]),
which is a splice variant of GenBank Accession Number ABOl 1122 (HIAA0550
protein
[Homo sapiens]), and shares amino acid similarity with other members of the
BAI/secretin
protein families. The members of the BAI/secretin protein families are G-
protein-coupled
2 0 receptors. The TopPredII profiles for some members of the BAI/secretin
protein families
are strikingly similar to that of vb24_1, with one transmembrane domain
predicted at the
N-terminus (approximately within the first 20 amino acids) and multiple
transmembrane
domains near the C-terminus. The N-terminal transmembrane domains of the
BAI/secretin
protein family members are described as leader/signal sequences, consistent
with the first
transmembrane domain in the predicted vb24_1 protein being a leader/signal
sequence.
Clone "vc64 1"
A polynucleotide of the present invention has been identified as clone "vc64 1
".
vc64_1 was isolated from a human fetal brain cDNA library and was identified
as encoding
3 0 a secreted or transmembrane protein on the basis of computer analysis of
the amino acid
sequence of the encoded protein. vc64_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc64_1 protein")
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The nucleotide sequence of vc64_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 vc64_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:4. Amino acids
20 to 32
of SEQ 1D N0:4 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 33. Due to the hydrophobic nature of the
predicted
leader/signal sequence, the TopPredII computer program predicts that is likely
to act as a
transmembrane domain should the predicted leader/signal sequence not be
separated from
the remainder of the vc64_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc64_1 should be approximately 2022 bp.
The nucleotide sequence disclosed herein for vc64_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc64_1 demonstrated at least some similarity with
sequences
identified as AI217133 (qf47c10.x1 Soares testis NHT Homo sapiens cDNA clone
IMAGE:1753170 3', mRNA sequence), T19353 (Human gene signature HUMGS00377;
standard; cDNA to mRNA), and 249239 (A.thaliana mRNA for putative dTDP-glucose
4-6-dehydratases). The predicted amino acid sequence disclosed herein for
vc64_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
2 0 BLASTX search protocol. The predicted vc64_1 protein demonstrated at least
some
similarity to sequences identified as 898529 (dTDP-glucose dehydratase encoded
by the
acbB gene), U40800 (similar to thymidine diphosphoglucose 4,6-dehydratase
[Caenorhabditis elegans)), and the dehydratases of many disparate species. The
hydratase
protein family is very diverse with proteins ranging in length from less than
300 to more
than 400 amino acids. The vc64_1 protein appears to be an alternatively
spliced variant
of certain hydratases, and the existence of splice variants is also consistent
with the
diversity of the hydratase family. Based upon sequence similarity, vc64_1
proteins and
each similar protein or peptide may share at least some activity.
vc64_1 protein was expressed in a COS cell expression system, and an expressed
3 0 protein band of approximately 5 kDa was detected in conditioned medium
using SDS
polyacrylamide gel electrophoresis.
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Clone"vp20 1"
A polynucleotide of the present invention has been identified as clone
"vp20_1".
vp20_1 was isolated from a human adult prostate 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. vp20_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vp20_1 protein").
The nucleotide sequence of vp20_1 as presently determined is reported in SEQ
ID
NO:S, and includes a poly(A) tail. What applicants presently believe to be the
proper
reading frame and the predicted amino acid sequence of the vp20_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:6. Amino acids
34 to 46
of SEQ ID N0:6 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 47. 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 vp20_ 1
protein.
Another potential vp20_1 reading frame and predicted amino acid sequence is
encoded by basepairs 910 to 1293 of SEQ ID NO:S and is reported as SEQ ID
N0:88.
Amino acids 9 to 21 of SEQ ID N0:88 are a predicted leader/signal sequence,
with the
predicted mature amino acid sequence beginning at amino acid 22. Due to the
hydrophobic
nature of this predicted leader/signal sequence, it is likely to act as a
transmembrane
2 0 domain should the predicted leader/signal sequence not be separated from
the remainder
of the protein of SEQ ID N0:88.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vp20_1 should be approximately 1916 bp.
The nucleotide sequence disclosed herein for vp20_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vp20_1 demonstrated at least some similarity with
sequences
identified as AA044732 (zk67e09.s1 Soares pregnant uterus NbHPU Homo sapiens
cDNA
clone 487912 3', mRNA sequence) and AA044769 (zk67e09.r1 Soares pregnant
uterus
NbHPU Homo sapiens cDNA clone 487912 5', mRNA sequence). Based upon sequence
3 0 similarity, vp20_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 vp20_1 protein sequence, one centered around
amino
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acid 60 and another around amino acid 87 of SEQ ID N0:6. The TopPredII
computer
program also predicts one additional potential transmembrane domain within the
protein
of SEQ ID N0:88, centered around amino acid 80 of SEQ ID N0:88. The nucleotide
sequence of the vp20_1 clone indicates that it may contain one or more MIR
repeat
sequences.
Clone"vq4 1"
A polynucleotide of the present invention has been identified as clone
"vq4_1".
vq4_1 was isolated from a human adult lung 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. vq4_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vq4_1 protein").
The nucleotide sequence of vq4_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
reading frame and the predicted amino acid sequence of the vq4_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
leader/signal sequence, it is likely to act as a transmembrane domain should
the predicted
2 0 leader/signal sequence not be separated from the remainder of the vq4_1
protein.
Were the 'G' residue at position 336 of SEQ ID N0:7 to be deleted, two
alternative
overlapping vq4_1 reading frames and predicted amino acid sequences would
result: the
first alternative amino acid sequence is encoded by SEQ ID N0:7 from
nucleotide 129 to
what would then be nucleotide 359, and is reported in SEQ ID N0:89; the second
2 5 alternative amino acid sequence is encoded by SEQ ID N0:7 from nucleotide
275 to what
would then be nucleotide 730, and is reported in SEQ ID N0:90.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vq4_1 should be approximately 831 bp.
The nucleotide sequence disclosed herein for vq4_1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vq4_1 demonstrated at least some similarity with
sequences
identified as M75099 . (Human rapamycin- and FK506-binding protein, complete
cds),
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N36303 (yx99e09.r1 Homo sapiens cDNA clone 269896 5' similar to SW:FKB3 MOUSE
P45878 FK506-BINDING PROTEIN PRECURSOR), and T18037 (Human FKBP-13
immunophilin cDNA; standard; cDNA). The predicted amino acid sequence
disclosed
herein for vq4_1 was searched against the GenPept and GeneSeq amino acid
sequence
databases using the BLASTX search protocol. The predicted vq4_1 protein
demonstrated
at least some similarity to sequences identified as M75099 (rapamycin- and
FK506-binding
protein [Homo sapiens]) and 828980 (hRFKBP). Based upon sequence similarity,
vq4_1
proteins and each similar protein or peptide may share at least some activity.
The TopPredII
computer program predicts two potential transmembrane domains within the vq4_
1 protein
sequence, one centered around amino acid 14 and another around amino acid 164
of SEQ
ID N0:8.
Clone"vo7 1"
A polynucleotide of the present invention has been identified as clone "vo7 1
".
vo7_1 was isolated from a human adult pancreas 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. vo7_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo7_1 protein").
The nucleotide sequence of vo7_1 as presently determined is reported in SEQ ID
2 0 N0:9, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vo7_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID NO:10. Amino acids
14 to 26
of SEQ ID NO:10 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 27. Due to the hydrophobic nature of the
predicted
2 5 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 vo7_1
protein.
If a nucleotide were added to the nucleotide sequence of SEQ ID N0:9 between
residue 477 and residue 484, and if a purine residue were added to the
nucleotide sequence
of SEQ ID N0:9 between residue 896 and residue 900, another potential vo7_1
reading
3 0 frame and predicted amino acid sequence encoded by what would then be
basepairs 143
to 1336 of SEQ ID N0:9 is reported in SEQ ID N0:91. Amino acids 14 to 26 of
SEQ ID
N0:91 are a predicted leader/signal sequence, with the predicted mature amino
acid
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sequence beginning at amino acid 27. 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 protein of
SEQ ID
N0:91.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo7_1 should be approximately 1740 bp.
The nucleotide sequence disclosed herein for vo7_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vo7_1 demonstrated at least some similarity with
sequences
identified as L04733 (Homo Sapiens kinesin light chain mRNA, complete cds) and
W07481 (za96d09.r1 Soares fetal lung NbHLI9W Homo sapiens cDNA clone 300401 5'
similar to gb L04733 KINESIN LIGHT CHAIN (HUMAN); mRNA sequence). The
predicted amino acid sequence disclosed herein for vo7_1 was searched against
the
GenPept and GeneSeq amino acid sequence databases using the BLASTX search
protocol.
The predicted vo7_1 protein demonstrated at least some similarity to sequences
identified
as L04733 (kinesin light chain [Homo sapiens]). Movement of membrane-bounded
organelles to intracellular destinations requires properly oriented
microtubules and
force-generating enzymes, such as the microtubule-stimulated ATPase kinesin.
(See Cyr
et al., 1991, Proc. Natl. Acad. Sci. USA 88(22): 10114-10118, which is
incorporated by
2 0 reference herein). Based upon sequence similarity, vo7_1 proteins and each
similar protein
or peptide may share at least some activity.
Clone "vc65 1"
A polynucleotide of the present invention has been identified as clone "vc65
1".
2 5 vc65_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. vc65_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc65_1 protein").
The nucleotide sequence of vc65_1 as presently determined is reported in SEQ
ID
3 0 NO: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 vc65_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:12. Amino acids
14 to 26
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of SEQ ID N0:12 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 27. 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 vc65_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc65_1 should be approximately 826 bp.
The nucleotide sequence disclosed herein for vc65_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vc65_1 demonstrated at least some similarity with
sequences
identified as AA506313 (nh45c03.s1 NCI CGAP_Pr5 Homo sapiens cDNA clone
IMAGE:955300 similar to TR:G685170 6685170 ADHERIN; mRNA sequence) and
T22080 (Human gene signature HUMGS03624). Based upon sequence similarity,
vc65_1
proteins and each similar protein or peptide may share at least some activity.
Clone "vc66 1"
A polynucleotide of the present invention has been identified as clone "vc66 1
".
vc66_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. vc66_1 is a full-length clone, including the
entire coding
2 0 sequence of a secreted protein (also referred to herein as "vc66_1
protein")
The nucleotide sequence of vc66_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
reading frame and the predicted amino acid sequence of the vc66_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:14. Amino acids
28 to 40
2 5 of SEQ ID N0:14 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 vc66_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
3 0 vc66_ 1 should be approximately 1652 bp.
The nucleotide sequence disclosed herein for vc66_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
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FASTA search protocols. vc66_1 demonstrated at least some similarity with
sequences
identified as AA291293 (zsl8dll.sl NCI CGAP_GCBl Homo sapiens cDNA clone
IMAGE 685557 3', mRNA sequence). Based upon sequence similarity, vc66_1
proteins
and each similar protein or peptide may share at least some activity. The
nucleotide
sequence of vc66_1 indicates that it may contain a LIMAS repeat region.
Clone"vc68 1"
A polynucleotide of the present invention has been identified as clone "vc68 1
".
vc68_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. vc68_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc68_1 protein")
The nucleotide sequence of vc68_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 vc68_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:16. Amino acids
15 to 27
of SEQ ID N0:16 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
2 0 leader/signal sequence not be separated from the remainder of the vc68_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc68_1 should be approximately 2652 bp.
The nucleotide sequence disclosed herein for vc68_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc68_1 demonstrated at least some similarity with
sequences
identified as AI147732 (qb47e06.x1 NCI CGAP_Brn23 Homo sapiens cDNA clone
IMAGE 1703266 3' similar to WP F55C5.2 CE11152
GLYCEROPHOSPHORYLDIESTER PHOSPHODIESTERASE LIKE; mRNA sequence),
AC003108 (Human Chromosome 16 BAC clone CIT987SK-327024, complete sequence),
3 0 and T26462 (Human gene signature HUMGS08704). The predicted amino acid
sequence
disclosed herein for vc68_1 was searched against the GenPept and GeneSeq amino
acid
sequence databases using the BLASTX search protocol. The predicted vc68_ 1
protein
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demonstrated at least some similarity to sequences identified as AC00310
(Unknown gene
product [Homo sapiens]) and W89783 (Staphylococcus aureus protein SEQ ID
#5231).
Based upon sequence similarity, vc68_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 vc68_1 protein sequence centered
around
amino acid 38 of SEQ ID N0:16. The nucleotide sequence of vc68_1 indicates
that it may
contain an Alu repetitive element.
Clone "vk6 1"
A polynucleotide of the present invention has been identified as clone "vk6_1
".
vk6_1 was isolated from a human adult 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. vk6_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vk6_1 protein").
The nucleotide sequence of vk6_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 vk6_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:18. Amino acids
10 to 22
of SEQ ID N0:18 are a predicted leader/signal sequence, with the predicted
mature amino
2 0 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 vk6_1
protein.
If nine nucleotides encoding the amino acid sequence Met-Ile-Phe were inserted
between nucleotide 678 and nucleotide 679 of SEQ ID N0:17, another potential
vk6_1
2 5 reading frame and predicted amino acid sequence, encoded by what would
then be
basepairs 79 to 2427 of SEQ ID N0:17, is reported in SEQ ID N0:92.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vk6_1 should be approximately 4899 bp.
The nucleotide sequence disclosed herein for vk6_1 was searched against the
3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vk6_1 demonstrated at least some similarity with
sequences
identified as AC006208 (Homo Sapiens 3p21.1-9 PAC RPCI4-793P23 (Roswell Park
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Cancer Institute Human PAC Library) complete sequence), AI127070 (qb97e10.x1
Soares
fetal heart NbHHI9W Homo sapiens cDNA clone IMAGE 1708074 3', mRNA sequence),
U28369 (Homo sapiens semaphorin V mRNA, complete cds), and V35367 (Human
semaphorin encoding cDNA). The predicted amino acid sequence disclosed herein
for
vk6_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vk6_1 protein demonstrated at
least
some similarity to sequences identified as U28369 (semaphorin V [Homo
sapiens]) and
W63748 (Human semaphorin). The vk6_1 amino acid sequence also demonstrated
significant similarities to the semaphorin and collapsin proteins of many
species. "The
semaphorin genes encode a family of transmembrane and secreted growth cone
guidance
molecules." (Kolodkin et al., 1993, Cell 75(7): 1389-99, which is incorporated
by
reference herein). Based upon sequence similarity, vk6_1 proteins and each
similar protein
or peptide may share at least some activity. Motif analysis detects an ATP/GTP-
binding
site motif A (P-loop) around residue 747 of SEQ ID N0:18. The TopPredII
computer
program predicts two additional potential transmembrane domains within the
vk6_1 protein
sequence, one centered around amino acid 140 and another around amino acid 336
of SEQ
ID N0:18.
Clone "vo4 1 "
2 0 A polynucleotide of the present invention has been identified as clone
"vo4 1 ".
vo4_1 was isolated from a human adult pancreas 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. vo4_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo4_1 protein").
The nucleotide sequence of vo4_1 as presently determined is reported in SEQ ID
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 vo4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:20. Amino acids
11 to 23
of SEQ ID N0:20 are a predicted leader/signal sequence, with the predicted
mature amino
3 0 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 vo4_1
protein.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo4_1 should be approximately 2383 bp.
The nucleotide sequence disclosed herein for vo4_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vo4_1 demonstrated at least some similarity with
sequences
identified as AA613523 (nq22dOl .s 1 NCI CGAP_Co 10 Homo Sapiens cDNA clone
IMAGE:1144609, mRNA sequence), E 12646 (cDNA encoding cell growth inhibiting
factor), and Q60729 (Human brain Expressed Sequence Tag EST00852). The
predicted
amino acid sequence disclosed herein for vo4_1 was searched against the
GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The
predicted vo4_1 protein demonstrated at least some similarity to sequences
identified as
W74956 (Human secreted protein encoded by gene 77 clone HOEAS24) and 292825
(C13C4.5 [Caeno-rhabditis elegans]). Based upon sequence similarity, vo4._1
proteins and
each similar protein or peptide may share at least some activity. The
TopPredII computer
program predicts four additional potential transmembrane domains within the
vo4 1
protein sequence, centeres around amino acids 69, 114, 169, and 207 of SEQ ID
N0:20,
respectively.
Clone"vo8 1"
2 0 A polynucleotide of the present invention has been identified as clone
"vo8 1".
vo8_1 was isolated from a human adult pancreas 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. vo8_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo8_1 protein").
The nucleotide sequence of vo8_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
reading frame and the predicted amino acid sequence of the vo8_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:22. Amino acids
10 to 22
of SEQ ID N0:22 are a predicted leader/signal sequence, with the predicted
mature amino
3 0 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 vo8_1
protein.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo8_1 should be approximately 3243 bp.
The nucleotide sequence disclosed herein for vo8_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vo8_1 demonstrated at least some similarity with
sequences
identified as AF007138 (Homo sapiens clone 23631 mRNA sequence), AI204925
(an02a08.x 1 Stratagene schizo brain S 11 Homo sapiens cDNA clone IMAGE
1684406 3'
similar to TR Q92597 Q92597 RTP, COMPLETE CDS; mRNA sequence), and Q59200
(Human brain Expressed Sequence Tag EST00134). The predicted amino acid
sequence
disclosed herein for vo8_1 was searched against the GenPept and GeneSeq amino
acid
sequence databases using the BLASTX search protocol. The predicted vo8_1
protein
demonstrated at least some similarity to sequences identified as AF045564
(development-related protein [Rattus norvegicus]). Based upon sequence
similarity, vo8_1
proteins and each similar protein or peptide may share at least some activity.
Clone"vol0 1"
A polynucleotide of the present invention has been identified as clone "vol0 1
".
vol0_1 was isolated from a human adult pancreas 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. vo 10_1 is a full-length
clone, including the
entire coding sequence of a secreted protein (also referred to herein as "vo
10_ 1 protein").
The nucleotide sequence of vol0_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 vol0_1 protein
corresponding
2 5 to the foregoing nucleotide sequence is reported in SEQ ID N0:24. Amino
acids 15 to 27
of SEQ ID N0:24 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 vol0_1
protein.
3 0 The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vol0_1 should be approximately 1048 bp.
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The nucleotide sequence disclosed herein for vol0_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vol0_1 demonstrated at least some similarity with
sequences
identified as AI193090 (qe69e08.x1 Soares_fetal_lung NbHLI9W Homo Sapiens cDNA
clone IMAGE:1744262 3' similar to WP:F45G2.10 CE16053; mRNA sequence) and
T 19307 (Human gene signature HUMGS00329). The predicted amino acid sequence
disclosed herein for vol0_1 was searched against the GenPept and GeneSeq amino
acid
sequence databases using the BLASTX search protocol. The predicted vol0_1
protein
demonstrated at least some similarity to sequences identified as 293382
(F45G2.10
[Caenorhabditis elegans]). Based upon sequence similarity, vol0_1 proteins and
each
similar protein or peptide may share at least some activity.
Clone"vo20 1"
A polynucleotide of the present invention has been identified as clone "vo20
1".
vo20_1 was isolated from a human adult pancreas 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. vo20_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo20_ 1 protein").
The nucleotide sequence of vo20_1 as presently determined is reported in SEQ
ID
2 0 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 vo20_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:26. Amino acids
6 to 18
of SEQ ID N0:26 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
2 5 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 vo20_1
protein.
If a nucleotide residue was deleted from the sequence beginning at nucleotide
770
and ending at nucleotide 774 of SEQ ID N0:25, another potential vo20_1 reading
frame
and predicted amino acid sequence, encoded by what would then be basepairs 102
to 932
3 0 of SEQ ID N0:25, is reported in SEQ ID N0:93.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo20_1 should be approximately 2067 bp.
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The nucleotide sequence disclosed herein for vo20_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vo20_1 demonstrated at least some similarity with
sequences
identified as AA452380 (zx29bl l.rl Soares total fetus Nb2HF8 9w Homo sapiens
cDNA
clone 787869 5', mRNA sequence), L13291 Human ADP-ribosylarginine hydrolase
mRNA, complete cds), and V05140 (cDNA encoding human ADP-ribosylarginine
hydrolase). The predicted amino acid sequence disclosed herein for vo20_ 1 was
searched
against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vo20_1 protein demonstrated at least some
similarity to
sequences identified as L13291 (ADP-ribosylarginine hydrolase [Homo sapiensJ)
and
W46493 (Human ADP-ribosylarginine hydrolase). Based upon sequence similarity,
vo20_1 proteins and each similar protein or peptide may share at least some
activity. The
predicted vo20_1 protein demonstrated at least some similarity to ADP-
ribosylarginine
hydrolases from other species as well, which catalyze the reverse reaction of
mono-ADP-ribosylation. "ADP-ribosylarginine hydrolases specifically cleave the
alpha-anomer, leading to release of ADP-ribose and regeneration of the free
guanidino
group of arginine" (Moss et al., 1997, Adv. Exp. Med. Biol. 419: 25-33, which
is
incorporated by reference herein). Moss et al. also proport that there might
be a cell
surface version of the hydrolase. The TopPredII computer program predicts two
additional
2 0 potential transmembrane domains within the vo20_1 protein sequence, one
centered around
amino acid 176 and another around amino acid 314 of SEQ ID N0:26.
Clone "vo21 1"
A polynucleotide of the present invention has been identified as clone "vo21 1
".
vo21_1 was isolated from a human adult pancreas 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. vo21_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo21_1 protein").
The nucleotide sequence of vo21_1 as presently determined is reported in SEQ
ID
3 0 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 vo21_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:28. Amino acids
18 to 30
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of SEQ ID N0:28 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
the predicted
leader/signal sequence not be separated from the remainder of the vo21_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo21_1 should be approximately 2560 bp.
The nucleotide sequence disclosed herein for vo21_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. No significant sequence similarities were identified.
Motif
analysis revealed a cytochrome C motif around residue 3 of SEQ ID N0:28. The
TopPredII computer program predicts an additional potential transmembrane
domain
within the vo21_1 protein sequence centered around amino acid 193 of SEQ ID
N0:28.
The nucleotide sequence of vo21_1 indicates that it may contain an Alu
repetitive element.
Clone "vp24 1 "
A polynucleotide of the present invention has been identified as clone "vp24_1
".
vp24_1 was isolated from a human adult prostate 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. vp24_1 is a full-length clone,
including the
2 0 entire coding sequence of a secreted protein (also referred to herein as
"vp24_1 protein").
The nucleotide sequence of vp24_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
reading frame and the predicted amino acid sequence of the vp24_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:30. Amino acids
7 to 19
2 5 of SEQ ID N0:30 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
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 vp24_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
3 0 vp24_1 should be approximately 1536 bp.
The nucleotide sequence disclosed herein for vp24_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
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FASTA search protocols. vp24_1 demonstrated at least some similarity with
sequences
identified as AA947280 (ok20a12.s1 Soares NSF F8 9W_OT PA P S1 Homo Sapiens
cDNA clone IMAGE 1508350 3', mRNA sequence). Based upon sequence similarity,
vp24_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 vp24_1 protein sequence centered around amino acid 55 of SEQ ID
N0:30.
Clone "vol7 1"
A polynucleotide of the present invention has been identified as clone "vo 17
1 ".
vol7_1 was isolated from a human adult pancreas 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. vol7_1 is a full-length clone,
including the
entire coding sequence of a protein (also referred to herein as "vol7_1
protein")
The nucleotide sequence of vol7_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 vol7_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 amino
acid sequence beginning at amino acid 34.
Another potential vol7_1 reading frame and predicted amino acid sequence,
encoded by basepairs 2530 to 2691 of SEQ ID N0:31, is reported in SEQ ID
N0:94.
Amino acids 2 to 14 of SEQ ID N0:94 are a possible 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
2 5 should the predicted leader/signal sequence not be separated from the
remainder of the
protein of SEQ ID N0:94.
Another potential vol7_1 reading frame and predicted amino acid sequence,
encoded by basepairs 402 to 785 of SEQ ID N0:31, is reported in SEQ ID N0:95.
Amino
acids 32 to 44 of SEQ ID N0:95 are a possible leader/signal sequence, with the
predicted
3 0 mature amino acid sequence beginning at amino acid 45. Due to the
hydrophobic nature
of the predicted leader/signal sequence, it is likely to act as a
transmembrane domain
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should the predicted leader/signal sequence not be separated from the
remainder of the
protein of SEQ ID N0:95.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vol7_1 should be approximately 2755 bp.
The nucleotide sequence disclosed herein for vol7_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vol7_1 demonstrated at least some similarity with
sequences
identified as AF020762 (Homo sapiens clone 1400 unknown protein mRNA, partial
cds),
N91173 (zb12c08.s1 Soares fetal lung NbHLI9W Homo sapiens cDNA clone 301838
3',
mRNA sequence), and Q60597 (Human brain Expressed Sequence Tag EST02608). The
predicted amino acid sequence disclosed herein for vol7_1 was searched against
the
GenPept and GeneSeq amino acid sequence databases using the BLASTX search
protocol.
The predicted vol7_1 protein demonstrated at least some similarity to
sequences identified
as AF020762 (unknown protein [Homo sapiens]) and AF022770 (peripherial
benzodiazepine receptor associated protein [Mus musculus]). Benzodiazepine
receptors
are responsible for the manifestation of peripheral-type benzodiazepine
recognition sites
and are most likely to comprise binding domains for benzodiazepines and
isoquinoline
carboxamides. These integral membrane protein receptors play a role in the
transport of
porphyrins and heme and have a mitochondria) subcellular localization. Based
upon
2 0 sequence similarity, vol7_1 proteins and each similar protein or peptide
may share at least
some activity.
Clone "v lq 1 1"
A polynucleotide of the present invention has been identified as clone "vql
l_1 ".
2 5 vql l_1 was isolated from a human adult lung 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. vql l_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vql l_1 protein").
The nucleotide sequence of vql 1_1 as presently determined is reported in SEQ
ID
3 0 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 vql l_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ 117 N0:34. Amino acids
15 to 27
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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 vql l_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vql 1_1 should be approximately 1177 bp.
The nucleotide sequence disclosed herein for vql l_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vql l_1 demonstrated at least some similarity with
sequences
identified as 839062 (yd08g1l.sl Homo sapiens cDNA clone 25117 3'). Based upon
sequence similarity, vql 1_1 proteins and each similar protein or peptide may
share at least
some activity.
Clone "v lq 2 1"
A polynucleotide of the present invention has been identified as clone "vq 12_
1 ".
vq 12_1 was isolated from a human adult lung 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. vql2_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vql2_1 protein")
2 0 The nucleotide sequence of vq 12_ 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 vql2_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:36. Amino acids
2 to 14
of SEQ ID N0:36 are a predicted leader/signal sequence, with the predicted
mature amino
2 5 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 vql2_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vq 12_ 1 should be approximately 1435 bp.
30 The nucleotide sequence disclosed herein for vql2_1 was searched against
the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vql2_1 demonstrated at least some similarity with
sequences
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identified as AI479299 (tm56hOl.x1 NCI CGAP Kidll Homo sapiens cDNA clone
IMAGE:2162161 3', mRNA sequence). Based upon sequence similarity, vql2_1
proteins
and each similar protein or peptide may share at least some activity. Motifs
analysis
detects a glycoprotein hormones beta chain signature centered approximately
around amino
acid 192 of SEQ ID N0:36.
Clone "v lq 4 1 "
A polynucleotide of the present invention has been identified as clone "vq 14_
1 ".
vql4_1 was isolated from a human adult lung 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. vql4_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vql4_1 protein")
The nucleotide sequence of vql4_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 vql4_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:38. Amino acids
3 to 15
of SEQ ID N0:38 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
2 0 leader/signal sequence not be separated from the remainder of the vq 14_1
protein.
If two nucleotides were inserted between nucleotide 651 and nucleotide 657 of
SEQ
ID N0:37, another potential vql4_1 reading frame and predicted amino acid
sequence,
encoded by what would then be basepairs 32 to 712 of SEQ ID N0:37, is reported
in SEQ
ID N0:96. Amino acids 3 to 15 of SEQ ID N0:96 are a predicted leader/signal
sequence,
2 5 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 protein of SEQ ID N0:96.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
3 0 vql4_1 should be approximately 1183 bp.
The nucleotide sequence disclosed herein for vql4_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
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FASTA search protocols. vql4_1 demonstrated at least some similarity with
sequences
identified as AI291113 (qm10d12.x1 NCI CGAP_Lu5 Homo sapiens cDNA clone
IMAGE:1881431 3' similar to contains LTRl.t3 TAR1 repetitive element; mRNA
sequence) and T80413 (Tylactone synthase gene cluster). Based upon sequence
similarity,
vql4_1 proteins and each similar protein or peptide may share at least some
activity. The
TopPredII computer program predicts 7 additional potential transmembrane
domains
within the vql4_1 protein sequence, centered around amino acids 59, 108, 137,
176, 220,
240, and 250 of SEQ ID N0:38, respectively. The protein of SEQ ID N0:96 is
also
predicted to have 4 additional potential transmembrane domains, centered
around amino
acids 59, 108, 137, and 176 of SEQ ID N0:96, respectively.
Clone "vql5 1"
A polynucleotide of the present invention has been identified as clone
"vql5_1".
vql5_1 was isolated from a human adult lung 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. vql5_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vql5_1 protein").
The nucleotide sequence of vql5_1 as presently determined is reported in SEQ
ID
N 039, 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 vql5_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:40. Amino acids
74 to 86
of SEQ ID N0:40 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 87. Due to the hydrophobic nature of the
predicted
leader/signal sequence, it is likely to act as a transmembrane domain should
the predicted
2 5 leader/signal sequence not be separated from the remainder of the vq 15_1
protein.
Another potential vql5_1 reading frame and predicted amino acid sequence,
encoded by basepairs 18 to 353 of SEQ ID N0:39, is reported in SEQ ID N0:97.
Amino
acids 24 to 36 of SEQ ID N0:97 are a possible leader/signal sequence, with the
predicted
mature amino acid sequence beginning at amino acid 37. Due to the hydrophobic
nature
3 0 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
protein of SEQ ID N0:97.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vql5_1 should be approximately 1519 bp.
The nucleotide sequence disclosed herein for vql5_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vql5_1 demonstrated at least some similarity with
sequences
identified as AA573785 (nk07e12.s1 NCI CGAP_Co2 Homo sapiens cDNA clone
IMAGE 1012846, mRNA sequence), AF115384 (Homo sapiens LR8 (LR8) mRNA,
complete cds), and T20820 (Human gene signature HUMGS02069). The predicted
amino
acid sequence disclosed herein for vql5_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
vql5_1
protein demonstrated at least some similarity to sequences identified as
AF11538 (LR8
[Homo sapiens]) and W75125 (Human secreted protein encoded by gene 69 clone
HPEBD70). LR8 is a protein of unknown function, "expressed by a subpopulation
of
human lung fibroblasts by differential display" (Lurton et al., 1999, Am J
Respir Cell Mol
Biol 20(2): 327-31, which is incorporated by reference herein). Based upon
sequence
similarity, vql5_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 vql5_1 protein sequence, one centered around
amino
acid 138 and another around amino acid 218 of SEQ ID N0:40.
Clone "vql7 1"
A polynucleotide of the present invention has been identified as clone "vql7_1
".
vql7_1 was isolated from a human adult lung cDNA library and was identified as
encoding
a secreted or transmembrane protein on the basis of computer analysis of the
amino acid
2 5 sequence of the encoded protein. vq 17_1 is a full-length clone, including
the entire coding
sequence of a secreted protein (also referred to herein as "vql7_1 protein").
The nucleotide sequence of vql7_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 vql7_1 protein
corresponding
3 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:42. Amino
acids 7 to 19
of SEQ ID N0:42 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 vql7_1
protein.
Another potential vql7_1 reading frame and predicted amino acid sequence,
encoded by basepairs 1947 to 2342 of SEQ ID N0:41, is reported in SEQ ID
N0:98.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vql7_1 should be approximately 2869 bp.
The nucleotide sequence disclosed herein for vql7_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vql7_1 demonstrated at least some similarity with
sequences
identified as AA225412 (nc24f07.s1 NCI CGAP_Prl Homo Sapiens cDNA clone
IMAGE:1009093, mRNA sequence) and T20503 (Human gene signature HUMGS01709).
Based upon sequence similarity, vql7_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 vql7_1 protein sequence centered
around
amino acid 65 of SEQ ID N0:42. The TopPredII computer program predicts two
potential
transmembrane domains within the protein sequence of SEQ ID N0:98, one
centered
around amino acid 66 and another around amino acid 79 of SEQ ID N0:98.
Clone "v lq 8 1"
2 0 A polynucleotide of the present invention has been identified as clone "vq
18_1 ".
vq 18_1 was isolated from a human adult lung 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. vql8_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vq 18_ 1 protein")
2 5 The nucleotide sequence of vq 18_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 vql8_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
3 0 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 vql8_1
protein.
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The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vq 18_ 1 should be approximately 687 bp.
The nucleotide sequence disclosed herein for vql8_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vql8_1 demonstrated at least some similarity with
sequences
identified as 847882 (yj62dll.rl Soares breast 2NbHBst Homo sapiens cDNA clone
IMAGE 153333 5', mRNA sequence). Based upon sequence similarity, vql8_1
proteins
and each similar protein or peptide may share at least some activity. The
vql8_1 protein
appears to be one member of a family of proteins produced by alternative
splicing (see, for
example, the yd51_1 protein of International Application No. PCT/US99/10843,
which is
incorporated by reference herein).
Clone "v 2q 2 1 "
A polynucleotide of the present invention has been identified as clone
"vq22_1".
vq22_1 was isolated from a human adult lung 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. vq22_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vq22_1 protein").
The nucleotide sequence of vq22_1 as presently determined is reported in SEQ
ID
2 0 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 vq22_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:46. Amino acids
16 to 28
of SEQ ID N0:46 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
2 5 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 vq22_1
protein.
If the following changes were made to the nucleotide sequence of SEQ ID N0:45
- deletion of nucleotides 1096 and 1097; deletion of one nucleotide from the
group of
nucleotides 1142, 1143, and 1144; deletion of one nucleotide from the group of
nucleotides
3 0 1159, 1160, and 1161; deletion of one nucleotide from the group of
nucleotides 1187, 1188,
and 1189; and insertion of a "G" residue between nucleotide 1204 and
nucleotide 1207 -
another potential reading frame would be createdfrom what would then be
nucleotides 65
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to 1327, with a predicted amino acid sequence reported as SEQ ID N0:99. Amino
acids
16 to 28 of SEQ ID N0:99 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
protein of SEQ ID N0:99.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vq22_1 should be approximately 1653 bp.
The nucleotide sequence disclosed herein for vq22_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vq22_1 demonstrated at least some similarity with
sequences
identified as AA716162 (zg63fOl.s1 Soares fetal_heart_NbHHI9W Homo sapiens
cDNA
clone IMAGE:398041 3', mRNA sequence) and T26470 (Human gene signature
HUMGS08712). The predicted amino acid sequence disclosed herein for vq22_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
BLASTX search protocol. The predicted vq22_1 protein demonstrated at least
some
similarity to sequences identified as U58748 (similar to potential
transmembrane domains
in S. cerevisiae nuclear division RFTl protein (SP P38206) [Caenorhabditis
elegans]).
Based upon sequence similarity, vq22_1 proteins and each similar protein or
peptide may
2 0 share at least some activity. The TopPredII computer program predicts four
potential
transmembrane domains within both the vq22_1 protein sequence and the amino
acid
sequence of the protein of SEQ ID N0:99, centered around amino acids 96, 126,
181, and
343, respectively, of SEQ ID N0:46 and of SEQ ID N0:99.
2 5 Clone "vr3 1 "
A polynucleotide of the present invention has been identified as clone "vr3_1
".
vr3_1 was isolated from a human adult muscle 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. vr3_1 is a full-length clone,
including the
3 0 entire coding sequence of a secreted protein (also referred to herein as
"vr3_1 protein")
The nucleotide sequence of vr3_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
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reading frame and the predicted amino acid sequence of the vr3_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:48. Amino acids
2 to 14
of SEQ ID N0:48 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 vr3_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vr3_1 should be approximately 3133 bp.
The nucleotide sequence disclosed herein for vr3_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vr3_1 demonstrated at least some similarity with
sequences
identified as AI302099 (qn57g 10.x 1 NCI CGAP_Kids Homo sapiens cDNA clone
IMAGE 1902402 3' similar to gb M14058 COMPLEMENT C1R COMPONENT
PRECURSOR (HUMAN); mRNA sequence) and M14058 (Human complement Clr
mRNA, complete cds). The predicted amino acid sequence disclosed herein for
vr3_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
BLASTX search protocol. The predicted vr3_1 protein demonstrated at least some
similarity to sequences identified as M14058 (human complement Clr [Homo
sapiens]).
C 1 r is a zymogen of a serine protease that is involved in the activation of
the first
2 0 component of the classical pathway of the complement system (Leytus et
al., 1986,
Biochemistry 25 (17): 4855-4863, which is incorporated by reference herein).
Based upon
sequence similarity, vr3_1 proteins and each similar protein or peptide may
share at least
some activity. Motifs analysis detects a serine proteases, trypsin family,
active site around
residue 407 of SEQ ID N0:48. Hidden Markov Model analysis detects a CUB domain
2 5 from residue 16 to residue 137 of SEQ ID N0:48, and a trypsin profile from
residue 222
to residue 456 of SEQ ID N0:48. The nucleotide sequence of vr3_1 indicates
that it may
contain an Alu repetitive element.
Clone"vb26 1"
3 0 A polynucleotide of the present invention has been identified as clone
"vb26 1 ".
vb26_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
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sequence of the encoded protein. vb26_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vb26_1 protein").
The nucleotide sequence of vb26_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 vb26_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:50. Amino acids
13 to 25
of SEQ ID N0:50 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 vb26_1
protein.
The nucleotide and amino acid sequences of vb26_1 are related to those of
clone
vc8_1, described in U.S. application Ser. No. 09/298,733. Clone vb26 1
contains the
entire coding sequence of clone vc8_1, and has an additional three nucleotides
at
nucleotides 1283 to 1285 of SEQ ID N0:49.
The EcoRIlNotI restriction fragment obtainable from the deposit containing
clone
vb26_1 should be approximately 2974 bp.
The nucleotide' sequence disclosed herein for vb26_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vb26_1 demonstrated at least some similarity with
sequences
2 0 identified as AI807015 (wf37b05.x 1 Soares NFL_T GBC_S 1 Homo Sapiens cDNA
clone
IMAGE:2357745 3' similar to SW:NDC1 RABIT Q28615 RENAL SODIUM/
DICARBOXYLATE COTRANSPORTER; mRNA sequence), U26209 (Human renal
sodium/dicarboxylate cotransporter (NADC1) mRNA, complete cds), and V27580
(Human
hepatocyte nuclear factor 4 isoform gamma DNA). The predicted amino acid
sequence
disclosed herein for vb26_1 was searched against the GenPept and GeneSeq amino
acid
sequence databases using the BLASTX search protocol. The predicted vb26_1
protein
demonstrated at least some similarity to sequences identified as U87318 (NaDC-
2
[Xenopus laevis]) and W98815 (H. pylori GHPO 1401 protein). Human renal
sodium/dicarboxylate cotransporter (NADC1) displays remarkably wide substrate
3 0 selectivity, covering endogenous substrates such as cyclic nucleotides, a
prostaglandin and
uric acid, and a variety of drugs with different structures (e.g. antibiotics,
a nonsteroidal
anti-inflammatory drug, diuretics, an antineoplastic drug, and a uricosuric
drug); this
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protein is a multispecific organic anion transporter at the basolateral
membrane of the
proximal tubule (Sekine et al., 1997, J. Biol. Chem. 272 (30): 18526-9, which
is
incorporated by reference herein). Based upon sequence similarity, vb26_1
proteins and
each similar protein or peptide may share at least some activity. The
TopPredII computer
program predicts 11 probable transmembrane domains within the vb26_1 protein
sequence,
centered around amino acids 46, 61, 132, 282, 323, 385, 423, 508, 529, 556,
and 598 of
SEQ ID N0:50, respectively, and an additional two putative transmernbrane
domains
centered around residues 91 and 472 of SEQ ID N0:50.
Clone "vc70 1"
A polynucleotide of the present invention has been identified as clone "vc70 1
".
vc70_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. vc70_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vc70_1 protein").
The nucleotide sequence of vc70_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 vc70_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:52. Amino acids
15 to 27
2 0 of SEQ ID N0:52 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 vc70_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vc70_1 should be approximately 2187 bp.
The nucleotide sequence disclosed herein for vc70_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vc70_1 demonstrated at least some similarity with
sequences
identified as AI423223 (tf26fOl.x1 NCI CGAP_Brn23 Homo sapiens cDNA clone
3 0 IMAGE:2097337 3', mRNA sequence) and X33812 (Coding sequence for human
secreted
protein cb96_10). The predicted amino acid sequence disclosed herein for
vc70_1 was
searched against the GenPept and GeneSeq amino acid sequence databases using
the
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BLASTX search protocol. The predicted vc70_1 protein demonstrated at least
some
similarity to sequences identified as Y05319 (Human secreted protein cb96_10).
Based
upon sequence similarity, vc70_1 proteins and each similar protein or peptide
may share
at least some activity. The TopPredII computer program predicts eight
additional potential
transmembrane domains within the vc70_1 protein sequence, centered around
amino acids
58, 110, 153, 204, 316, 373, 420, and 502 of SEQ ID N0:52, respectively. The
vc70_1
protein appears to be a splice variant of the cb96_10 protein, with the vc70_1
protein
having an additional 73 amino acids at the N-terminal end containing a signal
sequence and
an additional transmembrane domain.
Clone "vo28 1 "
A polynucleotide of the present invention has been identified as clone "vo28 1
".
vo28_1 was isolated from a human adult pancreas cDNA library and was
identified as
encoding a novel protein on the basis of computer analysis of the amino acid
sequence of
the encoded protein. vo28_1 is a full-length clone, including the entire
coding sequence
of a novel protein (also referred to herein as "vo28_1 protein")
The nucleotide sequence of vo28_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 vo28_1 protein
corresponding
2 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:54.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo28_1 should be approximately 2056 bp.
The nucleotide sequence disclosed herein for vo28_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vo28_1 demonstrated at least some similarity with
sequences
identified as F22780 (HSPD07683 HM3 Homo Sapiens cDNA clone LL44B 10, mRNA
sequence). Based upon sequence similarity, vo28_1 proteins and each similar
protein or
peptide may share at least some activity. The nucleotide sequence of vo28_1
indicates that
it may contain an Alu repetitive element.
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Clone"vo29 1"
A polynucleotide of the present invention has been identified as clone "vo29 1
".
vo29_1 was isolated from a human adult pancreas 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. vo29_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo29_1 protein").
The nucleotide sequence of vo29_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 vo29_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:56. Amino acids
8 to 20
of SEQ ID N0:56 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 21; amino acids 5 to 17 of SEQ ID N0:56
are also
a possible leader/signal sequence, with the predicted mature amino acid
sequence
beginning in that case at amino acid 18; and amino acids 11 to 23 of SEQ ID
N0:56 are also
a possible leader/signal sequence, with the predicted mature amino acid
sequence
beginning in that case at amino acid 24. Due to the hydrophobic nature of
these predicted
leader/signal sequences, each is likely to act as a transmembrane domain
should it not be
separated from the remainder of the protein of SEQ ID N0:56.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
2 0 vo29_1 should be approximately 1803 bp.
The nucleotide sequence disclosed herein for vo29_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vo29_1 demonstrated at least some similarity with
sequences
identified as AI433801 (th81f07.x1 Soares NhHMPu_S1 Homo sapiens cDNA clone
2 5 IMAGE:2125093 3' similar to SW:YMNO YEAST Q03103 HYPOTHETICAL 65.0 KD
PROTEIN IN COX 14 5'REGION PRECURSOR; mRNA sequence), AR018794 (Sequence
76 from patent US 5783182), and X19751 (Mammalian Erol DNA). The predicted
amino
acid sequence disclosed herein for vo29_1 was searched against the GenPept and
GeneSeq
amino acid sequence databases using the BLASTX search protocol. The predicted
vo29_1
3 0 protein demonstrated at least some similarity to sequences identified as
AC00577
(unknown protein [Arabidopsis thaliana)), W99801 (Mammalian Erol protein), and
Y03632 (Hypoxia-regulated gene RTP241 product). Erol regulates the oxidation
potential
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of the endoplasmic reticulum, and may be used to increase disulfide bond
formation in
proteins during their production and/or purification. Based upon sequence
similarity,
vo29_1 proteins and each similar protein or peptide may share at least some
activity.
Motifs analysis detects an EF-hand calcium binding domain centered around
amino acid
159 of SEQ ID N0:56.
Clone"vo30 1"
A polynucleotide of the present invention has been identified as clone
"vo30_1".
vo30_1 was isolated from a human adult pancreas 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. vo30_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vo30_1 protein").
The nucleotide sequence of vo30_1 as presently determined is reported in SEQ
ID
N0:57, and includes a poly(A) tail. What applicants presently believe to be
the proper
reading frame and the predicted amino acid sequence of the vo30_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:58. Amino acids
10 to 22
of SEQ ID N0:58 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
2 0 leader/signal sequence not be separated from the remainder of the vo30_1
protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vo30_1 should be approximately 1356 bp.
The nucleotide sequence disclosed herein for vo30_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTNBLASTX and
FASTA search protocols. vo30_1 demonstrated at least some similarity with
sequences
identified as AA397685 (zt87d03.r1 Soares testis NHT Homo sapiens cDNA clone
IMAGE 729317 5', mRNA sequence) and AI983410 (wu19c10.x1 Soares Dieckgraefe
colon NHCD Homo sapiens cDNA clone IMAGE:990757 3' similar to contains TARl.t3
TAR1 repetitive element; mRNA sequence). Based upon sequence similarity,
vo30_1
3 0 proteins and each similar protein or peptide may share at least some
activity. Motifs
analysis detects an ATP/GTP binding site motif A (P-loop) centered around
amino acid 38
of SEQ ID N0:58.
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Clone "v 2p 5 1 "
A polynucleotide of the present invention has been identified as clone "vp25_1
".
vp25_1 was isolated from a human adult prostate 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. vp25_1 is a full-length clone,
including the
entire coding sequence of a secreted protein (also referred to herein as
"vp25_1 protein").
The nucleotide sequence of vp25_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 vp25_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:60. Amino acids
15 to 27
of SEQ ID N0:60 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 vp25_1
protein.
Another potential reading frame, encoded by nucleotides 1362 to 1622 of SEQ ID
N0:59, is reported as the amino acid sequence of SEQ ID NO:100. Amino acids 5
to 17
of SEQ ID NO:100 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
2 0 leader/signal sequence not be separated from the remainder of the protein
of SEQ ID
NO:100.
Another potential reading frame, encoded by nucleotides 2560 to 2820 of SEQ ID
N0:59, is reported as the amino acid sequence of SEQ ID NO:101. Amino acids 21
to 33
of SEQ ID NO:101 are a predicted leader/signal sequence, with the predicted
mature amino
2 5 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 protein of
SEQ ID
NO:101.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
3 0 vp25_ 1 should be approximately 2989 bp.
The nucleotide sequence disclosed herein for vp25_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
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FASTA search protocols. vp25_1 demonstrated at least some similarity with
sequences
identified as AA481107 (aa29dOl.r1 NCI CGAP_GCB 1 Homo Sapiens cDNA clone
IMAGE:814657 5', mRNA sequence), AF146793 (Mus musculus protein B gene,
partial
cds; and CLOCK (Clock), PFT27 (pFT27), and HSAR (HSAR) genes, complete cds),
AI081234 (oy67a03.x1 NCI CGAP_CLL1 Homo sapiens cDNA clone IMAGE 1670860
3' similar to SW PF27_MOUSE P52875 TRANSMEMBRANE PROTEIN PFT27;
contains MSRl.tl MSR1 repetitive element), and X37441 (Human secreted protein
cDNA
fragment containing gene 55). The predicted amino acid sequence disclosed
herein for
vp25_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vp25_1 protein demonstrated at
least
some similarity to sequences identified as AF14679 (PFT27 [Mus musculus]) and
Y07843
(Human secreted protein fragment #2 encoded from gene 55). Based upon sequence
similarity, vp25_1 proteins and each similar protein or peptide may share at
least some
activity. The vp25_1 protein and the proteins of database entries AF14679 and
Y07843
appear to be members of a family of proteins produced as splice variants. The
nucleotide
sequence of vp25_1 indicates that it may contain an Alu repetitive element.
Clone"vq25 1"
A polynucleotide of the present invention has been identified as clone "vq25_1
".
2 0 vq25_1 was isolated from a human adult lung 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. vq25_1 is a full-length clone, including the
entire coding
sequence of a secreted protein (also referred to herein as "vq25_1 protein").
The nucleotide sequence of vq25_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 vq25_1 protein
corresponding
to the foregoing nucleotide sequence is reported in SEQ ID N0:62. Amino acids
2 to 14
of SEQ ID N0:62 are a predicted leader/signal sequence, with the predicted
mature amino
acid sequence beginning at amino acid 15; amino acids 4 to 16 of SEQ ID N0:62
are also
3 0 a predicted leader/signal sequence, with the predicted mature amino acid
sequence
beginning in that case at amino acid 17. Due to the hydrophobic nature of
these predicted
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leader/signal sequence, each is likely to act as a transmembrane domain should
it not be
separated from the remainder of the vq25_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing
clone
vq25_1 should be approximately 2048 bp.
The nucleotide sequence disclosed herein for vq25_1 was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vq25_1 demonstrated at least some similarity with
sequences
identified as AC007026 (Homo sapiens clone DJ0751 G 11, complete sequence),
AI087294
(oz77hOl .x 1 Soares senescent fibroblasts NbHSF Homo sapiens cDNA clone IMAGE
1681393 3' similar to SW CTCF_HUMAN P49711 TRANSCRIPTIONAL REPRESSOR
CTCF; mRNA sequence), AW003280 (wq64h08.x1 NCI CGAP_GC6 Homo sapiens
cDNA clone IMAGE:2476095 3' similar to TR:Q60694 Q60694 REl-SILENCING
TRANSCRIPTION FACTOR; mRNA sequence), and X00648 (Human secreted protein
gene 38 clone HODCV74). The predicted amino acid sequence disclosed herein for
vq25_1 was searched against the GenPept and GeneSeq amino acid sequence
databases
using the BLASTX search protocol. The predicted vq25_1 protein demonstrated at
least
some similarity to sequences identified as AC00487 (zinc finger-like; similar
to P52742
(PID g 1731411 ) [Homo sapiens]) and 899364 (Human REST protein DNA binding
domain). Based upon sequence similarity, vq25_1 proteins and each similar
protein or
2 0 peptide may share at least some activity. Motifs analysis detects three
Zinc-finger, C2H2-
type, domains centered around amino acids 149, 359, and 387 of SEQ ID N0:62,
respectively. Hidden markov model analysis detects eight of these Zinc-forger,
C2H2-type,
domains approximately at amino acids 91 to 113, 119 to 141, 147 to 169, 301 to
323, 329
to 351, 357 to 379, 385 to 407, and 413 to 435 of SEQ ID N0:62, respectively.
Deposit of Clones
Clones vb24_l, vc64_1, vp20_1, and vq4_1 were deposited on February 17, 1999
with the ATCC (American Type Culture Collection, 10801 University Boulevard,
Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the
Budapest Treaty
3 0 and were given the accession number 207113, from which each clone
comprising a
particular polynucleotide is obtainable.
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Clone vo7_1 was deposited on July 15, 1999 with the ATCC (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 PTA-
362, from which the vo7_1 clone comprising a particular polynucleotide is
obtainable.
Clones vc65_1, vc66_l, vc68_1, vk6_1, vo4_l, vo8_l, vol0_l, vo20_1, vo21_l,
and vp24_ 1 were deposited on July 15, 1999 with the ATCC (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
PTA-361,
from which each clone comprising a particular polynucleotide is obtainable.
Clone vol7_1 was deposited on July 15, 1999 with the ATCC (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 PTA-
366, from which the vol7_1 clone comprising a particular polynucleotide is
obtainable.
Clones vql l_1, vql2_1, vql4_1, vql5_1, vql7_l, vql8_1, vq22_1, and vr3_1
were deposited on July 15, 1999 with the ATCC (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 PTA-367,
from
which each clone comprising a particular polynucleotide is obtainable.
Clone vb26_1 was deposited on August 11, 1999 with the ATCC (American Type
2 0 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
PTA-501. (Note that due to a typographical error, the deposit of clone vb26_ 1
under the
accession number PTA-501 was initially recorded at the ATCC as a deposit of
clone
"YB26_ 1 ".)
Clones vc70_1, vo28_1, vo29_l, vo30_1, vp25_1, and vq25_1 were deposited on
December 21, 1999 with the ATCC (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 PTA-1074, from which each
clone
comprising a particular polynucleotide is obtainable.
3 0 All restrictions on the availability to the public of the deposited
material will be
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 provided
2 0 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 Sequence
vb24_1 SEQ ID N0:63
vc64_1 SEQ ID N0:64
vp20_1 SEQ ID N0:65
vq4_1 SEQ ID N0:66
vo7_1 SEQ ID N0:67
3 0 vc65_1 SEQ ID N0:68
vc66_1 SEQ ID N0:69
vc68_1 SEQ ID N0:70
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vk6_ 1 SEQ ID N0:71


vo4_ 1 SEQ ID N0:72


vo8_ 1 SEQ ID N0:73


vol0 _1 SEQ ID N0:74


vo20 _1 SEQ ID N0:75


vo21 _1 SEQ ID N0:76


vp24 _1 SEQ ID N0:77


vol7 _1 SEQ ID N0:78


vq 11 _ 1 SEQ ID N0:79


vql2_1 SEQ ID N0:80


vql4 _1 SEQ ID N0:81


vql5 _1 SEQ ID N0:82


vql7 _1 SEQ ID N0:83


vql8 _1 SEQ ID N0:84


vq22_1 SEQ ID N0:85


vr3_ SEQ ID N0:86
1


vb26_ 1 SEQ ID N0:87


In preferred probes/primers, the second nucleotide position is occupied by a
biotinylated
2 0 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
parameters:
2 5 (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).
The oligonucleotide should preferably be labeled with y-32P ATP (specific
activity 6000
3 0 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
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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 ~.~1 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 pg/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
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 le+6 dpm/mL. The filter is then
preferably
2 0 incubated at 65°C with gentle agitation overnight. The filter is
then preferably washed in
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
2 5 visualize the positives on the X-ray film. Other known hybridization
methods can also 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.
3 0 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
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described in H.U. Saragovi, et al., Bio/Technology 10, 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 carrier
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
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 the ATCC) in a suitable
mammalian cell
or other host cell. The sequences) of the mature forms j of the protein may
also be
determinable from the amino acid sequence of the full-length form.
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
2 0 derived and may include contiguous regions of the genome necessary for the
regulated
expression of such genes. Corresponding genes may therefore include but are
not limited
to coding sequences, 5' and 3' untranslated regions, alternatively spliced
exons, introns,
promoters, enhancers, and silencer or suppressor elements. The corresponding
genes can
be isolated in accordance with known methods using the sequence information
disclosed
2 5 herein. Such methods include the preparation of probes or primers from the
disclosed
sequence information for identification and/or amplification of genes in
appropriate
genomic libraries or other sources of genomic materials. An "isolated gene" is
a gene that
has been separated from the adjacent coding sequences, if any, present in the
genome of
the organism from which the gene was isolated.
3 0 The chromosomal location corresponding to the polynucleotide sequences
disclosed
herein may also be determined, for example by hybridizing appropriately
labeled
polynucleotides of the present invention to chromosomes in situ. It may also
be possible
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CA 02362538 2001-08-16
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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.nlm.nih.gov/UniGene/, 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 mRNA transcribed from the gene (Albert
and Morns,
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). The desired change in gene expression
can also be
achieved through the use of double-stranded ribonucleotide molecules having
some
2 0 complementarity to the mRNA transcribed from the gene, and which interfere
with the
transcription, stability, or expression of the mRNA ("RNA intereference" or
"RNAi"; Fire
et al., 1998, Nature 391 (6669): 806-811; Montgomery et al., 1998, Proc. Natl.
Acad. Sci.
USA 95 (26): 15502-15507; and Sharp, 1999, Genes Dev. 13 (2): 139-141; all of
which are
incorporated by reference herein). Transgenic animals that have multiple
copies of the
2 5 genes) corresponding to the polynucleotide sequences disclosed herein,
preferably
produced by transformation of cells with genetic constructs that are stably
maintained
within the transformed cells and their progeny, are provided. Transgenic
animals that have
modified genetic control regions that increase or reduce gene expression
levels, or that
change temporal or spatial patterns of gene expression, are also provided (see
European
3 0 Patent No. 0 649 464 B 1, 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
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sequences into the corresponding genes) or through deletion of all or part of
the
corresponding gene(s). Partial or complete gene inactivation can be
accomplished through
insertion, preferably followed by imprecise excision, of transposable elements
(Plasterk,
1992, Bioessays 14(9): 629-633; Zwaal et al., 1993, Proc. Natl. Acad. Sci. USA
90(16):
7431-7435; Clark et al., 1994, Proc. Natl. Acad. Sci. USA 91(2): 719-722; all
of which are
incorporated by reference herein), or through homologous recombination,
preferably
detected by positive/negative genetic selection strategies (Mansour et al.,
1988, Nature
336: 348-352; U.S. Patent Nos. 5,464,764; 5,487,992; 5,627,059; 5,631,153;
5,614, 396;
5,616,491; and 5,679,523; all of which are incorporated by reference herein).
These
organisms with altered gene expression are preferably eukaryotes and more
preferably are
mammals. Such organisms are useful for the development of non-human models for
the
study of disorders involving the corresponding gene(s), and for the
development of assay
systems for the identification of molecules that interact with the protein
products) of the
corresponding gene(s).
Where the protein of the present invention is membrane-bound (e.g., is a
receptor),
the present invention also provides for soluble forms of such protein. In such
forms, part
or all of the intracellular and transmembrane domains of the protein are
deleted such that
the protein is fully secreted from the cell in which it is expressed. The
intracellular and
transmembrane domains of proteins of the invention can be identified in
accordance with
2 0 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 acid 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).
2 5 Proteins and protein fragments of the present invention include proteins
with amino
acid sequence lengths that are at least 25%(more preferably at least 50%, and
most
preferably at least 75%) of the length of a disclosed protein and have at
least 60% sequence
identity (more preferably, at least 75% identity; most preferably at least 90%
or 95% identity) with
that disclosed protein, where sequence identity is determined by comparing the
amino acid
3 0 sequences of the proteins when aligned so as to maximize overlap and
identity while minimizing
sequence gaps. Also included in the present invention are proteins and protein
fragments that
contain a segment preferably comprising 8 or more (more preferably 20 or more,
most preferably
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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 (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 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/blast/executables. 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,
2 0 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
2 5 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, 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
3 0 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
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comparison matrix is BLOSLJM62, but other amino acid 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
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
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, Hylobates concolor, Macaca mulatta, Papio papio, Papio hamadryas,
Cercopitheccas aethiops, Cebus capucinus, Aotus trivirgatus, Sanguinus
Oedipus,
2 0 Microcebus murinus, Mus musculus, Rattus norvegicus, Cricetulus griseus,
Felis catus,
Mustela visors, Canis familiaris, Oryctolagus cuniculus, Bos taurus, Ovis
aries, Sus scrofa,
and Equcas 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,
2 5 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).
The invention also encompasses allelic variants of the disclosed
polynucleotides or
3 0 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%
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sequence identity (more preferably, at least 75% identity; most preferably at
least 90°Io
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.
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
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.
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CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
StringencyPolynucleotideHybridHybridization TemperatureWash
ConditionHybrid Lengthand Temperature
(bP)~ Bufferr and
Buffed


A DNA:DNA z 50 65C; lxSSC -or- 65C; 0.3xSSC
42C; lxSSC, 50% formamide


B DNA:DNA <50 TB*; lxSSC TB*; lxSSC


C DNA:RNA z 50 67C; lxSSC -or- 67C; 0.3xSSC
45C; lxSSC, 50% formamide


D DNA:RNA <50 TD*; IxSSC TD*; lxSSC


E RNA:RNA z 50 70C; IxSSC -or- 70C; 0.3xSSC
50C; lxSSC, 50% formamide


F RNA:RNA <50 TF*; lxSSC TF*; IxSSC


G DI~TA:DNA z 50 65C; 4xSSC -or- 65C; lxSSC
42C; 4xSSC, 50% formamide


1 H DNA:DNA <50 TH*; 4xSSC TH*; 4xSSC
O


I DI~TA:RNA Z 50 67C; 4xSSC -or- 67C; lxSSC
45C; 4xSSC, 50% formamide


J DNA:RNA <50 T,*; 4xSSC T,*; 4xSSC


K RNA:RNA s 50 70C; 4xSSC -or- 67C; lxSSC
50C; 4xSSC, 50% formamide


L RNA:RNA <50 TL*; 2xSSC T~*; 2xSSC


M DNA:DNA s 50 50C; 4xSSC -or- 50C; 2xSSC
40C; 6xSSC, 50% formamide


N DNA:DNA <50 T,,*; 6xSSC TN*; 6xSSC


O DNA:RNA s 50 55C; 4xSSC-or- 55C; 2xSSC
42C; 6xSSC, 50% formamide


P DNA:RNA <50 TP*; 6xSSC Tp*; 6xSSC


Q RNA:RNA z 50 60C; 4xSSC -or- 60C; 2xSSC
45C; 6xSSC, 50% formamide


2 R RNA:RNA <50 TR*; 4xSSC TR*; 4xSSC
O


$: 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 hybrid length can be
2 5 determined by aligning the sequences of the polynucleotides and
identifying the region or regions of optimal sequence
complementarity.
': SSPE (lxSSPE is 0.15M NaCI, lOmM NaH2P04, and 1.25mM EDTA, pH 7.4) can be
substituted for SSC (lxSSC is
0.15M NaCI and l5rru'vI sodium citrate) in the hybridization and wash buffers;
washes are performed for 15 minutes after
hybridization is complete.
3 0 *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, Tm(°C) = 2(# of A + T bases)
+ 4(# of G + C bases). For hybrids between 18
and 49 base pairs in length, Tm(°C) = 81.5 + 16.6(log,o[Na+]) + 0.41
(%G+C) - (600/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).
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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 1 l, 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%(rnore preferably at least 50%, and most preferably at least 75%) of the
length of the
polynucleotide of the present invention to which it hybridizes, and has at
least 60% sequence
identity (more preferably, at least 75% identity; most preferably at least 90%
or 95% identity) with
the polynucleotide of the present invention to which it hybridizes, where
sequence identity is
determined by comparing the sequences of the hybridizing polynucleotides when
aligned so as to
maximize overlap and identity while minimizing sequence gaps.
The isolated polynucleotide endcoing the protein of the invention may be
operably
linked to an expression control sequence such as the pMT2 or pED expression
vectors
disclosed in Kaufman et al., Nucleic Acids Res. 19, 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 185, 537-566 ( 1990). As
defined
herein "operably linked" means that the isolated polynucleotide of the
invention and an
2 0 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
protein. Mammalian host cells include, for example, monkey COS cells, Chinese
Hamster
2 5 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
strains derived from in vitro 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
3 0 as yeast or in prokaryotes such as bacteria. Potentially suitable yeast
strains include
Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains,
Candida,
or any yeast strain capable of expressing heterologous proteins. Potentially
suitable
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CA 02362538 2001-08-16
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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 Agricultural Experiment Station
Bulletin No
1555 ( 1987), incorporated herein by reference. As used herein, an 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 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
2 0 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
such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffinity
chromatography.
2 5 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
(TRX). Kits for expression and purification of such fusion proteins are
commercially
available from New England BioLabs (Beverly, MA), Pharmacia (Piscataway, NJ)
and
3 0 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.
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CA 02362538 2001-08-16
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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 (RP-
HPLC) steps employing hydrophobic RP-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 transgenic
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
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
2 0 immunological substitutes for natural, purified proteins in screening of
therapeutic
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
2 5 sequences can be made by those skilled in the art using known techniques.
Modifications
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,
3 0 replacement, insertion or deletion are well known to those skilled in the
art (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.
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CA 02362538 2001-08-16
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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
present invention.
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
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
2 0 stage of tissue differentiation or development or in disease states); as
molecular weight
markers on Southern gels; as chromosome markers or tags (when labeled) to
identify
chromosomes or to map related gene positions; to compare with endogenous DNA
sequences in patients to identify potential genetic disorders; as probes to
hybridize and thus
discover novel, related DNA sequences; as a source of information to derive
PCR primers
2 5 for genetic fingerprinting; as a probe to "subtract-out" known sequences
in the process of
discovering other novel polynucleotides; for selecting and making oligomers
for attachment
to a "gene chip" or other support, including for examination of expression
patterns; to raise
anti-protein antibodies using DNA immunization techniques; and as an antigen
to raise
anti-DNA antibodies or elicit another immune response. Where the
polynucleotide encodes
3 0 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 described in Gyuris et al., 1993, Cell75: 791-803
and in Rossi
161



CA 02362538 2001-08-16
WO 00/49134 PCT/US00104340
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.
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:
2 0 A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press,
Sambrook, J., E.F.
Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to
Molecular
Cloning Techniques", Academic Press, Berger, S.L. and A.R. Kimmel eds., 1987.
Nutritional Uses
2 5 Polynucleotides and proteins of the present invention can also be used as
nutritional
sources or supplements. Such uses include without limitation use as a protein
or amino
acid supplement, use as a carbon source, use as a nitrogen source and use as a
source of
carbohydrate. In such cases the protein or polynucleotide of the invention can
be added to
the feed of a particular organism or can be administered as a separate solid
or liquid
3 0 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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CA 02362538 2001-08-16
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Cytokine 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-l, Mo7e and CMK.
The activity of a protein of the invention may, among other means, be measured
by
the following methods:
Assays for T-cell or thymocyte proliferation include without limitation those
described in: Current Protocols in Immunology, Ed by 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. i 37:3494-3500,
1986;
Bertagnolli et al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al.,
Cellular
Immunology 133:327-341, 1991; Bertagnolli, et al., J. Immunol. 149:3778-3783,
1992;
2 0 Bowman et al., J. Immunol. 152: 1756-1761, 1994.
Assays for cytokine production and/or proliferation of spleen cells, lymph
node
cells or thymocytes include, without limitation, those described in:
Polyclonal T cell
stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in
Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto.
1994; and
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
3 0 Interleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky,
P.E. In Current
Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John
Wiley and
Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau
et al.,
163



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A.
80:2931-2938,
1983; Measurement of mouse and human interleukin 6 - Nordan, R. In Current
Protocols
in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and
Sons, Toronto.
1991; Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986;
Measurement of
human Interleukin 11 - 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.
11:405-41 l, 1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et
al., J. Immunol.
140:508-512, 1988.
Immune Stimulati~ or Suppressin Activi
A protein of the present invention may also exhibit immune stimulating or
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
2 5 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
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,
3 0 bacterial, fungal or other infection may be treatable using a protein of
the present
invention, including infections by HIV, hepatitis viruses, herpesviruses,
mycobacteria,
Leishmania spp., malaria spp. and various fungal infections such as
candidiasis. Of course,
164



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
in this regard, a protein of the present invention may also be useful where a
boost to the
immune system generally may be desirable, i.e., in the treatment of cancer.
Autoimmune disorders which may be treated using a protein of the present
invention include, for example, connective tissue disease, multiple sclerosis,
systemic lupus
erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation,
Guillain-Barre
syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis,
myasthenia gravis,
graft-versus-host disease and autoimmune inflammatory eye disease. Such a
protein of the
present invention may also to be useful in the treatment of allergic reactions
and conditions,
such as asthma (particularly allergic asthma) or other respiratory problems.
Other
conditions, in which immune suppression is desired (including, for example,
organ
transplantation), may also be treatable using a protein of the present
invention.
Using the proteins of the invention it may also be possible to 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
2 0 immunosuppression in that it is generally antigen-specific and persists
after exposure to the
tolerizing agent has ceased. Operationally, tolerance can be demonstrated by
the lack of
a T cell response upon reexposure to specific antigen in the absence of the
tolerizing agent.
Down regulating or preventing one or more antigen functions (including without
limitation B lymphocyte antigen functions (such as , for example, B7)), e.g.,
preventing
2 5 high level lymphokine synthesis by activated T cells, will be useful in
situations of tissue,
skin and organ transplantation and in graft-versus-host disease (GVHD). For
example,
blockage of T cell function should result in reduced tissue destruction in
tissue
transplantation. Typically, in tissue transplants, rejection of the transplant
is initiated
through its recognition as foreign by T cells, followed by an immune reaction
that destroys
3 0 the transplant. The administration of a molecule which inhibits or blocks
interaction of a
B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a
soluble,
monomeric form of a peptide having B7-2 activity alone or in conjunction with
a
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CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
monomeric form of a peptide having an activity of another B lymphocyte antigen
(e.g., B7-
l, B7-3) or blocking antibody), prior to transplantation can lead to the
binding of the
molecule to the natural ligand(s) on the immune cells without transmitting the
corresponding costimulatory signal. Blocking B lymphocyte antigen function in
this matter
prevents cytokine synthesis by immune cells, such as T cells, and thus acts as
an
immunosuppressant. Moreover, the lack of costimulation may also be sufficient
to
anergize the T cells, thereby inducing tolerance in a subject. Induction of
long-term
tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of
repeated
administration of these blocking reagents. To achieve sufficient
immunosuppression or
tolerance in a subject, it may also be necessary to block the function of a
combination of
B lymphocyte antigens.
The efficacy of particular blocking reagents in preventing organ transplant
rejection
or GVHD can be assessed using animal models that are predictive of efficacy in
humans.
Examples of appropriate systems which can be used include allogeneic cardiac
grafts in rats
and xenogeneic pancreatic islet cell grafts in mice, both of which have been
used to
examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as
described
in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. Natl.
Acad. Sci
USA, 89:11102-11105 (1992). In addition, murine models of GVHD (see Paul ed.,
Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used
to
2 0 determine the effect of blocking B lymphocyte antigen function in vivo on
the development
of that disease.
Blocking antigen function may also be therapeutically useful for treating
autoimmune diseases. Many autoimmune disorders are the result of inappropriate
activation of T cells that are reactive against self tissue and which promote
the production
2 5 of cytokines and autoantibodies involved in the pathology of the diseases.
Preventing the
activation of autoreactive T cells may reduce or eliminate disease symptoms.
Administration of reagents which block costimulation of T cells by disrupting
receptor:ligand interactions of B lymphocyte antigens can be used to inhibit T
cell
activation and prevent production of autoantibodies or T cell-derived
cytokines which may
3 0 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
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CA 02362538 2001-08-16
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disorders can be determined using a number of well-characterized animal models
of human
autoimmune diseases. Examples include murine experimental autoimmune
encephalitis,
systemic lupus erythmatosis in MRLllprllpr mice or NZB hybrid mice, murine
autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and
murine
experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven
Press,
New York, 1989, pp. 840-856).
Upregulation of an antigen function (preferably a B lymphocyte antigen
function),
as a means of up regulating immune responses, may also be useful in therapy.
Upregulation of immune responses may be in the form of enhancing an existing
immune
response or eliciting an initial immune response. For example, enhancing an
immune
response through stimulating B lymphocyte antigen function may be useful in
cases of viral
infection. In addition, systemic viral diseases such as influenza, the 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
2 0 responses would be to isolate infected cells from a patient, transfect
them with a nucleic
acid encoding a protein of the present invention as described herein such that
the cells
express all or a portion of the protein on their surface, and reintroduce the
transfected cells
into the patient. The infected cells would now be capable of delivering a
costimulatory
signal to, and thereby activate, T cells in vivo.
2 5 In another application, up regulation or enhancement of antigen function
(preferably
B lymphocyte antigen function) may be useful in the induction of tumor
immunity. Tumor
cells (e.g., sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, carcinoma)
transfected with a nucleic acid encoding at least one peptide of the present
invention can
be administered to a subject to overcome tumor-specific tolerance in the
subject. If desired,
3 0 the tumor cell can be transfected to express a combination of peptides.
For example, tumor
cells obtained from a patient can be transfected ex vivo with an expression
vector directing
the expression of a peptide having B7-2-like activity alone, or in conjunction
with a peptide
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having B7-1-like activity and/or B7-3-like activity. The transfected tumor
cells are
returned to the patient to result in expression of the peptides on the surface
of the
transfected cell. Alternatively, gene therapy techniques can be used to target
a tumor cell
for transfection in vivo.
The presence of the peptide of the present invention having the activity of a
B
lymphocyte antigens) on the surface of the tumor cell provides the necessary
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
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 ~i2 microglobulin
protein or an
MHC class II a chain protein and an MHC class II ~3 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
2 0 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,
2 5 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); Hernnann et al., Proc. Natl.
Acad. Sci.
USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982;
Handa et
3 0 al., J. Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-
3500, 1986;
Takai et al., J. Immunol. 140:508-512, 1988; Herrmann et al., Proc. Natl.
Acad. Sci. USA
78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et
al., J.
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Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986;
Bowmanet al., J. Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512,
1988;
Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Brown et al., J.
Immunol.
153:3079-3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching
(which will identify, among others, proteins that modulate T-cell dependent
antibody
responses and that affect Thl/Th2 profiles) include, without limitation, those
described in:
Maliszewski, J. Immunol. 144:3028-3033, 1990; and Assays for B cell function:
In vitro
antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in
Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto.
1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others,
proteins that generate predominantly Thl and CTL responses) include, without
limitation,
those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M.
Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing
Associates
and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte
Function 3.1-
3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol.
137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli
et al., J.
Immunol. 149:3778-3783, 1992.
Dendritic cell-dependent assays (which will identify, among others, proteins
2 0 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
3 0 lymphocyte homeostasis) include, without limitation, those described in:
Darzynkiewicz
et al., Cytometry 13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993;
Gorczyca
et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243,
1991;
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CA 02362538 2001-08-16
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Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry
14:891-897, 1993; Gorczyca et al., International Journal of Oncology 1:639-
648, 1992.
Assays for proteins that influence early steps of T-cell commitment and
development include, without limitation, those described in: Antica et al.,
Blood
84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et
al., Blood
85:2770-2778, 1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.
Hematopoiesis Re ulatin~ Activity
A protein of the present invention may be useful in regulation of
hematopoiesis and,
consequently, in the treatment of myeloid or lymphoid cell deficiencies. Even
marginal
biological activity in support of colony forming cells or of factor-dependent
cell lines
indicates involvement in regulating hematopoiesis, e.g. in supporting the
growth and
proliferation of erythroid progenitor cells alone or in combination with other
cytokines,
thereby indicating utility, for example, in treating various anemias or for
use in conjunction
with irradiation/chemotherapy to stimulate the production of erythroid
precursors and/or
erythroid cells; in supporting the growth and proliferation of myeloid cells
such as
granulocytes and monocytes/macrophages (i.e., traditional CSF activity)
useful, for
example, in conjunction with chemotherapy to prevent or treat consequent myelo-

suppression; in supporting the growth and proliferation of megakaryocytes and
2 0 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
2 5 (such as those usually treated with transplantation, including, without
limitation, aplastic
anemia and paroxysmal nocturnal hemoglobinur~ia), 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.
3 0 The activity of a protein of the invention may, among other means, be
measured by
the following methods:
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Suitable assays for proliferation and differentiation of various hematopoietic
lines
are cited above.
Assays for embryonic stem cell differentiation (which will identify, among
others,
proteins that influence embryonic differentiation hematopoiesis) include,
without
limitation, those described in: Johansson et al. Cellular Biology 15:141-151,
1995; Keller
et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al.,
Blood
81:2903-2915, 1993.
Assays for stem cell survival and differentiation (which will identify, among
others,
proteins that regulate lympho-hematopoiesis) include, without limitation,
those described
in: Methylcellulose colony forming assays, Freshney, M.G. In Culture of
Hematopoietic
Cells. R.I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York,
NY. 1994;
Hirayama et al., Proc. Natl. Acad. Sci. 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, 1994;
Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of
Hematopoietic Cells.
R.I. Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc.., New York, NY.
1994; Long term
bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter,
M. and Allen,
T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 163-
179,
2 0 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 Activity
2 5 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
3 0 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
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fracture reduction and also in the improved fixation of artificial joints. De
novo bone
formation induced by an osteogenic agent contributes to the repair of
congenital, trauma
induced, or oncologic resection induced craniofacial defects, and also is
useful in cosmetic
plastic surgery.
A protein of this invention may also be used in the treatment of periodontal
disease,
and in other tooth repair processes. Such agents may provide an environment to
attract
bone-forming cells, stimulate growth of bone-forming cells or induce
differentiation of
progenitors of bone-forming cells. A protein of the invention may also be
useful in the
treatment of osteoporosis or osteoarthritis, such as through stimulation of
bone and/or
cartilage repair or by blocking inflammation or processes of tissue
destruction (collagenase
activity, osteoclast activity, etc.) mediated by inflammatory processes.
Another category of tissue regeneration activity that may be attributable to
the
protein of the present invention is tendon/ligament formation. A protein of
the present
invention, which induces tendon/ligament-like tissue or other tissue formation
in
circumstances where such tissue is not normally formed, has application in the
healing of
tendon or ligament tears, deformities and other tendon or ligament defects in
humans and
other animals. Such a preparation employing a tendon/ligament-like tissue
inducing
protein may have prophylactic use in preventing damage to tendon or ligament
tissue, as
well as use in the improved fixation of tendon or ligament to bone or other
tissues, and in
2 0 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
2 5 ligament-forming cells, stimulate growth of tendon- or ligament-forming
cells, induce
differentiation of progenitors of tendon- or ligament-forming cells, or induce
growth of
tendon/ligament cells or progenitors ex vivo for return in vivo to effect
tissue repair. The
compositions of the invention may also be useful in the treatment of
tendinitis, carpal
tunnel syndrome and other tendon or ligament defects. The compositions may
also include
3 0 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
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CA 02362538 2001-08-16
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peripheral nervous system diseases and neuropathies, as well as mechanical and
traumatic
disorders, which involve degeneration, death or trauma to neural cells or
nerve tissue.
More specifically, a protein may be used in the treatment of diseases of the
peripheral
nervous system, such as peripheral nerve injuries, peripheral neuropathy and
localized
neuropathies, and central nervous system diseases, such as Alzheimer's,
Parkinson's
disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager
syndrome.
Further conditions which may be treated in accordance with the present
invention include
mechanical and traumatic disorders, such as spinal cord disorders, head trauma
and
cerebrovascular diseases such as stroke. Peripheral neuropathies resulting
from
chemotherapy or other medical therapies may also be treatable using a protein
of the
invention.
Proteins of the invention may also be useful to promote better or faster
closure of
non-healing wounds, including without limitation pressure ulcers, ulcers
associated with
vascular insufficiency, surgical and traumatic wounds, and the like.
It is expected that a protein of the present invention may also exhibit
activity for
generation or regeneration of other tissues, such as organs (including, for
example,
pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth,
skeletal or cardiac)
and vascular (including vascular endothelium) tissue, or for promoting the
growth of cells
comprising such tissues. Part of the desired effects may be by inhibition or
modulation of
2 0 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.
2 5 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:
3 0 Assays for tissue generation activity include, without limitation, those
described in:
International Patent Publication No. W095/16035 (bone, cartilage, tendon);
International
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CA 02362538 2001-08-16
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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, Inc., Chicago, as modified by Eaglstein and Mertz, J.
Invest.
Dermatol 71:382-84 (1978).
Activin/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
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 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,
2 0 United States Patent 4,798,885. A protein of the invention may also be
useful for
advancement of the onset of fertility in sexually immature mammals, so as to
increase the
lifetime reproductive performance of domestic animals such as cows, sheep and
pigs.
The activity of a protein of the invention may, among other means, be measured
by
the following methods:
2 5 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.
3 0 Chemotactic/Chemokinetic Activity
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,
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CA 02362538 2001-08-16
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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.
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
assay for cell chemotaxis.
The activity of a protein of the invention may, among other means, be measured
by
the following methods:
Assays for chemotactic activity (which will identify proteins that induce or
prevent
chemotaxis) consist of assays that measure the ability of a protein to induce
the migration
of cells across a membrane as well as the ability of a protein to induce the
adhesion of one
cell population to another cell population. Suitable assays for movement and
adhesion
2 0 include, without limitation, those described in: Current Protocols in
Immunology, Ed by
J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub.
Greene
Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of
alpha and
beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376,
1995; Lind et
al. APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25: 1744-1748;
Gruber et al.
2 5 J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153:
1762-1768, 1994.
Hemostatic and Thrombolytic ActivitX
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
3 0 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
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CA 02362538 2001-08-16
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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.
Receptor/Li~and Activity
A protein of the present invention may also demonstrate activity as receptors,
receptor ligands or inhibitors or agonists of receptor/ligand interactions.
Examples of such
receptors and ligands include, without limitation, cytokine receptors and
their ligands,
receptor kinases and their ligands, receptor phosphatases and their ligands,
receptors
involved in cell-cell interactions and their ligands (including without
limitation, cellular
adhesion molecules (such as selectins, integrins and their ligands) and
receptor/ligand pairs
involved in antigen presentation, antigen recognition and development of
cellular and
humoral immune responses). Receptors and ligands are also useful for screening
of
potential peptide or small molecule inhibitors of the relevant receptor/ligand
interaction.
2 0 A protein of the present invention (including, without limitation,
fragments of receptors and
ligands) may themselves be useful as inhibitors of receptor/ligand
interactions.
The activity of a protein of the invention may, among other means, be measured
by
the following methods:
Suitable assays for receptor-ligand activity include without limitation those
2 5 described in:Current Protocols in Immunology, Ed by J.E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and
Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under
static
conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-
6868, 1987;
Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp.
Med.
3 0 169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994;
Stitt et al.,
Cell 80:661-670, 1995.
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CA 02362538 2001-08-16
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Anti-Inflammatory Activity
Proteins of the present invention may also exhibit anti-inflammatory activity.
The
anti-inflammatory activity may be achieved by providing a stimulus to cells
involved in the
inflammatory response, by inhibiting or promoting cell-cell interactions (such
as, for
example, cell adhesion), by inhibiting or promoting chemotaxis of cells
involved in the
inflammatory process, inhibiting or promoting cell extravasation, or by
stimulating or
suppressing production of other factors which more directly inhibit or promote
an
inflammatory response. Proteins exhibiting such activities can be used to
treat
inflammatory conditions including chronic or acute conditions), including
without
limitation inflammation associated with infection (such as septic shock,
sepsis or systemic
inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin
lethality,
arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or
chemokine-
induced lung injury, inflammatory bowel disease, Crohn's disease or resulting
from over
production of 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 Sup~pressor ActivitX
Cadherins are calcium-dependent adhesion molecules that appear to play major
roles during
development, particularly in defining specific cell types. Loss or alteration
of normal cadherin
2 0 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.
The cadherin superfamily includes well over forty members, each with a
distinct pattern of
2 5 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
3 0 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
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CA 02362538 2001-08-16
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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
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 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
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
2 0 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 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
2 5 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
3 0 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.
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CA 02362538 2001-08-16
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Tumor Inhibition Activity
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
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
(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
2 0 fertility of male or female subjects; effecting the metabolism,
catabolism, anabolism,
processing, utilization, storage or elimination of dietary fat, lipid,
protein, carbohydrate,
vitamins, minerals, cofactors or other nutritional factors or component(s);
effecting
behavioral characteristics, including, without limitation, appetite, libido,
stress, cognition
(including cognitive disorders), depression (including depressive disorders)
and violent
2 5 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
3 0 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.
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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
Garner.
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
"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
Garner 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-l, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9,
IL-10, IL-
11, IL-12, IL-13, IL-14, IL-15, IFN, 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, or to minimize side effects. Conversely, protein of the present
invention may
be included in formulations of the particular cytokine, lymphokine, other
hematopoietic
2 0 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.
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
2 5 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
3 0 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. MHC and structurally related
proteins
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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
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
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
sufficient
2 0 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
a
combination, the term refers to combined amounts of the active ingredients
that result in
2 5 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
3 0 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
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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.
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
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 oils
may be added. The liquid form of the pharmaceutical composition may further
contain
2 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.
2 5 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
3 0 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,
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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 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 O.lng
to about 10 mg, more preferably about 0.1 qg 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
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
2 0 range of 12 to 24 hours of continuous intravenous administration.
Ultimately the attending
physician will decide on the appropriate duration of intravenous 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
2 5 term "antibody" includes without limitation a polyclonal antibody, a
monoclonal antibody,
a chimeric antibody, a single-chain antibody, a CDR-grafted 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.
3 0 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,
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CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
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
murine antibodies in accordance with well known methods (see for example, U.S.
Patent
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
using either the entire protein or fragments thereof as an immunogen. The
peptide
2 0 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. 85, 2149-2154 (1963); J.L. Krstenansky, et al., FEBS Lett. 211,
10
( 1987).
2 5 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
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
3 0 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.
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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. 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 matrices
for the compositions may be biodegradable and chemically defined calcium
sulfate,
2 0 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 chemically
defined, such
as sintered hydroxapatite, bioglass, aluminates, or other ceramics. Matrices
may be
2 5 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-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
3 0 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
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CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
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.
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
TGF-~3), and insulin-like growth factor (IGF).
2 0 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 various
2 5 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 the
pharmaceutical
3 0 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
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CA 02362538 2001-08-16
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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
<120> SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
<130> GI 6918X
<140>
<141>
<160> 101
<170> PatentIn Ver. 2.0
<210> 1
<211> 5948
<212> DNA
<213> Homo sapiens
<400> 1
cgactgcgcg ccggcgcgca cacccgagac agagctttac tatctcgctc cctctcgcgc 60
ctccctcctc gctgggcatt caaacagctt tccgacatca ccagccaagg atttttttcc 120
ccgctctcct tagtcgccgt ccgtccatca gtacctgcag gggggaggag gaggagggag 180
gaaagcggaa agaggaaaaa gcataagctt gagccttccg atccgaccac gaatactcct 240
gtaataaacc caccgcccca acaaatctgc catagcagcc gccgccgccg ccggtcactt 300
ctcgtctcag ctctttcttt gcttcttggt ttgttggggg tagcttttat gaaacaaatc 360
tttgctatta agccacttac attttggggg gttccttaga gtctcccttg ggggggcttc 420
tccctccctt tagcccccct cggtttggag gtt,ggattca gttggatacg gcgcaaggtt 480
ctgggctcct gctggctttt ttttcctctc tctcatcgac ccccctttgg ttcccacccc 540
ccaccttttg cttttcgtat gtatgcattt ttaaaaataa atcctgattt tggaagctga 600
gccggggaaa atgggcaacg gtgattggga ccgaagggga gtctctccgt cactgttgct 660
gggacgcgtg cctgtgctgg tgtcttagag caagagcctc cctgagcttt cggagtggaa 720
ggccaaatga cataggatga aggctgttcg taacctgctg atttatatat tttccaccta 780
tctcctggtt atgtttggat ttaatgctgc ccaagacttc tggtgttcaa ctttggtgaa 840
gggagtcatt tatggatcgt attctgtaag tgaaatgttt cctaaaaact ttacaaactg 900
cacttggacg ctggaaaatc cagatccaac caaatatagc atttacctga aattttccaa 960
aaaggacctt agctgctcta acttttcact cctggcttat cagtttgatc atttttccca 1020
tgaaaaaata aaggatcttt taagaaagaa tcattctata atgcaactct gcaattccaa 1080
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aactaatttc ccaggattac agaaaaaagg ggaagaagat cagaaatctt tttttgagtt 1200
tttggtattg aacaaggtca gcccaagcca gtttggttgc catgtattat gtacttggtt 1260
ggagagctgc ttaaaatcag aaaatgggag aacagaatca tgtgggatca tgtatacaaa 1320
atgcacctgc cctcagcatt tgggagagtg ggggatcgac gaccagtcgc tgattttgtt 1380
aaataacgtg gtgttacccc tgaatgagca gacagagggc tgcctgaccc aggagctgca 1440
aaccacccaa gtctgcaatc ttaccaggga ggccaagcga ccacccaaag aagaatttgg 1500
aatgatggga gatcatacaa ttaaaagtca gcgacctcga tctgttcatg aaaaaagggt 1560
ccctcaggaa caagctgatg ctgctaaatt tatggcacaa actggtgaat ctggtgtgga 1620
agagtggtcc cagtggagca catgttcggt tacttgtggt caagggtcgc aggtgcgaac 1680
cagaacttgt gtatcacctt acgggacaca ctgcagcggc ccattaagag aatcaagggt 1740
ttgcaataac actgccctct gtccagtaca cggagtatgg gaggaatggt caccatggag 1800
tttatgttca tttacatgtg gtcgaggcca aagaacaaga acaaggtcat gcacacctcc 1860
tcagtatgga ggaaggccgt gtgaaggacc tgaaacacat cataagcctt gtaatattgc 1920
tctttgccca gttgatggac agtggcaaga gtggagttcg tggagccagt gctcagtaac 1980
gtgctcgaat gggactcagc agagaagccg gcagtgcact gcagctgccc atggaggctc 2040
cgaatgcaga gggccatggg cagaaagcag agagtgctat aaccctgaat gtacagccaa 2100
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CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
tggtcaatgg aatcagtggg gtcattggag tggttgttcc aagtcctgtg atggcggctg 2160
ggaaaggcga ataaggacct gtcagggtgc agtgataaca gggcagcaat gtgaaggaac 2220
gggcgaagaa gtgagaagat gcagtgagca gcgatgccct gcaccttatg aaatatgccc 2280
tgaggattat ctgatgtcga tggtgtggaa aagaactcca gcaggcgact tggcattcaa 2340
tcaatgtccc ctgaatgcca caggcaccac tagcagacgc tgctctctca gtcttcatgg 2400
agtggccttc tgggaacagc cgagctttgc aagatgcata tcaaatgagt acagacactt 2460
gcagcattca attaaagagc accttgctaa ggggcagcga atgctggcag gtgatggaat 2520
gtcccaggtg accaagacac tgttggattt aactcagaga aaaaatttct atgcaggcga 2580
tcttctgatg tctgtggaga tcctgagaaa tgtgacagac acatttaaaa gggcaagtta 2640
catccctgca tctgatggtg tccagaactt ctttcaaata gttagcaacc ttctagatga 2700
agaaaacaag gaaaaatggg aagatgcaca acagatttat ccagggtcaa tagagttaat 2760
gcaggtgatt gaagatttta tacacattgt tggaatgggg atgatggact ttcagaattc 2820
atacttaatg actggaaatg tagtggctag tattcagaag cttcctgcag cctctgttct 2880
aacagacatc aactttccaa tgaaaggacg gaagggaatg gttgactggg caagaaactc 2940
agaagatagg gtagtaattc caaaaagcat tttcactccg gtgtcatcaa aagaattaga 3000
tgaatcatct gtatttgttc ttggcgcagt cctatacaaa aacttagatc taattttgcc 3060
cactttgaga aattatactg tcattaattc caaaatcatc gtggtcacaa taaggcctga 3120
acccaaaaca accgattcgt ttctggagat agaactagct catttggcta atggtacttt 3180
gaatccctat tgtgtattgt gggatgactc caaaacgaac gagtctttgg gaacgtggtc 3240
cacccaggga tgtaaaactg tgcttaccga tgcatcccat acgaaatgct tatgtgatcg 3300
tctctctacc ttcgccattt tggctcagca acctagagaa ataatcatgg aatcctctgg 3.360
cacaccttca gttaccctaa tagtaggcag tggtctttct tgcttggcct tgattaccct 3420
agcagttgtc tatgcagcat tatggaggta catacgctct gagagatcca taatactaat 3480
taacttctgc ctgtctatca tctcatccaa tatcctcata ctggttggac agactcagac 3540
acataataag agtatctgca caaccaccac tgcatttttg cactttttct tcctggcttc 3600
attctgttgg gttttgactg aggcgtggca atcatatatg gctgtaactg gaaaaattag 3660
gacacggctt ataagaaaac gctttttgtg ccttggatgg ggtttaccag cattagtagt 3720
ggccacatca gtaggcttca ccagaacaaa aggatatggc actgatcact actgctggct 3780
ctctcttgaa ggaggactac tctatgcttt tgtgggacct gcagccgctg ttgtcctggt 3840
caacatggtg attggcattt tggtatttaa taaacttgtt tccagagatg gaatcctaga 3900
taaaaagctc aaacacagag ccggtcagat gagtgagcct catagcggtt tgacgctcaa 3960
atgtgccaag tgtggagtag tttcaacaac agctttgtca gccaccaccg ccagtaacgc 4020
catggcgtct ctttggagct cctgtgtggt gttgcccctt ctggctttga cgtggatgtc 4080
tgcggttctg gccatgacag ataaacgctc catattgttt caaatacttt ttgctgtgtt 4140
tgattcattg caaggctttg ttatagtcat ggtccactgc attcttcgga gagaggttca 4200
ggatgcattt agatgccgat tgagaaactg tcaggatccc atcaatgcag attcttcgag 4260
ttcgtttcct aatgggcatg ctcaaatcat gacagacttt gaaaaggatg tagacattgc 4320
ctgtcgatca gttcttcata aggatattgg tccttgccga gcagccacaa taacaggaac 4380
actttctagg atttctctaa atgatgatga agaagaaaag ggaacaaacc ctgaagggct 4440
aagctattca acattgcctg gaaatgtcat ttccaaagtc atcatccagc aacccacagg 4500
tttgcacatg cccatgagta tgaatgagct tagcaatcca tgtttgaaaa aagaaaatag 4560
tgaattgcgg agaactgtgt acttatgtac ggatgataat ttgagagggg ctgacatgga 4620
catagtccat cctcaagaaa gaatgatgga aagtgactat attgtgatgc ccagaagttc 4680
tgtaaataac cagccttcaa tgaaagaaga aagcaaaatg aatattggca tggaaacctt 4740
gccacatgaa aggctattgc actacaaagt aaaccctgaa ttcaatatga atccccctgt 4800
aatggaccag ttcaatatga acttagagca acatctcgca ccccaggaac atatgcagaa 4860
tttgcccttt gaacctcgca cagctgtgaa gaatttcatg gcctctgagt tggatgataa 4920
tgcaggacta tcaagaagtg aaactggatc aacgatatca atgagttctt tagagagaag 4980
aaaatcacga tattcagacc ttgactttga gaaggtcatg catacaagga agaggcatat 5040
ggaactattt caagaactaa atcagaaatt tcaaactttg gacagatttc gggatatacc 5100
aaatacaagc agtatggaaa accccgcacc aaacaagaat ccatgggaca ctttcaaaaa 5160
ccccagtgaa tacccgcatt acaccacaat caatgtctta gacacagagg caaaggatgc 5220
tttggaactg aggccagcag agtgggagaa gtgtctgaat ttgcctctgg atgtgcaaga 5280
gggtgacttt caaacagaag tttaaaaaaa tcaaaatgga ctaaggtaga gacaaaactt 5340
tattgcactg acacttaaga cttgggaagc ctgacatttc tatctggaca gtgtgactat 5400
cttatgtcag gaccttcatg tgccaaacgt cagtggtgtt ttcatatggt aacttctcac 5460
tagtcaggct agtggagaga tgaccaggtg tacagttctg accatcctgt gttgtaagta 5520
cccgtggaat ggatttgtaa ggtaatcttt atagataaac ctcaagcaac gattcatgtt 5580
gtaaccgctt catatggttt agttttcaaa aaacttcacc atgaagcaca atgtatatat 5640
ttatgcagtt tttaaagttt ataacagtct gtttggccat tactacactt tttactttat 5700
2
agagtggtcc cagtggagca catgttcggt tacttgtggt caagggtcgc aggtgcga



CA 02362538 2001-08-16
WO 00/49134 PCT/L1S00/04340


aatataaaagcaaagttt tt tcattaaat ttgttgagctacattcttcattgc5760
g gaatgt


tttaaatgcaataaagtaat atctcactt gaataatatatttcacatctttat5820
a ttatat


tattgcagttttctctagaa gctctgaga ctctgctgcagctgtgtataaaat5880
a agcttt


atttaaaatgttgtatggtg aaataaact tgtctacatatcaaaaaaaaaaaaaaaa5940
t tt


aaaaaaaa 5948


<210> 2


<211> 1522


<212> PRT


<213> HomoSapiens


<400> 2


Met Lys ValArgAsnLeuLeuIleTyrIlePheSerThrTyrLeu
Ala


1 5 10 15


Leu Val PheGlyPheAsnAlaAlaGlnAspPheTrpCysSerThr
Met


20 25 30


Leu Val GlyValIleTyrGlySerTyrSerValSerGluMetPhe
Lys


35 40 45


Pro Lys PheThrAsnCysThrTrpThrLeuGluAsnProAspPro
Asn


50 55 60


Thr Lys SerIleTyrLeuLysPheSerLysLysAspLeuSerCys
Tyr


65 70 75 80


Ser Asn SerLeuLeuAlaTyrGlnPheAspHisPheSerHisGlu
Phe


85 90 95


Lys Ile AspLeuLeuArgLysAsnHisSerIleMetGlnLeuCys
Lys


100 105 110


Asn Ser AsnAlaPheValPheLeuGlnTyrAspLysAsnPheIle
Lys


115 120 125


Gln Ile ArgValPheProThrAsnPheProGlyLeuGlnLysLys
Arg


130 135 140


Gly Glu AspGlnLysSerPhePheGluPheLeuValLeuAsnLys
Glu


145 150 155 160


Val Ser SerGlnPheGlyCysHisValLeuCysThrTrpLeuGlu
Pro


165 170 175


Ser Cys LysSerGluAsnGlyArgThrGluSerCysGlyIleMet
Leu


180 185 190


Tyr Thr CysThrCysProGlnHisLeuGlyGluTrpGlyIleAsp
Lys


195 200 205


Asp Gln LeuIleLeuLeuAsnAsnValValLeuProLeuAsnGlu
Ser


210 215 220


Gln Thr GlyCysLeuThrGlnGluLeuGlnThrThrGlnValCys
Glu


225 230 235 240


Asn Leu ArgGluAlaLysArgProProLysGluGluPheGlyMet
Thr


245 250 255


3



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Met Gly Asp His Thr Ile Lys Ser Gln Arg Pro Arg Ser Val His Glu
260 265 270
Lys Arg Val Pro Gln Glu Gln Ala Asp Ala Ala Lys Phe Met Ala Gln
275 280 285
Thr Gly Glu Ser Gly Val Glu Glu Trp Ser Gln Trp Ser Thr Cys Ser
290 295 300
Val Thr Cys Gly Gln Gly Ser Gln Val Arg Thr Arg Thr Cys Val Ser
305 310 315 320
Pro Tyr Gly Thr His Cys Ser Gly Pro Leu Arg Glu Ser Arg Val Cys
325 330 335
Asn Asn Thr Ala Leu Cys Pro Val His Gly Val Trp Glu Glu Trp Ser
340 345 350
Pro Trp Ser Leu Cys Ser Phe Thr Cys Gly Arg Gly Gln Arg Thr Arg
355 360 365
Thr Arg Ser Cys Thr Pro Pro Gln Tyr Gly Gly Arg Pro Cys Glu Gly
370 375 380
Pro Glu Thr His His Lys Pro Cys Asn Ile Ala Leu Cys Pro Val Asp
385 390 395 400
Gly Gln Trp Gln Glu Trp Ser Ser Trp Ser Gln Cys Ser Val Thr Cys
405 410 415
Ser Asn Gly Thr Gln Gln Arg Ser Arg Gln Cys Thr Ala Ala Ala His
420 425 430
Gly Gly Ser Glu Cys Arg Gly Pro Trp Ala Glu Ser Arg Glu Cys Tyr
435 440 445
Asn Pro Glu Cys Thr Ala Asn Gly Gln Trp Asn Gln Trp Gly His Trp
450 455 460
Ser Gly Cys Ser Lys Ser Cys Asp Gly Gly Trp Glu Arg Arg Ile Arg
465 470 475 480
Thr Cys Gln Gly Ala Val Ile Thr Gly Gln Gln Cys Glu Gly Thr Gly
485 490 495
Glu Glu Val Arg Arg Cys Ser Glu Gln Arg Cys Pro Ala Pro Tyr Glu
500 505 510
Ile Cys Pro Glu Asp Tyr Leu Met Ser Met Val Trp Lys Arg Thr Pro
515 520 525
Ala Gly Asp Leu Ala Phe Asn Gln Cys Pro Leu Asn Ala Thr Gly Thr
530 535 540
Thr Ser Arg Arg Cys Ser Leu Ser Leu His Gly Val Ala Phe Trp Glu
545 550 555 560
Gln Pro Ser Phe Ala Arg Cys Ile Ser Asn Glu Tyr Arg His Leu Gln
565 570 575
4



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
His Ser Ile Lys Glu His Leu Ala Lys Gly Gln Arg Met Leu Ala Gly
580 585 590
Asp Gly Met Ser Gln Val Thr Lys Thr Leu Leu Asp Leu Thr Gln Arg
595 600 605
Lys Asn Phe Tyr Ala Gly Asp Leu Leu Met Ser Val Glu Ile Leu Arg
610 615 620
Asn Val Thr Asp Thr Phe Lys Arg Ala Ser Tyr Ile Pro Ala Ser Asp
625 630 635 640
Gly Val Gln Asn Phe Phe Gln Ile Val Ser Asn Leu Leu Asp Glu Glu
645 650 655
Asn Lys Glu Lys Trp Glu Asp Ala Gln Gln Ile Tyr Pro Gly Ser Ile
660 665 670
Glu Leu Met Gln Val Ile Glu Asp Phe Ile His Ile Val Gly Met Gly
675 680 685
Met Met Asp Phe Gln Asn Ser Tyr Leu Met Thr Gly Asn Val Val Ala
690 695 700
Ser Ile Gln Lys Leu Pro Ala Ala Ser Val Leu Thr Asp Ile Asn Phe
705 710 715 720
Pro Met Lys Gly Arg Lys Gly Met Val Asp Trp Ala Arg Asn Ser Glu
725 730 735
Asp Arg Val Val Ile Pro Lys Ser Ile Phe Thr Pro Val Ser Ser Lys
740 745 750
Glu Leu Asp Glu Ser Ser Val Phe Val Leu Gly Ala Val Leu Tyr Lys
755 760 765
Asn Leu Asp Leu Ile Leu Pro Thr Leu Arg Asn Tyr Thr Val Ile Asn
770 775 780
Ser Lys Ile Ile Val Val Thr Ile Arg Pro Glu Pro Lys Thr Thr Asp
785 790 795 800
Ser Phe Leu Glu Ile Glu Leu Ala His Leu Ala Asn Gly Thr Leu Asn
805 810 815
Pro Tyr Cys Val Leu Trp Asp Asp Ser Lys Thr Asn Glu Ser Leu Gly
820 825 830
Thr Trp Ser Thr Gln Gly Cys Lys Thr Val Leu Thr Asp Ala Ser His
835 840 845
Thr Lys Cys Leu Cys Asp Arg Leu Ser Thr Phe Ala Ile Leu Ala Gln
850 855 860
Gln Pro Arg Glu Ile Ile Met Glu Ser Ser Gly Thr Pro Ser Val Thr
865 870 875 880
Leu Ile Val Gly Ser Gly Leu Ser Cys Leu Ala Leu Ile Thr Leu Ala
885 890 895



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Val Val Tyr Ala Ala Leu Trp Arg Tyr Ile Arg Ser Glu Arg Ser Ile
900 905 910
Ile Leu Ile Asn Phe Cys Leu Ser Ile Ile Ser Ser Asn Ile Leu Ile
915 920 925
Leu Val Gly Gln Thr Gln Thr His Asn Lys Ser Ile Cys Thr Thr Thr
930 935 940
Thr Ala Phe Leu His Phe Phe Phe Leu Ala Ser Phe Cys Trp Val Leu
945 950 955 960
Thr Glu Ala Trp Gln Ser Tyr Met Ala Val Thr Gly Lys Ile Arg Thr
965 970 975
Arg Leu Ile Arg Lys Arg Phe Leu Cys Leu Gly Trp Gly Leu Pro Ala
980 985 990
Leu Val Val Ala Thr Ser Val Gly Phe Thr Arg Thr Lys Gly Tyr Gly
995 1000 1005
Thr Asp His Tyr Cys Trp Leu Ser Leu Glu Gly Gly Leu Leu Tyr Ala
1010 1015 1020
Phe Val Gly Pro Ala Ala Ala Val Val Leu Val Asn Met Val Ile Gly
1025 1030 1035 1040
Ile Leu Val Phe Asn Lys Leu Val Ser Arg Asp Gly Ile Leu Asp Lys
1045 1050 1055
Lys Leu Lys His Arg Ala Gly Gln Met Ser Glu Pro His Ser Gly Leu
1060 1065 1070
Thr Leu Lys Cys Ala Lys Cys Gly Val Val Ser Thr Thr Ala Leu Ser
1075 1080 1085
Ala Thr Thr Ala Ser Asn Ala Met Ala Ser Leu Trp Ser Ser Cys Val
1090 1095 1100
Val Leu Pro Leu Leu Ala Leu Thr Trp Met Ser Ala Val Leu Ala Met
1105 1110 1115 1120
Thr Asp Lys Arg Ser Ile Leu Phe Gln Ile Leu Phe Ala Val Phe Asp
1125 1130 1135
Ser Leu Gln Gly Phe Val Ile Val Met Val His Cys Ile Leu Arg Arg
1140 1145 1150
Glu Val Gln Asp Ala Phe Arg Cys Arg Leu Arg Asn Cys Gln Asp Pro
1155 1160 1165
Ile Asn Ala Asp Ser Ser Ser Ser Phe Pro Asn Gly His Ala Gln Ile
1170 1175 1180
Met Thr Asp Phe Glu Lys Asp Val Asp Ile Ala Cys Arg Ser Val Leu
1185 1190 1195 1200
His Lys Asp Ile Gly Pro Cys Arg Ala Ala Thr Ile Thr Gly Thr Leu
1205 1210 1215
6



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Ser Arg Ile Ser Leu Asn Asp Asp Glu Glu Glu Lys Gly Thr Asn Pro
1220 1225 1230
Glu Gly Leu Ser Tyr Ser Thr Leu Pro Gly Asn Val Ile Ser Lys Val
1235 1240 1245
Ile Ile Gln Gln Pro Thr Gly Leu His Met Pro Met Ser Met Asn Glu
1250 1255 1260
Leu Ser Asn Pro Cys Leu Lys Lys Glu Asn Ser Glu Leu Arg Arg Thr
1265 1270 1275 1280
Val Tyr Leu Cys Thr Asp Asp Asn Leu Arg Gly Ala Asp Met Asp Ile
1285 1290 1295
Val His Pro Gln Glu Arg Met Met Glu Ser Asp Tyr Ile Val Met Pro
1300 1305 1310
Arg Ser Ser Val Asn Asn Gln Pro Ser Met Lys Glu Glu Ser Lys Met
1315 1320 1325
Asn Ile Gly Met Glu Thr Leu Pro His Glu Arg Leu Leu His Tyr Lys
1330 1335 1340
Val Asn Pro Glu Phe Asn Met Asn Pro Pro Val Met Asp Gln Phe Asn
1345 1350 1355 1360
Met Asn Leu Glu Gln His Leu Ala Pro Gln Glu His Met Gln Asn Leu
1365 1370 1375
Pro Phe Glu Pro Arg Thr Ala Val Lys Asn Phe Met Ala Ser Glu Leu
1380 1385 1390
Asp Asp Asn Ala Gly Leu Ser Arg Ser Glu Thr Gly Ser Thr Ile Ser
1395 1400 1405
Met Ser Ser Leu Glu Arg Arg Lys Ser Arg Tyr Ser Asp Leu Asp Phe
1410 1415 1420
Glu Lys Val Met His Thr Arg Lys Arg His Met Glu Leu Phe Gln Glu
1425 1430 1435 1440
Leu Asn Gln Lys Phe Gln Thr Leu Asp Arg Phe Arg Asp Ile Pro Asn
1445 1450 1455
Thr Ser Ser Met Glu Asn Pro Ala Pro Asn Lys Asn Pro Trp Asp Thr
1460 1465 1470
Phe Lys Asn Pro Ser Glu Tyr Pro His Tyr Thr Thr Ile Asn Val Leu
1475 1480 1485
Asp Thr Glu Ala Lys Asp Ala Leu Glu Leu Arg Pro Ala Glu Trp Glu
1490 1495 1500
Lys Cys Leu Asn Leu Pro Leu Asp Val Gln Glu Gly Asp Phe Gln Thr
1505 1510 1515 1520
Glu Val
7



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 3
<211> 1955
<212> DNA
<213> Homo Sapiens
<400> 3
gattgtgcag caggcgggcc cccgcgcggc agggccctgg acccgcgcgg ctcccgggga 60
tggtgagcaa ggcgctgctg cgcctcgtgt ctgccgtcaa ccgcaggagg atgaagctgc 120
tgctgggcat cgccttgctg gcctacgtcg cctctgtttg gggcaacttc gttaatatga 180
ggtctatcca ggaaaatggt gaactaaaaa ttgaaagcaa gattgaagag atggttgaac 240
cactaagaga gaaaatcaga gatttagaaa aaagctttac ccagaaatac ccaccagtaa 300
agtttttatc agaaaaggat cggaaaagaa ttttgataac aggaggcgca gggttcgtgg 360
gctcccatct aactgacaaa ctcatgatgg acggccacga ggtgaccgtg gtggacaatt 420
tcttcacggg caggaagaga aacgtggagc actggatcgg acatgagaac ttcgagttga 480
ttaaccacga cgtggtggag cccctctaca tcgaggttga ccagatatac catctggcat 540
ctccagcctc ccctccaaac tacatgtata atcctatcaa gacattaaag accaatacga 600
ttgggacatt aaacatgttg gggctggcaa aacgagtcgg tgcccgtctg ctcctggcct 660
ccacatcgga ggtgtatgga gatcctgaag tccaccctca aagtgaggat tactggggcc 720
acgtgaatcc aataggacct cgggcctgct acgatgaagg caaacgtgtt gcagagacca 780
tgtgctatgc ctacatgaag caggaaggcg tggaagtgcg agtggccaga atcttcaaca 840
cctttgggcc acgcatgcac atgaacgatg ggcgagtagt cagcaacttc atcctgcagg 900
cgctccaggg ggagccactc acggtatacg gatccgggtc tcagacaagg gcgttccagt 960
acgtcagcga tctagtgaat ggcctcgtgg ctctcatgaa cagcaacgtc agcagcccgg 1020
tcaacctggg gaacccagaa gaacacacaa tcctagaatt tgctcagtta attaaaaacc 1080
ttgttggtcc cgctggagga aggtttaaac aaagcaattc actacttccg taaagaactc 1140
gagtaccagg caaataatca gtacatcccc aaaccaaagc ctgccagaat aaagaaagga 1200
cggactcgcc acagctgaac tcctcacttt taggacacaa gactaccatt gtacacttga 1260
tgggatgtat ttttggcttt tttttgttgt cgtttaaaga aagactttaa caggtgtcat 1320
gaagaacaaa ctggaatttc attctgaagc ttgctttaat gaaatggatg tgcctaaaag 1380
ctcccctcaa aaaactgcag attttgcctt gcactttttg aatctctctt tttatgtaaa 1440
atagcgtaga tgcatctctg cgtattttca agttttttta tcttgctgtg agagcatatg 1500
ttgtgactgt cgttgacagt tttatttact ggtttctttg tgaagctgaa aaggaacatt 1560
aagcgggaca aaaaatgccg attttattta taaaagtggg tacttaataa atgagtcgtt 1620
atactatgca taaagaaaaa tcctagcagt attgtcaggt ggtggtgcgc cggcattgat 1680
tttagggcag ataaaagaat tctgtgtgag agctttatgt ttctctttta attcagagtt 1740
tttccaaggt ctacttttga gttgcaaact tgactttgaa atattcctgt tggtcatgat 1800
caaggatatt tgaaatcact actgtgtttt gctgcgtatc tggggcgggg gcaggttggg 1860
gggcacaaag ttaacatatt cttggttaac catggttaaa tatgctattt taataaaata 1920
ttgaaactca ccaaaaaaaa aaaaaaaaaa aaaaa 1955
<210> 4
<211> 357
<212> PRT
<213> Homo sapiens
<400> 4
Met Val Ser Lys Ala Leu Leu Arg Leu Val Ser Ala Val Asn Arg Arg
1 5 10 15
Arg Met Lys Leu Leu Leu Gly Ile Ala Leu Leu Ala Tyr Val Ala Ser
20 25 30
Val Trp Gly Asn Phe Val Asn Met Arg Ser Ile Gln Glu Asn Gly Glu
35 40 45
Leu Lys Ile Glu Ser Lys Ile Glu Glu Met Val Glu Pro Leu Arg Glu
50 55 60
Lys Ile Arg Asp Leu Glu Lys Ser Phe Thr Gln Lys Tyr Pro Pro Val
g



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
65 70 75 80
Lys Phe Leu Ser Glu Lys Asp Arg Lys Arg Ile Leu Ile Thr Gly Gly
85 90 95
Ala Gly Phe Val Gly Ser His Leu Thr Asp Lys Leu Met Met Asp Gly
100 105 110
His Glu Val Thr Val Val Asp Asn Phe Phe Thr Gly Arg Lys Arg Asn
115 120 125
Val Glu His Trp Ile Gly His Glu Asn Phe Glu Leu Ile Asn His Asp
130 135 140
Val Val Glu Pro Leu Tyr Ile Glu Val Asp Gln Ile Tyr His Leu Ala
145 150 155 160
Ser Pro Ala Ser Pro Pro Asn Tyr Met Tyr Asn Pro Ile Lys Thr Leu
165 170 175
Lys Thr Asn Thr Ile Gly Thr Leu Asn Met Leu Gly Leu Ala Lys Arg
180 185 190
Val Gly Ala Arg Leu Leu Leu Ala Ser Thr Ser Glu Val Tyr Gly Asp
195 200 205
Pro Glu Val His Pro Gln Ser Glu Asp Tyr Trp Gly His Val Asn Pro
210 215 220
Ile Gly Pro Arg Ala Cys Tyr Asp Glu Gly Lys Arg Val Ala Glu Thr
225 230 235 240
Met Cys Tyr Ala Tyr Met Lys Gln Glu Gly Val Glu Val Arg Val Ala
245 250 255
Arg Ile Phe Asn Thr Phe Gly Pro Arg Met His Met Asn Asp Gly Arg
260 265 270
Val Val Ser Asn Phe Ile Leu Gln Ala Leu Gln Gly Glu Pro Leu Thr
275 280 285
Val Tyr Gly Ser Gly Ser Gln Thr Arg Ala Phe Gln Tyr Val Ser Asp
290 295 300
Leu Val Asn Gly Leu Val Ala Leu Met Asn Ser Asn Val Ser Ser Pro
305 310 315 320
Val Asn Leu Gly Asn Pro Glu Glu His Thr Ile Leu Glu Phe Ala Gln
325 330 335
Leu Ile Lys Asn Leu Val Gly Pro Ala Gly Gly Arg Phe Lys Gln Ser
340 345 350
Asn Ser Leu Leu Pro
355
<210> 5
<211> 1874
<212> DNA
9



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<213> Homo sapiens
<400> 5
aaattctcca tgaagtgtac tatgttccat cattccttcc caaagccacc ggaagcattc 60
cttctaggaa aggtggagtc ggtagtgaga agccggaggt gagaagaccc ctaagcggat 120
ggattcattc attttctgaa tttcctatgt gaggacagta ttagagccca gtgaggcttt 180
gagaggcccc aaagatgagc gccaacagca gcagagtggg ccagcttctc ttgcagggtt 240
cagcgtgcat taggtggaag caggatgtgg aaggggctat ctaccaccta gccaactgcc 300
tcttactcct gggcttcatg gggggcagtg gggtgtatgg atgcttctat ctttttggct 360
tcctgagtgc aggttacctg tgctgcgtgc tgtggggctg gttcagtgcc tgtggcctgg 420
acattgttct ttggagcttc ctgctggctg tggtctgcct gctccagctg gcacacctgg 480
tataccgcct gcgtgaggac accctccctg aggagtttga cctcctctac aagacgctgt 540
gcctgccctt gcaggtgccc ctacagacat acaaggagat tgttcactgc tgtgaggagc 600
aggtcttaac tctggccact gaacagacct atgctgtgga gggtgagaca cccatcaacc 660
gcctgtccct gctgctctct ggccgggttc gtgtgagcca ggatgggcag tttctgcact 720
acatctttcc ataccagttc atggactctc ctgagtggga atcactacag ccttctgagg 780
agggggtgtt ccaggtcact ctgactgctg agacctcatg tagctacatt tcctggcccc 840
ggaaaagtct ccatcttctt ctgaccaaag agcgatacat ctcctgcctc ttctcggctc 900
tgctgggata tgacatctcg gagaagctct acactctcaa tgacaagctc tttgctaagt 960
ttgggctgcg ctttgacatc cgccttccca gcctctacca tgtcctgggt cccactgctg 1020
cagatgctgg accagagtcc gagaagggtg atgaggaagt ctgtgagcca gctgtgtccc 1080
ctcctcaggc cacacccacc tctctccagc aaacaccccc ttgttctacc cctccagcta 1140
ccaccaactt tcctgcacct cctacccggg ccaggttgtc caggccagac agtggcatac 1200
tgggtgagga ctccaccagt ctggtgctgg aggattttga ggaggtgtca ggatcagaat 1260
cgtttatgga ttataggagt gatggggagt acatgaggtg aagggagaac taacatgggc 1320
acagccaccg gctcaggatc ctatcttcta gaattcctct ccagagctac tctcaagtta 1380
tatccagggg acaggcccct ttggctccaa cccacacgcc tgaactttaa ggatcattgg 1440
actatcttct ctgtggccag cgcagctctc ttctgtgttc acagaatggc cactgatagg 1500
cacgcctctt ttcccaccca ctggaaggct cacaggcaag gtgagagagg acacagaagg 1560
tgccaacact gtcgctacag taaggacctg aagtgacttt gagaaattca ccctcacaaa 1620
ccttccttca ggagcaggca ttggtagtgc agaggcacag attccgtcct ttaccagctg 1680
cagaatcttg ggcaagttac atagcctctg tgagcctcat cggtaaacag tgggggttat 1740
gaaacccacc tcacagggtt gttgtgagga tccaatgagt tgatttaggt aagcacctag 1800
cacatgccat ggcaccaagt aagcactcaa taaatcactc aactccttta aaaaaaaaaa 1860
aaaaaaaaaa aaaa 1874
<210> 6
<211> 368
<212> PRT
<213> Homo Sapiens
<400> 6
Met Ser Ala Asn Ser Ser Arg Val Gly Gln Leu Leu Leu Gln Gly Ser
1 5 10 15
Ala Cys Ile Arg Trp Lys Gln Asp Val Glu Gly Ala Ile Tyr His Leu
20 25 30
Ala Asn Cys Leu Leu Leu Leu Gly Phe Met Gly Gly Ser Gly Val Tyr
35 40 45
Gly Cys Phe Tyr Leu Phe Gly Phe Leu Ser Ala Gly Tyr Leu Cys Cys
50 55 60
Val Leu Trp Gly Trp Phe Ser Ala Cys Gly Leu Asp Ile Val Leu Trp
65 70 75 80
Ser Phe Leu Leu Ala Val Val Cys Leu Leu Gln Leu Ala His Leu Val
85 90 95



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Tyr Arg Leu Arg Glu Asp Thr Leu Pro Glu Glu Phe Asp Leu Leu Tyr
.. ._~_ --..100 105 110
Lys Thr Leu Cys Leu Pro Leu Gln Val Pro Leu Gln Thr Tyr Lys Glu
115 120 125
Ile Val His Cys Cys Glu Glu Gln Val Leu Thr Leu Ala Thr Glu Gln
130 135 140
Thr Tyr Ala Val Glu Gly Glu Thr Pro Ile Asn Arg Leu Ser Leu Leu
145 150 155 160
Leu Ser Gly Arg Val Arg Val Ser Gln Asp Gly Gln Phe Leu His Tyr
165 170 175
Ile Phe Pro Tyr Gln Phe Met Asp Ser Pro Glu Trp Glu Ser Leu Gln
180 185 190
Pro Ser Glu Glu Gly Val Phe Gln Val Thr Leu Thr Ala Glu Thr Ser
195 200 205
Cys Ser Tyr Ile Ser Trp Pro Arg Lys Ser Leu His Leu Leu Leu Thr
210 215 220
Lys Glu Arg Tyr Ile Ser Cys Leu Phe Ser Ala Leu Leu Gly Tyr Asp
225 230 235 240
Ile Ser Glu Lys Leu Tyr Thr Leu Asn Asp Lys Leu Phe Ala Lys Phe
245 250 255
Gly Leu Arg Phe Asp Ile Arg Leu Pro Ser Leu Tyr His Val Leu Gly
260 265 270
Pro Thr Ala Ala Asp Ala Gly Pro Glu Ser Glu Lys Gly Asp Glu Glu
275 280 285
Val Cys Glu Pro Ala Val Ser Pro Pro Gln Ala Thr Pro Thr Ser Leu
290 295 300
Gln Gln Thr Pro Pro Cys Ser Thr Pro Pro Ala Thr Thr Asn Phe Pro
305 310 315 320
Ala Pro Pro Thr Arg Ala Arg Leu Ser Arg Pro Asp Ser Gly Ile Leu
325 330 335
Gly Glu Asp Ser Thr Ser Leu Val Leu Glu Asp Phe Glu Glu Val Ser
340 345 350
Gly Ser Glu Ser Phe Met Asp Tyr Arg Ser Asp Gly Glu Tyr Met Arg
355 360 365
<210> 7
<211> 782
<212> DNA
<213> Homo Sapiens
<400> 7
aggagctcta gcatcgcgac ccgccccgtc ccgtccagtc tggcctgggc gccgcgggaa 60
cgctgtccta gctgccgcca cccgaacagc ctgtcctggt gccccggctc cctgccccgc 120
11



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
gcccagtcat gaccctgcgc ccctcactcc tcccgctcca tctgctgctg ctgctgctgc 180
tcagtgcggc ggtgtgccgg gctgaggctg ggctcgaaac cgaaagtccc gtccggaccc 240
tccaagtgga gaccctggtg gagcccccag aaccatgtgc cgagcccgct gcttttggag 300
acacgcttca catacactac acgggaagct tggtagatgg acgtattatt gacacctccc 360
tgaccagaga ccctctggtt atagaacttg gccaaaagca ggtgattcca ggtctggagc 420
agagtcttct cgacatgtgt gtgggagaga agcgaagggc aatcattcct tctcacttgg 480
cctatggaaa acggggattt ccaccatctg tcccagcgga tgcagtggtg cagtatgacg 540
tggagctgat tgcactaatc cgagccaact actggctaaa gctggtgaag ggcattttgc 600
ctctggtagg gatggccatg gtgccagccc tcctgggcct cattgggtat cacctataca 660
gaaaggccaa tagacccaaa gtctccaaaa agaagctcaa ggaagagaaa cgaaacaaga 720
gcaaaaagaa ataataaata ataaatttta aaaaacttaa aaaaaaaaaa aaaaaaaaaa 780
as 782
<210> 8
<211> 201
<212> PRT
<213> Homo sapiens
<400> 8
Met Thr Leu Arg Pro Ser Leu Leu Pro Leu His Leu Leu Leu Leu Leu
1 5 10 15
Leu Leu Ser Ala Ala Val Cys Arg Ala Glu Ala Gly Leu Glu Thr Glu
20 25 30
Ser Pro Val Arg Thr Leu Gln Val Glu Thr Leu Val Glu Pro Pro Glu
35 40 45
Pro Cys Ala Glu Pro Ala Ala Phe Gly Asp Thr Leu His Ile His Tyr
50 55 60
Thr Gly Ser Leu Val Asp Gly Arg Ile Ile Asp Thr Ser Leu Thr Arg
65 70 75 80
Asp Pro Leu Val Ile Glu Leu Gly Gln Lys Gln Val Ile Pro Gly Leu
85 90 95
Glu Gln Ser Leu Leu Asp Met Cys Val Gly Glu Lys Arg Arg Ala Ile
100 105 110
Ile Pro Ser His Leu Ala Tyr Gly Lys Arg Gly Phe Pro Pro Ser Val
115 120 125
Pro Ala Asp Ala Val Val Gln Tyr Asp Val Glu Leu Ile Ala Leu Ile
130 135 140
Arg Ala Asn Tyr Trp Leu Lys Leu Val Lys Gly Ile Leu Pro Leu Val
145 150 155 160
Gly Met Ala Met Val Pro Ala Leu Leu Gly Leu Ile Gly Tyr His Leu
165 170 175
Tyr Arg Lys Ala Asn Arg Pro Lys Val Ser Lys Lys Lys Leu Lys Glu
180 185 190
Glu Lys Arg Asn Lys Ser Lys Lys Lys
195 200
<210> 9
12



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<211> 1700
<212> DNA
<213> Homo Sapiens
<400> 9
gctggtcagc caagggctag aggccctacg cagtgaacac caggccgtgc tgcaaagcct 60
gtcccagacc attgagtgtc tgcagcaggg aggccatgag gaagggctgg tgcatgagaa 120
ggcccggcag cttcgccgtt ctatggaaaa cattgagctc gggctgagtg aggcccaggt 180
gatgctggct ctagccagcc acctgagcac agtggagtcg gagaaacaga agctgcgggc 240
tcaggtgcgg cggctatgcc aggagaacca gtggctgcgg gatgagctgg ctggcaccca 300
gcagcggcta cagcgcagtg aacaggctgt ggctcagctg gaggaggaaa agaagcacct 360
ggagttcctg gggcagctgc ggcagtatga tgaggatgga catacctcgg aggagaaaga 420
aggcgatgcc accaaggatt ccctggatga cctctttcct aatgaggagg aagaggaccc 480
agcaatggct tgtcccgtgg tcaaggtgct acagcagctc agcagggtgg atatgagatc 540
ccagcaaggt tgcggacgtt gcacaacctg gtgatccagt acgcagccca aggtcgctat 600
gaggtggccg tgccactctg taagcaggca ctagaggacc tggagcgcac atcaggccgt 660
ggccaccctg atgtcgccac catgctcaac atccttgctt tggtgtatcg tgaccagaat 720
aagtataagg aagctgccca cctgctgaat gatgccctta gcatccggga gagcaccttg 780
ggacctgacc atcctgctgt ggctgccaca ctcaacaatt tggctgtgct ctatggcaaa 840
aggggcaagt acaaggaggc agagcctctg tgccagcggg cactggagat tcgagaaagg 900
tcctgggcac gaatcatcca gatgtggcaa aacagctgaa caacctggcc ctcttgtgcc 960
aaaaccaggg caagtatgag gccgtggaac gctactacca gcgagcactg gccatctacg 1020
aggggcagct ggggccggac aaccctaatg tagcccggac caagaacaac ctggcttcct 1080
gttacctgaa acagggcaaa tatgctgagg ctgagacact atacaaagag atcctgaccc 1140
gtgcccatgt acaggagttt gggtctgtgg atgatgacca caagcccatc tggatgcatg 1200
cagaggagcg ggaggaaatg agcaaaagcc ggcaccatga gggtgggaca ccctatgctg 1260
agtatggagg ctgggtcccc ccacccccac agccctcaca gcattcccca ttgctcctgg 1320
ctcttcccca cccctaggtg ggacagtgaa ggggagcagt ttaaccagaa gattgctgct 1380
gcccttaggg tctcagctcc ctcctcagga atcctcttag gaaggtgtct taggacaccc 1440
tctctgcacc ctgtggtcct ctagagtagc tagctctgag gccccaaggt gggtacaaag 1500
caggtatggc cctcagagat gcagcctgct gctggctttt cagtcagagg gttgggggct 1560
ggccagccaa gctgccttgc cctggccgct cttactccct ccctctgctg tctcacttca 1620
ggtccatgta tttcactttt cttaaataaa agaatcaggt aaaaaaaaaa aaaaaaaaaa 1680
aaaaaaaaaa aaaaaaaaaa 1700
<210> 10
<211> 143
<212> PRT
<213> Homo Sapiens
<400> 10
Met Glu Asn Ile Glu Leu Gly Leu Ser Glu Ala Gln Val Met Leu Ala
1 5 10 15
Leu Ala Ser His Leu Ser Thr Val Glu Ser Glu Lys Gln Lys Leu Arg
20 25 30
Ala Gln Val Arg Arg Leu Cys Gln Glu Asn Gln Trp Leu Arg Asp Glu
35 40 45
Leu Ala Gly Thr Gln Gln Arg Leu Gln Arg Ser Glu Gln Ala Val Ala
50 55 60
Gln Leu Glu Glu Glu Lys Lys His Leu Glu Phe Leu Gly Gln Leu Arg
65 70 75 80
Gln Tyr Asp Glu Asp Gly His Thr Ser Glu Glu Lys Glu Gly Asp Ala
85 90 95
Thr Lys Asp Ser Leu Asp Asp Leu Phe Pro Asn Glu Glu Glu Glu Asp
13



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
100 105 110
Pro Ala Met Ala Cys Pro Val Val Lys Val Leu Gln Gln Leu Ser Arg
115 120 125
Val Asp Met Arg Ser Gln Gln Gly Cys Gly Arg Cys Thr Thr Trp
130 135 140
<210> 11
<211> 781
<212> DNA
<213> Homo Sapiens
<400> 11
tcatcactgc cgtggcccac ccaggagcca agtctgtgcc ccccaagcca gcaaacacag 60
ctgcagcccg ggccatcttc ccaccagctt ctcaccgctc ccccatcagc catgaaggct 120
ccctgtcctc agctgccatg tcccccagct tctcaccctc tctgtctcct ctggctgctc 180
gctcacccgt tgtctcacca tttggggtgg cccagggtcc ctcagcctca gcactcagcg 240
cagagtctgg cctggagcca cctgatgaca cggagctgca catctagctg tggcccaggc 300
tgggccccga cctgggatgc gcacagtgtc cccaacgcag gccccactct gagcctgccc 360
tgggcagcct cggactatga ctggctacgg ggaggccacc accaggcccc agctctccac 420
cctgaactcc ccagccccct cagagtacta ggaccacaga agccctgttg ctcactgacc 480
tgtgaccagg tccaatgtgg ggagaaatat gaaggaggta gcagccctgg gttctcctca 540
gtgagggatc cctgccctgc accagcaccc tgagatggag ctgagacttt atttattggg 600
ggtaggggga tggaggaggt ccctccaaca tgtttggacc cagctccttt gggttccact 660
gacacccctg cccctgcccc tgcccagaac caagtgccat ttctcactct ggagccttaa 720
taaactgcaa tttgtatcca gtcaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 780
a 781
<210> 12
<211> 153
<212> PRT
<213> Homo Sapiens
<400> 12
Met Lys Ala Pro Cys Pro Gln Leu Pro Cys Pro Pro Ala Ser His Pro
1 5 10 15
Leu Cys Leu Leu Trp Leu Leu Ala His Pro Leu Ser His His Leu Gly
20 25 30
Trp Pro Arg Val Pro Gln Pro Gln His Ser Ala Gln Ser Leu Ala Trp
35 40 45
Ser His Leu Met Thr Arg Ser Cys Thr Ser Ser Cys Gly Pro Gly Trp
50 55 60
Ala Pro Thr Trp Asp Ala His Ser Val Pro Asn Ala Gly Pro Thr Leu
65 70 75 80
Ser Leu Pro Trp Ala Ala Ser Asp Tyr Asp Trp Leu Arg Gly Gly His
85 90 95
His Gln Ala Pro Ala Leu His Pro Glu Leu Pro Ser Pro Leu Arg Val
100 105 110
Leu Gly Pro Gln Lys Pro Cys Cys Ser Leu Thr Cys Asp Gln Val Gln
115 120 125
14



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Cys Gly Glu Lys Tyr Glu Gly Gly Ser Ser Pro Gly Phe Ser Ser Val
130 135 140
Arg Asp Pro Cys Pro Ala Pro Ala Pro
145 150
<210> 13
<211> 1605
<212> DNA
<213> Homo Sapiens
<400> 13
ttcatgagag tcacaattcc cttctacaag acttgtctcc aactgaagag gaagagccag 60
agcatccttt tggggtgggc ggtgtggaca gcgtgtctga gagcactggc agcatcctca 120
gcaagctgga ctggaatgcc atcgaagaca tggtggccag cgtggaggac cagggcctgt 180
ctgtccactg ggccctggac ctgtaagacc tggatatcat tgggtttcca tgcacaggcc 240
agcacctcag taatgtggtt ctgaaagatt aacaggttta agggacagaa gcaatgaaag 300
aagcaatgtg aattttccat ttgctttcat attattacct ggattagcca ttaccagagg 360
aaaaataaac atttctcagt aactttgcct ttatggggaa agggttgact attgatgtat 420
tatatgtttt tgtatttgat gcatcattag gcataatttt taaaatgata agtacctttc 480
aagccaagtt tgcataacct actttcaata aaaaccctct atcttgcctc ctcctttatt 540
accctctgag ttttgagaaa caaccatata cagatgaatc taataggaaa aaaaaaatct 600
tttcattgag aagaaaatca gtctcacctg agaactcaat tatgaaccct attttaaaac 660
acctatgcag ggtttagcct aggagtgaaa agaaaaacca actacctttt accaaccctg 720
aatctctaaa taagcaaagt ttcatggagg ccaggagatc ttctgtcttc tgccctgtag 780
cctgaagcct tggaggaaga aacaggaatg gatgctttgg gcaggaaagt aagggaatat 840
gactccggcc tctagaaggc tcatcttaaa tttgtaagaa ccatggtaca gagacctgat 900
tagtttttgg tattgtgctc caataatgtc atagttttaa gagataattt ttatgagaat 960
tgactaagaa ccagtatcct tcaactactt catcaatgtt tggtataata taaaagcaca 1020
ctatcatctg aaaaagctat taaatacccc tctttttcca aatatctacc tgtgtgaagc 1080
caggttttac aacatgtatt gcagcaagtt gaatgcagaa gcaggtatgg taattcagct 1140
gccttctatc aagctaaaca ttaaagagat ttgtagaact ataaaacaat gctactctcc 1200
ttaccaaatt gttttagaaa atagctttat aggctaacat tattgttaat tgtcatttaa 1260
ttgttttgtc atttaaaata ttttaaattg ttttctgtta gtttcttttt tgtatattct 1320
atgggtattt tattgataca tgatagttgt acatttttat ggggtgcatg tgatattttg 1380
atatgtgcat acaatgtgta gcaatcaaat cagggtaatt gggatattca tcacctcaaa 1440
catttatcat ttatttgtgt tggaaacatt caaacctttt cttctagcta tttatccatt 1500
gttggatact tatatcaatt ctatatctta gctgttgtga atagagctgc aataaatgta 1560
ggagtgcaga taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 1605
<210> 14
<211> 86
<212> PRT
<213> Homo Sapiens
<400> 14
Met Arg Val Thr Ile Pro Phe Tyr Lys Thr Cys Leu Gln Leu Lys Arg
1 5 10 15
Lys Ser Gln Ser Ile Leu Leu Gly Trp Ala Val Trp Thr Ala Cys Leu
20 25 30
Arg Ala Leu Ala Ala Ser Ser Ala Ser Trp Thr Gly Met Pro Ser Lys
35 40 45
Thr Trp Trp Pro Ala Trp Arg Thr Arg Ala Cys Leu Ser Thr Gly Pro
50 55 60
Trp Thr Cys Lys Thr Trp Ile Ser Leu Gly Phe His Ala Gln Ala Ser
IS



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
65 70 75 80
Thr Ser Val Met Trp Phe
<210> 15
<211> 2607
<212> DNA
<213> Homo sapiens
<400> 15
attgtgcggc gctggtcccc tcagagggtt cctgctgctg ccggtgcctt ggaccctccc 60
cctcgcttct cgttctactg ccccaggagc ccggcgggtc cgggactccc gtccgtgccg 120
gtgcgggcgc cggcatgtgg ctgtgggagg accagggcgg cctcctgggc cctttctcct 180
tcctgctgct agtgctgctg ctggtgacgc ggagcccggt caatgcctgc ctcctcaccg 240
gcagcctctt cgttctactg cgcgtcttca gctttgagcc ggtgccctct tgcagggccc 300
tgcaggtgct caagccccgg gaccgcattt ctgccatcgc ccaccgtggc ggcagccacg 360
acgcgcccga gaacacgctg gcggccattc ggcaggcagc taagaatgga gcaacaggcg 420
tggagttgga cattgagttt acttctgacg ggattcctgt cttaatgcac gataacacag 480
tagataggac gactgatggg actgggcgat tgtgtgattt gacatttgaa caaattagga 540
agctgaatcc tgcagcaaac cacagactca ggaatgattt ccctgatgaa aagatcccta 600
ccctaaggga agctgttgca gagtgcctaa accataacct cacaatcttc tttgatgtca 660
aaggccatgc acacaaggct actgaggctc taaagaaaat gtatatggaa tttcctcaac 720
tgtataataa tagtgtggtc tgttctttct tgccagaagt tatctacaag atgagacaaa 780
cagatcggga tgtaataaca gcattaactc acagaccttg gagcctaagc catacaggag 840
atgggaaacc acgctatgat actttctgga aacattttat atttgttatg atggacattt 900
tgctcgattg gagcatgcat aatatcttgt ggtacctgtg tggaatttca gctttcctca 960
tgcaaaagga ttttgtatcc ccggcctact tgaagaagtg gtcagctaaa ggaatccagg 1020
ttgttggttg gactgttaat acctttgatg aaaagagtta ctacgaatcc catcttggtt 1080
ccagctatat cactgacagc atggtagaag actgcgaacc tcacttctag actttcacgg 1140
tgggacgaaa cgggttcaga aactgccagg ggcctcatac agggatatca aaataccctt 1200
tgtgctagcc caggccctgg ggaatcaggt gactcacaca aatgcaatag ttggtcactg 1260
catttttacc tgaaccaaag ctaaacccgg tgttgccacc atgcaccatg gcatgccaga 1320
gttcaacact gttgctcttg aaaatctggg tctgaaaaaa cgcacaagag cccctgccct 1380
gccctagctg aggcacacag ggagacccag tgaggataag cacagattga attgtacagt 1440
ttgcagatgc agatgtaaat gcatgggaca tgcatgataa ctcagagttg acattttaaa 1500
acttgccaca cttatttcaa atatttgtac tcagctatgt taacatgtac tgtagacatc 1560
aaacttgtgg ccatactaat aaaattatta aaaggagcac taaaggaaaa ctgtgtgcca 1620
agcatcatat cctaaggcat acggaatttg gggaagccac catgcaatcc agtgaggctt 1680
cagtgtacag caaccaaaat ggtagggagg tcttgaagcc aatgagggat ttatagcatc 1740
ttgaatagag agctgcaaac caccaggggg cagagttgca tttttccagg ctttttagga 1800
agctctgcaa cagatgtgat ctgatcatag gcaattagaa ctggaagaaa cttccaaaaa 1860
tatctaggtt tgtcctcatt ttacaaatga ggaaactaaa ctctgtggaa gggaaggggt 1920
tgcctcaaaa gtcacagctt agctgggcac agtggctcat gccgataatc ccagcaattc 1980
agaaagctga ggcaggagga ttacttgagg ccagactggg caatatagca agaccccatc 2040
tctaaaaaat taggcatggt ggtgcatgcc tgtattccca gctactcagg aggttgaggt 2100
gggaggatca cttgagccca gaagttcaag gctgcaatga gccatgatta caccacggca 2160
ctacaacctt ggtggcacag tgagaacctg actcttaaaa aaaaaaaaaa aaaaaaaaaa 2220
aaaaaggata actagaactt ctagaacatc ttgtttacag ttagccagaa actatacaag 2280
tggtttaaca tgcattatct tactcaatcc atacaaaagt cttatggagg tgttagcact 2340
ctttctactg atgaagaact gaggtacttc ataaaaccac ttacccaagg tgtcttgagt 2400
ctggtacaac tggcattcaa atctaggtca gtctgccccc agagccacta cccttacccc 2460
tcactgaatc tgcctttata ttgttgagcc cttgacccca aactgctctt tccaatttga 2520
acttccaggg attttattgt gaacttacat agcaacatta aaatgaagtt gaattgttta 2580
aaaaaaaaaa aaaaaaaaaa aaaaaaa 2607
<210> 16
<211> 331
<212> PRT
16



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<213> Homo Sapiens
<400> 16
Met Trp Leu Trp Glu Asp Gln Gly Gly Leu Leu Gly Pro Phe Ser Phe
1 5 10 15
Leu Leu Leu Val Leu Leu Leu Val Thr Arg Ser Pro Val Asn Ala Cys
20 25 30
Leu Leu Thr Gly Ser Leu Phe Val Leu Leu Arg Val Phe Ser Phe Glu
35 40 45
Pro Val Pro Ser Cys Arg Ala Leu Gln Val Leu Lys Pro Arg Asp Arg
50 55 60
Ile Ser Ala Ile Ala His Arg Gly Gly Ser His Asp Ala Pro Glu Asn
65 70 75 80
Thr Leu Ala Ala Ile Arg Gln Ala Ala Lys Asn Gly Ala Thr Gly Val
85 90 95
Glu Leu Asp Ile Glu Phe Thr Ser Asp Gly Ile Pro Val Leu Met His
100 105 110
Asp Asn Thr Val Asp Arg Thr Thr Asp Gly Thr Gly Arg Leu Cys Asp
115 120 125
Leu Thr Phe Glu Gln Ile Arg Lys Leu Asn Pro Ala Ala Asn His Arg
130 135 140
Leu Arg Asn Asp Phe Pro Asp Glu Lys Ile Pro Thr Leu Arg Glu Ala
145 150 155 160
Val Ala Glu Cys Leu Asn His Asn Leu Thr Ile Phe Phe Asp Val Lys
165 170 175
Gly His Ala His Lys Ala Thr Glu Ala Leu Lys Lys Met Tyr Met Glu
180 185 190
Phe Pro Gln Leu Tyr Asn Asn Ser Val Val Cys Ser Phe Leu Pro Glu
195 200 205
Val Ile Tyr Lys Met Arg Gln Thr Asp Arg Asp Val Ile Thr Ala Leu
210 215 220
Thr His Arg Pro Trp Ser Leu Ser His Thr Gly Asp Gly Lys Pro Arg
225 230 235 240
Tyr Asp Thr Phe Trp Lys His Phe Ile Phe Val Met Met Asp Ile Leu
245 250 255
Leu Asp Trp Ser Met His Asn Ile Leu Trp Tyr Leu Cys Gly Ile Ser
260 265 270
Ala Phe Leu Met Gln Lys Asp Phe Val Ser Pro Ala Tyr Leu Lys Lys
275 280 285
Trp Ser Ala Lys Gly Ile Gln Val Val Gly Trp Thr Val Asn Thr Phe
290 295 300
17



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Asp Glu Lys Ser Tyr Tyr Glu Ser His Leu Gly Ser Ser Tyr Ile Thr
305 310 315 320
Asp Ser Met Val Glu Asp Cys Glu Pro His Phe
325 330
<210> 17
<211> 4859
<212> DNA
<213> Homo Sapiens
<400> 17
gaaaactaca accggcggcc agcgggacca gagggcggct ctgcaggcag gcggcagcgg 60
tgccctcagt tccccagcat ggccccctcg gcctgggcca tttgctggct gctagggggc 120
ctcctgctcc atgggggtag ctctggcccc agccccggcc ccagtgtgcc ccgcctgcgg 180
ctctcctacc gagacctcct gtctgccaac cgctctgcca tctttctggg cccccagggc 240
tccctgaacc tccaggccat gtacctagat gagtaccgag accgcctctt tctgggtggc 300
ctggacgccc tctactctct gcggctggac caggcatggc cagatccccg ggaggtcctg 360
tggccaccgc agccaggaca gagggaggag tgtgttcgaa agggaagaga tcctttgaca 420
gagtgcgcca acttcgtgcg ggtgctacag cctcacaacc ggacccacct gctagcctgt 480
ggcactgggg ccttccagcc cacctgtgcc ctcatcacag ttggccaccg tggggagcat 540
gtgctccacc tggagcctgg cagtgtggaa agtggccggg ggcggtgccc tcacgagccc 600
agccgtccct ttgccagcac cttcatagac ggggagctgt acacgggtct cactgctgac 660
ttcctggggc gagaggccat gatcttccga agtggaggtc ctcggccagc tctgcgttcc 720
gactctgacc agagtctctt gcacgacccc cggtttgtga tggccgcccg gatccctgag 780
aactctgacc aggacaatga caaggtgtac ttcttcttct cggagacggt cccctcgccc 840
gatggtggct cgaaccatgt cactgtcagc cgcgtgggcc gcgtctgcgt gaatgatgct 900
gggggccagc gggtgctggt gaacaaatgg agcactttcc tcaaggccag gctggtctgc 960
tcggtgcccg gccctggtgg tgccgagacc cactttgacc agctagagga tgtgttcctg 1020
ctgtggccca aggccgggaa gagcctcgag gtgtacgcgc tgttcagcac cgtcagtgcc 1080
gtgttccagg gcttcgccgt ctgtgtgtac cacatggcag acatctggga ggttttcaac 1140
gggccctttg cccaccgaga tgggcctcag caccagtggg ggccctatgg gggcaaggtg 1200
cccttccctc gccctggcgt gtgccccagc aagatgaccg cacagccagg acggcctttt 1260
ggcagcacca aggactaccc agatgaggtg ctgcagtttg cccgagccca ccccctcatg 1320
ttctggcctg tgcggcctcg acatggccgc cctgtccttg tcaagaccca cctggcccag 1380
cagctacacc agatcgtggt ggaccgcgtg gaggcagagg atgggaccta cgatgtcatt 1440
ttcctgggga ctgactcagg gtctgtgctc aaagtcatcg ctctccaggc agggggctca 1500
gctgaacctg aggaagtggt tctggaggag ctccaggtgt ttaaggtgcc aacacctatc 1560
accgaaatgg agatctctgt caaaaggcaa atgctatacg tgggctctcg gctgggtgtg 1620
gcccagctgc ggctgcacca atgtgagact tacggcactg cctgtgcaga gtgctgcctg 1680
gcccgggacc catactgtgc ctgggatggt gcctcctgta cccactaccg ccccagcctt 1740
ggcaagcgcc ggttccgccg gcaggacatc cggcacggca accctgccct gcagtgcctg 1800
ggccagagcc aggaagaaga ggcagtggga cttgtggcag ccaccatggt ctacggcacg 1860
gagcacaata gcaccttcct ggagtgcctg cccaagtctc cccaggctgc tgtgcgctgg 1920
ctcttgcaga ggccagggga tgaggggcct gaccaggtga agacggacga gcgagtcttg 1980
cacacggagc gggggctgct gttccgcagg cttagccgtt tcgatgcggg cacctacacc 2040
tgcaccactc tggagcatgg cttctcccag actgtggtcc gcctggctct ggtggtgatt 2100
gtggcctcac agctggacaa cctgttccct ccggagccaa agccagagga gcccccagcc 2160
cggggaggcc tggcttccac cccacccaag gcctggtaca aggacatcct gcagctcatt 2220
ggcttcgcca acctgccccg ggtggatgag tactgtgagc gcgtgtggtg caggggcacc 2280
acggaatgct caggctgctt ccggagccgg agccggggca agcaggccag gggcaagagc 2340
tgggcagggc tggagctagg caagaagatg aagagccggg tgcatgccga gcacaatcgg 2400
acgccccggg aggtggaggc cacgtagaag ggggcagagg aggggtggtc aggatgggct 2460
ggggggccca ctagcagccc ccagcatctc ccacccaccc agctagggca gaggggtcag 2520
gatgtctgtt tgcctcttag agacaggtgt ctctgccccc acaccgctac tggggtctaa 2580
tggaggggct gggttcttga agcctgttcc ctgcccttct ctgtgctctt agacccagct 2640
ggagccagca ccctctggct gctggcagcc ccaagggatc tgccatttgt tctcagagat 2700
ggcctggctt ccgcaacaca tttccgggtg tgcccagagg caagagggtt gggtggttct 2760
ttcccagcct acagaacaat ggccattctg agtgaccctc agagtgggtg tgtgggtgcg 2820
Ig



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
tctagggggt atcccggtag ggggcctgca gggagccaga gggtggaaat ggcctctaag 2880
ctagcacccc gtaagaagag cctacctgac cgacttgggg agggaacaca gaggtgttgg 2940
gaaggtggag caacaatgca cctcccctcc tgtcgcgccg tgatatcttg gtggctccct 3000
gccactgccc accg~ctctt ctccatctga gaatcacgga gaggtgtaga taatctagag 3060
gcatagactg ctagagcccc cagggatctg gggtggtcag ggctcgggct tcactttgta 3120
aaccaggtgg gggcatctca cagcctgact tcccttcccc aggccagggt tgctgggatg 3180
cctgcccctc ctgagaggac cccctcccca ttgtcaggct ctccatgtcc acgagcgggg 3240
aggggtgggt tctggggcat tgttgtccct tgtgtctgtg gactagagat agggtggggg 3300
agctggggaa gggtgcaggc gggaagagtg ggctgtcttt cccagggtga tgcaagcatg 3360
ccgcagccct ggaggctggg aatgtggagg ctctgtgagc cctgcagccc tcagaatcag 3420
ggccagggat gcagaagatt gagaggatat ggagatggat agagggcagg agacccttag 3480
gatagattgt gggacccagg caggaacagg tgtccacaag aactcaggat ggcatcagtt 3540
agctcagaag ccacctggaa gacccagtgt ttccatctct ggaatctctg ttttatgcta 3600
aatggattta ggaagactgt ttttctttta agggggaaac aaggtagaga aaaggacgaa 3660
gaagtgtaag tcccgctgat tctcgggggt aaggctcgga tggcaaggac gcgttctgcc 3720
tgggcatgta ggggaggtgt ttttgccatc accagtttct caggctgggg agcacagagg 3780
ggaggaggag gactaaatga aaagttgttc ccagcctgca catgaacaca ttcatgacac 3840
acaaaactgg ctggaaggag ataagagcac tgggtttgag attccctcca ttaaaacaac 3900
caagacaaag aaaggagggg aaaaaaagat aaaaagcaag ccagggttcc ctgccctatt 3960
gaaactcaaa cccagactgc cttgggtttt atctttccct tacccctggc acctccagag 4020
aactgggacc tgaaatagtc cctccgttct cccctttgac catgtaataa atgaaccaga 4080
agcactgaga ttaacctatc aacgccctga gaagccttcc agcctgcggt gctgtctgct 4140
gggaggtcag ctggtcaagg cagaggagga gaggaggaaa ggatgggggc tgaagagcag 4200
aagggagggg agacagaggg gattaaagag gggaggagag agtgcagagc tccaggaaag 4260
ggtatcagag ctgcagccag ctctgccctc taccctaggg aggccagaaa gacacaaaca 4320
gccctccggg cctttacgct ggactctggc ttggcaggct ccaggcaggg tcctctggga 4380
agttactcta gaaaacgaag ggaggaggag cacaagatcc tcagcaacga acacctgcac 4440
ttagaaaaag tggacagctt ctgccaacca caccctaccc atggtactgt atgctattaa 4500
ctcctggaaa cgccccgtaa atgcgagttg tttttgtatt tgtgtgttga gatgggcctt 4560
gtggtttctc tgtactcaga gcacatttct tgtaattact attgttattt ttattgtcat 4620
gactgcccct gagctctggt gagaaaagct gaatttacaa ggaaagggat gaagttaata 4680
tttgcatcac ataattatat cattactgtg tatctgtgta ttgtactaaa tggactgatg 4740
ctgcgcacat gagctgaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 4800
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 4859
<210> 18
<211> 782
<212> PRT
<213> Homo Sapiens
<400> 18
Met Ala Pro Ser Ala Trp Ala Ile Cys Trp Leu Leu Gly Gly Leu Leu
1 5 10 15
Leu His Gly Gly Ser Ser Gly Pro Ser Pro Gly Pro Ser Val Pro Arg
20 25 30
Leu Arg Leu Ser Tyr Arg Asp Leu Leu Ser Ala Asn Arg Ser Ala Ile
35 40 45
Phe Leu Gly Pro Gln Gly Ser Leu Asn Leu Gln Ala Met Tyr Leu Asp
50 55 60
Glu Tyr Arg Asp Arg Leu Phe Leu Gly Gly Leu Asp Ala Leu Tyr Ser
65 70 75 80
Leu Arg Leu Asp Gln Ala Trp Pro Asp Pro Arg Glu Val Leu Trp Pro
85 90 95
Pro Gln Pro Gly Gln Arg Glu Glu Cys Val Arg Lys Gly Arg Asp Pro
19



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
100 105 110
Leu Thr Glu Cys Ala Asn Phe Val Arg Val Leu Gln Pro His Asn Arg
115 120 125
Thr His Leu Leu Ala Cys Gly Thr Gly Ala Phe Gln Pro Thr Cys Ala
130 135 140
Leu Ile Thr Val Gly His Arg Gly Glu His Val Leu His Leu Glu Pro
145 150 155 160
Gly Ser Val Glu Ser Gly Arg Gly Arg Cys Pro His Glu Pro Ser Arg
165 170 175
Pro Phe Ala Ser Thr Phe Ile Asp Gly Glu Leu Tyr Thr Gly Leu Thr
180 185 190
Ala Asp Phe Leu Gly Arg Glu Ala Met Ile Phe Arg Ser Gly Gly Pro
195 200 205
Arg Pro Ala Leu Arg Ser Asp Ser Asp Gln Ser Leu Leu His Asp Pro
210 215 220
Arg Phe Val Met Ala Ala Arg Ile Pro Glu Asn Ser Asp Gln Asp Asn
225 230 235 240
Asp Lys Val Tyr Phe Phe Phe Ser Glu Thr Val Pro Ser Pro Asp Gly
245 250 255
Gly Ser Asn His Val Thr Val Ser Arg Val Gly Arg Val Cys Val Asn
260 265 270
Asp Ala Gly Gly Gln Arg Val Leu Val Asn Lys Trp Ser Thr Phe Leu
275 280 285
Lys Ala Arg Leu Val Cys Ser Val Pro Gly Pro Gly Gly Ala Glu Thr
290 295 300
His Phe Asp Gln Leu Glu Asp Val Phe Leu Leu Trp Pro Lys Ala Gly
305 310 315 320
Lys Ser Leu Glu Val Tyr Ala Leu Phe Ser Thr Val Ser Ala Val Phe
325 330 335
Gln Gly Phe Ala Val Cys Val Tyr His Met Ala Asp Ile Trp Glu Val
340 345 350
Phe Asn Gly Pro Phe Ala His Arg Asp Gly Pro Gln His Gln Trp Gly
355 360 365
Pro Tyr Gly Gly Lys Val Pro Phe Pro Arg Pro Gly Val Cys Pro Ser
370 375 380
Lys Met Thr Ala Gln Pro Gly Arg Pro Phe Gly Ser Thr Lys Asp Tyr
385 390 395 400
Pro Asp Glu Val Leu Gln Phe Ala Arg Ala His Pro Leu Met Phe Trp
405 410 415
Pro Val Arg Pro Arg His Gly Arg Pro Val Leu Val Lys Thr His Leu



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
420 425 430
Ala Gln Gln Leu His Gln Ile Val Val Asp Arg Val Glu Ala Glu Asp
435 440 445
Gly Thr Tyr Asp Val Ile Phe Leu Gly Thr Asp Ser Gly Ser Val Leu
450 455 460
Lys Val Ile Ala Leu Gln Ala Gly Gly Ser Ala Glu Pro Glu Glu Val
465 470 475 480
Val Leu Glu Glu Leu Gln Val Phe Lys Val Pro Thr Pro Ile Thr Glu
485 490 495
Met Glu Ile Ser Val Lys Arg Gln Met Leu Tyr Val Gly Ser Arg Leu
500 505 510
Gly Val Ala Gln Leu Arg Leu His Gln Cys Glu Thr Tyr Gly Thr Ala
515 520 525
Cys Ala Glu Cys Cys Leu Ala Arg Asp Pro Tyr Cys Ala Trp Asp Gly
530 535 540
Ala Ser Cys Thr His Tyr Arg Pro Ser Leu Gly Lys Arg Arg Phe Arg
545 550 555 560
Arg Gln Asp Ile Arg His Gly Asn Pro Ala Leu Gln Cys Leu Gly Gln
565 570 575
Ser Gln Glu Glu Glu Ala Val Gly Leu Val Ala Ala Thr Met Val Tyr
580 585 590
Gly Thr Glu His Asn Ser Thr Phe Leu Glu Cys Leu Pro Lys Ser Pro
595 600 605
Gln Ala Ala Val Arg Trp Leu Leu Gln Arg Pro Gly Asp Glu Gly Pro
610 615 620
Asp Gln Val Lys Thr Asp Glu Arg Val Leu His Thr Glu Arg Gly Leu
625 630 635 640
Leu Phe Arg Arg Leu Ser Arg Phe Asp Ala Gly Thr Tyr Thr Cys Thr
645 650 655
Thr Leu Glu His Gly Phe Ser Gln Thr Val Val Arg Leu Ala Leu Val
660 665 670
Val Ile Val Ala Ser Gln Leu Asp Asn Leu Phe Pro Pro Glu Pro Lys
675 680 685
Pro Glu Glu Pro Pro Ala Arg Gly Gly Leu Ala Ser Thr Pro Pro Lys
690 695 700
Ala Trp Tyr Lys Asp Ile Leu Gln Leu Ile Gly Phe Ala Asn Leu Pro
705 710 715 720
Arg Val Asp Glu Tyr Cys Glu Arg Val Trp Cys Arg Gly Thr Thr Glu
725 730 735
Cys Ser Gly Cys Phe Arg Ser Arg Ser Arg Gly Lys Gln Ala Arg Gly
21



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
740 745 750
Lys Ser Trp Ala Gly Leu Glu Leu Gly Lys Lys Met Lys Ser Arg Val
755 760 765
His Ala Glu His Asn Arg Thr Pro Arg Glu Val Glu Ala Thr
770 775 780
<210> 19
<211> 2342
<212> DNA
<213> Homo sapiens
<400> 19
tatgaaggcc ctgattcgaa accgcagcta cgtcttctcc tccctggcca cgtcggctgt 60
ctccttcgcc acgggggccc tgggcatgtg gatcccgctc tacctgcacc gcgcccaagt 120
tgtgcagaag acagcagaga cgtgcaacag cccgccctgt ggggccaagg acagcctcat 180
ctttggggcc atcacctgct ttacgggatt tctgggcgtg gtcacggggg caggagccac 240
gcgctggtgc cgcctgaaga cccagcgggc cgacccactg gtgtgtgccg tgggcatgct 300
gggctctgcc atcttcatct gcctgatctt cgtggctgcc aagagcagca tcgtaggagc 360
ctatatctgt atcttcgtcg gggagacgct gctgttttct aactgggcca tcactgcaga 420
catcctcatg tacgtggtca tccccacgcg gcgcgccact gccgtggcct tgcagagctt 480
cacctcccac ctgctggggg acgccgggag cccctacctc attggcttta tctcagacct 540
gatccgccag agcactaagg actccccgct ctgggagttc ctgagcctgg gctacgcgct 600
catgctctgc cctttcgtcg tggtcctggg cggcatgttc ttcctcgcca ctgtgctctt 660
cttcgtcagc gaccgcgcca gggctgagca gcaggtgaac cagctggcga tgccgcccgc 720
atctgtgaaa gtctgaggtg gtgccattgg gacaatgaag aacccacact cccacctcgt 780
ctgggaggtg tcctacagcg tccgggaccg gctgggctgc cccaaagctt tctgtgtgat 840
ccacggctag gcacccaccc tctctggccc aggcctgctg agtggccctg gcatcaagag 900
gaggctgtgt cctcagttac cctggaagga tgtgtgtgtt ggagccacac ggttggacag 960
gttcccagcc ctaggtttgg gccgcagggc ccctggggcc aaggaagaag acagccccaa 1020
gtgggtgtcc ggggagagcc tggcctgcca ccagcttatg tgatcttggg caagtccctg 1080
ccctccctgg aacgaagggc cagggggctg gactttccca cacaacttgc tgggcaaagc 1140
acgatctgca gctttgaaga ctcaacagac cctggaccat acggagagca ggtggcccag 1200
gcctcagggc ggcagtcccg gctttgaggc tcacgcgagg gcctggtatg cagggaccac 1260
tgctcagctg ggcctcggac cttggggata ttggacgcaa catggcaaat gaagctgggc 1320
gcccaagtct ctgggtactc cctggaggac actgtctcac tgtctcgggt tggctcccag 1380
cctggaggtc ccagatgggg actgttctga caagctggca tcaccagggg tgaaggccct 1440
ggctgcagct gtacaccacc tgtgccccca ggctcaaggt ctctggcagg tgcacaccag 1500
cccaactctg cagggcttct ctccctgcca ccacccccca agccaggacc ccactccttc 1560
cccgaggctg agctgagcct tttccagggg cagggcccag gagaccattc ccagaatcca 1620
tggggcagta gccagggctc cggctgctgg aggaagcagc tatccacaaa gcttcctgcc 1680
ccagagctga ggctgaggcc ccgggagagg cggcccctac ccaaacactg gctgctggca 1740
ttccaccaag tgaccccagg ggccaggcct tcgatcaccc acctcccatc catgcacaca 1800
ccaggatgca gctgccaact tcacaccagc cccaacccgc tttgggggag cttagccccc 1860
tgcgtcaccc actccctgca cttctgctgc aatcaaggtg gttctggtgc gggggtgggg 1920
tggggggtga ggccttgtgg ccaatggggg accccccaag agccagcttg gacaatgctc 1980
ttcttgcccc ttagttactg gctggctgtg gcttcagtgg tgtgtaagca ggtggaatac 2040
tcacccacca agctctgggg taccccgagg gcctgacaag aggatggggt gggggtggca 2100
tcctccaaag accagcctcc acccccactc cagcctcagc ggggccccag cgatgttttc 2160
ttgttgtaca agaaccaggt ccgagtgttg cctcctcttc cttccggaag ccaaactgct 2220
cctttatttt ttagagctgc tgattgtgaa tctcagagtc ttaagagaga agccaaatat 2280
attcctcttg taaatgaaga aataaaccta tttaaatcaa aaaaaaaaaa aaaaaaaaaa 2340
as
2342
<210> 20
<211> 244
<212> PRT
<213> Homo Sapiens
22



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<400> 20
Met Lys Ala Leu Ile Arg Asn Arg Ser Tyr Val Phe Ser Ser Leu Ala
1 5 10 15
Thr Ser Ala Val Ser Phe Ala Thr Gly Ala Leu Gly Met Trp Ile Pro
20 25 30
Leu Tyr Leu His Arg Ala Gln Val Val Gln Lys Thr Ala Glu Thr Cys
35 40 45
Asn Ser Pro Pro Cys Gly Ala Lys Asp Ser Leu Ile Phe Gly Ala Ile
50 55 60
Thr Cys Phe Thr Gly Phe Leu Gly Val Val Thr Gly Ala Gly Ala Thr
65 70 75 80
Arg Trp Cys Arg Leu Lys Thr Gln Arg Ala Asp Pro Leu Val Cys Ala
85 90 95
Val Gly Met Leu Gly Ser Ala Ile Phe Ile Cys Leu Ile Phe Val Ala
100 105 110
Ala Lys Ser Ser Ile Val Gly Ala Tyr Ile Cys Ile Phe Val Gly Glu
115 120 125
Thr Leu Leu Phe Ser Asn Trp Ala Ile Thr Ala Asp Ile Leu Met Tyr
130 135 140
Val Val Ile Pro Thr Arg Arg Ala Thr Ala Val Ala Leu G1n Ser Phe
145 150 155 160
Thr Ser His Leu Leu Gly Asp Ala Gly Ser Pro Tyr Leu Ile Gly Phe
165 170 175
Ile Ser Asp Leu Ile Arg Gln Ser Thr Lys Asp Ser Pro Leu Trp Glu
180 185 190
Phe Leu Ser Leu Gly Tyr Ala Leu Met Leu Cys Pro Phe Val Val Val
195 200 205
Leu Gly Gly Met Phe Phe Leu Ala Thr Val Leu Phe Phe Val Ser Asp
210 215 220
Arg Ala Arg Ala Glu Gln Gln Val Asn Gln Leu Ala Met Pro Pro Ala
225 230 235 240
Ser Val Lys Val
<210> 21
<211> 3202
<212> DNA
<213> Homo sapiens
<400> 21
gagagcgctc ctggctgtga gctgctcctg ccgcttcgct ccgcgctctc ctgccgctcc 60
gctccgggtc tcccgcgctc ctctccccgg ctcggccgag cgcgctgccc cgacgccgcc 120
acccagagcc gggccgcgcc gggcgccgag atgaaggtgc tgggacaccg gctggagctg 180
23



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
ctcacaggcc tcctgctcca cgacgtgacc atggccgggc tgcaggagct gcgattccct 240
gaggagaagc cgctgctccg gggccaggac gccaccgagc tggagagctc cgatgccttc 300
ctcttggctg cagacacaga ctggaaggaa catgacatcg agacacccta cggccttctg 360
catgtagtga tccggggctc ccccaagggg aaccgcccag ccatcctcac ctaccatgat 420
gtgggcctca accacaaact atgcttcaac accttcttca acttcgagga catgcaggag 480
atcaccaagc actttgtggt gtgtcacgtg gatgcccctg gacaacaggt gggggcgtcg 540
cagtttcctc aggggtacca gttcccctcc atggagcagc tggctgccat gctccccagc 600
gtggtgcagc atttcgggtt caagtatgtg attggcatcg gagtgggcgc cggagcctat 660
gtgctggcca agtttgcact catcttcccc gacctggtgg aggggctggt gctggtgaac 720
atcgacccca atggcaaagg ctggatagac tgggctgcca ccaagctctc cggcctaact 780
agcactttac ccgacacggt gctctcccac ctcttcagcc aggaggagct ggtgaacaac 840
acagagttgg tgcagagcta ccggcagcag attgggaacg tggtgaacca ggccaacctg 900
cagctcttct ggaacatgta caacagccgc agagacctgg acattaaccg gcctggaacg 960
gtgcccaatg ccaagacgct ccgctgcccc gtgatgctgg tggttgggga taatgcaccc 1020
gctgaggacg gggtggtgga gtgcaactcc aaactggacc cgaccactac gaccttcctg 1080
aagatggcag actctggagg gctgccccag gtcacacagc cagggaagct gactgaagcc 1140
ttcaaatact tcctgcaagg catgggctac atgccctcag ccagcatgac ccgcctggca 1200
cgctcccgca ctgcatccct caccagtgcc agctcggtgg atggcagccg cccacaggcc 1260
tgcacccact cagagagcag cgaggggctg ggccaggtca accacaccat ggaggtgtcc 1320
tgttgaagcc cttgatcccg ctgacgacgc ccacgtcgag gccccaccgc catccttgcg 1380
ccggctcatg ttccctttag tttatttttg tgagggcaaa ggggaggaaa tggggttctg 1440
tttgaaaaaa atgaggggat cttagatgct gcagcagaac agtctccagg tgttttaagg 1500
ggctcagtcc tcctcatccc atctcactct ccgtggtaac ttagccaact tgacccctct 1560
catcccactc ccggcggccc aggcacagaa gggcagggcc atagggaggg agattcgcta 1620
cggatccagg ccattcctgg gtgagccctt gggcaggcat gtttggagat gagagaggct 1680
tcgagagggt gggtgctggg ccacaggggt gcggggccag ctcaggcact ggcgtgggag 1740
ccctgggaga ccccttcccc caccctccac caagcacacc tgtttctgtc tcatagcaca 1800
tgtgacaatc atctggacaa cagccacaag ggggcgctcg gaccaggcag ccactttcct 1860
ggtgctctct gggcccagct ggtgctgtag ggccacgcag gcaggggcgt caaggggttt 1920
ctctgcccaa ggaagacaga acatggagaa ccgtcagggc aggaacccca cagactgtcc 1980
cttccagccc acactctgcc acctcctggc cctgtcccaa ttctgagcca aggcctcccc 2040
gaggcagaag ttgcctggtc ctctgtcccc acagtgacct gactgggggt gagggagaag 2100
gaggagagag cccatgtgtg gtgtgtgtgc ccctgagaac ttcgtggtga ctgcctttgg 2160
gagcccgcag gtggccagag gcaggggtag ctgagttcct ggagacccct tttttgcccc 2220
caggttcccc agagggcaac gccatcagta gcagtgtggt gtttcaggca gagctctggc 2280
caggctgtgc cagtgtgtcc cggacgcatc actaaggaag agagagttta tttagtcaac 2340
tggcccaagg cagcgaggct tctacagtcc cacaccccat agccgcctgg gctggggctt 2400
actgggggct gaaggttctg gacatgaaca agggtcaggt agaagagaaa ggcttcccct 2460
acaccccagc ctcctgctgt cccctgaagc ccaggactgc gttgtatgct ttccatccac 2520
tcaccttacc ccatagcatc ttgcggccca gaaaccagag ccatttgtct cagaccctaa 2580
atcaataatc acaaacccca aaacgggaga gagcagtgaa aacatgcagg gctgtggacg 2640
ggggaagggt tgtggcgggt gttctgaggc tgagaggaca cctatatgcg tatttcctct 2700
acacacatca ccccccttct ataatcttaa gccatgacta gcctggtggc gtgttagttt 2760
ctgcccagtt ctaccccctc atgtgcttct tctgaatact gaatgtgact gtttgaaagc 2820
tggtagaatt catccctctt actgtagata acactgcaaa tcttggaatt ttgttttttg 2880
ctgtttccag atgtatctat aaatatctat acattatatg tgtgtgtgtg tgtgtgtgtg 2940
tgtgtgtgtg tacatcgggt cctcccatgt gtggtgttct tctggaggtt gtctctttgg 3000
tcaaggtgaa cttttaatgt ttattatttt cttctccgca caaagtaaag agcctaattt 3060
tgtgtattct ggtggctgct gtcatgagat gataaaatgt aaaacaaaac tctagtcaac 3120
gtagaaagag ttaactgtgc tgaaaaacta ataaagaacc taagaagaaa aaaaaaaaaa 3180
aaaaaaaaaa aaaaaaaaaa as 3202
<210> 22
<211> 391
<212> PRT
<213> Homo sapiens
<400> 22
Met Lys Val Leu Gly His Arg Leu Glu Leu Leu Thr Gly Leu Leu Leu
1 5 10 15
24



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
His Asp Val Thr Met Ala Gly Leu Gln Glu Leu Arg Phe Pro Glu Glu
20 25 30
Lys Pro Leu Leu Arg Gly Gln Asp Ala Thr Glu Leu Glu Ser Ser Asp
35 40 45
Ala Phe Leu Leu Ala Ala Asp Thr Asp Trp Lys Glu His Asp Ile Glu
50 55 60
Thr Pro Tyr Gly Leu Leu His Val Val Ile Arg Gly Ser Pro Lys Gly
65 70 75 80
Asn Arg Pro Ala Ile Leu Thr Tyr His Asp Val Gly Leu Asn His Lys
85 90 95
Leu Cys Phe Asn Thr Phe Phe Asn Phe Glu Asp Met Gln Glu Ile Thr
100 105 110
Lys His Phe Val Val Cys His Val Asp Ala Pro Gly Gln Gln Val Gly
115 120 125
Ala Ser Gln Phe Pro Gln Gly Tyr Gln Phe Pro Ser Met Glu Gln Leu
130 135 140
Ala Ala Met Leu Pro Ser Val Val Gln His Phe Gly Phe Lys Tyr Val
145 150 155 160
Ile Gly Ile Gly Val Gly Ala Gly Ala Tyr Val Leu Ala Lys Phe Ala
165 170 175
Leu Ile Phe Pro Asp Leu Val Glu Gly Leu Val Leu Val Asn Ile Asp
180 185 190
Pro Asn Gly Lys Gly Trp Ile Asp Trp Ala Ala Thr Lys Leu Ser Gly
195 200 205
Leu Thr Ser Thr Leu Pro Asp Thr Val Leu Ser His Leu Phe Ser Gln
210 215 220
Glu Glu Leu Val Asn Asn Thr Glu Leu Val Gln Ser Tyr Arg Gln Gln
225 230 235 240
Ile Gly Asn Val Val Asn Gln Ala Asn Leu Gln Leu Phe Trp Asn Met
245 250 255
Tyr Asn Ser Arg Arg Asp Leu Asp Ile Asn Arg Pro Gly Thr Val Pro
260 265 270
Asn Ala Lys Thr Leu Arg Cys Pro Val Met Leu Val Val Gly Asp Asn
275 280 285
Ala Pro Ala Glu Asp Gly Val Val Glu Cys Asn Ser Lys Leu Asp Pro
290 295 300
Thr Thr Thr Thr Phe Leu Lys Met Ala Asp Ser Gly Gly Leu Pro Gln
305 310 315 320
Val Thr Gln Pro Gly Lys Leu Thr Glu Ala Phe Lys Tyr Phe Leu Gln
325 330 335



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Gly Met Gly Tyr Met Pro Ser Ala Ser Met Thr Arg Leu Ala Arg Ser
340 345 350
Arg Thr Ala Ser Leu Thr Ser Ala Ser Ser Val Asp Gly Ser Arg Pro
355 360 365
Gln Ala Cys Thr His Ser Glu Ser Ser Glu Gly Leu Gly Gln Val Asn
370 375 380
His Thr Met Glu Val Ser Cys
385 390
<210> 23
<211> 1007
<212> DNA
<213> Homo sapiens
<400> 23
ggccttttct ctgctctcct gaacctttag gcttgtctcg gcccatttga agaccaggaa 60
gttgatcaat cccgaggctg ctgagagacg gtggcgcgat tgggacagtc gccagggatg 120
gctgagcgtg aagatgcagc gggtgtccgg gctgctctcc tggacgctga gcagagtcct 180
gtggctctcc ggcctctctg agccgggagc tgcccggcag ccccggatca tggaagagaa 240
agcgctagag gtttatgatt tgattagaac tatccgggac ccagaaaagc ccaatacttt 300
agaagaactg gaagtggtct cggaaagttg tgtggaagtt caggagataa atgaagaaga 360
atatctggtt attatcaggt tcacgccaac agtacctcat tgctctttgg cgactcttat 420
tgggctgtgc ttaagagtaa aacttcagcg atgtttacca tttaaacata agttggaaat 480
ctacatttct gaaggaaccc actcaacaga agaagacatc aataagcaga taaatgacaa 540
agagcgagtg gcagctgcaa tggaaaaccc caacttacgg gaaattgtgg aacagtgtgt 600
ccttgaacct gactgatagc tgttttaaga gccactggcc tgtaattgtt tgatatattt 660
gtttaaactc tttgtataat gtcagagact catgtttaat acataggtga tttgtacctc 720
agagcatttt ttaaaggatt ctttccaagc gagatttaat tataaggtag tacctaattt 780
gttcaatgta taacattctc aggatttgta acacttaaat gatcagacag aataatattt 840
tctagttatt atgtgtaaga tgagttgcta tttttctgat gctcattctg atacaactat 900
ttttcgtgtc aaatatctac tgtgcccaaa tgtactcaat ttaaatcatt actctgtaaa 960
ataaataagc agatgattct taaaaaaaaa aaaaaaaaaa aaaaaaa 1007
<210> 24
<211> 160
<212> PRT
<213> Homo sapiens
<400> 24
Met Gln Arg Val Ser Gly Leu Leu Ser Trp Thr Leu Ser Arg Val Leu
10 15
Trp Leu Ser Gly Leu Ser Glu Pro Gly Ala Ala Arg Gln Pro Arg Ile
20 25 30
Met Glu Glu Lys Ala Leu Glu Val Tyr Asp Leu Ile Arg Thr Ile Arg
35 40 45
Asp Pro Glu Lys Pro Asn Thr Leu Glu Glu Leu Glu Val Val Ser Glu
50 55 60
Ser Cys Val Glu Val Gln Glu Ile Asn Glu Glu Glu Tyr Leu Val Ile
65 70 75 80
Ile Arg Phe Thr Pro Thr Val Pro His Cys Ser Leu Ala Thr Leu Ile
26



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
85 90 95
Gly Leu Cys Leu Arg Val Lys Leu Gln Arg Cys Leu Pro Phe Lys His
100 105 110
Lys Leu Glu Ile Tyr Ile Ser Glu Gly Thr His Ser Thr Glu Glu Asp
115 120 125
Ile Asn Lys Gln Ile Asn Asp Lys Glu Arg Val Ala Ala Ala Met Glu
130 135 140
Asn Pro Asn Leu Arg Glu Ile Val Glu Gln Cys Val Leu Glu Pro Asp
145 150 155 160
<210> 25
<211> 2026
<212> DNA
<213> Homo sapiens
<400> 25
ggacagtgac acagtgacca ctataaaagt caggcgggct gaggaggaga caaaggccag 60
gacgctccgc agctgttggg gaagaggagc tgcctcctgg gatggagaaa tttaaggctg 120
cgatgttgct ggggagcgtc ggcgatgctc ttggctacag aaatgtctgc aaggagaaca 180
gcactgtagg catgaagatc caggaggagc tgcaacgttc cgggggcctg gaccacctcg 240
tactctcgcc aggagaatgg cccgtgagtg acaacaccat catgcacatc gcaaccgccg 300
aggccctcac cacagactac tggtgcctgg atgatctgta ccgggagatg gtgagatgct 360
atgtggaaat cgttgagaag cttccagaac gccggccaga cccagctacc attgaaggct 420
gtgctcagct aaagcccaat aactaccttc tcgcctggca cacaccgttc aatgaaaaag 480
gctcagggtt tggagcggcc accaaggcca tgtgcatcgg cctgcggtac tggaagcctg 540
agcggctgga gaccctcatc gaggtcagcg tggagtgcgg ccggatgacc cacaaccatc 600
ccacaggctt cctgggctcc ctgtgcacgg ccctgtttgt gtcgttcgcc gcacaaggaa 660
agcccctggt ccagtggggg agagacatgc tgcgggcggt gcctctggca gaagagtact 720
gcaggaagac catccggcac acggcagaat accaggagca ctggttttac tttgaagcta 780
aatggcaatt ttatttggag gagaggaaaa tcagtaaaga ctcagaaaat aaagccatct 840
tccccgacaa ttatgatgca gaagagaggg aaaagaccta caggaagtgg agctcggaag 900
gtcgaggggg aagacgaggc cacgatgccc ccatgatagc ctatgacgcc ctccttgcag 960
caggaaacag ctggactgag ctgtgtcacc gggccatgtt tcatggaggg gagagcgcgg 1020
ccacgggcac cattgcaggc tgcctgttcg ggttgctgta cggcctggac ctcgttccca 1080
aaggcttgta ccaggacctg gaggacaagg agaagctgga ggacctgggc gcggctctct 1140
accgcctgtc cacagaggag aagtaaagcc atttctgcca ctttccccct agagagccga 1200
ttccaccccg gggcccgtag ggccctctcg cagcccctgg gtgagggtgt ctctgtgagg 1260
ctccactgcg gtctgtgcct gactggccac atctaactct ctgtttccaa tttcagaatc 1320
ctaactgttg cataaaatac attgtttgtc ctgcgagaat attttccgtc ctccaccatc 1380
aacattgaca ctgcgtagat ttgccgcact tggacctcca tgcgtggcac tcacccgcag 1440
tctcctggac aggcgctgta ttttattctg tcgcagagct aatgctgttt actcactcac 1500
ttcaacaaca ctaactgcgg tggtggcctc cagcaggccc ccccgctgca gaccctctgt 1560
cctgcctctg cctccaggca tgcgtttccc cgtgagggcc aatgcacctc cccccacccc 1620
ccaccctccc atgtccacag tgggtcgtgt gttcctggac agagaaacag tccacactgg 1680
ggcctgcggg acacatatag cagcatattt tgctcttaac cccacccacc tttttaatca 1740
cactagattt taagatcaat ccctttttga aacaactcac ggagaaaacc agaacataaa 1800
tggcctcctg ccagctccgg cgtctctctg tggtctgcct tagtgggcca agtccaaatg 1860
cagagaaggc ctttcccttc cgcgcctgcc ccatcgggct cgctgacgag gaagcgctgt 1920
ccctgtgatg aggttctctc tcagagagtc ttggaaaaga gaccacttgc tcttgtttaa 1980
aataaatttg gacgtgattt taaaaaaaaa aaaaaaaaaa aaaaaa 2026
<210> 26
<211> 354
<212> PRT
<213> Homo sapiens
27



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<400> 26
Met Glu Lys Phe Lys Ala Ala Met Leu Leu Gly Ser Val Gly Asp Ala
1 5 10 15
Leu Gly Tyr Arg Asn Val Cys Lys Glu Asn Ser Thr Val Gly Met Lys
20 25 30
Ile Gln Glu Glu Leu Gln Arg Ser Gly Gly Leu Asp His Leu Val Leu
35 40 45
Ser Pro Gly Glu Trp Pro Val Ser Asp Asn Thr Ile Met His Ile Ala
50 55 60
Thr Ala Glu Ala Leu Thr Thr Asp Tyr Trp Cys Leu Asp Asp Leu Tyr
65 70 75 80
Arg Glu Met Val Arg Cys Tyr Val Glu Ile Val Glu Lys Leu Pro Glu
85 90 95
Arg Arg Pro Asp Pro Ala Thr Ile Glu Gly Cys Ala Gln Leu Lys Pro
100 105 110
Asn Asn Tyr Leu Leu Ala Trp His Thr Pro Phe Asn Glu Lys Gly Ser
115 120 125
Gly Phe Gly Ala Ala Thr Lys Ala Met Cys Ile Gly Leu Arg Tyr Trp
130 135 140
Lys Pro Glu Arg Leu Glu Thr Leu Ile Glu Val Ser Val Glu Cys Gly
145 150 155 160
Arg Met Thr His Asn His Pro Thr Gly Phe Leu Gly Ser Leu Cys Thr
165 170 175
Ala Leu Phe Val Ser Phe Ala Ala Gln Gly Lys Pro Leu Val Gln Trp
180 185 190
Gly Arg Asp Met Leu Arg Ala Val Pro Leu Ala Glu Glu Tyr Cys Arg
195 200 205
Lys Thr Ile Arg His Thr Ala Glu Tyr Gln Glu His Trp Phe Tyr Phe
210 215 220
Glu Ala Lys Trp Gln Phe Tyr Leu Glu Glu Arg Lys Ile Ser Lys Asp
225 230 235 240
Ser Glu Asn Lys Ala Ile Phe Pro Asp Asn Tyr Asp Ala Glu Glu Arg
245 250 255
Glu Lys Thr Tyr Arg Lys Trp Ser Ser Glu Gly Arg Gly Gly Arg Arg
260 265 270
Gly His Asp Ala Pro Met Ile Ala Tyr Asp Ala Leu Leu Ala Ala Gly
275 280 285
Asn Ser Trp Thr Glu Leu Cys His Arg Ala Met Phe His Gly Gly Glu
290 295 300
Ser Ala Ala Thr Gly Thr Ile Ala Gly Cys Leu Phe Gly Leu Leu Tyr
28



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
305 310 315 320
Gly Leu Asp Leu Val Pro Lys Gly Leu Tyr Gln Asp Leu Glu Asp Lys
325 330 335
Glu Lys Leu Glu Asp Leu Gly Ala Ala Leu Tyr Arg Leu Ser Thr Glu
340 345 350
Glu Lys
<210> 27
<211> 2512
<212> DNA
<213> Homo Sapiens
<400> 27
tgcactgtgt ggttggcacc taacccatct gaatgtaact ccttaaagtg cttgcaaata 60
aaaccgatgc tttgccttct ctgccacatc gcaaaaagag gtacttttgt taattggata 120
atttatctct tattattttt tcctcatact cagcttggaa atcagaactt acctgccagt 180
gtgttggagg taaatgcttc acagacacac agacaaacca caccagaagc ttctcctccg 240
tgccctcctt ccgtggtacc tttgaaccga gccactttct caccaggcag tggcaccagc 300
tcagcatcac tcagccttcc gccccccgat ggtgtggggt cttcacgcct gcataatccc 360
cagagccttt cccattgctt atacaaacac ctgctcccag ctccagaaag cctcatccac 420
agccacgaca caggctctct gacaacagac tcctccctgg ccgagcactc ctcccgctcg 480
gagagtgagt cctccacagc catgctggag gagctgcaga ttggtgactc tgacaccact 540
ggccgttctg agacaccctc ccccacctgg ggtcagaggt ctgctgtgac agatggcacc 600
accttaacca cccctgcggc cactcatgta attattctgc ctttctttgc ctccaccgtt 660
tccttaaaag gactgatttg ttgtgccatc tcatttttcg gctgacattt ttatttacat 720
aggtgttgat tcccaaacca attctatgcc atctgtcagg gaaatcatta gtcatcctat 780
aagcttgctt aaggctgaaa aagtcacttc attctcttca ttcattttag aattacttat 840
agttactcta aaatagttac ttacggtttc ccgtgttact gtagctggta agttctacag 900
tgatttgcct tattagctaa gtatacatca caatatgttg tgatcataaa gtctaaaatt 960
tttcaaaaaa ttttaaccca gtattaatac atgttagcag tttttctcac agactcacat 1020
taatgtgtcc tgtgtgactc ttttctatat cctttttctc acataaatga ttactgactg 1080
catgaggcta atttttcttg ttcctccttc tctaacagct acaacttttg aactcatcta 1140
ttgtccagga gtgaatgatg tcgataatcc tatctacctt tcagaaattt agctgttcga 1200
tttttaaaaa ttattcttcc tgagccattt caggacagaa atttatgaat acatttttta 1260
ttttgtttat caataatttg tctttcattt atagcaatat atacatcttt tccatacata 1320
tattatttaa atatatctat gtgataagca atccctaata aatgatctgt gaatggctaa 1380
aatgtttcaa aattttatgg cacagattct atattgcata taatgtctaa gtaatggctt 1440
ccatttaaga gacacatagc ttcaggcaaa aaaatcagat ttttttttta aattgatatt 1500
ataatgaagt tccgaataag cactgtcata gacaaaattt tatttgtgct acattgtttt 1560
atgttctatc aagctgataa gtctgcaaat tttatgcgca gagaaatgtt ataataagcc 1620
atatgttttt taagacacta caatttacat aaagtaaaag atgctttttt tggtaatggg 1680
atttggtatt cccccaatgg ctgtgtctaa cactttgcat tcaaatgctc cattcagaga 1740
ctggctacag aaggagcctc attttccagg cctaacccca tagcgagtcc ctccctgcca 1800
cagaggacca gcccaactac gggcaccagg agcacagcag gtgtgggttc ctcccatgcc 1860
ctactgtgct tcaatggttc ttagctttta aaactttacc aggaccttta accaaaaaaa 1920
gaaggcagtg agagggtatc aatctaccaa ctaacctgtt caattttctg tttttaagac 1980
tttacaggag actaactgtc ttatatacag tcttgtgggc acgagcagag ctacttgtaa 2040
gggaaattaa ttgcaattat cagtttaaaa ttgcaaatag attattcatg acatgttttt 2100
cctaataatg aattcactat aacaatacag tattttctaa aatgctaatg atagtatttt 2160
agtcataaaa tcctgattgg ttgaacacaa taaaagaata aatctaggcc gggcgcggtg 2220
gctcacgcct gtaatcccag cactttggga ggccgaggtg ggtggatcac gaggtcagga 2280
gatcgagacc atcctggcta acatggtgaa accccgtctc tactaaaaat acaaaaaatt 2340
agccgggcgt ggtggtgggc gcctgtagtc ccaactactc gggaggctga ggcaggagaa 2400
tgacatgaac ccgggaggcg gagcttgcag tgagccgaga ctgcgccact gcactccagc 2460
ctgggcgaca gagcgagact ccatctcaaa aaaaaaaaaa aaaaaaaaaa as 2512
29



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 28
<211> 212
<212> PRT
<213> Homo Sapiens
<400> 28
Met Leu Cys Leu Leu Cys His Ile Ala Lys Arg Gly Thr Phe Val Asn
1 5 10 15
Trp Ile Ile Tyr Leu Leu Leu Phe Phe Pro His Thr Gln Leu Gly Asn
20 25 30
Gln Asn Leu Pro Ala Ser Val Leu Glu Val Asn Ala Ser Gln Thr His
35 40 45
Arg Gln Thr Thr Pro Glu Ala Ser Pro Pro Cys Pro Pro Ser Val Val
50 55 60
Pro Leu Asn Arg Ala Thr Phe Ser Pro Gly S-er Gly Thr Ser Ser Ala
65 70 75 80
Ser Leu Ser Leu Pro Pro Pro Asp Gly Val Gly Ser Ser Arg Leu His
85 90 95
Asn Pro Gln Ser Leu Ser His Cys Leu Tyr Lys His Leu Leu Pro Ala
100 105 110
Pro Glu Ser Leu Ile His Ser His Asp Thr Gly Ser Leu Thr Thr Asp
115 120 125
Ser Ser Leu Ala Glu His Ser Ser Arg Ser Glu Ser Glu Ser Ser Thr
130 135 140
Ala Met Leu Glu Glu Leu Gln Ile Gly Asp Ser Asp Thr Thr Gly Arg
145 150 155 160
Ser Glu Thr Pro Ser Pro Thr Trp Gly Gln Arg Ser Ala Val Thr Asp
165 170 175
Gly Thr Thr Leu Thr Thr Pro Ala Ala Thr His Val Ile Ile Leu Pro
180 185 190
Phe Phe Ala Ser Thr Val Ser Leu Lys Gly Leu Ile Cys Cys Ala Ile
195 200 205
Ser Phe Phe Gly
210
<210> 29
<211> 1495
<212> DNA
<213> Homo Sapiens
<400> 29
tcagaggcag ggcttgcgac ggaagtggcc tctctgcttc tgcagggctg gggaagatgc 60
tgcgtccagc gttaccgtgg ctgtgccttg gcctctgcag cctcctggtg ggggaggcag 120
aggccccgag ccccgtggat ccgctggagc ggagccggcc gtacgcggtg ctgcgagggc 180
agaacctggt gttgatggga accattttca gcatcctgct ggtgactgtc atccttatgg 240



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
cattttgtgt ctacaagccc attcggcgtc ggtgacagcc agacaagttc ttcaatgagt 300
atttgggaat aggataagtt gtgttgcaca caggccagtg gagaagttgg aaccaaaact 360
ttcctacttg gaaatgacct ttggtctgga cagttggtaa atgctaaatg aattagaaga 420
aaacatgtac tagacattat tttttcctaa cactgtagcg caaataattg gcccctgagt 480
ccgcttctca gtgtttctga ctgtacttgt taaaagtaag acctgaaagc tccaaaggtc 540
agtgtaaaga tggagtgttc atgagaaaga aaacatggta accttgtgag tgcctgtaag 600
aaccacactg taaagaactc atcattaatg cttgaaaatg ttattaagaa ggagacttac 660
catgcagaca ttccctattt aagaaccatt tggttacagt gggttaagaa tcacagattt 720
ttttttttaa tctcacctga gttagcctag aatgcgctgg ttgcaaagtg gtgtcagctg 780
tggggatctt gggccctcgt tcctcacctg catcctgccc tgcactcagg tgctccccct 840
gaagtcaggg tcacatcagg tagacctgtt actatatgca cctttggcct ggaatgctct 900
gaagttggac tggaaatgtt actaggttgg cctgttacaa aaaggacccc atcctgctta 960
aacacattga tctcccttgc cctgcatttg agtctttcta gcccacggtc tgaaacttga 1020
ggcagctttc cagatttgga atgtaaaagg ctcagtgggc actctgttca tccctgggtg 1080
gggagggccc agccaacaga agtgcatgtc cactgtgcgg gccagtgtgt gtttacacaa 1140
atttcatctc agctttgaaa atgctgctat tagtttccac tgttggtgaa ctggattttt 1200
tcctcctatt gaaatgatac tttcatactt ataaagctgt cgtcaatatt tatttcaagg 1260
tgctagattt aattttgtta ttaaattgaa atgcttatct tgtgttcaag cacagcactg 1320
attttaacaa cctgcattta atgtgaagta accgaagtag gatactgtaa ctgtgtaagg 1380
attttgtttg taatcttgta acattgaacc attgaaatgt tcagttcttt gcttttgagc 1440
aaaacgtcaa ttaaaactaa agtaaaatcc taaaaaaaaa aaaaaaaaaa aaaaa 1495
<210> 30
<211> 72
<212> PRT
<213> Homo sapiens
<400> 30
Met Leu Arg Pro Ala Leu Pro Trp Leu Cys Leu Gly Leu Cys Ser Leu
1 5 10 15
Leu Val Gly Glu Ala Glu Ala Pro Ser Pro Val Asp Pro Leu Glu Arg
20 25 30
Ser Arg Pro Tyr Ala Val Leu Arg Gly Gln Asn Leu Val Leu Met Gly
35 40 45
Thr Ile Phe Ser Ile Leu Leu Val Thr Val Ile Leu Met Ala Phe Cys
50 55 60
Val Tyr Lys Pro Ile Arg Arg Arg
65 70
<210> 31
<211> 2714
<212> DNA
<213> Homo Sapiens
<400> 31
tatccgccag ttgcaggagc aacactatca gcagtacatg cagcagttgt atcaagtcca 60
gcttgcacag caacaggcag cattacagaa acaacaggaa gtagtagtgg ctgggttttc 120
cttgcctaca tcatcaaaag tgaatgcaac tgtaccaagt aatatgatgt cagttaatgg 180
acaggccaaa acacacactg acagctccga aaaagaactg gaaccagaag ctgcagaaga 240
agccctggag aatggaccaa aagaatctct tccagtaata gcagctccat ccatgtggac 300
acgacctcag atcaaagact tcaaagagaa gattcagcag gatgcagatt ccgtgattac 360
agtgggccga ggagaagtgg tcactgttcg agtacccacc catgaagaag gatcatatct 420
cttttgggaa tttgccacag acaattatga cattgggttt ggggtgtatt ttgaatggac 480
agactctcca aacactgctg tcagcgtgca tgtcagtgag tccagcgatg acgacgagga 540
ggaagaagaa aacatcggtt gtgaagagaa agccaaaaag aatgccaaca agcctttgct 600
31



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
ggatgagatt gtgcctgtgt accgacggga ctgtcatgag gaggtgtatg ctggcagcca 660
tcaatatcca gggagaggag tctatctcct caagtttgac aactcctact ctttgtggcg 720
gtcaaaatca gtctactaca gagtctatta tactagataa aaatgttgtt acaaagtctg 780
gagtctaggg ttgggcagaa gatgacattt aatttggaaa tttcttttta cttttgtgga 840
gcattagagt cacagtttac cttattgata ttggtctgat ggtttgtgaa ctcttgctgg 900
gaatcaaaat ttccttgaga ctctttagca ttcatacttt ggggttaaag gagattcctc 960
agactcatcc agcccttggg tgctgaccag cagagtcact agtggatgct gaagttacat 1020
gagctacatg ttaaatattt aaagtctcca aaataaaaca ccccaacgtt gaccttaccc 1080
ggctgatggt tagccccttg ctgcctgctc catgtgtctt atgagagccc gtagttacag 1140
tgtcctctaa tttgaaatcc ataagttaac aagtctatat caggtgcagc tggctttgat 1200
taaaggccat ttttaaaact taaaaactca acacctcaca gattataata gaaaaagaaa 1260
tggcctcagt ttgatctcgt tcagaatgac ccagattgtt tctgctttgg gtgcagctgt 1320
ttagttcaga gttatattac agagaattat tttctgagat aatcttaaac tagaatgttc 1380
aaaactaatt gataattgaa gtatcaagat acgtagaaca cctcagagat ttttcttcag 1440
gaacttccac aaactttgaa tccttgtatc tttatttggt attcatacta ctagtagcaa 1500
aatacaggtt ttttgttttg ttttgttttg ttttggcttc atagagtatc tcaaattgaa 1560
acttttctgc acaaagaata aaattaagga ttttataaac tcaaattggc acctactgaa 1620
ttaaaataca taaaatcatt taaatataat tcagcatatg ggaagtaaca ttgcactaat 1680
atggaaatca ctgccagaga cagtctattt tcttttaatt tgttactact tagtcacaaa 1740
ccccacatta ttccagtttg gaattactta ttaaggagaa ttggaaatac atatgcccat 1800
gcttaaattt tatagcttta atttgtgtta tttctttatt gacgggaaga ggtacatctt 1860
tttttcctta ctgaaaacaa atatggatta attgcctcaa atttgtataa gtgattggct 1920
agtgattctt gttttcagaa gggagagtgg tatagataga aaatgacaaa gatggcaata 1980
tacacttaat gttgttattg tatgttgtta ctgaagtact tagattttta aaatttcaaa 2040
tcctaaatca cttcttgtag gagggttttc attaactgca gtatatacag ttcactacat 2100
atgggttgtt tgagtttttt gtgtgctgta tttctttctg ttttttaata cctggttttg 2160
tacatatcta actctgttct cttttggttg ttcagaaact ggattttttt ttttcttaag 2220
cagtgcttaa tttgtgtttt ttaattttga ttcagaagta gtcccagctc ataggtgttc 2280
atactgttac atccagaaca tttgtcaggc tctctgtcag ctttcatgta catatggtat 2340
agaaaccatg gagttaggca cttcctggat ttttttttta tgagaaaaat actgtattta 2400
aaatgtaaaa taaactttta aaaagcaggc actaatatat atttcttcca gcctttgatc 2460
acaaatttgt ccttgcacat gttaagatga attatctcct aaaaatatca ttgttcttgg 2520
gagcagtgta tgttacttta catagcagcg gttcctgtca tgtgttcatg tcagaatatt 2580
tttggtttta aactttctta ttgcctttgg ctgttgatta gtacagtaca agtgcgattt 2640
caaaaagatc ttgaaagtaa tatatttaat caattaaaat gtttatctgt aaaaaaaaaa 2700
aaaaaaaaaa aaaa 2714
<210> 32
<211> 240
<212> PRT
<213> Homo Sapiens
<400> 32
Met Gln Gln Leu Tyr Gln Val Gln Leu Ala Gln Gln Gln Ala Ala Leu
1 5 10 15
Gln Lys Gln Gln Glu Val Val Val Ala Gly Phe Ser Leu Pro Thr Ser
20 25 30
Ser Lys Val Asn Ala Thr Val Pro Ser Asn Met Met Ser Val Asn Gly
35 40 45
Gln Ala Lys Thr His Thr Asp Ser Ser Glu Lys Glu Leu Glu Pro Glu
50 55 60
Ala Ala Glu Glu Ala Leu Glu Asn Gly Pro Lys Glu Ser Leu Pro Val
65 70 75 80
Ile Ala Ala Pro Ser Met Trp Thr Arg Pro Gln Ile Lys Asp Phe Lys
85 90 95
32



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
.Glu Lys Ile Gln Gln Asp Ala Asp Ser Val Ile Thr Val Gly Arg Gly
100 105 110
Glu Val Val Thr Val Arg Val Pro Thr His Glu Glu Gly Ser Tyr Leu
115 120 125
Phe Trp Glu Phe Ala Thr Asp Asn Tyr Asp Ile Gly Phe Gly Val Tyr
130 135 140
Phe Glu Trp Thr Asp Ser Pro Asn Thr Ala Val Ser Val His Val Ser
145 150 155 160
Glu Ser Ser Asp Asp Asp Glu Glu Glu Glu Glu Asn Ile Gly Cys Glu
165 170 175
Glu Lys Ala Lys Lys Asn Ala Asn Lys Pro Leu Leu Asp Glu Ile Val
180 185 190
Pro Val Tyr Arg Arg Asp Cys His Glu Glu Val Tyr Ala Gly Ser His
195 200 205
Gln Tyr Pro Gly Arg Gly Val Tyr Leu Leu Lys Phe Asp Asn Ser Tyr
210 215 220
Ser Leu Trp Arg Ser Lys Ser Val Tyr Tyr Arg Val Tyr Tyr Thr Arg
225 230 235 240
<210> 33
<211> 1136
<212> DNA
<213> Homo Sapiens
<400> 33
tagttctctt ccatttataa gactcactcc tccatcccaa cccctgcacc acaggacaag 60
gaagtgttct tggtcttcaa ctttcatccc tgatggtgaa agcagttgct cctgacctat 120
ttgcccacca gcttctcctc tggagcctga ggcttctgat gcctgcctgg ctggttctca 180
gtaagaaggt caagttcaac cagaggggag atgctgatgc ctttcagtac ttaaatatga 240
gttcagaccc tggggcctgg acataagatt tggggtcccc tggatataag atttctgaaa 300
acactcagac tgtggagacc cctgctgagg gagaagctcc aaactgtggc ttcaggggaa 360
tgcaccaagg ctctcattga ggccaccttc tccaacaagc tcccctcctg cttccccatg 420
gctggcatgg ctgaggaaaa aggacactga gcacagcccg tgcatgagcg gcttgccatg 480
caacaggata aaacccataa tgccactcag caagccttgg ttgtaaatct agtttgatta 540
catttgtaat caaatgatgg ccatttgttc tgtttctggt ttgtgaacca actgaagaca 600
taagcagggc ctcagctaac ccacaaatag cacatgtgtg caaactggaa aaatgaaccc 660
ttcttctggg aggacgccag cccaggccag gtcacccggc ttggccagca gaacacagag 720
tggattttgg tcccgtttgt tccccagtgg ggtatctatc cttgtgcagg gcacaagcct 780
acatggtggc tctggtcata tcattagaaa atagacagaa atgggctgca caccagaatg 840
aatgaattga attgaaaggg aggagtgatg gtggaaaaaa aaacaagtca attcatttag 900
actggtagaa ccagaaccac tgtgtagtac atccaaacgg ttaaaattcc ctggaagatg 960
ttacataatc ctatcatggt gtttatttat ggaaatctat tttaaaaatt ttatgtaata 1020
ctgcacagtc tgtttgcatg atgccttgta cgtagtagca actcagtaaa tactttttga 1080
atgaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 1136
<210> 34
<211> 57
<212> PRT
<213> Homo Sapiens
33



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<400> 34
Met Val Lys Ala Val Ala Pro Asp Leu Phe Ala His Gln Leu Leu Leu
10 15
Trp Ser Leu Arg Leu Leu Met Pro Ala Trp Leu Val Leu Ser Lys Lys
20 25 30
Val Lys Phe Asn Gln Arg Gly Asp Ala Asp Ala Phe Gln Tyr Leu Asn
35 40 45
Met Ser Ser Asp Pro Gly Ala Trp Thr
50 55
<210> 35
<211> 1394
<212> DNA
<213> Homo Sapiens
<400> 35
gagggtgctg agcgtgtgac cagcagtgag cagaggccgg ccatggccag cctggggctg 60
ctgctcctgc tcttactgac agcactgcca ccgctgtggt cctcctcact gcctgggctg 120
gacactgctg aaagtaaagc caccattgca gacctgatcc tgtctgcgct ggagagagcc 180
accgtcttcc tagaacagag gctgcctgaa atcaacctgg atggcatggt gggggtccga 240
gtgctggaag agcagctaaa aagtgtccgg gagaagtggg cccaggagcc cctgctgcag 300
ccgctgagcc tgcgcgtggg gatgctgggg gagaagctgg aggctgccat ccagagatcc 360
ctccactacc tcaagctgag tgatcccaag tacataagag agttccagct gaccctccag 420
cccgggtttt ggaagctccc acatgcctgg atccacactg atgcctcctt ggtgtacccc 480
acgttcgggc ctcaggactc attctcagag gagagaagtg acgtgtgcct ggtgcagctg 540
ctgggaaccg ggacggacag cagcgagccc tgcggcctct cagacctctg caggagcctc 600
atgaccaagc ccggctgctc aggctactgc ctgtcccacc aactgctctt cttcctctgg 660
gccagaatga gggggtgcac acagggacca ctccaacaga gccaggacta tatcaacctc 720
ttctgcgcca acatgatgga cttgaaccgc agagctgagg ccatcggata cgcctaccct 780
acccgggaca tcttcatgga aaacatcatg ttctgtggaa tgggcggctt ctccgacttc 840
tacaagctcc ggtggctgga ggccattctc agctggcaga aacagcagga aggatgcttc 900
ggggagcctg atgctgaaga tgaagaatta tctaaagcta ttcaatatca gcagcatttt 960
tcgaggagag tgaagaggcg agaaaaacaa tttccagatg gctgctcctc ccacaacaca 1020
gccacagcag tggcagccct gggtggcttc ctatacatcc tggcagaata ccccccagca 1080
aacagagagc cacacccatc cacaccgcca ccaccaagca gccgctgaga cggacggttc 1140
catgccagct gcctggagga ggaacagacc cctttagtcc tcatccctta gatcctggag 1200
ggcacggatc acatcctggg aagaaggcat ctggaggata agcaaagcca ccccgacacc 1260
caatcttgga agccctgagt aggcagggcc agggtaggtg ggggccggga gggacccagg 1320
tgtgaacgga tgaataaagt tcaactgcaa ctgaaaaaaa aaaaaaaaaa aaaaaaaaaa 1380
aaaaaaaaaa aaaa 1394
<210> 36
<211> 361
<212> PRT
<213> Homo Sapiens
<400> 36
Met Ala Ser Leu Gly Leu Leu Leu Leu Leu Leu Leu Thr Ala Leu Pro
1 5 10 15
Pro Leu Trp Ser Ser Ser Leu Pro Gly Leu Asp Thr Ala Glu Ser Lys
20 25 30
Ala Thr Ile Ala Asp Leu Ile Leu Ser Ala Leu Glu Arg Ala Thr Val
35 40 45
34



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Phe Leu Glu Gln Arg Leu Pro Glu Ile Asn Leu Asp Gly Met Val Gly
50 55 60
Val Arg Val Leu Glu Glu Gln Leu Lys Ser Val Arg Glu Lys Trp Ala
65 70 75 80
Gln Glu Pro Leu Leu Gln Pro Leu Ser Leu Arg Val Gly Met Leu Gly
85 90 95
Glu Lys Leu Glu Ala Ala Ile Gln Arg Ser Leu His Tyr Leu Lys Leu
100 105 110
Ser Asp Pro Lys Tyr Ile Arg Glu Phe Gln Leu Thr Leu Gln Pro Gly
115 120 125
Phe Trp Lys Leu Pro His Ala Trp Ile His Thr Asp Ala Ser Leu Val
130 135 140
Tyr Pro Thr Phe Gly Pro Gln Asp Ser Phe Ser Glu Glu Arg Ser Asp
145 150 155 160
Val Cys Leu Val Gln Leu Leu Gly Thr Gly Thr Asp Ser Ser Glu Pro
165 170 175
Cys Gly Leu Ser Asp Leu Cys Arg Ser Leu Met Thr Lys Pro Gly Cys
180 185 190
Ser Gly Tyr Cys Leu Ser His Gln Leu Leu Phe Phe Leu Trp Ala Arg
195 200 205
Met Arg Gly Cys Thr Gln Gly Pro Leu Gln Gln Ser Gln Asp Tyr Ile
210 215 220
Asn Leu Phe Cys Ala Asn Met Met Asp Leu Asn Arg Arg Ala Glu Ala
225 230 235 240
Ile Gly Tyr Ala Tyr Pro Thr Arg Asp Ile Phe Met Glu Asn Ile Met
245 250 255
Phe Cys Gly Met Gly Gly Phe Ser Asp Phe Tyr Lys Leu Arg Trp Leu
260 265 270
Glu Ala Ile Leu Ser Trp Gln Lys Gln Gln Glu Gly Cys Phe Gly Glu
275 280 285
Pro Asp Ala Glu Asp Glu Glu Leu Ser Lys Ala Ile Gln Tyr Gln Gln
290 295 300
His Phe Ser Arg Arg Val Lys Arg Arg Glu Lys Gln Phe Pro Asp Gly
305 310 315 320
Cys Ser Ser His Asn Thr Ala Thr Ala Val Ala Ala Leu Gly Gly Phe
325 330 335
Leu Tyr Ile Leu Ala Glu Tyr Pro Pro Ala Asn Arg Glu Pro His Pro
340 345 350
Ser Thr Pro Pro Pro Pro Ser Ser Arg
355 360



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 37
<211> 1138
<212> DNA
<213> Homo Sapiens
<400> 37
tctcttcttt gtccccttgt cttacctgct gatggtgact gtcatcctcc tcccctatgt 60
cagcaaggtc accggctggt gcagagacag gctcctgggc cacagggagc cctcggctca 120
cccagtggaa gtcttctcgt ttgacctcca cgagccactc agcaaggagc gcgtggaagc 180
cttcagcgac ggagtctacg ccatcgtggc cacgcttctc atcctggaca tctgcgaaga 240
caacgtcccg gaccccaagg atgtgaagga gaggttcagc ggcagcctcg tggccgccct 300
gagtgcgacc gggccgcgct tcctggcgta cttcggctcc ttcgccacag tgggactgct 360
gtggttcgcc caccactcac tcttcctgca tgtgcgcaag gccacgcggg ccatggggct 420
gctgaacacg ctctcgctgg ccttcgtggg tggcctccca ctagcctacc agcagacctc 480
ggccttcgcc cggcagcccc gcgatgagct ggagcgcgtg cgtgtcagct gcaccatcat 540
cttcctggcc agcatcttcc agctggccac gtggaccacg gcgctgctgc accaggcgga 600
gacgctgcag ccctcggtgt ggtttggcgg ccgggagcat gtgctcatgt tcgccaagct 660
ggcgctgtac ccctgtgcca gcctgctggc cttcgcctcc acctgcctgc tgagcaggtt 720
cagtgtgggc atcttccacc tcatggagat cgccgtgccc tgcgccttcc tgttgctgcg 780
cctgctcgtg ggcctggccc tggccaccct gcgggtcctg cggggcctcg cccggcccga 840
acaccccccg ccagccccca cgggccagga cgacccacag tcccagctcc tccctgcccc 900
ctgctagcag ccacagagcc cactcccagc cgtcctcacc agagatggac cagggaggac 960
aggatgctgg gcaggggaag ccaagtcacg ggcaggccgc agtggttctt gcgtggcctg 1020
gttttatttt cgttgtgaaa tatcatgctc ttatttcagt cctcaaaaaa aaaaaaaaaa 1080
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1138
<210> 38
<211> 291
<212> PRT
<213> Homo Sapiens
<400> 38
Met Val Thr Val Ile Leu Leu Pro Tyr Val Ser Lys Val Thr Gly Trp
1 5 10 15
Cys Arg Asp Arg Leu Leu Gly His Arg Glu Pro Ser Ala His Pro Val
20 25 30
Glu Val Phe Ser Phe Asp Leu His Glu Pro Leu Ser Lys Glu Arg Val
35 40 45
Glu Ala Phe Ser Asp Gly Val Tyr Ala Ile Val Ala Thr Leu Leu Ile
50 55 60
Leu Asp Ile Cys Glu Asp Asn Val Pro Asp Pro Lys Asp Val Lys Glu
65 70 75 80
Arg Phe Ser Gly Ser Leu Val Ala Ala Leu Ser Ala Thr Gly Pro Arg
85 90 95
Phe Leu Ala Tyr Phe Gly Ser Phe Ala Thr Val Gly Leu Leu Trp Phe
100 105 110
Ala His His Ser Leu Phe Leu His Val Arg Lys Ala Thr Arg Ala Met
115 120 125
Gly Leu Leu Asn Thr Leu Ser Leu Ala Phe Val Gly Gly Leu Pro Leu
130 135 140
36



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Ala Tyr Gln Gln Thr Ser Ala Phe Ala Arg Gln Pro Arg Asp Glu Leu
145 150 155 160
Glu Arg Val Arg Val Ser Cys Thr Ile Ile Phe Leu Ala Ser Ile Phe
165 170 175
Gln Leu Ala Thr Trp Thr Thr Ala Leu Leu His Gln Ala Glu Thr Leu
180 185 190
Gln Pro Ser Val Trp Phe Gly Gly Arg Glu His Val Leu Met Phe Ala
195 200 205
Lys Leu Ala Leu Tyr Pro Cys Ala Ser Leu Leu Ala Phe Ala Ser Thr
210 215 220
Cys Leu Leu Ser Arg Phe Ser Val Gly Ile Phe His Leu Met Glu Ile
225 230 235 240
Ala Val Pro Cys Ala Phe Leu Leu Leu Arg Leu Leu Val Gly Leu Ala
245 250 255
Leu Ala Thr Leu Arg Val Leu Arg Gly Leu Ala Arg Pro Glu His Pro
260 265 270
Pro Pro Ala Pro Thr Gly Gln Asp Asp Pro Gln Ser Gln Leu Leu Pro
275 280 285
Ala Pro Cys
290
<210> 39
<211> 1478
<212> DNA
<213> Homo sapiens
<400> 39
agagggggct gctgaccatg ctggaactgc ggcgactact gagcctgcgg gaacctcccc 60
tttcgcccaa gatctgctct gtccccctca tcctcctccc agggccctgg cgtctgggtc 120
aagcagcgcc ccacacctcg acccctcacc ccctcctccc gggctcttcc tgcggcctcc 180
cctccacagt ccgcaggctc tgggacagga ccgagtcctt ggctgcctgt ggagctcctg 240
tgccagcagc tgcgccccgg ctgcgctccg gataccccca tccccgccac cgccgacctc 300
ccgctccacc gactgctgct cacgcccgac gggttcacgc cgcccctgcc ccgtgaagga 360
ccgcgctgcg gtgcggaggc aggatgacgc aaaacacggt gattgtgaat ggagttgcta 420
tggcctctag gccatcccag cccacccacg tcaacgtcca catccaccag gagtcagctt 480
tgacacaact gctgaaagct ggaggttctc tgaagaagtt tctttttcac cctggggaca 540
ctgtgccttc cacagccagg attggttatg agcagctggc tctaggggtg actcagatat 600
tgctgggggt tgtgagttgt gttcttggag tgtgtctcag cttggggccc tggactgtgc 660
tgagtgcctc aggctgtgcc ttctgggcgg ggtctgtggt gatcgcagca ggagctgggg 720
ccattgtcca tgagaagcac ccgggcaaac ttgctggcta tatatccagc ctgctcaccc 780
tggcaggctt tgctacagct atggctgctg ttgtcctctg cgtgaatagc ttcatctggc 840
aaactgaacc ctttttatac atcgacactg tgtgtgatcg ctcagaccct gtcttcccta 900
ccactgggta cagatggatg cggcgaagtc aagagaacca atggcagaag gaggagtgta 960
gagcttacat gcagatgctg aggaagttgt tcacagcaat ccgtgccctg ttcctggctg 1020
tctgtgtctt gaaggtcatt gtgtccttgg tttccttggg agtaggtctt cgaaacttgt 1080
ttggccagag ctcccagccc ctgaatgagg aaggatcaga gaagaggcta ctgggggaga 1140
attcagtgcc cccttcgccc tctagggagc agacctccac tgccattgtc ctgtgagctg 1200
ccaaagaccc cacggggtgc ccgcatgtcc ctgtctaggg cagcccaggg cccccactcc 1260
tggctcctca cacttgcctc ccctatggcc gctctccaga ccctcctcct ttcttctccc 1320
cacatccgca cctgctgttc ccactctggg gttctcaagt ccatgaacag atattgttgc 1380
37



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
attttccaca atgctgatta aacataataa acaatccaga aaagcagttt tgcccagaaa 1440
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1478
<210> 40
<211> 270
<212> PRT
<213> Homo sapiens
<400> 40
Met Thr Gln Asn Thr Val Ile Val Asn Gly Val Ala Met Ala Ser Arg
1 5 10 15
Pro Ser Gln Pro Thr His Val Asn Val His Ile His Gln Glu Ser Ala
20 25 30
Leu Thr Gln Leu Leu Lys Ala Gly Gly Ser Leu Lys Lys Phe Leu Phe
35 40 45
His Pro Gly Asp Thr Val Pro Ser Thr Ala Arg Ile Gly Tyr Glu Gln
50 55 60
Leu Ala Leu Gly Val Thr Gln Ile Leu Leu Gly Val Val Ser Cys Val
65 70 75 80
Leu Gly Val Cys Leu Ser Leu Gly Pro Trp Thr Val Leu Ser Ala Ser
85 90 95
Gly Cys Ala Phe Trp Ala Gly Ser Val Val Ile Ala Ala Gly Ala Gly
100 105 110
Ala Ile Val His Glu Lys His Pro Gly Lys Leu Ala Gly Tyr Ile Ser
115 120 125
Ser Leu Leu Thr Leu Ala Gly Phe Ala Thr Ala Met Ala Ala Val Val
130 135 140
Leu Cys Val Asn Ser Phe Ile Trp Gln Thr Glu Pro Phe Leu Tyr Ile
145 150 155 160
Asp Thr Val Cys Asp Arg Ser Asp Pro Val Phe Pro Thr Thr Gly Tyr
165 170 175
Arg Trp Met Arg Arg Ser Gln Glu Asn Gln Trp Gln Lys Glu Glu Cys
180 185 190
Arg Ala Tyr Met Gln Met Leu Arg Lys Leu Phe Thr Ala Ile Arg Ala
195 200 205
Leu Phe Leu Ala Val Cys Val Leu Lys Val Ile Val Ser Leu Val Ser
210 215 220
Leu Gly Val Gly Leu Arg Asn Leu Phe Gly Gln Ser Ser Gln Pro Leu
225 230 235 240
Asn Glu Glu Gly Ser Glu Lys Arg Leu Leu Gly Glu Asn Ser Val Pro
245 250 255
Pro Ser Pro Ser Arg Glu Gln Thr Ser Thr Ala Ile Val Leu
260 265 270
38



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 41
<211> 2828
<212> DNA
<213> Homo Sapiens
<400> 41
atcccagagt gctccctcca ggcctgcttc ttggttttgt ttgatcactg cgttcttcaa 60
gggatgaatc cagagccctc catgaggcca agcttgtcct tcaatcatgt ttcctctcag 120
atgcgtccgt gatgcctcct aatgtggaac tggttgtcca ttgtttgggc ctatggccaa 180
gtcacccagc tgtggaagca gaggtagaag acgaggccag ccaggagggc gacttcagtc 240
acagctccca tgcctcagct ttgtacctgt tttcaaaagc acaactgagg tgtgcgggct 300
ggagctgtct tgcagtgatt ctggccttct ggctcatggt tcagtccagc agcctggctg 360
acccactatt tctcctctgc ttcagaggaa acccaggaaa tgcccttact gccaggctga 420
gtctccaccc atgctggttg gtgctggcta ggctgagggg gccaccactt ttcctggcta 480
gaagctactt gacctttgat gtttgagttc tgtaagtctt cgtgttctga cttactgctt 540
cagagggatt ggcctgtccc ctttcccttt ctcggctatg ggaaggaagg attgctcatt 600
ggttgccttc atcagttaca gcatgagacg gaattcatca ttccttccga aacccctgat 660
atttaatatt taatatttaa aaacccaaat tatcaaacca ttaagaactc attactggtt 720
ctcagcctcc tccagtacta gcctcagtgt ggctgctgca taagtatctg tagcctgtct 780
acctcctgca gtggggccgc tcgcctcttc cctgtctact gctcaggctc tcccacttcg 840
tggcatccat gtaaagtagg tggcagggca gagatgtcac tctcattcaa cagggaggat 900
gtctgttgct cagagaggtt gtcctgaggg gctgggtgat tcctgggcct acattcttcc 960
cgaggctcca ggccgctgtc tctggaagta aaagagcctt gtctgacctt aatgcaagca 1020
gtctgtttga acccctgtag gctgcattca ggagacagaa ggtgtctggg ccatcctggg 1080
cggccggtca gcgttgctag gcaggctcgg ctgtctggcc gggacttggg cctgggtggc 1140
ttttgagacc agtgaagaag ggagagccgg cctcatgccg atggggcttg tggcacggct 1200
gggatgtgag ggaggactca gatctacaca cagaaacccc tcttctcccc gccctccccc 1260
agctcctacc tgcctcccac gcctcaggtg tggctgcctg tgggaccatc ccccaacccc 1320
tttcctcgca cctccttgtc ctcacccagt tcctgcagtg tctctgaccc acgcctcccg 1380
cctcctggcc gacttgccca ggaggtgtct ctggctcacc tccgtctgtt catcaccttc 1440
ctccccagtg tttccactta tcttggatgt tttagattga aacagcctga ttcccggaag 1500
aatcctcttc attcattgct agtgcttccc ctcacctccc actctccact tcccagtttg 1560
caaatgtggc tttcgcccac caagtgaaag cggactgaga gcagcccttg gggacggccc 1620
ggtgcctggc tgcaaggccg cgctggggct ctgtcttggt gcacatggct tgaccggact 1680
ttccctgctt cccaccactt ccctcactcc cagacctccc tcattctttt tgtctcttct 1740
ttttgcctaa agccagtcct taacacccta ttcttcctct gcaggtggct tgcagacttt 1800
tccccacctt tggggctcgt ggtggtggag agggcagctg gtgttaagaa tgtaggttac 1860
cgggcatgac ccggcagatg cttgcccagt agttctggag gaaggcccgg gaatctgcaa 1920
atgagcgcat tccccaggca gttcccatgc aggtgatcca cggaccacat gttgagaaac 1980
tgcagtcacc cttagggcca caccgtccct ctcctcgctg tcccctctct gtagtgactg 2040
gccctgacct tcaggagtgc actttccact ctaccaggaa gccctatgac atcctcaggc 2100
tccccagacc tgcagcttgc atggggcccc tcccttcttc cacacccacc ctccgtatgg 2160
tcccctgctc tgccctcgtg ctttgctggc ccctgcccgc tactcccact ctcagacacc 2220
caggggtggt gggccctaac tggctggccc ctcccagcgc tgccctctgc cgtccagatg 2280
ctgcagtgtg gccagattta ccttccagta acatacttct agtcacccct cctcctgcga 2340
agtgatctgc agtggctgtt tgaccagacc acaaagttca catctcctga gcttagtgtc 2400
cgtggctgtc cacctcccag ccatacttga ctgtccccaa actctccctg cagccacatg 2460
tttcccatga cctgtgggct ctgcagatgg acctctctcc gctagagatg cccttctccc 2520
aaatggcttc cctcctggaa ggcccagcct gagtcctcgt ctcctttcca gtgcttctgc 2580
cagaagcatc cccatgatgt tgtgaccgca cagcactttg tgtctcgctt tgagcacttg 2640
ccactctggc tggtgctgct gccactgatt gtgtactgtc ttgctgccct ttctagactg 2700
tgagctcctc gtgggcaggg accgcctgtg ttctctgtat ttcccacggc gcctagcaca 2760
gtgccttgca cttgataggt gcttaataaa tgtctgctca actgaaaaaa aaaaaaaaaa 2820
aaaaaaaa 2828
<210> 42
<211> 124
<212> PRT
<213> Homo Sapiens
39



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<400> 42
Met Pro Pro Asn Val Glu Leu Val Val His Cys Leu Gly Leu Trp Pro
1 5 10 15
Ser His Pro Ala Val Glu Ala Glu Val Glu Asp Glu Ala Ser Gln Glu
20 25 30
Gly Asp Phe Ser His Ser Ser His Ala Ser Ala Leu Tyr Leu Phe Ser
35 40 45
Lys Ala Gln Leu Arg Cys Ala Gly Trp Ser Cys Leu Ala Val Ile Leu
50 55 60
Ala Phe Trp Leu Met Val Gln Ser Ser Ser Leu Ala Asp Pro Leu Phe
65 70 75 80
Leu Leu Cys Phe Arg Gly Asn Pro Gly Asn Ala Leu Thr Ala Arg Leu
85 90 95
Ser Leu His Pro Cys Trp Leu Val Leu Ala Arg Leu Arg Gly Pro Pro
100 105 110
Leu Phe Leu Ala Arg Ser Tyr Leu Thr Phe Asp Val
115 120
<210> 43
<211> 646
<212> DNA
<213> Homo Sapiens
<400> 43
attcgccgcc cggcccctgc tccgtggctg gttttctccg cgggcgcctc gggcggaacc 60
tggagataat gggcagcacc tgggggagcc ctggctgggt gcggctcgct ctttgcctga 120
cgggcttagt gctctcgctc tacgcgctgc acgtgaaggc ggcgcgcgcc cgggaccggg 180
attaccgcgc gctctgcgac gtgggcaccg ccatcagctg ttcgcgcgtc ttctcctcca 240
ggtggggcag gggtttcggg ctggtggagc atgtgctggg acaggacagc atcctcaatc 300
aatccaacag catattcggt tgcatcttct acacactaca gctattgtta ggttgcctgc 360
ggacacgctg ggcctctgtc ctgatgctgc tgagccttgc ctaagggggc atatctgggt 420
ccctagaagg ccctagatgt ggggcttcta gattaccccc tcctcctgcc atacccgcac 480
atgacaatgg accaaatgtg ccacacgctc gctctttttt acacccagtg cctctgactc 540
tgtccccatg ggctggtctc caaagctctt tccattgccc agggagggaa ggttctgagc 600
aataaagttt cttagatcaa tcaaaaaaaa aaaaaaaaaa aaaaaa 646
<210> 44
<211> 111
<212> PRT
<213> Homo Sapiens
<400> 44
Met Gly Ser Thr Trp Gly Ser Pro Gly Trp Val Arg Leu Ala Leu Cys
1 5 10 15
Leu Thr Gly Leu Val Leu Ser Leu Tyr Ala Leu His Val Lys Ala Ala
20 25 30
Arg Ala Arg Asp Arg Asp Tyr Arg Ala Leu Cys Asp Val Gly Thr Ala
35 40 45



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Ile Ser Cys Ser Arg Val Phe Ser Ser Arg Trp Gly Arg Gly Phe Gly
50 55 60
Leu Val Glu His Val Leu Gly Gln Asp Ser Ile Leu Asn Gln Ser Asn
65 70 75 80
Ser Ile Phe Gly Cys Ile Phe Tyr Thr Leu Gln Leu Leu Leu Gly Cys
85 90 95
Leu Arg Thr Arg Trp Ala Ser Val Leu Met Leu Leu Ser Leu Ala
100 105 110
<210> 45
<211> 1612
<212> DNA
<213> Homo Sapiens
<400> 45
atcttatcgc gactaaacgg agtggcggcg gcatttcctg gtgtctgagc ctggcgcgga 60
ggctatgggc agccaggagg tgctgggcca cgcggcccgg ctggcctcct ccggtctcct 120
cctgcaggtg ttgtttcggt tgatcacctt tgtcttgaat gcatttattc ttcgcttcct 180
gtcaaaggaa atcgttggcg tagtaaatgt aagactaacg ctgctttact caaccaccct 240
cttcctggcc agagaggcct tccgcagagc atgtctcagt gggggcaccc agcgagactg 300
gagccagacc ctcaacctgc tgtggctaac agtccccctg ggtgtgtttt ggtccttatt 360
cctgggctgg atctggttgc agctgcttga agtgcctgat cctaatgttg tccctcacta 420
tgcaactgga gtggtgctgt ttggtctctc ggcagtggtg gagcttctag gagagccctt 480
ttgggtcttg gcacaagcac atatgtttgt gaagctcaag gtgattgcag agagcctgtc 540
ggtaattctt aagagcgttc tgacagcttt tctcgtgctg tggttgcctc actggggatt 600
gtacattttc tctttggccc agcttttcta taccacagtt ctggtgctct gctatgttat 660
ttatttcaca aagttactgg gttccccaga atcaaccaag cttcaaactc ttcctgtctc 720
cagaataaca gatctgttac ccaatattac aagaaatgga gcgtttataa actggaaaga 780
ggctaaactg acttggagtt ttttcaaaca gtctttcttg aaacagattt tgacagaagg 840
cgagcgatat gtgatgacat ttttgaatgt attgaacttt ggtgatcagg gtgtgtatga 900
tatagtgaat aatcttggct cccttgtggc cagattaatt ttccagccaa tagaggaaag 960
tttttatata ttttttgcta aggtgctgga gaggggaaag gatgccacac ttcagaagca 1020
ggaggacgtt gctgtggctg ctgcagtctt ggagtccctg ctcaagctgg ccctgctggc 1080
cggcctgacc atcactgttt ttggctttgc ctattctcag ctggctctgg atatctacgg 1140
agggaccatg cttagctcag gatccggtat tcctctgctg tgagcagggc tggccagcca 1200
gactggcaca cattgctgtg ggggccttct gtctgggagc aactctcggg acagcattcc 1260
tcacagagac caagctgatc catttcctca ggactcagtt aggtgtgccc agacgcactg 1320
acaaaatgac gtgacttcag ggaagcctgg acacccgagg cacctggacc agctatgggt 1380
agttctgtgg gtggaacaca ttctgtgtaa gagccccact gagggctctg cagcggagtg 1440
acagcaaccc cagagatgag gcaccagaga gtgccactgc atgagacacc tgtgaccatt 1500
cgaagtctga aatgcggggg gggagtttca tttttaagtg aagaccaaaa gcccttttga 1560
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1612
<210> 46
<211> 372
<212> PRT
<213> Homo Sapiens
<400> 46
Met Gly Ser Gln Glu Val Leu Gly His Ala Ala Arg Leu Ala Ser Ser
1 5 10 15
Gly Leu Leu Leu Gln Val Leu Phe Arg Leu Ile Thr Phe Val Leu Asn
20 25 30
Ala Phe Ile Leu Arg Phe Leu Ser Lys Glu Ile Val Gly Val Val Asn
41



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
35 40 45
Val Arg Leu Thr Leu Leu Tyr Ser Thr Thr Leu Phe Leu Ala Arg Glu
50 55 60
Ala Phe Arg Arg Ala Cys Leu Ser Gly Gly Thr Gln Arg Asp Trp Ser
65 70 75 80
Gln Thr Leu Asn Leu Leu Trp Leu Thr Val Pro Leu Gly Val Phe Trp
85 90 95
Ser Leu Phe Leu Gly Trp Ile Trp Leu Gln Leu Leu Glu Val Pro Asp
100 105 110
Pro Asn Val Val Pro His Tyr Ala Thr Gly Val Val Leu Phe Gly Leu
115 120 125
Ser Ala Val Val Glu Leu Leu Gly Glu Pro Phe Trp Val Leu Ala Gln
130 135 140
Ala His Met Phe Val Lys Leu Lys Val Ile Ala Glu Ser Leu Ser Val
145 150 155 160
Ile Leu Lys Ser Val Leu Thr Ala Phe Leu Val Leu Trp Leu Pro His
165 170 175
Trp Gly Leu Tyr Ile Phe Ser Leu Ala Gln Leu Phe Tyr Thr Thr Val
180 185 190
Leu Val Leu Cys Tyr Val Ile Tyr Phe Thr Lys Leu Leu Gly Ser Pro
195 200 205
Glu Ser Thr Lys Leu Gln Thr Leu Pro Val Ser Arg Ile Thr Asp Leu
210 215 220
Leu Pro Asn Ile Thr Arg Asn Gly Ala Phe Ile Asn Trp Lys Glu Ala
225 230 235 240
Lys Leu Thr Trp Ser Phe Phe Lys Gln Ser Phe Leu Lys Gln Ile Leu
245 250 255
Thr Glu Gly Glu Arg Tyr Val Met Thr Phe Leu Asn Val Leu Asn Phe
260 265 270
Gly Asp Gln Gly Val Tyr Asp Ile Val Asn Asn Leu Gly Ser Leu Val
275 280 285
Ala Arg Leu Ile Phe Gln Pro Ile Glu Glu Ser Phe Tyr Ile Phe Phe
290 295 300
Ala Lys Val Leu Glu Arg Gly Lys Asp Ala Thr Leu Gln Lys Gln Glu
305 310 315 320
Asp Val Ala Val Ala Ala Ala Val Leu Glu Ser Leu Leu Lys Leu Ala
325 330 335
Leu Leu Ala Gly Leu Thr Ile Thr Val Phe Gly Phe Ala Tyr Ser Gln
340 , 345 350
Leu Ala Leu Asp Ile Tyr Gly Gly Thr Met Leu Ser Ser Gly Ser Gly
42



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
355 360 365
Ile Pro Leu Leu
370
<210> 47
<211> 3094
<212> DNA
<213,> Homo Sapiens
<400> 47
gaggctgtcc aggcgcaatg tggtggctgc ttctctgggg agtcctccag gcttgcccaa 60
cccggggctc cgtcctcttg gcccaagagc taccccagca gctgacatcc cccgggtacc 120
cagagccgta tggcaaaggc caagagagca gcacggacat caaggctcca gagggctttg 180
ctgtgaggct cgtcttccag gacttcgacc tggagccgtc ccaggactgt gcaggggact 240
ctgtcacaat ctcattcgtc ggttcggatc caagccagtt ctgtggtcag caaggctccc 300
ctctgggcag gccccctggt cagagggagt ttgtatcctc agggaggagt ttgcggctga 360
ccttccgcac acagccttcc tcggagaaca agactgccca cctccacaag ggcttcctgg 420
ccctctacca aaccgtggct gtgaactata gtcagcccat cagcgaggcc agcaggggct 480
ctgaggccat caacgcacct ggagacaacc ctgccaaggt ccagaaccac tgccaggagc 540
cctattatca ggccgcggca gcaggggcac tcacctgtgc aaccccaggg acctggaaag 600
acagacagga tggggaggag gttcttcagt gtatgcctgt ctgcggacgg ccagtcaccc 660
ccattgccca gaatcagacg accctcggtt cttccagagc caagctgggc aacttcccct 720
ggcaagcctt caccagtatc cacggccgtg ggggcggggc cctgctgggg gacagatgga 780
tcctcactgc tgcccacacc gtctacccca aggacagtgt ttctctcagg aagaaccaga 840
gtgtgaatgt gttcttgggc cacacagcca tagatgagat gctgaaactg gggaaccacc 900
ctgtccaccg tgtcgttgtg caccccgact accgtcagaa tgagtcccat aactttagcg 960
gggacatcgc cctcctggag ctgcagcaca gcatccccct gggccccaac gtcctcccgg 1020
tctgtctgcc cgataatgag accctctacc gcagcggctt gttgggctac gtcagtgggt 1080
ttggcatgga gatgggctgg ctaactactg agctgaagta ctcgaggctg cctgtagctc 1140
ccagggaggc ctgcaacgcc tggctccaaa agagacagag acccgaggtg ttttctgaca 1200
atatgttctg tgttggggat gagacgcaaa ggcacagtgt ctgccagggg gacagtggca 1260
gcgtctatgt ggtatgggac aatcatgccc atcactgggt ggccacgggc attgtgtcct 1320
ggggcatagg gtgtggcgaa gggtatgact tctacaccaa ggtgctcagc tatgtggact 1380
ggatcaaggg agtgatgaat ggcaagaatt gaccctgggg gcttgaacag ggactgacca 1440
gcacagtgga ggccccaggc aacagagggc ctggagtgag gactgaacac tggggtaggg 1500
gttgggggtg gggggttggg ggaggcaggg aaatcctatt cacatcactg ttgcaccaag 1560
ccactgcaag agaaaccccc acccggcaag cccgccccat cccagacagg aagcagagtc 1620
ccacagaccg ctcctcctca ccctctacct ccctgtgctc atgcactagg ccccgggaag 1680
cctgtacatc tcaacaactt tcgccttgaa tgtccttaga accaccttcc cctacttcat 1740
ctgttgacac agcttttata ctcacctgtg gaagagtcag ctactcaccc gctattagag 1800
tatggaggaa ggggttttca ttgcattgca tttctgaaac attcctaaga ccctttagtt 1860
gaccttcaaa tattcaagct attctgcagc tccaagatgc aattatagaa acagctcctt 1920
ttttatttta tgtcctctat atgccaggtg cttcacctgt tatttcactt aatcctcata 1980
ccatatttgc aaaggatgtg ttattatcta tgtgtgacaa atgaggaaac tgaggctcag 2040
gggataaagg gacttgccca agtcccacag ctggtgtgtg actgcagaga ctgtgctctt 2100
cccagtgtgc tgcaatactt ctcaaccctc ctctaacctg ctgtgtcacc cgctttccct 2160
cccagccccc acatccttac cattttccct ccctgggaat tcctgcttct gcgaaaatgg 2220
tatcctctag ctcacacttt cctaatggcc ccatctcctg cagaagccag gtgagcccag 2280
cactggactg aagttcttgc agacacccca cctgtgcccc tatcatcagg ggaactgctc 2340
cacctgagag gaccaactct ttaattttta gtaaaacctg gaggtgatgg gccgggcgca 2400
gtggctcacg cctgtaatcc caacacctta ggagtccgag gtgggtggat cacgaggtca 2460
ggagatccag cccatcctgg ccaacatggt gaaaccccat ctctactaaa aatacaaaaa 2520
ttagccgggc gtggtgacac gtgcctgtag tcccagctac tcgggaggct gaggcaggag 2580
aatcacttga acctgggagg cggaggttgc agtgagctaa gatcacgcca ctgcactcca 2640
gcctgcggac agaccaagac ttcatccccc ccaaaaaaaa aagattggag gtgatttaca 2700
gtgaaagaca caaataaaat acaactgttc aatggaaata gaaaataaac accataaaag 2760
agagaagaga ggtaatttgt tagcatcaag agtcaagttg ctatatggtc aaaggttaaa 2820
tttatctcta aaaaatggca ggattcaaag ttgtacatac atgtgattac ttctgttttt 2880
43



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340


tacacccacatacagtac aa agattatta aatattcccaaaaggcaggtgcaatgat 2940
a aa


gcacacttatacccccagcc ctcaggagg gatgcaagaggatcgcttgagcccagga 3000
a ct


gttgaagtccagcctaagca catagtgaa cccatctccaaaaatataataataattc 3060
a ac


tctcaaaaaaaaaaaaaaaa aaaaaaaaa aa 3094
a aa


<210>
48


<211>
464


<212>
PRT


<213> sapiens
Homo


<400>
48


Met Trp LeuLeuLeuTrpGly ValLeuGlnAlaCysProThrArg
Trp


1 5 10 15


Gly Ser LeuLeuAlaGlnGlu LeuProGlnGlnLeuThrSerPro
Val


20 25 30


Gly Tyr GluProTyrGlyLys GlyGlnGluSerSerThrAspIle
Pro


35 40 45


Lys Ala GluGlyPheAlaVal ArgLeuValPheGlnAspPheAsp
Pro


50 55 60


Leu Glu SerGlnAspCysAla GlyAspSerValThrIleSerPhe
Pro


65 70 75 80


Val Gly AspProSerGlnPhe CysGlyGlnGlnGlySerProLeu
Ser


85 90 95


Gly Arg ProGlyGlnArgGlu PheValSerSerGlyArgSerLeu
Pro


100 105 110


Arg Leu PheArgThrGlnPro SerSerGluAsnLysThrAlaHis
Thr


115 120 125


Leu His GlyPheLeuAlaLeu TyrGlnThrValAlaValAsnTyr
Lys


130 135 140


Ser Gln IleSerGluAlaSer ArgGlySerGluAlaIleAsnAla
Pro


145 150 155 160


Pro Gly AsnProAlaLysVal GlnAsnHisCysGlnGluProTyr
Asp


165 170 175


Tyr Gln AlaAlaAlaGlyAla LeuThrCysAlaThrProGlyThr
Ala


180 185 190


Trp Lys ArgGlnAspGlyGlu GluValLeuGlnCysMetProVal
Asp


195 200 205


Cys Gly ProValThrProIle AlaGlnAsnGlnThrThrLeuGly
Arg


210 215 220


Ser Ser AlaLysLeuGlyAsn PheProTrpGlnAlaPheThrSer
Arg


225 230 235 240


Ile His ArgGlyGlyGlyAla LeuLeuGlyAspArgTrpIleLeu
Gly


245 250 255


Thr Ala HisThrValTyrPro LysAspSerValSerLeuArgLys
Ala


44



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
260 265 270
Asn Gln Ser Val Asn Val Phe Leu Gly His Thr Ala Ile Asp Glu Met
275 280 285
Leu Lys Leu Gly Asn His Pro Val His Arg Val Val Val His Pro Asp
290 295 300
Tyr Arg Gln Asn Glu Ser His Asn Phe Ser Gly Asp Ile Ala Leu Leu
305 310 315 320
Glu Leu Gln His Ser Ile Pro Leu Gly Pro Asn Val Leu Pro Val Cys
325 330 335
Leu Pro Asp Asn Glu Thr Leu Tyr Arg Ser Gly Leu Leu Gly Tyr Val
340 345 350
Ser Gly Phe Gly Met Glu Met Gly Trp Leu Thr Thr Glu Leu Lys Tyr
355 360 365
Ser Arg Leu Pro Val Ala Pro Arg Glu Ala Cys Asn Ala Trp Leu Gln
370 375 380
Lys Arg Gln Arg Pro Glu Val Phe Ser Asp Asn Met Phe Cys Val Gly
385 390 395 400
Asp Glu Thr Gln Arg His Ser Val Cys Gln Gly Asp Ser Gly Ser Val
405 410 415
Tyr Val Val Trp Asp Asn His Ala His His Trp Val Ala Thr Gly Ile
420 425 430
Val Ser Trp Gly Ile Gly Cys Gly Glu Gly Tyr Asp Phe Tyr Thr Lys
435 440 445
Val Leu Ser Tyr Val Asp Trp Ile Lys Gly Val Met Asn Gly Lys Asn
450 455 460
<210> 49
<211> 2927
<212> DNA
<213> Homo Sapiens
<400> 49
tgctttgcag gcccaggctc aaggcaaatt ataagtaggg aaccaatttg agggaaagac 60
atgtgaacag agttaaggta ccacgtcctg ggagcgacca gcagccccac ctgaagtccg 120
catgcaactc tgacaagctc aggtgcttgt tttaaggaaa ggggctacta gagtcttacc 180
aacagcgagc ccaggtggga gatgaaacag gtactcccca aaataggtca tccgagggag 240
gaaaactgat ggagagcaca atgtgctctg agcgttttta atgtttttaa gcttttaaat 300
gatttcttca aggccgagca gcagcagcaa aggtgtggct taaaggatta agggggtttc 360
tgctggcacc tagaatgaag ttactctatt actaatcaag ccgagaggag gcccactatg 420
cccccgttta tcatcctttc ccagttcctt tttgctggtc acaaaacgat gctcatcaat 480
cccacctaaa gcaggaggcc aggagcccag cctcttgtag aaacagcgag ggtataactg 540
ccctcccgtt ctgcccccaa gacgaaggag gactctcgga agccaagaaa ggtttaagaa 600
gtctttctgg atagagagca gtgcccaggc aggaagcctt tcgccggcag agcggggtcc 660
gaggacgagc tggagaggac agaggcgcga tgggcctgct gcagggcttg ctccgagtcc 720
ggaagctgct gctggtcgtc tgcgtcccgc tcctgctgct gcctctgccc gtcctccacc 780
ccagcagcga ggcctcgtgt gcttacgtgc tgatcgtgac tgctgtgtac tgggtgtcgg 840
aggcagtgcc tctgggagct gcagccctgg tgccggcctt cctctacccg ttcttcggag 900



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
tcctccggtc caatgaggtg gcggcggagt acttcaagaa caccacgctg ctgctggtgg 960
gggtcatctg cgtggcggct gccgtggaga agtggaacct gcataagcgc attgctctgc 1020
gcatggtctt gatggccggg gccaagccgg gcatgctgct gctctgcttc atgtgctgta 1080
ccacgttgct gtccatgtgg ctgtccaaca cctccaccac cgccatggtg atgcccatcg 1140
tggaggccgt gctgcaggag ctggtcagtg ctgaggacga gcagctcgtg gcgggcaact 1200
ccaacaccga agaggccgaa cccatcagtc tggatgtaaa gaacagccaa ccttctctgg 1260
aactcatctt tgtcaatgaa gacaggtcca acgcagacct caccactctg atgcacaacg 1320
agaacctgaa tggtgtgccc tcgatcacca accccatcaa aactgcaaac caacaccagg 1380
gcaagaagca acacccatcc caggaaaagc cacaagtcct gacccccagc cccaggaagc 1440
agaagctgaa cagaaagtac aggtcccacc atgaccagat gatctgcaag tgcctctccc 1500
tgagcatatc ctactccgct accattggcg gcctgaccac catcatcggc acctccacca 1560
gcctcatctt cctggaacac ttcaacaacc agtatccagc cgcagaggtg gtgaactttg 1620
gcacctggtt cctcttcagc ttccccatat ccctcatcat gctggtggtc agctggttct 1680
ggatgcactg gctgttcctg ggctgcaatt ttaaagagac ctgctctctg agcaagaaga 1740
agaagaccaa aagggaacag ttgtcagaga agaggatcca agaagaatat gaaaaactgg 1800
gagacattag ctacccagaa atggtgactg gatttttctt catcctgatg accgtactgt 1860
ggtttacccg ggagcctggc tttgtccctg gctgggattc tttctttgaa aagaaaggct 1920
accgtactga tgccacagtc tctgtcttcc ttggcttcct cctcttcctc attccagcga 1980
agaagccctg ctttgggaaa aagaatgatg gagagaacca ggagcactca ctggggaccg 2040
agcccatcat cacgtggaag gacttccaga agaccatgcc ctgggagatt gtcattctgg 2100
ttgggggagg ctatgctctg gcttctggta gcaagagctc tggcctctct acatggattg 2160
ggaaccagat gttgtccctg agcagcctcc caccgtgggc tgtcaccctg ctggcatgca 2220
tcctcgtgtc cattgtcact gagtttgtga gcaacccagc aaccatcacc atcttcctgc 2280
ccatcctgtg cagcctgtct gaaacgctgc acattaaccc cctctacacc ctgatcccag 2340
tcaccatgtg catctccttt gcagtgatgc tgcctgtggg caatccccct aatgccatcg 2400
tcttcagcta tgggcactgc cagatcaaag atatggtgaa agctggcctg ggagtcaacg 2460
ttattggact ggtgatagta atggtggcca tcaacacctg gggagttagc ctcttccacc 2520
tggacactta cccagcatgg gcgagggtca gcaacatcac tgatcaagcc taacgccaag 2580
tgtacaaact ggcccaacca caggagctgc cagtatccag cagtatctgg accacaggca 2640
aagaaaacca ctaggaccac caggagcaca caaccccaga cccacgccgg agggcatccc 2700
tccaccagaa gattccgcca cctcaagtga actgcaggaa tcctccaaca accacaaaca 2760
catgcttcgc tgttagtgtc ttcttcctgc cctcagcacc acagctcaag aaaacctaaa 2820
gtttcaatac aagccatagg ctcacagaaa aagaaaaaga aaataaaaat taaattaaaa 2880
aaaaagaaga caaagaaaac ctaaaaaaaa aaaaaaaaaa aaaaaaa 2927
<210> 50
<211> 627
<212> PRT
<213> Homo Sapiens
<400> 50
Met Gly Leu Leu Gln Gly Leu Leu Arg Val Arg Lys Leu Leu Leu Val
1 5 10 15
Val Cys Val Pro Leu Leu Leu Leu Pro Leu Pro Val Leu His Pro Ser
20 25 30
Ser Glu Ala Ser Cys Ala Tyr Val Leu Ile Val Thr Ala Val Tyr Trp
35 40 45
Val Ser Glu Ala Val Pro Leu Gly Ala Ala Ala Leu Val Pro Ala Phe
50 55 60
Leu Tyr Pro Phe Phe Gly Val Leu Arg Ser Asn Glu Val Ala Ala Glu
65 70 75 80
Tyr Phe Lys Asn Thr Thr Leu Leu Leu Val Gly Val Ile Cys Val Ala
85 90 95
Ala Ala Val Glu Lys Trp Asn Leu His Lys Arg Ile Ala Leu Arg Met
46



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
100 105 110
Val Leu Met Ala Gly Ala Lys Pro Gly Met Leu Leu Leu Cys Phe Met
115 120 125
Cys Cys Thr Thr Leu Leu Ser Met Trp Leu Ser Asn Thr Ser Thr Thr
130 135 140
Ala Met Val Met Pro Ile Val Glu Ala Val Leu Gln Glu Leu Val Ser
145 150 155 160
Ala Glu Asp Glu Gln Leu Val Ala Gly Asn Ser Asn Thr Glu Glu Ala
165 170 175
Glu Pro Ile Ser Leu Asp Val Lys Asn Ser Gln Pro Ser Leu Glu Leu
180 185 190
Ile Phe Val Asn Glu Asp Arg Ser Asn Ala Asp Leu Thr Thr Leu Met
195 200 205
His Asn Glu Asn Leu Asn Gly Val Pro Ser Ile Thr Asn Pro Ile Lys
210 215 220
Thr Ala Asn Gln His Gln Gly Lys Lys Gln His Pro Ser Gln Glu Lys
225 230 235 240
Pro Gln Val Leu Thr Pro Ser Pro Arg Lys Gln Lys Leu Asn Arg Lys
245 250 255
Tyr Arg Ser His His Asp Gln Met Ile Cys Lys Cys Leu Ser Leu Ser
260 265 270
Ile Ser Tyr Ser Ala Thr Ile Gly Gly Leu Thr Thr Ile Ile Gly Thr
275 280 285
Ser Thr Ser Leu Ile Phe Leu Glu His Phe Asn Asn Gln Tyr Pro Ala
290 295 300
Ala Glu Val Val Asn Phe Gly Thr Trp Phe Leu Phe Ser Phe Pro Ile
305 310 315 320
Ser Leu Ile Met Leu Val Val Ser Trp Phe Trp Met His Trp Leu Phe
325 330 335
Leu Gly Cys Asn Phe Lys Glu Thr Cys Ser Leu Ser Lys Lys Lys Lys
340 345 350
Thr Lys Arg Glu Gln Leu Ser Glu Lys Arg Ile Gln Glu Glu Tyr Glu
355 360 365
Lys Leu Gly Asp Ile Ser Tyr Pro Glu Met Val Thr Gly Phe Phe Phe
370 375 380
Ile Leu Met Thr Val Leu Trp Phe Thr Arg Glu Pro Gly Phe Val Pro
385 390 395 400
Gly Trp Asp Ser Phe Phe Glu Lys Lys Gly Tyr Arg Thr Asp Ala Thr
405 410 415
Val Ser Val Phe Leu Gly Phe Leu Leu Phe Leu Ile Pro Ala Lys Lys
47



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
420 425 430
Pro Cys Phe Gly Lys Lys Asn Asp Gly Glu Asn Gln Glu His Ser Leu
435 440 445
Gly Thr Glu Pro Ile Ile Thr Trp Lys Asp Phe Gln Lys Thr Met Pro
450 455 460
Trp Glu Ile Val Ile Leu Val Gly Gly Gly Tyr Ala Leu Ala Ser Gly
465 470 475 480
Ser Lys Ser Ser Gly Leu Ser Thr Trp Ile Gly Asn Gln Met Leu Ser
485 490 495
Leu Ser Ser Leu Pro Pro Trp Ala Val Thr Leu Leu Ala Cys Ile Leu
500 505 510
Val Ser Ile Val Thr Glu Phe Val Ser Asn Pro Ala Thr Ile Thr Ile
515 520 525
Phe Leu Pro Ile Leu Cys Ser Leu Ser Glu Thr Leu His Ile Asn Pro
530 535 540
Leu Tyr Thr Leu Ile Pro Val Thr Met Cys Ile Ser Phe Ala Val Met
545 550 555 560
Leu Pro Val Gly Asn Pro Pro Asn Ala Ile Val Phe Ser Tyr Gly His
565 570 575
Cys Gln Ile Lys Asp Met Val Lys Ala Gly Leu Gly Val Asn Val Ile
580 585 590
Gly Leu Val Ile Val Met Val Ala Ile Asn Thr Trp Gly Val Ser Leu
595 600 605
Phe His Leu Asp Thr Tyr Pro Ala Trp Ala Arg Val Ser Asn Ile Thr
610 615 620
Asp Gln Ala
625
<210> 51
<211>. 2134
<212> DNA
<213> Homo Sapiens
<400> 51
gaacctttag ggtgcgcggg tgcagtatat ctcgcgctct ctcccctttc cccctcccct 60
ttccccaccc cgggcgctca ggttggtctg gaccggaagc gaagatggcg acttctggcg 120
cggcctcggc ggagctggtg atcggctggt gcatattcgg cctcttacta ctggctattt 180
tggcattctg ctggatatat gttcgtaaat accaaagtcg gcgggaaagt gaagttgtct 240
ccaccataac agcaattttt tctctagcaa ttgcacttat cacatcagca cttctaccag 300
tggatatatt tttggtttct tacatgaaaa atcaaaatgg tacatttaag gactgggcta 360
atgctaatgt cagcagacag attgaggaca ctgtattata cggttactat actttatatt 420
ctgttatatt gttctgtgtg ttcttctgga tcccttttgt ctacttctat tatgaagaaa 480
aggatgatga tgatactagt aaatgtactc aaattaaaac ggcactcaag tatactttgg 540
gatttgttgt gatttgtgca ctgcttcttt tagttggtgc ctttgttcca ttgaatgttc 600
ccaataacaa aaattctaca gagtgggaaa aagtgaagtc cctatttgaa gaacttggaa 660
gtagtcatgg tttagctgca ttgtcatttt ctatcagttc tctgaccttg attggaatgt 720
48



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
tggcagctat aacttacaca gcctatggca tgtctgcgtt acctttaaat ctgataaaag 780
gcactagaag cgctgcttat gaacgtttgg aaaacactga agacattgaa gaagtagaac 840
aacacattca aacgattaaa tcaaaaagca aagatggtcg acctttgcca gcaagggata 900
aacgcgcctt aaaacaattt gaagaaaggt tacgaacact taagaagaga gagaggcatt 960
tagaattcat tgaaaacagc tggtggacaa aattttgtgg cgctctgcgt cccctgaaga 1020
tcgtctgggg aatatttttc atcttagttg cattgctgtt tgtaatttct ctcttcttgt 1080
caaatttaga taaagctctt cattcagctg gaatagattc tggtttcata atttttggag 1140
ctaacctgag taatccactg aatatgcttt tgcctttact acaaacagtt ttccctcttg 1200
attatattct tataacaatt attattatgt actttatttt tacttcaatg gcaggaattc 1260
gaaatattgg catatggttc ttttggatta gattatataa aatcagaaga ggtagaacca 1320
ggccccaagc actccttttt ctctgcatga tacttctgct tattgtcctt cacactagct 1380
acatgattta tagtcttgct ccccaatatg ttatgtatgg aagccaaaat tacttaatag 1440
agactaatat aacttctgat aatcataaag gcaattcaac cctttctgtg ccaaagagat 1500
gtgatgcaga agctcctgaa gatcagtgta ctgttacccg gacataccta ttccttcaca 1560
agttctggtt cttcagtgct gcttactatt ttggtaactg ggcctttctt ggggtatttt 1620
tgattggatt aattgtatcc tgttgtaaag ggaagaaatc ggttattgaa ggagtagatg 1680
aagattcaga cataagtgat gatgagccct ctgtctattc tgcttgacag ccttctgtct 1740
taaaggtttt ataatgctga ctgaatatct gttatgcatt tttaaagtat taaactaaca 1800
ttaggatttg ctaactagct ttcatcaaaa atgggagcat ggctataaga caactatatt 1860
ttattatatg ttttctgaag taacattgta tcatagatta acattttaaa ttaccataat 1920
catgctatgt aaatataaga ctactggctt tgtgagggaa tgtttgtgca aaattttttc 1980
ctctaatgta taatagtgtt aaattgatta aaaatcttcc agaattaata ttcccttttg 2040
tcactttttg aaaacataat aaatcatttg tatctgtgaa aaaaaaaaaa aaaaaaaaaa 2100
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa 2134
<210> 52
<211> 540
<212> PRT
<213> Homo Sapiens
<400> 52
Met Ala Thr Ser Gly Ala Ala Ser Ala Glu Leu Val Ile Gly Trp Cys
1 5 10 15
Ile Phe Gly Leu Leu Leu Leu Ala Ile Leu Ala Phe Cys Trp Ile Tyr
20 25 30
Val Arg Lys Tyr Gln Ser Arg Arg Glu Ser Glu Val Val Ser Thr Ile
35 40 45
Thr Ala Ile Phe Ser Leu Ala Ile Ala Leu Ile Thr Ser Ala Leu Leu
50 55 60
Pro Val Asp Ile Phe Leu Val Ser Tyr Met Lys Asn Gln Asn Gly Thr
65 70 75 80
Phe Lys Asp Trp Ala Asn Ala Asn Val Ser Arg Gln Ile Glu Asp Thr
85 90 95
Val Leu Tyr Gly Tyr Tyr Thr Leu Tyr Ser Val Ile Leu Phe Cys Val
100 105 110
Phe Phe Trp Ile Pro Phe Val Tyr Phe Tyr Tyr Glu Glu Lys Asp Asp
115 120 125
Asp Asp Thr Ser Lys Cys Thr Gln Ile Lys Thr Ala Leu Lys Tyr Thr
130 135 140
Leu Gly Phe Val Val Ile Cys Ala Leu Leu Leu Leu Val Gly Ala Phe
145 150 155 160
49



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Val Pro Leu Asn Val Pro Asn Asn Lys Asn Ser Thr Glu Trp Glu Lys
165 170 175
Val Lys Ser Leu Phe Glu Glu Leu Gly Ser Ser His Gly Leu Ala Ala
180 185 190
Leu Ser Phe Ser Ile Ser Ser Leu Thr Leu Ile Gly Met Leu Ala Ala
195 200 205
Ile Thr Tyr Thr Ala Tyr Gly Met Ser Ala Leu Pro Leu Asn Leu Ile
210 215 220
Lys Gly Thr Arg Ser Ala Ala Tyr Glu Arg Leu Glu Asn Thr Glu Asp
225 230 235 240
Ile Glu Glu Val Glu Gln His Ile Gln Thr Ile Lys Ser Lys Ser Lys
245 250 255
Asp Gly Arg Pro Leu Pro Ala Arg Asp Lys Arg Ala Leu Lys Gln Phe
260 265 270
Glu Glu Arg Leu Arg Thr Leu Lys Lys Arg Glu Arg His Leu Glu Phe
275 280 285
Ile Glu Asn Ser Trp Trp Thr Lys Phe Cys Gly Ala Leu Arg Pro Leu
290 295 300
Lys Ile Val Trp Gly Ile Phe Phe Ile Leu Val Ala Leu Leu Phe Val
305 310 315 320
Ile Ser Leu Phe Leu Ser Asn Leu Asp Lys Ala Leu His Ser Ala Gly
325 330 335
Ile Asp Ser Gly Phe Ile Ile Phe Gly Ala Asn Leu Ser Asn Pro Leu
340 345 350
Asn Met Leu Leu Pro Leu Leu Gln Thr Val Phe Pro Leu Asp Tyr Ile
355 360 365
Leu Ile Thr Ile Ile Ile Met Tyr Phe Ile Phe Thr Ser Met Ala Gly
370 375 380
Ile Arg Asn Ile Gly Ile Trp Phe Phe Trp Ile Arg Leu Tyr Lys Ile
385 390 395 400
Arg Arg Gly Arg Thr Arg Pro Gln Ala Leu Leu Phe Leu Cys Met Ile
405 410 415
Leu Leu Leu Ile Val Leu His Thr Ser Tyr Met Ile Tyr Ser Leu Ala
420 425 430
Pro Gln Tyr Val Met Tyr Gly Ser Gln Asn Tyr Leu Ile Glu Thr Asn
435 440 445
Ile Thr Ser Asp Asn His Lys Gly Asn Ser Thr Leu Ser Val Pro Lys
450 455 460
Arg Cys Asp Ala Glu Ala Pro Glu Asp Gln Cys Thr Val Thr Arg Thr
465 470 475 480



CA 02362538 2001-08-16
WO 00/49134 PCT/US00104340
Tyr Leu Phe Leu His Lys Phe Trp Phe Phe Ser Ala Ala Tyr Tyr Phe
485 490 495
Gly Asn Trp Ala Phe Leu Gly Val Phe Leu Ile Gly Leu Ile Val Ser
500 505 510
Cys Cys Lys Gly Lys Lys Ser Val Ile Glu Gly Val Asp Glu Asp Ser
515 520 525
Asp Ile Ser Asp Asp Glu Pro Ser Val Tyr Ser Ala
530 535 540
<210> 53
<211> 1987
<212> DNA
<213> Homo sapiens
<400> 53
tgatggacgg agggctggaa cttgtggaaa aggctgggtg gacgcagcag ctacctgggg 60
accacccctc acacctccca ccccttcatc tgggttctgc tctccaaacc ccactgttgt 120
ctttacagac tgcggaggaa aaggaagccc cttcccaggc ccctgagggg gacgtgatct 180
cgatgcctcc cctccacaca tctgaggagg agctgggctt ctcgaagttt gtctcagcgt 240
agggcaggag gccctcctgg ccaggccagc agtgaagcag tatggctggc tggatcagca 300
ccgattcccg aaagctttcc acctcagcct cagagtccag ctgcccggac tccagggctc 360
tccccaccct ccccaggctc tcctcttgca tgttccagcc tgacctagaa gcgtttgtca 420
gccctggagc ccagagcggt ggccttgctc ttccggctgg agactgggac atccctgata 480
ggttcacatc cctgggcaga gtaccaggct gctgaccctc agcagggcca gacaaggctc 540
agtggatctg gtctgagttt caatctgcca ggaactcctg ggcctcatgc ccagtgtcgg 600
accctgcctt cctcccactc cagaccccac cttgtcttcc ctccctggcg tcctcagact 660
tagtcccacg gtctcctgca tcagctggtg atgaagagga gcatgctggg gtgagactgg 720
gattctggct tctctttgaa ccacctgcat cccagccctt caggaagcct gtgaaaaacg 780
tgattcctgg gccccaccaa gacccaccaa aaccatctct ggggcttggt gcaggactct 840
gaatttctaa caatgcccag tgactgtcgc acttgagttt gagggccagt gggcctgatg 900
aacgctcaga cccctccagc ttagagtctg catttgggct gtgacgtctc ccacctgccc 960
caataagatc tgctctgtct gcgacaccaa gatccagctg gggactcccc tgaggcctgc 1020
ctaagtccag gccttggtca ggtcaggtgc acattgcagg gataagccca ggaccggcag 1080
agagtggttg cctttccatt tgccctccct ggccatgcct tcttgccttt ggaaaaatga 1140
tgaagaaaac cttggctcct tccttgtctg gaaagggtta cttgcctatg ggttctggtg 1200
gctagagaga aaagtagaaa accagagtgc acgtaggtgt ctaacacaga ggagagtagg 1260
aacagggcgg atacctgaag gtgactccga gtccagcccc ctggagaagg ggtcgggggt 1320
ggtggtaaag tagcacaact actatttttt ttctttttcc attattattg ttttttaaga 1380
cagaatctcg tgctgctgcc caggctggag tgcagtggca cgatctgcaa actccgcctc 1440
ctgggttcaa gtgattcttc tgcctcagcc tcccgagtag ctgggattac aggcacgcac 1500
caccacacct ggctaatttt tgtactttta gtagagatgg ggtttcacca tgttggccag 1560
gctggtcttg aactcctgac ctcaaatgag cctcctgctt cagtctccca aattgccggg 1620
attacaggca tgagccactg tgtctggccc tatttccttt aaaaagtgaa attaagagtt 1680
gttcagtatg caaaacttgg aaagatggag gagaaaaaga aaaggaagaa aaaaatgtca 1740
cccatagtct caccagagac tatcattatt tcgttttgtt gtacttcctt ccactctttt 1800
cttcttcaca taatttgccg gtgttctttt tacagagcaa ttatcttgta tatacaactt 1860
tgtatcctgc cttttccacc ttatcgttcc atcactttat tccagcactt ctctgtgttt 1920
tacagacctt tttataaata aaatgttcat cagctgcata ttccaaaaaa aaaaaaaaaa 1980
aaaaaaa 1987
<210> 54
<211> 79
<212> PRT
<213> Homo sapiens
51



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<400> 54
Met Asp Gly Gly Leu Glu Leu Val Glu Lys Ala Gly Trp Thr Gln Gln
1 5 10 15
Leu Pro Gly Asp His Pro Ser His Leu Pro Pro Leu His Leu Gly Ser
20 25 30
Ala Leu Gln Thr Pro Leu Leu Ser Leu Gln Thr Ala Glu Glu Lys Glu
35 40 45
Ala Pro Ser Gln Ala Pro Glu Gly Asp Val Ile Ser Met Pro Pro Leu
50 55 60
His Thr Ser Glu Glu Glu Leu Gly Phe Ser Lys Phe Val Ser Ala
65 70 75
<210> 55
<211> 1747
<212> DNA
<213> Homo sapiens
<400> 55
gtgcggactg gcctcccaag cgtggggcga caagctgccg gagctgcaat gggccgcggc 60
tggggattct tgtttggcct cctgggcgcc gtgtggctgc tcagctcggg ccacggagag 120
gagcagcccc cggagacagc ggcacagagg tgcttctgcc aggttagtgg ttacttggat 180
gattgtacct gtgatgttga aaccattgat agatttaata actacaggct tttcccaaga 240
ctacaaaaac ttcttgaaag tgactacttt aggtattaca aggtaaacct gaagaggccg 300
tgtcctttct ggaatgacat cagccagtgt ggaagaaggg actgtgctgt caaaccatgt 360
caatctgatg aagttcctga tggaattaaa tctgcgagct acaagtattc tgaagaagcc 420
aataatctca ttgaagaatg tgaacaagct gaacgacttg gagcagtgga tgaatctctg 480
agtgaggaaa cacagaaggc tgttcttcag tggaccaagc atgatgattc ttcagataac 540
ttctgtgaag ctgatgacat tcagtcccct gaagctgaat atgtagattt gcttcttaat 600
cczgagcgct acactggtta caagggacca gatgcttgga aaatatggaa tgtcatctac 660
gaagaaaact gttttaagcc acagacaatt aaaagacctt taaatccttt ggcttctggt 720
caagggacaa gtgaagagaa cactttttac agttggctag aaggtctctg tgtagaaaaa 780
agagcattct acagacttat atctggccta catgcaagca ttaatgtgca tttgagtgca 840
agatatcttt tacaagagac ctggttagaa aagaaatggg gacacaacat tacagaattt 900
caacagcgat ttgatggaat tttgactgaa ggagaaggtc caagaaggct taagaacttg 960
tattttctct acttaataga actaagggct ttatccaaag tgttaccatt cttcgagcgc 1020
ccagattttc aactctttac tggaaataaa attcaggatg aggaaaacaa aatgttactt 1080
ctggaaatac ttcatgaaat caagtcattt cctttgcatt ttgatgagaa ttcatttttt 1140
gctggggata aaaaagaagc acacaaacta aaggaggact ttcgactgca ttttagaaat 1200
atttcaagaa ttatggattg tgttggttgt tttaaatgtc gtctgtgggg aaagcttcag 1260
actcagggtt tgggcactgc tctgaagatc ttattttctg agaaattgat agcaaatatg 1320
ccagaaagtg gacctagtta tgaattccat ctaaccagac aagaaatagt atcattattc 1380
aacgcatttg gaagaatttc tacaagtgtg aaagaattag aaaacttcag gaacttgtta 1440
cagaatattc attaaagaaa acaagctgat atgtgcctgt ttctggacaa tggaggcgaa 1500
agagtggaat ttcattcaaa ggcataatag caatgacagt cttaagccaa acattttata 1560
taaagttgct tttgtaaagg agaattatat tgttttaagt aaacacattt ttaaaaattg 1620
tgttaagtct atgtataata ctactgtgag taaaagtaat actttaataa tgtggtacaa 1680
attttaaagt ttaatattga ataaaaggag gattatcaaa ttcaaaaaaa aaaaaaaaaa 1740
aaaaaaa 1747
<210> 56
<211> 468
<212> PRT
<213> Homo sapiens
<400> 56
52



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Met Gly Arg Gly Trp Gly Phe Leu Phe Gly Leu Leu Gly Ala Val Trp
1 5 10 15
Leu Leu Ser Ser Gly His Gly Glu Glu Gln Pro Pro Glu Thr Ala Ala
20 25 30
Gln Arg Cys Phe Cys Gln Val Ser Gly Tyr Leu Asp Asp Cys Thr Cys
35 40 45
Asp Val Glu Thr Ile Asp Arg Phe Asn Asn Tyr Arg Leu Phe Pro Arg
50 55 60
Leu Gln Lys Leu Leu Glu Ser Asp Tyr Phe Arg Tyr Tyr Lys Val Asn
65 70 75 80
Leu Lys Arg Pro Cys Pro Phe Trp Asn Asp Ile Ser Gln Cys Gly Arg
85 90 95
Arg Asp Cys Ala Val Lys Pro Cys Gln Ser Asp Glu Val Pro Asp Gly
100 105 110
Ile Lys Ser Ala Ser Tyr Lys Tyr Ser Glu Glu Ala Asn Asn Leu Ile
115 120 125
Glu Glu Cys Glu Gln Ala Glu Arg Leu Gly Ala Val Asp Glu Ser Leu
130 135 140
Ser Glu Glu Thr Gln Lys Ala Val Leu Gln Trp Thr Lys His Asp Asp
145 150 155 160
Ser Ser Asp Asn Phe Cys Glu Ala Asp Asp Ile Gln Ser Pro Glu Ala
165 170 175
Glu Tyr Val Asp Leu Leu Leu Asn Pro Glu Arg Tyr Thr Gly Tyr Lys
180 185 190
Gly Pro Asp Ala Trp Lys Ile Trp Asn Val Ile Tyr Glu Glu Asn Cys
195 200 205
Phe Lys Pro Gln Thr Ile Lys Arg Pro Leu Asn Pro Leu Ala Ser Gly
210 215 220
Gln Gly Thr Ser Glu Glu Asn Thr Phe Tyr Ser Trp Leu Glu Gly Leu
225 230 235 240
Cys Val Glu Lys Arg Ala Phe Tyr Arg Leu Ile Ser Gly Leu His Ala
245 250 255
Ser Ile Asn Val His Leu Ser Ala Arg Tyr Leu Leu Gln Glu Thr Trp
260 265 270
Leu Glu Lys Lys Trp Gly His Asn Ile Thr Glu Phe Gln Gln Arg Phe
275 280 285
Asp Gly Ile Leu Thr Glu Gly Glu Gly Pro Arg Arg Leu Lys Asn Leu
290 295 300
Tyr Phe Leu Tyr Leu Ile Glu Leu Arg Ala Leu Ser Lys Val Leu Pro
305 310 315 320
53



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Phe Phe Glu Arg Pro Asp Phe Gln Leu Phe Thr Gly Asn Lys Ile Gln
325 330 335
Asp Glu Glu Asn Lys Met Leu Leu Leu Glu Ile Leu His Glu Ile Lys
340 345 350
Ser Phe Pro Leu His Phe Asp Glu Asn Ser Phe Phe Ala Gly Asp Lys
355 360 365
Lys Glu Ala His Lys Leu Lys Glu Asp Phe Arg Leu His Phe Arg Asn
370 375 380
Ile Ser Arg Ile Met Asp Cys Val Gly Cys Phe Lys Cys Arg Leu Trp
385 390 395 400
Gly Lys Leu Gln Thr Gln Gly Leu Gly Thr Ala Leu Lys Ile Leu Phe
405 410 415
Ser Glu Lys Leu Ile Ala Asn Met Pro Glu Ser Gly Pro Ser Tyr Glu
420 425 430
Phe His Leu Thr Arg Gln Glu Ile Val Ser Leu Phe Asn Ala Phe Gly
435 440 445
Arg Ile Ser Thr Ser Val Lys Glu Leu Glu Asn Phe Arg Asn Leu Leu
450 455 460
Gln Asn Ile His
465
<210> 57
<211> 1293
<212> DNA
<213> Homo sapiens
<400> 57
ttcgaggctg tgccccgcga ccccgccttc ggcgctcggc tcgcaggatg gatcccgtac 60
ccgggacaga ctcggcgccg ctggctggcc tggcctggtc gtcggcctct gcacccccgc 120
cgcgggggtt cagcgcgatc tcctgcaccg tcgagggggc acccgccagc tttggcaaga 180
gcttcgcgca gaaatctggc tacttcctgt gccttagttc tctgggcagc ctagagaacc 240
cgcaggagaa cgtggtggcc gatatccaga tcgtggtgga caagagcccc ctgccgctgg 300
gcttctcccc cgtctgcgac cccatggatt ccaaggcctc tgtgtccaag aagaaacgca 360
tgtgtgtgaa gctgttgccc ctgggagcca cggacacggc tgtgtttgat gtccggctga 420
gtgggaagac caagacagtg cctggatacc ttcgaatagg ggacatgggc ggctttgcca 480
tctggtgcaa gaaggccaag gccccgaggc cagtgcccaa gccccgaggt ctcagccggg 540
acatgcaggg cctctctctg gatgcagcca gccagccaag taagggcggc ctcctggagc 600
ggacagcgtc aaggctgggc tctcgggcat ccactctgcg gaggaatgac tccatctacg 660
aggcctccag cctctatggc atctcagcca tggatggggt tcccttcaca ctccacccac 720
gatttgaggg caagagctgc agccccctgg ccttctctgc ttttggggac ctgaccatca 780
agtctctggc ggacattgag gaggagtata actacggctt cgtggtggag aagaccgcgg 840
ctgcccgcct gccccccagc gtctcatagt ccctcaccct tccgcggaaa gagccccctt 900
actccacctc cccgccagcc tggggccacc ccccctcact gcatcctggg gccaccccca 960
ctcactgcat cctgggaacc ttcgccctgc aaggcgtttg ctatcttcag ccactgggcg 1020
gagctgcagc cctggaggag ggggcgggtc gaggctgcgt ggtgatgggg tctccgcccc 1080
cacgccctgc cgggcagggc tggagctgga cagaagccag tgcctttaag tcatttgtgt 1140
caaaaccctc tggggtccgg aggctgtgcg ggtgtcctcc tggcaataaa cactacccgg 1200
ttctcgccca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1260
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1293
54



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 58
<211> 273
<212> PRT
<213> Homo Sapiens
<400> 58
Met Asp Pro Val Pro Gly Thr Asp Ser Ala Pro Leu Ala Gly Leu Ala
1 5 10 15
Trp Ser Ser Ala Ser Ala Pro Pro Pro Arg Gly Phe Ser Ala Ile Ser
20 25 30
Cys Thr Val Glu Gly Ala Pro Ala Ser Phe Gly Lys Ser Phe Ala Gln
35 40 45
Lys Ser Gly Tyr Phe Leu Cys Leu Ser Ser Leu Gly Ser Leu Glu Asn
50 55 60
Pro Gln Glu Asn Val Val Ala Asp Ile Gln Ile Val Val Asp Lys Ser
65 70 75 80
Pro Leu Pro Leu Gly Phe Ser Pro Val Cys Asp Pro Met Asp Ser Lys
85 90 95
Ala Ser Val Ser Lys Lys Lys Arg Met Cys Val Lys Leu Leu Pro Leu
100 105 110
Gly Ala Thr Asp Thr Ala Val Phe Asp Val Arg Leu Ser Gly Lys Thr
115 120 125
Lys Thr Val Pro Gly Tyr Leu Arg Ile Gly Asp Met Gly Gly Phe Ala
130 135 140
Ile Trp Cys Lys Lys Ala Lys Ala Pro Arg Pro Val Pro Lys Pro Arg
145 150 155 160
Gly Leu Ser Arg Asp Met Gln Gly Leu Ser Leu Asp Ala Ala Ser Gln
165 170 175
Pro Ser Lys Gly Gly Leu Leu Glu Arg Thr Ala Ser Arg Leu Gly Ser
180 185 190
Arg Ala Ser Thr Leu Arg Arg Asn Asp Ser Ile Tyr Glu Ala Ser Ser
195 200 205
Leu Tyr Gly Ile Ser Ala Met Asp Gly Val Pro Phe Thr Leu His Pro
210 215 220
Arg Phe Glu Gly Lys Ser Cys Ser Pro Leu Ala Phe Ser Ala Phe Gly
225 230 235 240
Asp Leu Thr Ile Lys Ser Leu Ala Asp Ile Glu Glu Glu Tyr Asn Tyr
245 250 255
Gly Phe Val Val Glu Lys Thr Ala Ala Ala Arg Leu Pro Pro Ser Val
260 265 270
Ser



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 59
<211> 2941
<212> DNA
<213> Homo sapiens
<400> 59
ggactcca'gt ttagccgccg ccggagagga cgggcgccga gccggggctg cggacttcgg 60
cctgcccctc acctcactcc cgctgcttgc acctcccgga tggtgctgac tgctccctaa 120
gcggcggcgg cggcgagtcg tgaggacgcg ccgcggaggc tgttcggggt cgaggcttcc 180
cgtcgccggc acttcctctt gcggcgcccg tgcgcggccg gcccggcagg cgggatggcg 240
gccgcggctc cggggaacgg ccgcgcatcg gcgccccggc tgcttctgct ctttctggtt 300
ccgctgctgt gggccccggc tgcggtccgg gccggcccag atgaagacct tagccaccgg 360
aacaaagaac cgccggcgcc ggcccagcag ctgcagccgc agcctgtggc tgtgcagggc 420
cccgagccgg cccgggtcga ggtgagcggg ccgggatggg gcgagcgagg ctgcagggcc 480
ggctgcgccg agtaccaggc tccaggcctt tgaaagcgcc gcactccgcc ggcctcggct 540
gggggagggg agcccggccc ctgctcccgg ggtggagggc ggtcggctgc gctgttttcc 600
ggtgaggcct ggtcttgcgc gctcctttag ggaaagggag agggagagtc caagaggagc 660
ccgctataaa cgttgatctc cggagggcca agatgctgct ccgggatggg cgttttattg 720
atcagatgtg tcttagagta gctagaaaga ctcatcccta ccaaaaagtt tttaacagaa 780
ggctgctagg aggctttttg tattccctga ggatcatcac atcggccatt tcattgttga 840
aatagcttat gccaaactgc ttacccaaat tcaacttggc actgcctgtg ctttttgcca 900
aatatggatt atgaaccatg actctcactt tttaaaaatg tgctttggct agcaggaagt 960
agcctttagg aacgcagagg aattagtctc cggcagtaca gcgtgctgca gcgatgtggg 1020
atgccaaaac tacatttata agtaaaacag aatcctgtat tttgtccttc cctgaataga 1080
tactagaaat caacttttta atctgttaat agaattagtc cttagtcact tggcagcgtt 1140
ttaacatttc tcccttctcc cagtcgtggg ctttgtcgtc atttccagta tctgctccct 1200
gaatcccggc cagtgtggca ctcaaacccc cactcccacc caggccacat ccagcccatc 1260
tccacgtaac taatcttccc gaacattgaa ttctgccatc ttgtcagaag tcgtcggtga 1320
gttgcctcca ctaatttcag tccagccttt ttaggagagt gatgttcagg tttcttctga 1380
tctggctcca gctcacctcc aggcttttta gccaccgctt tcttgctcat atgctaaagg 1440
gttatgctca tctgcaaaaa agaatgtgct tcaagagccc tttgggacag gctttgtgct 1500
ctcttgccag ttcctcccta acacaagacc ttttcaaaga aaaaaaaaaa aagacctgga 1560
gtttgaagcc acggatcaac tcttcccacc ttggagaacc agcagatacc tactctctgt 1620
gaagacttcc ctaaaatttc ttggttaagg gtgatttatc tgaccctttc ctttcctttc 1680
ctttcctctc ctttctcctt tttcctttcc tctcctttct cctttttcct ttccattcct 1740
ttcatttctc ctttcctttc ctttttcctt tcctttctcc cttcctttcc tttttccttt 1800
ttctttgttg agacagggtc tcgctctgtc gcccaggctg gagtgcagtg gccccgtctt 1860
ggctcactgc aacctctaat tgatcctccc acctcagcct cctgagtggc tgggactgca 1920
tgcgtgtgct gacacgcccg gctaattttt gtttattttt tttttttgag agaggaggtc 1980
tcactatgtt gccgagtcta gtctcaaact cctgggctca agcgcttctc cggccttggc 2040
ctcccaagtg ctggtgagct ctcacaccgg tgcattgttt tcgtgtttca tgttttcgtt 2100
acatgttact ttcttaggct tttccaattt tctgttgttt ttctgtgtaa gaccgtagga 2160
tagaactttc tgagagactg atcttggttt cactaagcaa gaacatttgt aagaatcagt 2220
gctgtcccag atgtagtaat cgctattgag aaataatgaa gttcccctta ctggaagtac 2280
tcaggaagaa gttgaataac taactgccta tgaggagatt ctgatatggg agggaatctg 2340
ggagataaag ttactgggaa gtgaagattc tgggagccga tttaatcctc acaacagcac 2400
gttaaacagg tagaggaggt ttgtaaggaa tagtggttta atatcacaga gctagaagct 2460
agtttcagca gaaccagaat tagaatctgg acttctgtgc cttactaagt tttattagca 2520
ttcattgtgt cttactcttt tgacttattt aattcactaa tggattttaa tggtttattg 2580
gattgtatgc tggtgcagtt ctttgatctt gagcctagct ttctctttct ccttttttgg 2640
gaactttatt gtgtatgttg tggcatgttt acacacacat cttgctgcct tgggttcttg 2700
caagttgtgt gcgtgtttta tctgccccta ctagctttta ggtgtcttga gagcatgact 2760
ctggcttact catctgtcta ttccagaaga ccttgtctgt tcttggcatt tattaagtaa 2820
ttttctaaga ctgggttgaa gtagttgcat gtcaagttta tatcagctgt taaatacctt 2880
tctggaaaaa ctggctgtaa aataaactca accaggaaaa aaaaaaaaaa aaaaaaaaaa 2940
a
2941
<210> 60
<211> 92
56



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<212> PRT
<213> Homo Sapiens.....
<400> 60
Met Ala Ala Ala Ala Pro Gly Asn Gly Arg Ala Ser Ala Pro Arg Leu
1 5 10 15
Leu Leu Leu Phe Leu Val Pro Leu Leu Trp Ala Pro Ala Ala Val Arg
20 25 30
Ala Gly Pro Asp Glu Asp Leu Ser His Arg Asn Lys Glu Pro Pro Ala
35 40 45
Pro Ala Gln Gln Leu Gln Pro Gln Pro Val Ala Val Gln Gly Pro Glu
50 55 60
Pro Ala Arg Val Glu Val Ser Gly Pro Gly Trp Gly Glu Arg Gly Cys
65 70 75 80
Arg Ala Gly Cys Ala Glu Tyr Gln Ala Pro Gly Leu
85 90
<210> 61
<211> 1996
<212> DNA
<213> Homo Sapiens
<400> 61
actagattag tccagtgtaa gaggtagaca attcatgttg aattttctgg aattactgca 60
ggggagacct tgattcctag gagggaacta aagggatcat caaagctaag ggtggagcca 120
agcaagtggg gagaccataa gtgaaaaggg gagagtttgg agcctgatcc taccctatgc 180
tgatgtctct tcttatgtct atttcaccag gagactctct gggggccagg cctgggcttc 240
cctatgggct gagcgacgat gagtctgggg gcggccgggc actaagtgcg gagagtgaag 300
ttgaggagcc agccaggggt ccaggggagg ccaggggtga gaggccaggc ccagcctgcc 360
agctgtgtgg ggggccgaca ggtgaggggc cgtgttgtgg ggcaggaggg ccgggtgggg 420
ggcccctgct gcccccacgg ctactgtact catgccgcct ctgcaccttc gtgtcccact 480
actcgagcca cctgaagcgg cacatgcaga cacacagcgg agagaagccg ttccgctgtg 540
gccgctgccc ctacgcctca gcccagctcg tcaacctgac acgacatacc cgcacccaca 600
ctggcgagaa gccctaccgc tgtccccact gcccctttgc ctgcagcagc ctgggcaacc 660
tgaggcggca tcagcgtacc cacgcagggc cccccactcc tccctgcccg acctgtggct 720
tccgctgctg tactccacga ccagcccggc ctcccagtcc cacagagcag gagggggcgg 780
tgccccggcg acctgaagat gctctgctcc ttccagattt gagcctccat gtgccaccag 840
gtggtgccag tttcctgcca gactgtgggc agctgcgggg tgaaggggag ggcctctgcg 900
ggactggatc agaaccactg ccagagctgc tattcccttg gacctgccgg ggctgtggac 960
aagagctgga ggagggtgag ggtagtcggc tgggagctgc catgtgtggg cgctgcatgc 1020
gaggagaggc tggagggggt gccagtgggg ggccccaggg ccccagtgac aaaggctttg 1080
cctgtagcct ctgccccttt gccactcact atcccaacca cctggcccgg cacatgaaga 1140
cacacagtgg tgagaagccc ttccgctgcg cccgctgtcc ttatgcctct gctcatctgg 1200
ataacctgaa acggcaccag cgcgtccata caggagagaa gccctacaag tgccccctct 1260
gcccttatgc ctgtggcaat ctggccaacc tcaagcgtca tggtcgcatc cactctggtg 1320
acaaaccttt tcggtgtagc ctttgcaact acagctgcaa ccagagcatg aacctcaaac 1380
gtcacatgct gcggcacaca ggcgagaagc ccttccgctg tgccacctgc gcctatacca 1440
cgggccactg ggacaactac aagcgccacc agaaggtgca tggccacggt ggggcaggag 1500
ggcctggtct ctctgcctct gagggctggg ccccacctca tagcccaccc tctgttttga 1560
gctctcgggg cccaccagcc ctggggactg ctggcagccg ggctgtccac acagactcat 1620
cctgaactag gtccttcttc cccatgtttt atacagacgg accagaagcc acctttttct 1680
cccccgctgg ccaggggctc cacacagact aacgtaggca ctataaggac cagcccaacc 1740
ccatgggcgg gggggcccat atggaccagg ggaccttgcc ttgactgagg cacttcacga 1800
gctcagtgag aagggccctg tattcacctc cactgccccc aggggctgtg gacaaaccgg 1860
57



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
ctgggggact gcccagcctc ccacctgttt atttaactta tttcaagtgc tttataataa 1920
aggaaacact aacaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1980
aaaaaaaaaa aaaaaa 1996
<210> 62
<211> 482
<212> PRT
<213> Homo Sapiens
<400> 62
Met Leu Met Ser Leu Leu Met Ser Ile Ser Pro Gly Asp Ser Leu Gly
1 5 10 15
Ala Arg Pro Gly Leu Pro Tyr Gly Leu Ser Asp Asp Glu Ser Gly Gly
20 25~ 30
Gly Arg Ala Leu Ser Ala Glu Ser Glu Val Glu Glu Pro Ala Arg Gly
35 40 45
Pro Gly Glu Ala Arg Gly Glu Arg Pro Gly Pro Ala Cys Gln Leu Cys
50 55 60
Gly Gly Pro Thr Gly Glu Gly Pro Cys Cys Gly Ala Gly Gly Pro Gly
65 70 75 80
Gly Gly Pro Leu Leu Pro Pro Arg Leu Leu Tyr Ser Cys Arg Leu Cys
85 90 95
Thr Phe Val Ser His Tyr Ser Ser His Leu Lys Arg His Met Gln Thr
100 105 110
His Ser Gly Glu Lys Pro Phe Arg Cys Gly Arg Cys Pro Tyr Ala Ser
115 120 125
Ala Gln Leu Val Asn Leu Thr Arg His Thr Arg Thr His Thr Gly Glu
130 135 140
Lys Pro Tyr Arg Cys Pro His Cys Pro Phe Ala Cys Ser Ser Leu Gly
145 150 155 160
Asn Leu Arg Arg His Gln Arg Thr His Ala Gly Pro Pro Thr Pro Pro
165 170 175
Cys Pro Thr Cys Gly Phe Arg Cys Cys Thr Pro Arg Pro Ala Arg Pro
180 185 190
Pro Ser Pro Thr Glu Gln Glu Gly Ala Val Pro Arg Arg Pro Glu Asp
195 200 205
Ala Leu Leu Leu Pro Asp Leu Ser Leu His Val Pro Pro Gly Gly Ala
210 215 220
Ser Phe Leu Pro Asp Cys Gly Gln Leu Arg Gly Glu Gly Glu Gly Leu
225 230 235 240
Cys Gly Thr Gly Ser Glu Pro Leu Pro Glu Leu Leu Phe Pro Trp Thr
245 250 255
Cys Arg Gly Cys Gly Gln Glu Leu Glu Glu Gly Glu Gly Ser Arg Leu
260 265 270
58



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Gly Ala Ala Met Cys Gly Arg Cys Met Arg Gly Glu Ala Gly Gly Gly
275 280 285
Ala Ser Gly Gly Pro Gln Gly Pro Ser Asp Lys Gly Phe Ala Cys Ser
290 295 300
Leu Cys Pro Phe Ala Thr His Tyr Pro Asn His Leu Ala Arg His Met
305 310 315 320
Lys Thr His Ser Gly Glu Lys Pro Phe Arg Cys Ala Arg Cys Pro Tyr
325 330 335
Ala Ser Ala His Leu Asp Asn Leu Lys Arg His Gln Arg Val His Thr
340 345 350
Gly Glu Lys Pro Tyr Lys Cys Pro Leu Cys Pro Tyr Ala Cys Gly Asn
355 360 365
Leu Ala Asn Leu Lys Arg His Gly Arg Ile His Ser Gly Asp Lys Pro
370 375 380
Phe Arg Cys Ser Leu Cys Asn Tyr Ser Cys Asn Gln Ser Met Asn Leu
385 390 395 400
Lys Arg His Met Leu Arg His Thr Gly Glu Lys Pro Phe Arg Cys Ala
405 410 415
Thr Cys Ala Tyr Thr Thr Gly His Trp Asp Asn Tyr Lys Arg His Gln
420 425 430
Lys Val His Gly His Gly Gly Ala Gly Gly Pro Gly Leu Ser Ala Ser
435 440 445
Glu Gly Trp Ala Pro Pro His Ser Pro Pro Ser Val Leu Ser Ser Arg
450 455 460
Gly Pro Pro Ala Leu Gly Thr Ala Gly Ser Arg Ala Val His Thr Asp
465 470 475 480
Ser Ser
<210> 63
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 63
tctttttcca aggggtagag a
21
<210> 64
<211> 21
<212> DNA
<213> Artificial Sequence
59



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<220>


<223> oligonucleotide


<400> 64


cgcagcaaaa cacagtagtg a 21


<210> 65


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 65


tataccaggt gtgccagctg
20


<210> 66


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 66


ccaagcttcc cgtgtagtgt 20


<210> 67


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 67


agagagggtg tcctgagggt
20


<210> 68


<211> 20


<212> DNA


<213> Artificial Sequence


<220>
<223> oligonucleotide
<400> 68
tctcagctcc atctcagggt 20
<210> 69
<211> 21
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 69
ttggtaagga gagtagcatt g
21



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 70


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 70


tcaagtgatc ctcccacctc 20


<210> 71


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 71


agaaaccaca aggcccatct 20


<210> 72


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 72


aaaggagcag tttggcttcc
20


<210> 73


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 73


atgctttcca tccactcacc 20


<210> 74


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 74


tctcgcttgg aaagaatcct
20


<210> 75


<211> 20


<212> DNA


<213> Artificial Sequence


61



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<220>


<223> oligonucleotide


<400> 75


tttggacttg gcccactaag
20


<210> 76


<211> 21


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 76


aagtctgcaa attttatgcg c 21


<210> 77


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 77


gctgcctcaa gtttcagacc
20


<210> 78


<211> 21


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 78


tgcagttaat gaaaaccctc c 21


<210> 79


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 79


tgatatgacc agagccacca 20


<210> 80


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 80
62



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
agatgccttc ttcccaggat 20
<210> 81


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 81


gatctgcatg aggtggaaga 20


<210> 82


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 82


aaaggaggag ggtctggaga
20


<210> 83


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 83


aagcactgga aaggagacga 20


<210> 84


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 84


ggggtaatct agaagcccca 20


<210> 85


<211> 20


<212> DNA


<213> Artificial Sequence


<220>


<223> oligonucleotide


<400> 85


gctcgccttc tgtcaaaatc 20


<210> 86


<211> 21


<212> DNA


63



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 86
caactttgaa tcctgccatt t 21
<210> 87
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> oligonucleotide
<400> 87
gctctggcct ctctacatgg
<210> 88
<211> 128
<212> PRT
<213> Homo Sapiens
<400> 88
Met Thr Ser Arg Arg Ser Ser Thr Leu Ser Met Thr Ser Ser Leu Leu
1 5 10 15
Ser Leu Gly Cys Ala Leu Thr Ser Ala Phe Pro Ala Ser Thr Met Ser
20 25 30
Trp Val Pro Leu Leu Gln Met Leu Asp Gln Ser Pro Arg Arg Val Met
35 40 45
Arg Lys Ser Val Ser Gln Leu Cys Pro Leu Leu Arg Pro His Pro Pro
50 55 60
Leu Ser Ser Lys His Pro Leu Val Leu Pro Leu Gln Leu Pro Pro Thr
65 70 75 80
Phe Leu His Leu Leu Pro Gly Pro Gly Cys Pro Gly Gln Thr Val Ala
85 90 95
Tyr Trp Val Arg Thr Pro Pro Val Trp Cys Trp Arg Ile Leu Arg Arg
100 105 110
Cys Gln Asp Gln Asn Arg Leu Trp Ile Ile Gly Val Met Gly Ser Thr
115 120 125
<210> 89
<211> 77
<212> PRT
<213> Homo Sapiens
<400> 89
Met Thr Leu Arg Pro Ser Leu Leu Pro Leu His Leu Leu Leu Leu Leu
1 5 10 15
Leu Leu Ser Ala Ala Val Cys Arg Ala Glu Ala Gly Leu Glu Thr Glu
64



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
20 25 30
Ser Pro Val Arg Thr Leu Gln Val Glu Thr Leu Val Glu Pro Pro Glu
35 40 45
Pro Cys Ala Glu Pro Ala Ala Phe Gly Asp Thr Leu His Ile His Tyr
50 55 60
Thr Gly Ser Leu Val Met Asp Val Leu Leu Thr Pro Pro
65 70 75
<210> 90
<211> 152
<212> PRT
<213> Homo Sapiens
<400> 90
Met Cys Arg Ala Arg Cys Phe Trp Arg His Ala Ser His Thr Leu His
1 5 10 15
Gly Lys Leu Gly Asn Gly Arg Ile Ile Asp Thr Ser Leu Thr Arg Asp
20 25 30
Pro Leu Val Ile Glu Leu Gly Gln Lys Gln Val Ile Pro Gly Leu Glu
35 40 45
Gln Ser Leu Leu Asp Met Cys Val Gly Glu Lys Arg Arg Ala Ile Ile
50 55 60
Pro Ser His Leu Ala Tyr Gly Lys Arg Gly Phe Pro Pro Ser Val Pro
65 70 75 80
Ala Asp Ala Val Val Gln Tyr Asp Val Glu Leu Ile Ala Leu Ile Arg
85 90 95
Ala Asn Tyr Trp Leu Lys Leu Val Lys Gly Ile Leu Pro Leu Val Gly
100 105 110
Met Ala Met Val Pro Ala Leu Leu Gly Leu Ile Gly Tyr His Leu Tyr
115 120 125
Arg Lys Ala Asn Arg Pro Lys Val Ser Lys Lys Lys Leu Lys Glu Glu
130 135 140
Lys Arg Asn Lys Ser Lys Lys Lys
145 150
<210> 91
<211> 398
<212> PRT
<213> Homo Sapiens
<400> 91
Met Glu Asn Ile Glu Leu Gly Leu Ser Glu Ala Gln Val Met Leu Ala
1 5 10 15
Leu Ala Ser His Leu Ser Thr Val Glu Ser Glu Lys Gln Lys Leu Arg
20 25 30



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Ala Gln Val Arg Arg Leu Cys Gln Glu Asn Gln Trp Leu Arg Asp Glu
35 40 45
Leu Ala Gly Thr Gln Gln Arg Leu Gln Arg Ser Glu Gln Ala Val Ala
50 55 60
Gln Leu Glu Glu Glu Lys Lys His Leu Glu Phe Leu Gly Gln Leu Arg
65 70 75 80
Gln Tyr Asp Glu Asp Gly His Thr Ser Glu Glu Lys Glu Gly Asp Ala
85 90 95
Thr Lys Asp Ser Leu Asp Asp Leu Phe Pro Asn Glu Glu Glu Glu Asp
100 105 110
Pro Ser Asn Gly Leu Ser Arg Gly Gln Gly Ala Thr Ala Ala Gln Gln
115 120 125
Gly Gly Tyr Glu Ile Pro Ala Arg Leu Arg Thr Leu His Asn Leu Val
130 135 140
Ile Gln Tyr Ala Ala Gln Gly Arg Tyr Glu Val Ala Val Pro Leu Cys
145 150 155 160
Lys Gln Ala Leu Glu Asp Leu Glu Arg Thr Ser Gly Arg Gly His Pro
165 170 175
Asp Val Ala Thr Met Leu Asn Ile Leu Ala Leu Val Tyr Arg Asp Gln
180 185 190
Asn Lys Tyr Lys Glu Ala Ala His Leu Leu Asn Asp Ala Leu Ser Ile
195 200 205
Arg Glu Ser Thr Leu Gly Pro Asp His Pro Ala Val Ala Ala Thr Leu
210 215 220
Asn Asn Leu Ala Val Leu Tyr Gly Lys Arg Gly Lys Tyr Lys Glu Ala
225 230 235 240
Glu Pro Leu Cys Gln Arg Ala Leu Glu Ile Arg Glu Lys Val Leu Gly
245 250 255
Thr Asn His Pro Asp Val Ala Lys Gln Leu Asn Asn Leu Ala Leu Leu
260 265 270
Cys Gln Asn Gln Gly Lys Tyr Glu Ala Val Glu Arg Tyr Tyr Gln Arg
275 280 285
Ala Leu Ala Ile Tyr Glu Gly Gln Leu Gly Pro Asp Asn Pro Asn Val
290 295 300
Ala Arg Thr Lys Asn Asn Leu Ala Ser Cys Tyr Leu Lys Gln Gly Lys
305 310 315 320
Tyr Ala Glu Ala Glu Thr Leu Tyr Lys Glu Ile Leu Thr Arg Ala His
325 330 335
Val Gln Glu Phe Gly Ser Val Asp Asp Asp His Lys Pro Ile Trp Met
340 345 350
66



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
His Ala Glu Glu Arg Glu Glu Met Ser Lys Ser Arg His His Glu Gly
355 360 365
Gly Thr Pro Tyr Ala Glu Tyr Gly Ala Trp Val Pro Pro Pro Pro Gln
370 375 380
Pro Ser Gln His Ser Pro Leu Leu Leu Ala Leu Pro His Pro
385 390 395
<210> 92
<211> 785
<212> PRT
<213> Homo sapiens
<400> 92
Met Ala Pro Ser Ala Trp Ala Ile Cys Trp Leu Leu Gly Gly Leu Leu
1 5 10 15
Leu His Gly Gly Ser Ser Gly Pro Ser Pro Gly Pro Ser Val Pro Arg
20 25 30
Leu Arg Leu Ser Tyr Arg Asp Leu Leu Ser Ala Asn Arg Ser Ala Ile
35 40 45
Phe Leu Gly Pro Gln Gly Ser Leu Asn Leu Gln Ala Met Tyr Leu Asp
50 55 60
Glu Tyr Arg Asp Arg Leu Phe Leu Gly Gly Leu Asp Ala Leu Tyr Ser
65 70 75 80
Leu Arg Leu Asp Gln Ala Trp Pro Asp Pro Arg Glu Val Leu Trp Pro
85 90 95
Pro Gln Pro Gly Gln Arg Glu Glu Cys Val Arg Lys Gly Arg Asp Pro
100 105 110
Leu Thr Glu Cys Ala Asn Phe Val Arg Val Leu Gln Pro His Asn Arg
115 120 125
Thr His Leu Leu Ala Cys Gly Thr Gly Ala Phe Gln Pro Thr Cys Ala
130 135 140
Leu Ile Thr Val Gly His Arg Gly Glu His Val Leu His Leu Glu Pro
145 150 155 160
Gly Ser Val Glu Ser Gly Arg Gly Arg Cys Pro His Glu Pro Ser Arg
165 170 175
Pro Phe Ala Ser Thr Phe Ile Asp Gly Glu Leu Tyr Thr Gly Leu Thr
180 185 190
Ala Asp Phe Leu Gly Arg Glu Ala Met Ile Phe Met Ile Phe Arg Ser
195 200 205
Gly Gly Pro Arg Pro Ala Leu Arg Ser Asp Ser Asp Gln Ser Leu Leu
210 215 220
His Asp Pro Arg Phe Val Met Ala Ala Arg Ile Pro Glu Asn Ser Asp
67



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
225 230 235 240
Gln Asp Asn Asp Lys Val Tyr Phe Phe Phe Ser Glu Thr Val Pro Ser
245 250 255
Pro Asp Gly Gly Ser Asn His Val Thr Val Ser Arg Val Gly Arg Val
260 265 270
Cys Val Asn Asp Ala Gly Gly Gln Arg Val Leu Val Asn Lys Trp Ser
275 280 285
Thr Phe Leu Lys Ala Arg Leu Val Cys Ser Val Pro Gly Pro Gly Gly
290 295 300
Ala Glu Thr His Phe Asp Gln Leu Glu Asp Val Phe Leu Leu Trp Pro
305 310 315 320
Lys Ala Gly Lys Ser Leu Glu Val Tyr Ala Leu Phe Ser Thr Val Ser
325 330 335
Ala Val Phe Gln Gly Phe Ala Val Cys Val Tyr His Met Ala Asp Ile
340 345 350
Trp Glu Val Phe Asn Gly Pro Phe Ala His Arg Asp Gly Pro Gln His
355 360 365
Gln Trp Gly Pro Tyr Gly Gly Lys Val Pro Phe Pro Arg Pro Gly Val
370 375 380
Cys Pro Ser Lys Met Thr Ala Gln Pro Gly Arg Pro Phe Gly Ser Thr
385 390 395 400
Lys Asp Tyr Pro Asp Glu Val Leu Gln Phe Ala Arg Ala His Pro Leu
405 410 415
Met Phe Trp Pro Val Arg Pro Arg His Gly Arg Pro Val Leu Val Lys
420 425 430
Thr His Leu Ala Gln Gln Leu His Gln Ile Val Val Asp Arg Val Glu
435 440 445
Ala Glu Asp Gly Thr Tyr Asp Val Ile Phe Leu Gly Thr Asp Ser Gly
450 455 460
Ser Val Leu Lys Val Ile Ala Leu Gln Ala Gly Gly Ser Ala Glu Pro
465 470 475 480
Glu Glu Val Val Leu Glu Glu Leu Gln Val Phe Lys Val Pro Thr Pro
485 490 495
Ile Thr Glu Met Glu Ile Ser Val Lys Arg Gln Met Leu Tyr Val Gly
500 505 510
Ser Arg Leu Gly Val Ala Gln Leu Arg Leu His Gln Cys Glu Thr Tyr
515 520 525
Gly Thr Ala Cys Ala Glu Cys Cys Leu Ala Arg Asp Pro Tyr Cys Ala
530 535 540
Trp Asp Gly Ala Ser Cys Thr His Tyr Arg Pro Ser Leu Gly Lys Arg
68



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
545 550 555 560
Arg Phe Arg Arg Gln Asp Ile Arg His Gly Asn Pro Ala Leu Gln Cys
565 570 575
Leu Gly Gln Ser Gln Glu Glu Glu Ala Val Gly Leu Val Ala Ala Thr
580 585 590
Met Val Tyr Gly Thr Glu His Asn Ser Thr Phe Leu Glu Cys Leu Pro
595 600 605
Lys Ser Pro Gln Ala Ala Val Arg Trp Leu Leu Gln Arg Pro Gly Asp
610 615 620
Glu Gly Pro Asp Gln Val Lys Thr Asp Glu Arg Val Leu His Thr Glu
625 630 635 640
Arg Gly Leu Leu Phe Arg Arg Leu Ser Arg Phe Asp Ala Gly Thr Tyr
645 650 655
Thr Cys Thr Thr Leu Glu His Gly Phe Ser Gln Thr Val Val Arg Leu
660 665 670
Ala Leu Val Val Ile Val Ala Ser Gln Leu Asp Asn Leu Phe Pro Pro
675 680 685
Glu Pro Lys Pro Glu Glu Pro Pro Ala Arg Gly Gly Leu Ala Ser Thr
690 695 700
Pro Pro Lys Ala Trp Tyr Lys Asp Ile Leu Gln Leu Ile Gly Phe Ala
705 710 715 720
Asn Leu Pro Arg Val Asp Glu Tyr Cys Glu Arg Val Trp Cys Arg Gly
725 730 735
Thr Thr Glu Cys Ser Gly Cys Phe Arg Ser Arg Ser Arg Gly Lys Gln
740 745 ~ 750
Ala Arg Gly Lys Ser Trp Ala Gly Leu Glu Leu Gly Lys Lys Met Lys
755 760 765
Ser Arg Val His Ala Glu His Asn Arg Thr Pro Arg Glu Val Glu Ala
770 775 780
Thr
785
<210> 93
<211> 277
<212> PRT
<213> Homo Sapiens
<400> 93
Met Glu Lys Phe Lys Ala Ala Met Leu Leu Gly Ser Val Gly Asp Ala
1 5 10 15
Leu Gly Tyr Arg Asn Val Cys Lys Glu Asn Ser Thr Val Gly Met Lys
20 25 30
69



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Ile Gln Glu Glu Leu Gln Arg Ser Gly Gly Leu Asp His Leu Val Leu
35 40 45
Ser Pro Gly Glu Trp Pro Val Ser Asp Asn Thr Ile Met His Ile Ala
50 55 60
Thr Ala Glu Ala Leu Thr Thr Asp Tyr Trp Cys Leu Asp Asp Leu Tyr
65 70 75 80
Arg Glu Met Val Arg Cys Tyr Val Glu Ile Val Glu Lys Leu Pro Glu
85 90 95
Arg Arg Pro Asp Pro Ala Thr Ile Glu Gly Cys Ala Gln Leu Lys Pro
100 105 110
Asn Asn Tyr Leu Leu Ala Trp His Thr Pro Phe Asn Glu Lys Gly Ser
115 120 125
Gly Phe Gly Ala Ala Thr Lys Ala Met Cys Ile Gly Leu Arg Tyr Trp
130 135 140
Lys Pro Glu Arg Leu Glu Thr Leu Ile Glu Val Ser Val Glu Cys Gly
145 150 155 160
Arg Met Thr His Asn His Pro Thr Gly Phe Leu Gly Ser Leu Cys Thr
165 170 175
Ala Leu Phe Val Ser Phe Ala Ala Gln Gly Lys Pro Leu Val Gln Trp
180 185 190
Gly Arg Asp Met Leu Arg Ala Val Pro Leu Ala Glu Glu Tyr Cys Arg
195 200 205
Lys Thr Ile Arg His Thr Ala Glu Tyr Gln Glu His Trp Phe Tyr Leu
210 215 220
Lys Leu Asn Gly Asn Phe Ile Trp Arg Arg Gly Lys Ser Val Lys Thr
225 230 235 240
Gln Lys Ile Lys Pro Ser Ser Pro Thr Ile Met Met Gln Lys Arg Gly
245 250 255
Lys Arg Pro Thr Gly Ser Gly Ala Arg Lys Val Glu Gly Glu Asp Glu
260 265 270
Ala Thr Met Pro Pro
275
<210> 94
<211> 54
<212> PRT
<213> Homo sapiens
<400> 94
Met Leu Leu Tyr Ile Ala Ala Val Pro Val Met Cys Ser Cys Gln Asn
1 5 10 15
Ile Phe Gly Phe Lys Leu Ser Tyr Cys Leu Trp Leu Leu Ile Ser Thr
20 25 30



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Val Gln Val Arg Phe Gln Lys Asp Leu Glu Ser Asn Ile Phe Asn Gln
35 40 45
Leu Lys Cys Leu Ser Val
<210> 95
<211> 128
<212> PRT
<213> Homo Sapiens
<400> 95
Met Lys Lys Asp His Ile Ser Phe Gly Asn Leu Pro Gln Thr Ile Met
1 5 10 15
Thr Leu Gly Leu Gly Cys Ile Leu Asn Gly Gln Thr Leu Gln Thr Leu
20 25 30
Leu Ser Ala Cys Met Ser Val Ser Pro Ala Met Thr Thr Arg Arg Lys
35 40 45
Lys Lys Thr Ser Val Val Lys Arg Lys Pro Lys Arg Met Pro Thr Ser
50 55 60
Leu Cys Trp Met Arg Leu Cys Leu Cys Thr Asp Gly Thr Val Met Arg
65 70 75 80
Arg Cys Met Leu Ala Ala Ile Asn Ile Gln Gly Glu Glu Ser Ile Ser
85 90 95
Ser Ser Leu Thr Thr Pro Thr Leu Cys Gly Gly Gln Asn Gln Ser Thr
100 105 110
Thr Glu Ser Ile Ile Leu Asp Lys Asn Val Val Thr Lys Ser Gly Val
115 120 125
<210> 96
<211> 227
<212> PRT
<213> Homo Sapiens
<400> 96
Met Val Thr Val Ile Leu Leu Pro Tyr Val Ser Lys Val Thr Gly Trp
1 5 10 15
Cys Arg Asp Arg Leu Leu Gly His Arg Glu Pro Ser Ala His Pro Val
20 25 30
Glu Val Phe Ser Phe Asp Leu His Glu Pro Leu Ser Lys Glu Arg Val
35 40 45
Glu Ala Phe Ser Asp Gly Val Tyr Ala Ile Val Ala Thr Leu Leu Ile
50 55 60
Leu Asp Ile Cys Glu Asp Asn Val Pro Asp Pro Lys Asp Val Lys Glu
65 70 75 80
71



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Arg Phe Ser Gly Ser Leu Val Ala Ala Leu Ser Ala Thr Gly Pro Arg
85 90 95
Phe Leu Ala Tyr Phe Gly Ser Phe Ala Thr Val Gly Leu Leu Trp Phe
100 105 110
Ala His His Ser Leu Phe Leu His Val Arg Lys Ala Thr Arg Ala Met
115 120 125
Gly Leu Leu Asn Thr Leu Ser Leu Ala Phe Val Gly Gly Leu Pro Leu
130 135 140
Ala Tyr Gln Gln Thr Ser Ala Phe Ala Arg Gln Pro Arg Asp Glu Leu
145 150 155 160
Glu Arg Val Arg Val Ser Cys Thr Ile Ile Phe Leu Ala Ser Ile Phe
165 170 175
Gln Leu Ala Thr Trp Thr Thr Ala Leu Leu His Gln Ala Glu Thr Leu
180 185 190
Gln Pro Ser Val Trp Phe Gly Gly Arg Glu His Val Leu Met Phe Arg
195 200 205
Gln Gly Trp Arg Cys Thr Pro Val Pro Ala Cys Trp Pro Ser Pro Pro
210 215 220
Pro Ala Cys
225
<210> 97
<211> 112
<212> PRT
<213> Homo sapiens
<400> 97
Met Leu Glu Leu Arg Arg Leu Leu Ser Leu Arg Glu Pro Pro Leu Ser
1 5 10 15
Pro Lys Ile Cys Ser Val Pro Leu Ile Leu Leu Pro Gly Pro Trp Arg
20 25 30
Leu Gly Gln Ala Ala Pro His Thr Ser Thr Pro His Pro Leu Leu Pro
35 40 45
Gly Ser Ser Cys Gly Leu Pro Ser Thr Val Arg Arg Leu Trp Asp Arg
50 55 60
Thr Glu Ser Leu Ala Ala Cys Gly Ala Pro Val Pro Ala Ala Ala Pro
65 70 75 80
Arg Leu Arg Ser Gly Tyr Pro His Pro Arg His Arg Arg Pro Pro Ala
85 90 95
Pro Pro Thr Ala Ala His Ala Arg Arg Val His Ala Ala Pro Ala Pro
100 105 110
<210> 98
72



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<211> 132
<212> PRT
<213> Homo sapiens
<400> 98
Met Gln Val Ile His Gly Pro His Val Glu Lys Leu Gln Ser Pro Leu
1 5 10 15
Gly Pro His Arg Pro Ser Pro Arg Cys Pro Leu Ser Val Val Thr Gly
20 25 30
Pro Asp Leu Gln Glu Cys Thr Phe His Ser Thr Arg Lys Pro Tyr Asp
35 40 45
Ile Leu Arg Leu Pro Arg Pro Ala Ala Cys Met Gly Pro Leu Pro Ser
50 55 60
Ser Thr Pro Thr Leu Arg Met Val Pro Cys Ser Ala Leu Val Leu Cys
65 70 75 80
Trp Pro Leu Pro Ala Thr Pro Thr Leu Arg His Pro Gly Val Val Gly
85 90 95
Pro Asn Trp Leu Ala Pro Pro Ser Ala Ala Leu Cys Arg Pro Asp Ala
100 105 110
Ala Val Trp Pro Asp Leu Pro Ser Ser Asn Ile Leu Leu Val Thr Pro
115 120 125
Pro Pro Ala Lys
130
<210> 99
<211> 421
<212> PRT
<213> Homo Sapiens
<400> 99
Met Gly Ser Gln Glu Val Leu Gly His Ala Ala Arg Leu Ala Ser Ser
1 5 10 15
Gly Leu Leu Leu Gln Val Leu Phe Arg Leu Ile Thr Phe Val Leu Asn
20 25 30
Ala Phe Ile Leu Arg Phe Leu Ser Lys Glu Ile Val Gly Val Val Asn
35 40 45
Val Arg Leu Thr Leu Leu Tyr Ser Thr Thr Leu Phe Leu Ala Arg Glu
50 55 60
Ala Phe Arg Arg Ala Cys Leu Ser Gly Gly Thr Gln Arg Asp Trp Ser
65 70 75 80
Gln Thr Leu Asn Leu Leu Trp Leu Thr Val Pro Leu Gly Val Phe Trp
85 90 95
Ser Leu Phe Leu Gly Trp Ile Trp Leu Gln Leu Leu Glu Val Pro Asp
100 105 110
73



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
Pro Asn Val Val Pro His Tyr Ala Thr Gly Val Val Leu Phe Gly Leu
115 120 125
Ser Ala Val Val Glu Leu Leu Gly Glu Pro Phe Trp Val Leu Ala Gln
130 135 140
Ala His Met Phe Val Lys Leu Lys Val Ile Ala Glu Ser Leu Ser Val
145 150 155 160
Ile Leu Lys Ser Val Leu Thr Ala Phe Leu Val Leu Trp Leu Pro His
165 170 175
Trp Gly Leu Tyr Ile Phe Ser Leu Ala Gln Leu Phe Tyr Thr Thr Val
180 185 190
Leu Val Leu Cys Tyr Val Ile Tyr Phe Thr Lys Leu Leu Gly Ser Pro
195 200 205
Glu Ser Thr Lys Leu Gln Thr Leu Pro Val Ser Arg Ile Thr Asp Leu
210 215 220
Leu Pro Asn Ile Thr Arg Asn Gly Ala Phe Ile Asn Trp Lys Glu Ala
225 230 235 240
Lys Leu Thr Trp Ser Phe Phe Lys Gln Ser Phe Leu Lys Gln Ile Leu
245 250 255
Thr Glu Gly Glu Arg Tyr Val Met Thr Phe Leu Asn Val Leu Asn Phe
260 265 270
Gly Asp Gln Gly Val Tyr Asp Ile Val Asn Asn Leu Gly Ser Leu Val
275 280 285
Ala Arg Leu Ile Phe Gln Pro Ile Glu Glu Ser Phe Tyr Ile Phe Phe
290 295 ' 300
Ala Lys Val Leu Glu Arg Gly Lys Asp Ala Thr Leu Gln Lys Gln Glu
305 310 315 320
Asp Val Ala Val Ala Ala Ala Val Leu Glu Ser Leu Leu Lys Leu Ala
325 330 335
Leu Leu Ala Gly Leu Thr Ile Thr Phe Trp Leu Cys Leu Phe Ser Ala
340 345 350
Gly Ser Gly Tyr Leu Arg Arg Thr Met Leu Ser Ser Asp Pro Val Phe
355 360 365
Leu Cys Cys Glu Gln Ala Gly Gln Pro Asp Trp Ala His Ile Ala Val
370 375 380
Gly Ala Phe Cys Leu Gly Ala Thr Leu Gly Thr Ala Phe Leu Thr Glu
385 390 395 400
Thr Lys Leu Ile His Phe Leu Arg Thr Gln Leu Gly Val Pro Arg Arg
405 410 415
Thr Asp Lys Met Thr
420
74



CA 02362538 2001-08-16
WO 00/49134 PCT/US00/04340
<210> 100
<211> 86
<212> PRT
<213> Homo Sapiens
<400> 100
Met Phe Arg Phe Leu Leu Ile Trp Leu Gln Leu Thr Ser Arg Leu Phe
1 5 10 15
Ser His Arg Phe Leu Ala His Met Leu Lys Gly Tyr Ala His Leu Gln
20 25 30
Lys Arg Met Cys Phe Lys Ser Pro Leu Gly Gln Ala Leu Cys Ser Leu
35 40 45
Ala Ser Ser Ser Leu Thr Gln Asp Leu Phe Lys Glu Lys Lys Lys Lys
50 55 60
Thr Trp Ser Leu Lys Pro Arg Ile Asn Ser Ser His Leu Gly Glu Pro
65 70 75 gp
Ala Asp Thr Tyr Ser Leu
<210> 101
<211> 86
<212> PRT
<213> Homo Sapiens
<400> 101
Met Asp Phe Asn Gly Leu Leu Asp Cys Met Leu Val Gln Phe Phe Asp
1 5 10 15
Leu Glu Pro Ser Phe Leu Phe Leu Leu Phe Trp Glu Leu Tyr Cys Val
20 25 30
Cys Cys Gly Met Phe Thr His Thr Ser Cys Cys Leu Gly Phe Leu Gln
35 40 45
Val Val Cys Val Phe Tyr Leu Pro Leu Leu Ala Phe Arg Cys Leu Glu
50 55 60
Ser Met Thr Leu Ala Tyr Ser Ser Val Tyr Ser Arg Arg Pro Cys Leu
65 70 75 80
Phe Leu Ala Phe Ile Lys
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