EP1107978A1 - Secreted proteins and polynucleotides encoding them - Google Patents

Secreted proteins and polynucleotides encoding them

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Publication number
EP1107978A1
EP1107978A1 EP99945180A EP99945180A EP1107978A1 EP 1107978 A1 EP1107978 A1 EP 1107978A1 EP 99945180 A EP99945180 A EP 99945180A EP 99945180 A EP99945180 A EP 99945180A EP 1107978 A1 EP1107978 A1 EP 1107978A1
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seq
nucleotide
sequence
amino acid
nucleotide sequence
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French (fr)
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Dario Valenzuela
Olive Yuan
Heidi Hoffman
Jeff Hall
Peter Rapiejko
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Alphagene Inc
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Alphagene Inc
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Abstract

Novel polynucleotides and the proteins encoded thereby are disclosed.

Description

SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
This application is a continuation-in-part of the following applications:
(1) provisional application Ser. No. 60/097,638 (GI 6908), filed August 24, 1998;
(2) provisional application Ser. No. 60/097,659 (GI 6909), filed August 24, 1998;
(3) provisional application Ser. No. 60/099,618 (GI 6910), filed September 9, 1998; (4) provisional application Ser. No. 60/102,092 (GI 6912), filed September 28, 1998;
(5) provisional application Ser. No. 60/109,978 (GI 6914), filed November 25, 1998;
(6) provisional application Ser. No.60/113,645 (GI 6916), filed December 23, 1998; and
(7) provisional application Ser. No. 60/113,646 (GI 6917), filed December 23, 1998; all of which are incorporated by reference herein.
FIELD OF THE INVENΗON The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins.
BACKGROUND OF THE INVENTION Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs and mterleukins) 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. 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:l;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:l from nucleotide 683 to nucleotide 934;
(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vbll_l deposited with the ATCC under accession number 98846;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vbll_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vbll_l deposited with the ATCC under accession number 98846;
(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vbllJL deposited with the ATCC under accession number 98846;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:2;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:2;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h) and that has a length that is at least 25% of the length of SEQ ID NO:l.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:l from nucleotide 683 to nucleotide 934; the nucleotide sequence of the full-length protein coding sequence of clone vbll_l deposited with the ATCC under accession number 98846; or the nucleotide sequence of a mature protein coding sequence of clone vbll_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vbl 1_1 deposited with the ATCC under accession number 98846.
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:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:2, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of
SEQ ID NO:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 37 to amino acid 46 of SEQ ID NO:2.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:l. 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:l, but excluding the poly(A) tail at the 3' end of SEQ ID NO:l; and
(ab) the nucleotide sequence of the cDNA insert of clone vbll_l deposited with the ATCC under accession number 98846; (ii) hybridizing said probe(s) 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 NO:l, 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 vbll_l deposited with the ATCC under accession number 98846; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:l, 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:l , but excluding the poly(A) tail at the 3' end of SEQ ID NO:l. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:l from nucleotide 683 to nucleotide 934, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:l from nucleotide 683 to nucleotide 934, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:l from nucleotide 683 to nucleotide 934. 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: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 vbll_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:2. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:2, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 37 to amino acid 46 of SEQ ID NO: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
NO:3;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 63 to nucleotide 482;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 201 to nucleotide 482;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vbl2_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vbl2_l deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vbl2_l deposited with the ATCC under accession number 98846; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:4;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 ;
(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:3.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:3 from nucleotide 63 to nucleotide 482; the nucleotide sequence of SEQ ID NO:3 from nucleotide 201 to nucleotide 482; the nucleotide sequence of the full-length protein coding sequence of clone vbl2_l deposited with the ATCC under accession number 98846; or the nucleotide sequence of a mature protein coding sequence of clone vbl2_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846. 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:4 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:4, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4 having biological activity, the fragment comprising the amino acid sequence from amino acid 65 to amino acid 74 of SEQ ID NO:4.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ IDNO: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 NO:3, but excluding the poly(A) tail at the 3' end of SEQ ID NO:3; and
(ab) the nucleotide sequence of the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846;
(ii) hybridizing said probe(s) 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); 00/11015
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:3, but excluding the poly(A) tail at the 3' end of SEQ ID NO:3; and
(bb) the nucleotide sequence of the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:3, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:3 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:3 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:3. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:3 from nucleotide 63 to nucleotide 482, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:3 from nucleotide 63 to nucleotide 482, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:3 from nucleotide 63 to nucleotide 482. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
NO:3 from nucleotide 201 to nucleotide 482, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:3 from nucleotide 201 to nucleotide 482, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:3 from nucleotide 201 to nucleotide 482. 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: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 vbl2_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:4. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:4, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4 having biological activity, the fragment comprising the amino acid sequence from amino acid 65 to amino acid 74 of SEQ ID NO:4.
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:5;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:5 from nucleotide 1195 to nucleotide 1527;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:5 from nucleotide 1468 to nucleotide 1527;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vbl4_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vbl4_l deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vbl4_l deposited with the ATCC under accession number 98846; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:6; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:6;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:5.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:5 from nucleotide 1195 to nucleotide 1527; the nucleotide sequence of SEQ ID NO:5 from nucleotide 1468 to nucleotide 1527; the nucleotide sequence of the full-length protein coding sequence of clone vbl4_l deposited with the ATCC under accession number 98846; or the nucleotide sequence of a mature protein coding sequence of clone vbl4_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846.
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:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:6, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of
SEQ ID NO:6 having biological activity, the fragment comprising the amino acid sequence from amino acid 50 to amino acid 59 of SEQ ID NO:6.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:5. 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: O 00/11015
(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:5, but excluding the poly(A) tail at the 3' end of SEQ ID NO:5; and
(ab) the nucleotide sequence of the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846; (ii) hybridizing said probe(s) 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 NO:5, but excluding the poly(A) tail at the 3' end of SEQ ID NO:5; and
(bb) the nucleotide sequence of the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(ϋi). Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:5, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:5 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:5 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:5. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:5 from nucleotide 1195 to nucleotide 1527, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:5 from nucleotide 1195 to nucleotide 1527, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:5 from nucleotide 1195 to nucleotide 1527. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:5 from nucleotide 1468 to nucleotide 1527, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:5 from nucleotide 1468 to nucleotide 1527, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:5 from nucleotide 1468 to nucleotide 1527.
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: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 vbl4_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:6. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:6, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6 having biological activity, the fragment comprising the amino acid sequence from amino acid 50 to amino acid 59 of SEQ ID NO: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
NO:7;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:7 from nucleotide 82 to nucleotide 294;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:7 from nucleotide 109 to nucleotide 294;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vell_l deposited with the ATCC under accession number 98846; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vell_l deposited with the ATCC under accession number 98846;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:8;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 NO:7.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:7 from nucleotide 82 to nucleotide 294; the nucleotide sequence of SEQ ID NO:7 from nucleotide 109 to nucleotide 294; the nucleotide sequence of the full-length protein coding sequence of clone vell_l deposited with the ATCC under accession number 98846; or the nucleotide sequence of a mature protein coding sequence of clone vell_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846. 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:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:8, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 30 to amino acid 39 of SEQ ID NO:8.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 NO:7, but excluding the poly(A) tail at the 3' end of SEQ ID NO:7; and
(ab) the nucleotide sequence of the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846;
(ii) hybridizing said probe(s) 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 NO:7, but excluding the poly(A) tail at the
3' end of SEQ ID NO:7; and
(bb) the nucleotide sequence of the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:7, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:7 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:7 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:7. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:7 from nucleotide 82 to nucleotide 294, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:7 from nucleotide 82 to nucleotide 294, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:7 from nucleotide 82 to nucleotide 294. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:7 from nucleotide 109 to nucleotide 294, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:7 from nucleotide 109 to nucleotide 294, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:7 from nucleotide 109 to nucleotide 294. 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: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 vell_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:8. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:8, or a protein comprising a fragment of the arnino acid sequence of SEQ ID NO:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 30 to amino acid 39 of SEQ ID NO:8.
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:9; 00/11015
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9 from nucleotide 22 to nucleotide 468;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9 from nucleotide 118 to nucleotide 468; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vf2_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vf2_l deposited with the ATCC under accession number 98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vf2_l deposited with the ATCC under accession number 98846;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vf2_l deposited with the ATCC under accession number 98846;
(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;
(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:9. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:9 from nucleotide 22 to nucleotide 468; the nucleotide sequence of SEQ ID NO:9 from nucleotide 118 to nucleotide 468; the nucleotide sequence of the full-length protein coding sequence of clone vf2_l deposited with the ATCC under accession number 98846; or the nucleotide sequence of a mature protein coding sequence of clone vf2_l deposited with nft„ ι nι r PCT/US99/19351 00/11015
the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vf2_l deposited with the ATCC under accession number 98846. 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 69 to amino acid 78 of SEQ ID NO:10.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID O:9.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of :
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:9, but excluding the poly(A) tail at the 3' end of SEQ ID NO:9; and
(ab) the nucleotide sequence of the cDNA insert of clone vf2_l deposited with the ATCC under accession number 98846; (ii) hybridizing said probe(s) 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 NO:9, but excluding the ρoly(A) tail at the 3' end of SEQ ID NO:9; and (bb) the nucleotide sequence of the cDNA insert of clone vf2_l deposited with the ATCC under accession number 98846; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:9, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:9 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:9 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:9. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:9 from nucleotide 22 to nucleotide 468, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:9 from nucleotide 22 to nucleotide 468, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:9 from nucleotide 22 to nucleotide 468. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:9 from nucleotide 118 to nucleotide 468, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:9 from nucleotide 118 to nucleotide 468, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:9 from nucleotide 118 to nucleotide 468.
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 vf2_l deposited with the ATCC under accession number 98846; 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 arnino adds of SEQ ID NO:10, or a protein comprising a fragment of the amino add sequence of SEQ ID NO:10 having biological activity, the fragment comprising the amino acid sequence from amino acid 69 to amino acid 78 of SEQ ID NO:10. In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:ll;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:ll from nucleotide 124 to nucleotide 1641;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:ll from nucleotide 262 to nucleotide 1641;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vg2_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vg2_l deposited with the ATCC under accession number 98846;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of done vg2_l deposited with the ATCC under accession number 98846;
(g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vg2_l deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:12;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:12 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:12;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes 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:ll.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:ll from nudeotide 124 to nucleotide 1641; the nucleotide sequence of SEQ ID NO:ll from nudeotide 262 to nucleotide 1641; the nucleotide sequence of the full-length protein coding sequence of clone vg2_l deposited with the ATCC under accession number 98846; or the nudeotide sequence of a mature protein coding sequence of done vg2_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vg2_l deposited with the ATCC under accession number 98846. 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:12 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:12, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:12 having biological activity, the fragment comprising the amino acid sequence from amino acid 248 to amino acid 257 of SEQ ID NO:12.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID O:ll.
Further embodiments of the invention provide isolated polynudeotides 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:ll, but exduding the poly(A) tail at the 3' end of SEQ ID NO:ll; and
(ab) the nudeotide sequence of the cDNA insert of done vg2_l deposited with the ATCC under accession number 98846;
(ii) hybridizing said probe(s) 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 NO:ll, but excluding the poly(A) tail at the 3' end of SEQ ID NO:ll; and
(bb) the nucleotide sequence of the cDNA insert of clone vg2_l deposited with the ATCC under accession number 98846; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:ll, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:ll to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:ll , but excluding the poly(A) tail at the 3' end of SEQ ID NO:ll. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:ll from nudeotide 124 to nucleotide 1641, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:ll from nucleotide 124 to nucleotide 1641, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO: 11 from nucleotide 124 to nucleotide 1641. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
NO: 11 from nucleotide 262 to nucleotide 1641, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO: 11 from nucleotide 262 to nucleotide 1641, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:ll from nucleotide 262 to nucleotide 1641. 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: 12; 00/11015
(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 vg2_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:12. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO: 12 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO: 12, or a protein comprising a fragment of the amino add sequence of SEQ ID NO: 12 having biological activity, the fragment comprising the amino acid sequence from amino acid 248 to amino acid 257 of SEQ ID NO: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
NO:13;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:13 from nucleotide 380 to nucleotide 892;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:13 from nucleotide 416 to nucleotide 892;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vjl_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone γjl_l deposited with the ATCC under accession number
98846;
(f) a polynucleotide comprising the nudeotide sequence of a mature protein coding sequence of done vjl_l deposited with the ATCC under accession number 98846; (g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vjl_l deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino add sequence of SEQ ID NO:14; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:14 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:14;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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 polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:13.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:13 from nucleotide 380 to nucleotide 892; the nucleotide sequence of SEQ ID NO:13 from nucleotide 416 to nudeotide 892; the nucleotide sequence of the full-length protein coding sequence of clone vjl_l deposited with the ATCC under accession number 98846; or the nucleotide sequence of a mature protein coding sequence of clone vjl_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vjl_l deposited with the ATCC under accession number 98846. 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:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:14, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:14 having biological activity, the fragment comprising the amino acid sequence from amino acid 80 to amino acid 89 of SEQ ID NO:14.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQID NO:13; and (ab) the nucleotide sequence of the cDNA insert of clone vjl_l deposited with the ATCC under accession number 98846; (ii) hybridizing said probe(s) 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 NO:13; and
(bb) the nudeotide sequence of the cDNA insert of done vjl_l deposited with the ATCC under accession number 98846; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:13, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID NO:13 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:13 . Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:13 from nudeotide 380 to nucleotide 892, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO: 13 from nucleotide 380 to nucleotide 892, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:13 from nucleotide 380 to nudeotide 892. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:13 from nucleotide 416 to nucleotide 892, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:13 from nucleotide 416 to nucleotide 892, to a nudeotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:13 from nucleotide 416 to nucleotide 892. 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: 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 arnino acid sequence encoded by the cDNA insert of clone vjl_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:14. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO: 14, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 14 having biological activity, the fragment comprising the amino acid sequence from amino acid 80 to amino acid 89 of SEQ ID NO:14.
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:15; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:15 from nucleotide 62 to nucleotide 1057;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:15 from nucleotide 659 to nucleotide 1057;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vll_l deposited with the ATCC under accession number 98846;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vll_l deposited with the ATCC under accession number 98846; (f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vll_l deposited with the ATCC under accession number 98846;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vll_l deposited with the ATCC under accession number 98846;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:16;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:16 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:16;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ; (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:15. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:15 from nucleotide 62 to nucleotide 1057; the nucleotide sequence of SEQ ID NO:15 from nucleotide 659 to nucleotide 1057; the nucleotide sequence of the full-length protein coding sequence of done vll_l deposited with the ATCC under accession number 98846; or the nudeotide sequence of a mature protein coding sequence of clone vll_l deposited with the ATCC under accession number 98846. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vll_l deposited with the ATCC under accession number 98846. 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:16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO: 16, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 16 having biological activity, the fragment comprising the amino acid sequence from amino acid 161 to amino acid 170 of SEQ ID NO: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 done vll_l deposited with the ATCC under accession number 98846; (ii) hybridizing said probe(s) 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 nudeotide sequence selected from the group consisting of:
(ba) SEQ ID NO:15, but excluding the poly(A) tail at the 3' end of SEQ ID NO:15; and
(bb) the nudeotide sequence of the cDNA insert of done vll_l deposited with the ATCC under accession number 98846;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:15, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:15 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:15 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:15. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:15 from nucleotide 62 to nucleotide 1057, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO.T5 from nucleotide 62 to nucleotide 1057, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:15 from nucleotide 62 to nudeotide 1057. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:15 from nucleotide 659 to nucleotide 1057, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:15 from nucleotide 659 to nucleotide 1057, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:15 from nucleotide 659 to nucleotide 1057.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add 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 add sequence encoded by the cDNA insert of clone vll_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 16. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO: 16, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:16 having biological activity, the fragment comprising the amino acid sequence from amino acid 161 to amino acid 170 of SEQ ID NO: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
NO:17;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:17 from nucleotide 74 to nucleotide 529; 00/11015
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 17 from nucleotide 140 to nucleotide 529;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vk2_l deposited with the ATCC under accession number 98838;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vk2_l deposited with the ATCC under accession number 98838;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of done vk2_l deposited with the ATCC under accession number 98838;
(g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vk2_l deposited with the ATCC under accession number 98838;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:18;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:18 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:18;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes 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 polynudeotide that hybridizes under stringent conditions to any one of the polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:17.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:17 from nucleotide 74 to nucleotide 529; the nucleotide sequence of SEQ ID NO:17 from nucleotide 140 to nucleotide 529; the nucleotide sequence of the full-length protein coding sequence of clone vk2_l deposited with the ATCC under accession number 98838; or the nucleotide sequence of a mature protein coding sequence of clone vk2_l deposited with the ATCC under accession number 98838. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vk2_l deposited with the ATCC under accession number 98838. 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:18 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO: 18, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:18 having biological activity, the fragment comprising the amino acid sequence from amino acid 71 to amino acid 80 of SEQ ID NO:18.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:17.
Further embodiments of the invention provide isolated polynudeotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:17, but excluding the poly(A) tail at the 3' end of SEQ ID NO:17; and
(ab) the nudeotide sequence of the cDNA insert of done vk2_l deposited with the ATCC under accession number 98838;
(ii) hybridizing said probe(s) 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 nudeotide sequence selected from the group consisting of: (ba) SEQ ID NO:17, but excluding the poly(A) tail at the
3' end of SEQ ID NO:17; and
(bb) the nucleotide sequence of the cDNA insert of done vk2_l deposited with the ATCC under accession number 98838; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the 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:17, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID NO:17 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:17 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:17. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO: 17 from nucleotide 74 to nucleotide
529, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO: 17 from nucleotide 74 to nucleotide 529, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO: 17 from nucleotide 74 to nucleotide 529. Also preferably the polynucleotide isolated according to the above process comprises a nudeotide sequence corresponding to the cDNA sequence of SEQ ID
NO: 17 from nucleotide 140 to nucleotide 529, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:17 from nudeotide 140 to nucleotide 529, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:17 from nucleotide 140 to nucleotide 529.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selerted 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 vk2_l deposited with the ATCC under accession number 98838; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the arnino acid sequence of SEQ ID NO:18. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:18 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:18, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 18 having biological activity, the fragment comprising the amino acid sequence from amino acid 71 to amino acid 80 of SEQ ID NO: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
NO:19;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:19 from nucleotide 174 to nucleotide 3170;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:19 from nucleotide 1098 to nucleotide 3170;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vb21_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb21_l deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb21_l deposited with the ATCC under accession number 98862; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vb21_l deposited with the ATCC under accession number 98862; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:20;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:20 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:20;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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:19.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:19 from nudeotide 174 to nucleotide 3170; the nucleotide sequence of SEQ ID NO:19 from nucleotide 1098 to nucleotide 3170; the nucleotide sequence of the full-length protein coding sequence of clone vb21_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of clone vb21_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of done vb21_l deposited with the ATCC under accession number 98862.
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:20 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:20, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of
SEQ ID NO:20 having biological activity, the fragment comprising the amino acid sequence from amino acid 494 to amino acid 503 of SEQ ID NO:20.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:19.
Further embodiments of the invention provide isolated polynudeotides 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:19, but excluding the poly(A) tail at the 3' end of SEQ ID NO:19; and
(ab) the nucleotide sequence of the cDNA insert of done vb21_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said probe(s) 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 NO:19, but excluding the poly(A) tail at the 3' end of SEQ ID NO:19; and
(bb) the nucleotide sequence of the cDNA insert of clone vb21_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:19, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:19 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:19 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:19. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:19 from nucleotide 174 to nucleotide 3170, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:19 from nudeotide 174 to nucleotide 3170, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:19 from nucleotide 174 to nudeotide 3170. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:19 from nucleotide 1098 to nucleotide 3170, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:19 from nudeotide 1098 to nucleotide 3170, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:19 from nucleotide 1098 to nucleotide 3170. 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:20; (b) a fragment of the amino acid sequence of SEQ ID NO:20, the fragment comprising eight contiguous amino acids of SEQ ID NO:20; and
(c) the amino acid sequence encoded by the cDNA insert of clone vb21_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:20. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:20 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:20, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:20 having biological activity, the fragment comprising the amino add sequence from amino acid 494 to amino acid 503 of SEQ ID NO:20.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO-21;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:21 from nucleotide 74 to nucleotide 1453;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:21 from nucleotide 224 to nucleotide 1453;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc35_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc35_l deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc35_l deposited with the ATCC under accession number 98862; (g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vc35_l deposited with the ATCC under accession number 98862; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:22; (i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:22;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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:21.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:21 from nucleotide 74 to nucleotide 1453; the nucleotide sequence of SEQ ID NO:21 from nudeotide 224 to nudeotide 1453; the nudeotide sequence of the full-length protein coding sequence of clone vc35_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of done vc35_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc35_l deposited with the ATCC under accession number 98862. 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:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:22, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment comprising the amino acid sequence from amino acid 225 to amino acid 234 of SEQ ID NO:22.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:21. Further embodiments of the invention provide isolated polynudeotides 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:21, but excluding the poly(A) tail at the 3' end of SEQ ID NO:21; and
(ab) the nucleotide sequence of the cDNA insert of done vc35_l deposited with the ATCC under accession number 98862; (ii) hybridizing said probe(s) 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 nudeotide sequence selerted from the group consisting of:
(ba) SEQ ID NO:21, but excluding the poly(A) tail at the 3' end of SEQ ID NO:21; and
(bb) the nudeotide sequence of the cDNA insert of done vc35_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:21, and extending contiguously from a nudeotide sequence corresponding to the 5' end of SEQ ID NO:21 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:21 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:21. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:21 from nucleotide 74 to nucleotide 1453, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:21 from nucleotide 74 to nucleotide 1453, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:21 from nucleotide 74 to nudeotide 1453. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:21 from nucleotide 224 to nucleotide 1453, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:21 from nucleotide 224 to nucleotide 1453, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:21 from nucleotide 224 to nucleotide 1453.
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: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 vc35_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:22. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:22, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment comprising the amino acid sequence from amino acid 225 to amino acid 234 of SEQ ID NO: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
NO:23;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:23 from nucleotide 135 to nucleotide 368;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:23 from nucleotide 243 to nucleotide 368;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc36_l deposited with the ATCC under accession number 98862; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc36_l deposited with the ATCC under accession number 98862;
(g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:24;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:24;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides spedfied in (a)-(i); and (m) a polynudeotide that hybridizes under stringent conditions to any one of the polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:23.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:23 from nucleotide 135 to nucleotide 368; the nucleotide sequence of SEQ ID NO:23 from nudeotide 243 to nudeotide 368; the nucleotide sequence of the full-length protein coding sequence of done vc36_l deposited with the ATCC under accession number 98862; or the nudeotide sequence of a mature protein coding sequence of clone vc36_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862. 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:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:24, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment comprising the amino acid sequence from amino acid 34 to amino acid 43 of SEQ ID NO:24.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 NO:23, but excluding the poly(A) tail at the 3' end of SEQ ID NO:23; and
(ab) the nucleotide sequence of the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said probe(s) 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 NO:23, but excluding the poly(A) tail at the
3' end of SEQ ID NO:23; and
(bb) the nucleotide sequence of the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:23, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:23 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:23 , but excluding the ρoly(A) tail at the 3' end of SEQ ID NO:23. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:23 from nudeotide 135 to nudeotide 368, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:23 from nucleotide 135 to nucleotide 368, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:23 from nucleotide 135 to nucleotide 368. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:23 from nucleotide 243 to nucleotide 368, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:23 from nudeotide 243 to nudeotide 368, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:23 from nucleotide 243 to nucleotide 368. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add 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 vc36_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:24. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:24, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment comprising the amino acid sequence from amino acid 34 to amino acid 43 of SEQ ID NO: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 NO:25; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:25 from nucleotide 370 to nucleotide 1662;
(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc38_l deposited with the ATCC under accession number 98862;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc38_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc38_l deposited with the ATCC under accession number 98862;
(f) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vc38_l deposited with the ATCC under accession number 98862;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:26;
(h) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:26;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynudeotide which encodes a spedes homologue of the protein of (g) or (h) above ;
(k) a polynudeotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h) and that has a length that is at least 25% of the length of SEQ ID NO:25.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:25 from nucleotide 370 to nudeotide 1662; the nudeotide sequence of the full-length protein coding sequence of clone vc38_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of clone vc38_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc38_l deposited with the ATCC under accession number 98862. 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:26 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:26, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26 having biological activity, the fragment comprising the amino acid sequence from amino acid 210 to amino acid 219 of SEQ ID NO:26.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of :
(aa) SEQ ID NO:25, but excluding the poly(A) tail at the 3' end of SEQ ID NO:25; and
(ab) the nucleotide sequence of the cDNA insert of clone vc38_l deposited with the ATCC under accession number 98862; (ii) hybridizing said probe(s) 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 NO:25, but exduding the poly(A) tail at the 3' end of SEQ ID NO:25; and
(bb) the nucleotide sequence of the cDNA insert of clone vc38_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:25, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:25 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:25 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:25. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:25 from nudeotide 370 to nucleotide 1662, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:25 from nucleotide 370 to nucleotide 1662, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:25 from nucleotide 370 to nucleotide 1662.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence seleded 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 vc38_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:26. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:26, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26 having biological activity, the fragment comprising the amino acid sequence from amino acid 210 to amino acid 219 of SEQ ID NO:26. 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:27; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:27 from nucleotide 105 to nucleotide 365;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:27 from nucleotide 147 to nucleotide 365; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc39_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc39_l deposited with the ATCC under accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:28;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:28;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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 polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:27. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:27 from nucleotide 105 to nucleotide 365; the nucleotide sequence of SEQ ID NO:27 from nucleotide 147 to nucleotide 365; the nucleotide sequence of the full-length protein coding sequence of clone vc39_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of clone vc39_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862. 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:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:28, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment comprising the amino acid sequence from amino acid 38 to amino acid 47 of SEQ ID NO:28.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ IDNO:27.
Further embodiments of the invention provide isolated polynudeotides 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 selerted from the group consisting of:
(aa) SEQ ID NO:27, but exduding the poly(A) tail at the 3' end of SEQ ID NO:27; and
(ab) the nudeotide sequence of the cDNA insert of done vc39_l deposited with the ATCC under accession number 98862; (ii) hybridizing said ρrobe(s) 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 selerted from the group consisting of:
(ba) SEQ ID NO:27, but exduding the poly(A) tail at the 3' end of SEQ ID NO:27; and (bb) the nucleotide sequence of the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:27, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:27 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:27 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:27. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:27 from nudeotide 105 to nucleotide 365, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:27 from nucleotide 105 to nucleotide 365, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:27 from nucleotide 105 to nucleotide 365. Also preferably the polynucleotide isolated according to the above process comprises a nudeotide sequence corresponding to the cDNA sequence of SEQ ID NO:27 from nucleotide 147 to nucleotide 365, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:27 from nudeotide 147 to nucleotide 365, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:27 from nucleotide 147 to nucleotide 365.
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:28;
(b) a fragment of the amino acid sequence of SEQ ID NO:28, the fragment comprising eight contiguous amino acids of SEQ ID NO:28; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:28. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:28, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment comprising the amino acid sequence from amino acid 38 to amino acid 47 of SEQ ID NO: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 NO:29;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:29 from nucleotide 35 to nucleotide 1066;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:29 from nucleotide 128 to nucleotide 1066;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc40_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc40_l deposited with the ATCC under accession number 98862;
(g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:30;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:30 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:30;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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 polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:29.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:29 from nucleotide 35 to nucleotide 1066; the nucleotide sequence of SEQ ID NO:29 from nucleotide 128 to nucleotide 1066; the nudeotide sequence of the full-length protein coding sequence of clone vc40_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of done vc40_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862. 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:30 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:30, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:30 having biological activity, the fragment comprising the amino acid sequence from amino acid 167 to amino acid 176 of SEQ ID NO:30.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ IDNO: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 polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:29, but exduding the ρoly(A) tail at the 3' end of SEQ ID NO:29; and
(ab) the nucleotide sequence of the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said probe(s) 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 NO:29, but excluding the poly(A) tail at the 3' end of SEQ ID NO:29; and
(bb) the nucleotide sequence of the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:29, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:29 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:29 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:29. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:29 from nucleotide 35 to nucleotide 1066, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:29 from nucleotide 35 to nucleotide 1066, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:29 from nucleotide 35 to nudeotide 1066. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:29 from nucleotide 128 to nucleotide 1066, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:29 from nucleotide 128 to nucleotide 1066, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:29 from nucleotide 128 to nucleotide 1066. 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: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 vc40_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:30. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:30 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:30, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:30 having biological activity, the fragment comprising the amino acid sequence from amino acid 167 to amino acid 176 of SEQ ID NO:30.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:31;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:31 from nucleotide 38 to nucleotide 553;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:31 from nucleotide 104 to nucleotide 553;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc46_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc46_l deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc46_l deposited with the ATCC under accession number 98862; (g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vc46_l deposited with the ATCC under accession number 98862; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:32; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:32 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 NO:31.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:31 from nucleotide 38 to nucleotide 553; the nucleotide sequence of SEQ ID NO:31 from nudeotide 104 to nudeotide 553; the nucleotide sequence of the full-length protein coding sequence of clone vc46_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of done vc46_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc46_l deposited with the ATCC under accession number 98862. 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:32 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:32, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:32 having biological activity, the fragment comprising the amino acid sequence from amino acid 81 to amino acid 90 of SEQ ID NO:32.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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: 00/11015
(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:31, but excluding the ρoly(A) tail at the 3' end of SEQ ID NO:31; and
(ab) the nucleotide sequence of the cDNA insert of clone vc46_l deposited with the ATCC under accession number 98862; (ii) hybridizing said probe(s) 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 NO:31, but excluding the poly(A) tail at the 3' end of SEQ ID NO:31; and
(bb) the nudeotide sequence of the cDNA insert of done vc46_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii). Preferably the polynucleotide isolated according to the above process comprises a nudeotide sequence corresponding to the cDNA sequence of SEQ ID NO:31, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:31 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:31 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:31. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:31 from nucleotide 38 to nucleotide 553, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:31 from nucleotide 38 to nucleotide 553, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:31 from nucleotide 38 to nucleotide 553. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:31 from nucleotide 104 to nucleotide 553, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:31 from nudeotide 104 to nucleotide 553, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:31 from nucleotide 104 to nucleotide 553.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add 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 vc46_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:32. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:32 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:32, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:32 having biological activity, the fragment comprising the amino acid sequence from amino acid 81 to amino acid 90 of SEQ ID NO: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
NO:33;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:33 from nucleotide 164 to nucleotide 2548;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:33 from nucleotide 242 to nucleotide 2548;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc49_l deposited with the ATCC under accession number 98862; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc49_l deposited with the ATCC under accession number 98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc49_l deposited with the ATCC under accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc49_l deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:34;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:34;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes 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:33.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO.-33 from nudeotide 164 to nudeotide 2548; the nucleotide sequence of SEQ ID NO:33 from nudeotide 242 to nudeotide 2548; the nudeotide sequence of the full-length protein coding sequence of done vc49_l deposited with the ATCC under accession number 98862; or the nudeotide sequence of a mature protein coding sequence of clone vc49_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc49_l deposited with the ATCC under accession number 98862. 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:34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:34, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment comprising the amino acid sequence from arnino acid 392 to amino acid 401 of SEQ ID NO:34.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:33.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:33, but excluding the poly(A) tail at the 3' end of SEQ ID NO:33; and
(ab) the nucleotide sequence of the cDNA insert of done vc49_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said probe(s) 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 nudeotide sequence selected from the group consisting of: (ba) SEQ ID NO:33, but excluding the poly(A) tail at the
3' end of SEQ ID NO:33; and
(bb) the nudeotide sequence of the cDNA insert of clone vc49_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:33, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:33 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:33 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:33. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:33 from nucleotide 164 to nudeotide 2548, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:33 from nucleotide 164 to nudeotide 2548, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:33 from nucleotide 164 to nucleotide 2548. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:33 from nucleotide 242 to nucleotide 2548, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:33 from nucleotide 242 to nucleotide 2548, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:33 from nucleotide 242 to nucleotide 2548. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add 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 vc49_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino add sequence of SEQ ID NO:34. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:34, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment comprising the amino acid sequence from amino acid 392 to amino acid 401 of SEQ ID NO:34.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:35; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:35 from nucleotide 150 to nucleotide 776;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:35 from nucleotide 246 to nucleotide 776; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc50_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc50_l deposited with the ATCC under accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:36;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 NO:35. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:35 from nucleotide 150 to nucleotide 776; the nucleotide sequence of SEQ ID NO:35 from nucleotide 246 to nucleotide 776; the nucleotide sequence of the full-length protein coding sequence of clone vc50_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of clone vc50_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862. 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:36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:36, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36 having biological activity, the fragment comprising the amino acid sequence from amino acid 99 to amino acid 108 of SEQ ID NO:36.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 NO:35, but excluding the poly(A) tail at the 3' end of SEQ ID NO:35; and
(ab) the nucleotide sequence of the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862; (ii) hybridizing said probe(s) 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 NO:35, but excluding the poly(A) tail at the 3' end of SEQ ID NO:35; and (bb) the nucleotide sequence of the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:35, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:35 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:35 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:35. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:35 from nucleotide 150 to nucleotide 776, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:35 from nucleotide 150 to nucleotide 776, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:35 from nucleotide 150 to nucleotide 776. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:35 from nucleotide 246 to nucleotide 776, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:35 from nucleotide 246 to nucleotide 776, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:35 from nucleotide 246 to nucleotide 776.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:36;
(b) a fragment of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight contiguous amino acids of SEQ ID NO:36; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:36. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:36, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36 having biological activity, the fragment comprising the amino acid sequence from amino acid 99 to amino acid 108 of SEQ ID NO: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 NO:37;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:37 from nucleotide 139 to nucleotide 1308;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:37 from nucleotide 211 to nucleotide 1308;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc51_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc51_l deposited with the ATCC under accession number 98862;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:38;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:38 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:38;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spe es 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:37.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:37 from nucleotide 139 to nucleotide 1308; the nucleotide sequence of SEQ ID NO:37 from nucleotide 211 to nucleotide 1308; the nucleotide sequence of the full-length protein coding sequence of clone vc51_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of clone vc51_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862. 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:38 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:38, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:38 having biological activity, the fragment comprising the amino acid sequence from arnino acid 190 to amino acid 199 of SEQ ID NO:38.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:37, but excluding the poly(A) tail at the 3' end of SEQ ID NO:37; and
(ab) the nucleotide sequence of the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said probe(s) 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 NO:37, but excluding the poly(A) tail at the 3' end of SEQ ID NO:37; and
(bb) the nucleotide sequence of the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:37, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:37 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:37 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:37. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:37 from nucleotide 139 to nucleotide 1308, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:37 from nucleotide 139 to nucleotide 1308, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:37 from nucleotide 139 to nucleotide 1308. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
NO:37 from nucleotide 211 to nucleotide 1308, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:37 from nucleotide 211 to nucleotide 1308, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:37 from nucleotide 211 to nucleotide 1308. 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: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 vc51_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:38. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:38 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:38, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:38 having biological activity, the fragment comprising the amino acid sequence from amino acid 190 to amino acid 199 of SEQ ID NO:38.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:39;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:39 from nucleotide 21 to nucleotide 1142;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:39 from nucleotide 114 to nucleotide 1142;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc52_l deposited with the ATCC under accession number 98862;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc52_l deposited with the ATCC under accession number
98862;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc52_l deposited with the ATCC under accession number 98862; (g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vc52_l deposited with the ATCC under accession number 98862; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:40; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:40;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes 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:39.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:39 from nucleotide 21 to nucleotide 1142; the nucleotide sequence of SEQ ID NO:39 from nucleotide 114 to nucleotide 1142; the nucleotide sequence of the full-length protein coding sequence of clone vc52_l deposited with the ATCC under accession number 98862; or the nucleotide sequence of a mature protein coding sequence of clone vc52_l deposited with the ATCC under accession number 98862. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc52_l deposited with the ATCC under accession number 98862. 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:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:40, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40 having biological activity, the fragment comprising the amino acid sequence from amino acid 182 to amino acid 191 of SEQ ID NO:40.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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: 00/11015
(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:39, but excluding the poly(A) tail at the 3' end of SEQ ID NO:39; and
(ab) the nucleotide sequence of the cDNA insert of done vc52_l deposited with the ATCC under accession number 98862; (ii) hybridizing said probe(s) 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 NO:39, but excluding the poly(A) tail at the 3' end of SEQ ID NO:39; and
(bb) the nudeotide sequence of the cDNA insert of clone vc52_l deposited with the ATCC under accession number 98862;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:39, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:39 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:39 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:39. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:39 from nucleotide 21 to nucleotide 1142, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:39 from nucleotide 21 to nucleotide 1142, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:39 from nucleotide 21 to nucleotide 1142. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:39 from nucleotide 114 to nucleotide 1142, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:39 from nucleotide 114 to nucleotide 1142, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:39 from nucleotide 114 to nucleotide 1142.
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: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 vc52_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:40. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:40, or a protein comprising a fragment of the amino acid sequence of SEQ
ID NO:40 having biological activity, the fragment comprising the amino acid sequence from amino acid 182 to amino acid 191 of SEQ ID NO: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
NO:41;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:41 from nucleotide 13 to nucleotide 1416;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:41 from nucleotide 346 to nucleotide 1416;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc33_l deposited with the ATCC under accession number 98886; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc33_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:42;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:42;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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 polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:41.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:41 from nucleotide 13 to nucleotide 1416; the nucleotide sequence of SEQ ID NO:41 from nucleotide 346 to nucleotide 1416; the nucleotide sequence of the full-length protein coding sequence of clone vc33_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of done vc33_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886. 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:42 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:42, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42 having biological activity, the fragment comprising the amino acid sequence from amino acid 229 to amino acid 238 of SEQ ID NO:42.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:41.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:41, but excluding the poly(A) tail at the 3' end of SEQ ID NO:41; and
(ab) the nucleotide sequence of the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe(s) 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 NO:41, but excluding the poly(A) tail at the
3' end of SEQ ID NO:41; and
(bb) the nucleotide sequence of the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:41, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:41 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:41 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:41. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:41 from nucleotide 13 to nucleotide 1416, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:41 from nucleotide 13 to nucleotide 1416, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:41 from nucleotide 13 to nucleotide 1416. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:41 from nucleotide 346 to nucleotide 1416, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:41 from nucleotide 346 to nucleotide 1416, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:41 from nucleotide 346 to nucleotide 1416. 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: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 vc33_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:42. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:42, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42 having biological activity, the fragment comprising the amino acid sequence from amino acid 229 to amino acid 238 of SEQ ID NO:42.
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:43; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:43 from nucleotide 232 to nucleotide 1461;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:43 from nucleotide 280 to nucleotide 1461; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc34_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc34_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:44;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:44 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 polynudeotide 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:43. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:43 from nucleotide 232 to nucleotide 1461; the nucleotide sequence of SEQ ID NO:43 from nucleotide 280 to nucleotide 1461; the nucleotide sequence of the full-length protein coding sequence of clone vc34_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vc34_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886. 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:44 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:44, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:44 having biological activity, the fragment comprising the amino acid sequence from amino acid 200 to amino acid 209 of SEQ ID NO:44.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 NO:43, but excluding the poly(A) tail at the 3' end of SEQ ID NO:43; and
(ab) the nucleotide sequence of the cDNA insert of done vc34_l deposited with the ATCC under accession number 98886; (ii) hybridizing said probe(s) 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 NO:43, but excluding the poly(A) tail at the 3' end of SEQ ID NO:43; and (bb) the nucleotide sequence of the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:43, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:43 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:43 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:43. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:43 from nucleotide 232 to nucleotide 1461, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:43 from nucleotide 232 to nucleotide 1461, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:43 from nucleotide 232 to nucleotide 1461. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:43 from nucleotide 280 to nucleotide 1461, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:43 from nucleotide 280 to nucleotide 1461, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:43 from nucleotide 280 to nucleotide 1461.
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:44;
(b) a fragment of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight contiguous amino acids of SEQ ID NO:44; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:44. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:44 having biological activity, the fragment preferably 00/11015
comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:44, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:44 having biological activity, the fragment comprising the amino acid sequence from amino acid 200 to amino acid 209 of SEQ ID NO: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 NO:45;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:45 from nucleotide 1922 to nucleotide 2350;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:45 from nucleotide 2237 to nucleotide 2350;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc47_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc47_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:46;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:46;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a speries 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 00/11015
(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:45.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:45 from nucleotide 1922 to nucleotide 2350; the nucleotide sequence of SEQ ID NO:45 from nucleotide 2237 to nucleotide 2350; the nucleotide sequence of the full-length protein coding sequence of clone vc47_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vc47_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886.
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:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:46, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of
SEQ ID NO:46 having biological activity, the fragment comprising the amino acid sequence from amino acid 66 to amino acid 75 of SEQ ID NO:46.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:45.
Further embodiments of the invention provide isolated polynudeotides 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:45, but excluding the poly(A) tail at the 3' end of SEQ ID NO:45; and
(ab) the nucleotide sequence of the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe(s) 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 NO:45, but excluding the poly(A) tail at the 3' end of SEQ ID NO:45; and
(bb) the nudeotide sequence of the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:45, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:45 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:45 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:45. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:45 from nucleotide 1922 to nucleotide 2350, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:45 from nucleotide 1922 to nucleotide 2350, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:45 from nucleotide 1922 to nucleotide 2350. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of
SEQ ID NO:45 from nucleotide 2237 to nucleotide 2350, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:45 from nucleotide 2237 to nudeotide 2350, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:45 from nucleotide 2237 to nucleotide 2350. 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: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 vc47_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:46. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous arnino adds of SEQ ID NO:46, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46 having biological activity, the fragment comprising the amino acid sequence from amino acid 66 to amino acid 75 of SEQ ID NO:46.
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:47;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:47 from nucleotide 111 to nucleotide 1337;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:47 from nucleotide 246 to nucleotide 1337;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc54_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc54_l deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc54_l deposited with the ATCC under accession number 98886; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc54_l deposited with the ATCC under accession number 98886; (h) a polynucleotide encoding a protein comprising the amino add sequence of SEQ ID NO:48; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 NO:47.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:47 from nucleotide 111 to nucleotide 1337; the nucleotide sequence of SEQ ID NO:47 from nucleotide 246 to nucleotide 1337; the nucleotide sequence of the full-length protein coding sequence of clone vc54_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vc54_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc54_l deposited with the ATCC under accession number 98886. 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:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:48, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48 having biological activity, the fragment comprising the amino acid sequence from amino acid 199 to amino acid 208 of SEQ ID NO:48.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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: O 00/11015
(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:47, but excluding the poly(A) tail at the 3' end of SEQ ID NO:47; and
(ab) the nucleotide sequence of the cDNA insert of clone vc54_l deposited with the ATCC under accession number 98886; (ii) hybridizing said probe(s) 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 NO:47, but excluding the poly(A) tail at the 3' end of SEQ ID NO:47; and
(bb) the nucleotide sequence of the cDNA insert of clone vc54_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:47, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:47 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:47 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:47. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:47 from nucleotide 111 to nucleotide 1337, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:47 from nudeotide 111 to nucleotide 1337, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:47 from nucleotide 111 to nucleotide 1337. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:47 from nucleotide 246 to nucleotide 1337, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:47 from nucleotide 246 to nucleotide 1337, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:47 from nucleotide 246 to nucleotide 1337.
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: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 vc54_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:48. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:48, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48 having biological activity, the fragment comprising the amino acid sequence from amino acid 199 to amino acid 208 of SEQ ID NO:48.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:49;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:49 from nucleotide 189 to nucleotide 1637;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:49 from nucleotide 270 to nucleotide 1637;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc57_l deposited with the ATCC under accession number 98886; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc57_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:50;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:50 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:50;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes 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 polynudeotide 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:49.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:49 from nucleotide 189 to nucleotide 1637; the nucleotide sequence of SEQ ID NO:49 from nucleotide 270 to nudeotide 1637; the nucleotide sequence of the full-length protein coding sequence of done vc57_l deposited with the ATCC under accession number 98886; or the nudeotide sequence of a mature protein coding sequence of done vc57_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886. 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 twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:50, or a polynucleotide 00/11015
encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:50 having biological activity, the fragment comprising the amino acid sequence from amino acid 236 to amino acid 245 of SEQ ID NO:50.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO.-49.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:49, but excluding the poly(A) tail at the 3' end of SEQ ID NO:49; and
(ab) the nucleotide sequence of the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe(s) 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 NO:49, but excluding the poly(A) tail at the
3' end of SEQ ID NO:49; and
(bb) the nucleotide sequence of the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:49, and , , n, β PCT/US99/19351 00/11015
extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:49 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:49 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:49. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:49 from nudeotide 189 to nucleotide 1637, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:49 from nucleotide 189 to nucleotide 1637, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:49 from nucleotide 189 to nucleotide 1637. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:49 from nucleotide 270 to nucleotide 1637, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:49 from nucleotide 270 to nucleotide 1637, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:49 from nucleotide 270 to nucleotide 1637. 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:50;
(b) a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:50. In further preferred embodiments, the present invention provides 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 twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:50, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:50 having biological activity, the fragment comprising the amino acid sequence from amino acid 236 to amino acid 245 of SEQ ID NO: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 NO:51; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:51 from nucleotide 15 to nucleotide 1934;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:51 from nucleotide 1704 to nucleotide 1934; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vel3_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vel3_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vel3_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vel3_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:52;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:52 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:52;
(j) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ; (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and
(m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:51. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:51 from nucleotide 15 to nucleotide 1934; the nucleotide sequence of SEQ ID NO:51 from nucleotide 1704 to nucleotide 1934; the nucleotide sequence of the full-length protein coding sequence of clone vel3_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vel3_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of done vel3_l deposited with the ATCC under accession number 98886.
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:52 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:52, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of
SEQ ID NO:52 having biological activity, the fragment comprising the amino acid sequence from amino acid 315 to amino acid 324 of SEQ ID NO:52.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:51.
Further embodiments of the invention provide isolated polynudeotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of :
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:51, but exduding the poly(A) tail at the 3' end of SEQ ID NO:51; and
(ab) the nucleotide sequence of the cDNA insert of clone vel3_l deposited with the ATCC under accession number 98886; (ii) hybridizing said probe(s) 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 NO:51, but excluding the poly(A) tail at the 3' end of SEQ ID NO:51; and 00/11015
(bb) the nucleotide sequence of the cDNA insert of done vel3_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:51, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:51 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:51 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:51. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:51 from nucleotide 15 to nucleotide 1934, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:51 from nucleotide 15 to nucleotide 1934, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:51 from nucleotide 15 to nucleotide 1934. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:51 from nucleotide 1704 to nucleotide 1934, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:51 from nucleotide 1704 to nucleotide 1934, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:51 from nucleotide 1704 to nucleotide 1934.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add 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 vel3_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:52. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:52 having biological activity, the fragment preferably 00/11015
comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:52, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:52 having biological activity, the fragment comprising the amino acid sequence from amino acid 315 to amino acid 324 of SEQ ID NO:52. 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:53;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:53 from nucleotide 240 to nucleotide 503;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:53 from nucleotide 318 to nucleotide 503;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vel6_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vel6_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:54;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:54;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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:53.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:53 from nucleotide 240 to nucleotide 503; the nucleotide sequence of SEQ ID NO:53 from nucleotide 318 to nucleotide 503; the nucleotide sequence of the full-length protein coding sequence of clone vel6_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vel6_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886. 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:54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:54, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54 having biological activity, the fragment comprising the amino acid sequence from amino acid 39 to amino acid 48 of SEQ ID NO:54.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ IDNO: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 NO:53, but exduding the ρoly(A) tail at the 3' end of SEQ ID NO:53; and
(ab) the nucleotide sequence of the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe(s) 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 NO:53, but excluding the poly(A) tail at the 3' end of SEQ ID NO:53; and
(bb) the nucleotide sequence of the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:53, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:53 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:53 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:53. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:53 from nucleotide 240 to nucleotide 503, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:53 from nucleotide 240 to nucleotide 503, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:53 from nucleotide 240 to nucleotide 503. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:53 from nucleotide 318 to nucleotide 503, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:53 from nucleotide 318 to nucleotide 503, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:53 from nucleotide 318 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 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 vel6_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:54. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:54, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54 having biological activity, the fragment comprising the ar ino acid sequence from amino acid 39 to amino acid 48 of SEQ ID NO:54.
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:55;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:55 from nucleotide 11 to nucleotide 1063;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1063;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vf3_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vf3_l deposited with the ATCC under accession number
98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vf3_l deposited with the ATCC under accession number 98886; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vf3_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:56; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO: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 ;
(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:55.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:55 from nucleotide 11 to nucleotide 1063; the nucleotide sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1063; the nucleotide sequence of the full-length protein coding sequence of clone vf3_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vf3_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vf3_l deposited with the ATCC under accession number 98886. 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:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:56, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 170 to amino acid 179 of SEQ ID NO:56.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ 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 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID 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 done vf3_l deposited with the ATCC under accession number 98886; (ii) hybridizing said probe(s) 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 NO:55, but excluding the poly(A) tail at the 3' end of SEQ ID NO:55; and
(bb) the nucleotide sequence of the cDNA insert of done vf3_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:55, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:55 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:55 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:55. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:55 from nucleotide 11 to nucleotide 1063, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:55 from nucleotide 11 to nucleotide 1063, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:55 from nucleotide 11 to nucleotide 1063. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1063, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1063, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1063.
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: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 vf3_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:56. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:56, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 170 to amino acid 179 of SEQ ID NO:56.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:57;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:57 from nucleotide 542 to nucleotide 886;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:57 from nucleotide 755 to nucleotide 886;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vj2_l deposited with the ATCC under accession number 98886; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vj2_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:58;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:58 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:58;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide 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:57.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:57 from nucleotide 542 to nucleotide 886; the nucleotide sequence of SEQ ID NO:57 from nucleotide 755 to nucleotide 886; the nucleotide sequence of the full-length protein coding sequence of done vj2_l deposited with the ATCC under accession number 98886; or the nudeotide sequence of a mature protein coding sequence of clone vj2_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886. 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:58 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:58, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:58 having biological activity, the fragment comprising the amino acid sequence from amino acid 52 to amino acid 61 of SEQ ID NO:58.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 NO:57, but excluding the poly(A) tail at the 3' end of SEQ ID NO:57; and
(ab) the nucleotide sequence of the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe(s) 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 NO:57, but excluding the poly(A) tail at the
3' end of SEQ ID NO:57; and
(bb) the nucleotide sequence of the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:57, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:57 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:57 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:57. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:57 from nudeotide 542 to nucleotide 886, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:57 from nucleotide 542 to nucleotide 886, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:57 from nucleotide 542 to nucleotide 886. Also preferably the polynucleotide isolated according to the above process comprises a nudeotide sequence corresponding to the cDNA sequence of SEQ ID NO:57 from nucleotide 755 to nucleotide 886, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:57 from nucleotide 755 to nucleotide 886, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:57 from nucleotide 755 to nucleotide 886. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add 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 add sequence encoded by the cDNA insert of done vj2_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:58. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:58 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:58, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:58 having biological activity, the fragment comprising the amino acid sequence from amino acid 52 to amino acid 61 of SEQ ID NO: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 NO:59; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:59 from nucleotide 30 to nucleotide 344;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:59 from nucleotide 84 to nucleotide 344; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vp7_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of done vp7_l deposited with the ATCC under accession number 98886;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:60;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:60 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:60;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide 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 polynudeotide 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:59. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:59 from nucleotide 30 to nucleotide 344; the nucleotide sequence of SEQ ID NO:59 from nucleotide 84 to nucleotide 344; the nucleotide sequence of the full-length protein coding sequence of clone vp7_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vp7_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886. 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:60 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:60, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:60 having biological activity, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO:60.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:59.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of:
(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:59, but exduding the poly(A) tail at the 3' end of SEQ ID NO:59; and
(ab) the nucleotide sequence of the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886; (ii) hybridizing said probe(s) 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 NO:59, but excluding the poly(A) tail at the 3' end of SEQ ID NO:59; and (bb) the nucleotide sequence of the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:59, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:59 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:59 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:59. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:59 from nucleotide 30 to nucleotide 344, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:59 from nucleotide 30 to nucleotide 344, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:59 from nucleotide 30 to nudeotide 344. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:59 from nucleotide 84 to nucleotide 344, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:59 from nucleotide 84 to nucleotide 344, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:59 from nucleotide 84 to nucleotide 344.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of :
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID 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 vp7_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:60. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:60 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:60, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:60 having biological activity, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO: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 NO:61;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:61 from nucleotide 23 to nucleotide 757;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:61 from nucleotide 119 to nucleotide 757;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vp8_l deposited with the ATCC under accession number 98886;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vp8_l deposited with the ATCC under accession number 98886;
(g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:62;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:62 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:62;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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:61.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:61 from nucleotide 23 to nucleotide 757; the nucleotide sequence of SEQ ID NO:61 from nucleotide 119 to nucleotide 757; the nucleotide sequence of the full-length protein coding sequence of clone vp8_l deposited with the ATCC under accession number 98886; or the nucleotide sequence of a mature protein coding sequence of clone vp8_l deposited with the ATCC under accession number 98886. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886. 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:62 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:62, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:62 having biological activity, the fragment comprising the amino acid sequence from amino acid 117 to amino acid 126 of SEQ ID NO:62.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO: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 NO:61, but exduding the poly(A) tail at the 3' end of SEQ ID NO:61; and
(ab) the nucleotide sequence of the cDNA insert of done vp8_l deposited with the ATCC under accession number 98886;
(ii) hybridizing said probe(s) 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 NO:61, but excluding the poly(A) tail at the 3' end of SEQ ID NO:61; and
(bb) the nucleotide sequence of the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:61, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:61 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:61 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:61. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:61 from nucleotide 23 to nucleotide 757, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:61 from nucleotide 23 to nucleotide 757, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:61 from nucleotide 23 to nucleotide 757. Also preferably the polynucleotide isolated according to the above process comprises a nudeotide sequence corresponding to the cDNA sequence of SEQ ID NO:61 from nucleotide 119 to nucleotide 757, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:61 from nudeotide 119 to nudeotide 757, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:61 from nucleotide 119 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 consisting of:
(a) the amino acid sequence of SEQ ID NO:62; (b) a fragment of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight contiguous amino acids of SEQ ID NO:62; and
(c) the amino acid sequence encoded by the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:62. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:62 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:62, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:62 having biological activity, the fragment comprising the amino acid sequence from amino acid 117 to amino acid 126 of SEQ ID NO:62.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:63;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:63 from nucleotide 1048 to nucleotide 3726;
(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vb22_l deposited with the ATCC under accession number 98933;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb22_l deposited with the ATCC under accession number 98933;
(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:64;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:64; (i) a polynucleotide which is an allelic variant of a polynucleotide of
(a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ; (k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h) and that has a length that is at least
25% of the length of SEQ ID NO:63. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:63 from nucleotide 1048 to nucleotide 3726; the nucleotide sequence of the full-length protein coding sequence of clone vb22_l deposited with the ATCC under accession number 98933; or the nucleotide sequence of a mature protein coding sequence of clone vb22_l deposited with the ATCC under accession number 98933. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933.
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:64 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:64, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64 having biological activity, the fragment comprising the amino acid sequence from amino acid 441 to amino acid 450 of SEQ ID NO:64.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:63.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:63, but excluding the poly(A) tail at the 3' end of SEQ ID NO:63; and (ab) the nucleotide sequence of the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933; (ii) hybridizing said probe(s) 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 NO:63, but excluding the poly(A) tail at the 3' end of SEQ ID NO:63; and
(bb) the nudeotide sequence of the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:63, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:63 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:63 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:63. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:63 from nucleotide 1048 to nucleotide 3726, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:63 from nucleotide 1048 to nudeotide 3726, to a nudeotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:63 from nucleotide 1048 to nucleotide 3726.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:64; 00/11015
(b) a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64; and
(c) the amino acid sequence encoded by the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:64. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:64, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64 having biological activity, the fragment comprising the amino acid sequence from amino acid 441 to amino acid 450 of SEQ ID NO:64.
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:65;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:65 from nucleotide 134 to nucleotide 667;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:65 from nucleotide 191 to nucleotide 667;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc48_l deposited with the ATCC under accession number 98933;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number
98933;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc48_l deposited with the ATCC under accession number 98933; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:66; 00/11015
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:66;
(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:65.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:65 from nucleotide 134 to nucleotide 667; the nucleotide sequence of SEQ ID NO:65 from nucleotide 191 to nucleotide 667; the nucleotide sequence of the full-length protein coding sequence of clone vc48_l deposited with the ATCC under accession number 98933; or the nucleotide sequence of a mature protein coding sequence of clone vc48_l deposited with the ATCC under accession number 98933. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933. 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:66 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:66, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66 having biological activity, the fragment comprising the amino acid sequence from amino acid 84 to amino acid 93 of SEQ ID NO:66.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:65. 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: 00/11015
(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:65, but excluding the ρoly(A) tail at the 3' end of SEQ ID NO:65; and
(ab) the nucleotide sequence of the cDNA insert of done vc48_l deposited with the ATCC under accession number 98933; (ii) hybridizing said probe(s) 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 NO:65, but excluding the poly(A) tail at the 3' end of SEQ ID NO:65; and
(bb) the nudeotide sequence of the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933;
(ii) hybridizing said ρrimer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(ϋi). Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:65, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:65 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:65 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:65. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:65 from nucleotide 134 to nucleotide 667, and extending contiguously from a nucleotide sequence corresponding to the 5* end of said sequence of SEQ ID NO:65 from nucleotide 134 to nucleotide 667, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:65 from nucleotide 134 to nucleotide 667. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:65 from nucleotide 191 to nucleotide 667, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:65 from nucleotide 191 to nudeotide 667, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:65 from nucleotide 191 to nucleotide 667.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:66;
(b) a fragment of the amino acid sequence of SEQ ID NO:66, the fragment comprising eight contiguous amino acids of SEQ ID NO:66; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:66. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:66, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66 having biological activity, the fragment comprising the amino acid sequence from amino acid 84 to amino acid 93 of SEQ ID NO:66.
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:67;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:67 from nucleotide 65 to nucleotide 457;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:67 from nucleotide 158 to nucleotide 457;
(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vp3_l deposited with the ATCC under accession number 98933; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vp3_l deposited with the ATCC under accession number 98933;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:68;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:68 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:68;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide 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 polynudeotide 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:67.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:67 from nucleotide 65 to nucleotide 457; the nucleotide sequence of SEQ ID NO:67 from nucleotide 158 to nudeotide 457; the nucleotide sequence of the full-length protein coding sequence of done vp3_l deposited with the ATCC under accession number 98933; or the nucleotide sequence of a mature protein coding sequence of done vp3_l deposited with the ATCC under accession number 98933. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933. 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:68 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:68, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:68 having biological activity, the fragment comprising the amino acid sequence from amino acid 60 to amino acid 69 of SEQ ID NO:68.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:67.
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:67, but excluding the poly(A) tail at the 3' end of SEQ ID NO:67; and
(ab) the nucleotide sequence of the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933;
(ii) hybridizing said probe(s) 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 NO:67, but excluding the poly(A) tail at the
3' end of SEQ ID NO:67; and
(bb) the nucleotide sequence of the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the 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:67, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:67 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:67 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:67. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:67 from nucleotide 65 to nucleotide 457, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:67 from nucleotide 65 to nucleotide 457, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:67 from nucleotide 65 to nucleotide 457. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:67 from nucleotide 158 to nucleotide 457, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:67 from nudeotide 158 to nucleotide 457, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:67 from nucleotide 158 to nucleotide 457. 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:68;
(b) a fragment of the amino acid sequence of SEQ ID NO:68, the fragment comprising eight contiguous amino acids of SEQ ID NO:68; and
(c) the amino acid sequence encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:68. In further preferred embodiments, the present invention provides a protein comprising a fragment of the arnino add sequence of SEQ ID NO:68 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:68, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:68 having biological activity, the fragment comprising the amino acid sequence from amino acid 60 to amino acid 69 of SEQ ID NO:68.
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:69; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:69 from nucleotide 29 to nucleotide 1387;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:69 from nucleotide 113 to nucleotide 1387; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vc61_l deposited with the ATCC under accession number 207012;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc61_l deposited with the ATCC under accession number 207012;
(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:70;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:70 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:70;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a spedes 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 polynudeotide 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:69. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:69 from nucleotide 29 to nucleotide 1387; the nucleotide sequence of SEQ ID NO:69 from nucleotide 113 to nucleotide 1387; the nucleotide sequence of the full-length protein coding sequence of clone vc61_l deposited with the ATCC under accession number 207012; or the nucleotide sequence of a mature protein coding sequence of clone vc61_l 00/11015
deposited with the ATCC under accession number 207012. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012. 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:70 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:70, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:70 having biological activity, the fragment comprising the amino acid sequence from amino acid 221 to amino acid 230 of SEQ ID NO:70.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:69.
Further embodiments of the invention provide isolated polynudeotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of :
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nudeotide sequence selected from the group consisting of:
(aa) SEQ ID NO:69, but exduding the poly(A) tail at the 3' end of SEQ ID NO:69; and
(ab) the nudeotide sequence of the cDNA insert of done vc61_l deposited with the ATCC under accession number 207012; (ii) hybridizing said probe(s) 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 nudeotide sequence selected from the group consisting of:
(ba) SEQ ID NO:69, but excluding the poly(A) tail at the 3' end of SEQ ID NO:69; and (bb) the nucleotide sequence of the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:69, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:69 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:69 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:69. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:69 from nucleotide 29 to nucleotide 1387, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:69 from nucleotide 29 to nucleotide 1387, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:69 from nucleotide 29 to nucleotide 1387. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:69 from nucleotide 113 to nucleotide 1387, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:69 from nucleotide 113 to nucleotide 1387, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:69 from nucleotide 113 to nucleotide 1387.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:70;
(b) a fragment of the amino acid sequence of SEQ ID NO:70, the fragment comprising eight contiguous amino acids of SEQ ID NO:70; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:70. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:70 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:70, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:70 having biological activity, the fragment comprising the amino acid sequence from amino acid 221 to amino acid 230 of SEQ ID NO:70. 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:71;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:71 from nucleotide 44 to nucleotide 1513;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:71 from nucleotide 92 to nucleotide 1513;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:71 from nucleotide 1 to nucleotide 458; (e) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vpl5_l deposited with the ATCC under accession number 207012;
(f) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012;
(g) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vpl5_l deposited with the ATCC under accession number 207012;
(h) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012;
(i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:72;
(j) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:72 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:72;
(k) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(h) above;
(1) a polynucleotide which encodes a species homologue of the protein of (i) or (j) above ; (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j); and
(n) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j) and that has a length that is at least 25% of the length of SEQ ID NO:71.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:71 from nucleotide 44 to nucleotide 1513; the nucleotide sequence of SEQ ID NO:71 from nucleotide 92 to nucleotide 1513; the nucleotide sequence of SEQ ID NO:71 from nucleotide 1 to nucleotide 458; the nucleotide sequence of the full-length protein coding sequence of clone vpl5_l deposited with the ATCC under accession number 207012; or the nucleotide sequence of a mature protein coding sequence of clone vpl5_l deposited with the ATCC under accession number 207012. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of done vpl5_l deposited with the ATCC under accession number 207012. In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:72 from amino acid 1 to amino acid 139. In further preferred embodiments, the present invention provides a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:72 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:72, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:72 having biological activity, the fragment comprising the amino acid sequence from amino acid 240 to amino acid 249 of SEQ ID NO:72.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ IDNO:71.
Further embodiments of the invention provide isolated polynudeotides produced according to a process selected from the group consisting of: (a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:71, but excluding the poly(A) tail at the 3' end of SEQ ID NO:71; and O 00/11015
(ab) the nucleotide sequence of the cDNA insert of done vpl5_l deposited with the ATCC under accession number 207012; (ii) hybridizing said probe(s) 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 nudeotide sequence selected from the group consisting of:
(ba) SEQ ID NO:71, but exduding the poly(A) tail at the 3' end of SEQ ID NO:71; and
(bb) the nucleotide sequence of the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012;
(ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the 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:71, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID NO:71 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:71 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:71. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:71 from nucleotide 44 to nucleotide
1513, and extending contiguously from a nudeotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:71 from nucleotide 44 to nucleotide 1513, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:71 from nucleotide 44 to nucleotide 1513. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
NO:71 from nucleotide 92 to nucleotide 1513, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:71 from nucleotide 92 to nucleotide 1513, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:71 from nucleotide 92 to nucleotide 1513. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:71 from nucleotide 1 to nucleotide 458, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:71 from nucleotide 1 to nucleotide 458, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:71 from nucleotide 1 to nucleotide 458.
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:72;
(b) the amino acid sequence of SEQ ID NO:72 from amino acid 1 to amino acid 139;
(c) a fragment of the amino acid sequence of SEQ ID NO:72, the fragment comprising eight contiguous amino acids of SEQ ID NO:72; and
(d) the amino acid sequence encoded by the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:72 or the amino acid sequence of SEQ ID NO:72 from amino add 1 to amino acid 139. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:72 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:72, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:72 having biological activity, the fragment comprising the amino acid sequence from amino acid 240 to amino acid 249 of SEQ ID NO:72.
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:73;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:73 from nucleotide 348 to nucleotide 743;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:73 from nucleotide 414 to nucleotide 743; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vpl7_l deposited with the ATCC under accession number 207012;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vpl7_l deposited with the ATCC under accession number
207012;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vpl7_l deposited with the ATCC under accession number 207012; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of done vpl7_l deposited with the ATCC under accession number 207012; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:74;
(i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:74 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:74;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes homologue of the protein of (h) or (i) above ;
(1) a polynudeotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and
(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:73.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:73 from nucleotide 348 to nucleotide 743; the nucleotide sequence of SEQ ID NO:73 from nudeotide 414 to nudeotide 743; the nucleotide sequence of the full-length protein coding sequence of clone vpl7_l deposited with the ATCC under accession number 207012; or the nucleotide sequence of a mature protein coding sequence of clone vpl7_l deposited with the ATCC under accession number 207012. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vpl7_l deposited with the ATCC under accession number 207012. 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:74 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:74, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:74 having biological activity, the fragment comprising the amino acid sequence from amino acid 61 to amino acid 70 of SEQ ID NO:74.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:73.
Further embodiments of the invention provide isolated polynudeotides 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:73, but excluding the poly(A) tail at the
3' end of SEQ ID NO:73; and
(ab) the nucleotide sequence of the cDNA insert of clone vpl7_l deposited with the ATCC under accession number 207012; (ii) hybridizing said probe(s) 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 NO:73, but excluding the poly(A) tail at the 3' end of SEQ ID NO:73; and (bb) the nucleotide sequence of the cDNA insert of clone vpl7_l deposited with the ATCC under accession number 207012; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:73, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:73 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:73 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:73. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:73 from nucleotide 348 to nucleotide 743, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:73 from nucleotide 348 to nucleotide 743, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:73 from nucleotide 348 to nucleotide 743. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:73 from nucleotide 414 to nucleotide 743, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:73 from nucleotide 414 to nucleotide 743, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:73 from nucleotide 414 to nucleotide 743.
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:74;
(b) a fragment of the amino acid sequence of SEQ ID NO:74, the fragment comprising eight contiguous amino acids of SEQ ID NO:74; and
(c) the amino acid sequence encoded by the cDNA insert of clone vpl7_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:74. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:74 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:74, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:74 having biological activity, the fragment comprising the amino acid sequence from amino acid 61 to amino acid 70 of SEQ ID NO:74. 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:75; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:75 from nucleotide 144 to nucleotide 461;
(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vpl9_l deposited with the ATCC under accession number 207012; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012;
(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vpl9_l deposited with the ATCC under accession number 207012;
(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:76; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:76 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:76;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; (j) a polynucleotide which encodes a spedes homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h) and that has a length that is at least
25% of the length of SEQ ID NO:75.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:75 from nucleotide 144 to nucleotide 461; the nucleotide sequence of the full-length protein coding sequence of clone vpl9_l deposited with the ATCC under accession number 207012; or the nucleotide sequence of a mature protein coding sequence of clone vpl9_l deposited with the ATCC under accession number 207012. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012. 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:76 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:76, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:76 having biological activity, the fragment comprising the amino acid sequence from amino acid 48 to amino acid 57 of SEQ ID NO:76.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:75.
Further embodiments of the invention provide isolated polynudeotides 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:75, but excluding the poly(A) tail at the
3' end of SEQ ID NO:75; and
(ab) the nucleotide sequence of the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012; (ii) hybridizing said probe(s) 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 NO:75, but excluding the poly(A) tail at the 3' end of SEQ ID NO:75; and (bb) the nucleotide sequence of the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and
(iv) isolating the 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:75, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:75 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:75 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:75. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ TD NO:75 from nucleotide 144 to nucleotide 461, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:75 from nucleotide 144 to nucleotide 461, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:75 from nucleotide 144 to nucleotide 461.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:76;
(b) a fragment of the amino acid sequence of SEQ ID NO:76, the fragment comprising eight contiguous amino acids of SEQ ID NO:76; and
(c) the amino acid sequence encoded by the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:76. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:76 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:76, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:76 having biological activity, the fragment comprising the amino acid sequence from amino acid 48 to amino acid 57 of SEQ ID NO:76. 00/11015
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:77; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:77 from nucleotide 54 to nucleotide 368;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:77 from nucleotide 141 to nucleotide 368;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:77 from nucleotide 51 to nucleotide 332;
(e) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vql_l deposited with the ATCC under accession number 207012;
(f) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vql_l deposited with the ATCC under accession number
207012;
(g) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vql_l deposited with the ATCC under accession number 207012; (h) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012; (i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:78;
(j) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:78;
(k) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(h) above;
(1) a polynudeotide which encodes a spedes homologue of the protein of (i) or (j) above ;
(m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j); and 00/11015
(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 NO:77.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:77 from nucleotide 54 to nucleotide 368; the nucleotide sequence of SEQ ID NO:77 from nucleotide 141 to nucleotide 368; the nucleotide sequence of SEQ ID NO:77 from nucleotide 51 to nucleotide 332; the nucleotide sequence of the full-length protein coding sequence of clone vql_l deposited with the ATCC under accession number 207012; or the nudeotide sequence of a mature protein coding sequence of clone vql_l deposited with the ATCC under accession number 207012. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012. In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:78 from amino acid 1 to amino acid 93. 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:78 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:78, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78 having biological activity, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO:78.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:77.
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:77, but excluding the poly(A) tail at the
3' end of SEQ ID NO:77; and
(ab) the nucleotide sequence of the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012; (ii) hybridizing said probe(s) 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 NO:77, but excluding the poly(A) tail at the
3' end of SEQ ID NO:77; and
(bb) the nucleotide sequence of the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and
(iv) isolating the 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:77, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID NO:77 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:77 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:77. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:77 from nucleotide 54 to nucleotide 368, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:77 from nucleotide 54 to nucleotide 368, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:77 from nucleotide
54 to nucleotide 368. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:77 from nucleotide 141 to nucleotide 368, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:77 from nucleotide 141 to nucleotide 368, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:77 from nucleotide 141 to nucleotide 368. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:77 from nucleotide 51 to nucleotide 332, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:77 from nucleotide 51 to nucleotide 332, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:77 from nucleotide 51 to nucleotide 332.
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:78; (b) me ammo acid sequence of SEQ ID NO: 78 from amino acid 1 to amino acid 93;
(c) a fragment of the amino acid sequence of SEQ ID NO:78, the fragment comprising eight contiguous amino acids of SEQ ID NO:78; and
(d) the amino acid sequence encoded by the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:78 or the amino acid sequence of SEQ ID NO:78 from amino acid 1 to amino acid 93. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:78, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78 having biological activity, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO:78. 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:79;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:79 from nucleotide 2 to nucleotide 1018;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:79 from nucleotide 53 to nucleotide 1018; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone vpl4_l deposited with the ATCC under accession number 207011;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number
207011;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vρl4_l deposited with the ATCC under accession number 207011; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:80;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:80 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:80;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynudeotide which encodes a spedes homologue of the protein of (h) or (i) above ;
(1) a polynudeotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and
(m) a polynudeotide that hybridizes under stringent conditions to any one of the polynudeotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID NO:79.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:79 from nucleotide 2 to nucleotide 1018; the nucleotide sequence of SEQ ID NO:79 from nucleotide 53 to nudeotide 1018; the nucleotide sequence of the full-length protein coding sequence of clone vpl4_l deposited with the ATCC under accession number 207011; or the nucleotide sequence of a mature protein coding sequence of clone vpl4_l deposited with the ATCC under accession number 207011. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011. In further preferred embodiments, the present invention provides a 00/11015
polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:80 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:80, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:80 having biological activity, the fragment comprising the amino acid sequence from amino acid 164 to amino acid 173 of SEQ ID NO:80.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ ID NO:79.
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:79, but excluding the poly(A) tail at the
3' end of SEQ ID NO:79; and
(ab) the nucleotide sequence of the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011; (ii) hybridizing said probe(s) 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 NO:79, but excluding the poly(A) tail at the 3' end of SEQ ID NO:79; and (bb) the nucleotide sequence of the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011; (ii) hybridizing said primer(s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; (iii) amplifying human DNA sequences; and (iv) isolating the 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:79, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID NO:79 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:79 , but excluding the poly(A) tail at the 3' end of SEQ ID NO:79. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:79 from nucleotide 2 to nucleotide 1018, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:79 from nucleotide 2 to nucleotide 1018, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:79 from nucleotide 2 to nucleotide 1018. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO:79 from nucleotide 53 to nucleotide 1018, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:79 from nudeotide 53 to nucleotide 1018, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:79 from nucleotide 53 to nucleotide 1018.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:80;
(b) a fragment of the amino acid sequence of SEQ ID NO:80, the fragment comprising eight contiguous amino acids of SEQ ID NO:80; and
(c) the amino acid sequence encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:80. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:80 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino adds of SEQ ID NO:80, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:80 having biological activity, the fragment comprising the amino acid sequence from amino acid 164 to amino acid 173 of SEQ ID NO:80. 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 gene(s) 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 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 1A and IB are schematic representations of the pED6 and pNOTs vectors, respectively, used for deposit of clones disclosed herein.
DETAILED DESCRIPTION
ISOLATED PROTEINS AND POLYNUCLEOTIDES
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 add 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 "vbll 1"
A polynucleotide of the present invention has been identified as clone "vbll_l". vbll_l 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. vbll_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vbll_l protein").
The nucleotide sequence of vbll_l as presently determined is reported in SEQ ID
NO:l, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vbll_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:2. Another potential vbll_l reading frame and predicted amino acid sequence that could be encoded by basepairs 84 to 236 of SEQ ID NO:l is reported in SEQ ID NO:121. Amino acids 13 to 25 of SEQ ID NO:121 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26 of SEQ ID NO:121. 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:121.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vbll_l should be approximately 1751 bp.
The nucleotide sequence disclosed herein for vbll_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. vbll_l demonstrated at least some similarity with sequences identified as N94870 (yy63b05.rl Homo sapiens cDNA clone 278193 5'). Based upon sequence similarity, vbll_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts a potential transmembrane domain within the vbll_l protein sequence centered around amino acid 27 of SEQ ID NO:2.
Clone "vb!2 1" A polynucleotide of the present invention has been identified as clone "vbl2_l". vbl2_l 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 add sequence of the encoded protein. vbl2_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vbl2_l protein"). The nucleotide sequence of vbl2_l as presently determined is reported in SEQ ID
NO: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 vbl2_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:4. Amino adds 34 to 46 of SEQ ID NO:4 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino add 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 vbl2_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vbl2_l should be approximately 2289 bp.
The nucleotide sequence disclosed herein for vbl2_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vbl2_l demonstrated at least some similarity with sequences identified as AA426009 (zw49el l.sl Soares total fetus Nb2HF8 9w Homo sapiens cDNA clone 7734203', mRNA sequence). Based upon sequence similarity, vbl2_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts three additional potential transmembrane domains within the vbl2_l protein sequence, centered around amino acids 11, 60, and 104 of SEQ ID NO:4, respectively. The nucleotide sequence of vbl2_l indicates that it may contain a THE1B repeat sequence. vbl2_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 17 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis. Clone "vbl4 1"
A polynucleotide of the present invention has been identified as clone "vbl4_l". vbl4_l 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. vbl4_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vbl4_l protein"). The nucleotide sequence of vbl4_l as presently determined is reported in SEQ ID NO:5, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vbl4_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:6. Amino adds 79 to 91 of SEQ ID NO:6 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 92. 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 vbl4_l protein. Another potential vbl4_l reading frame and predicted amino acid sequence that could be encoded by basepairs 182 to 484 of SEQ ID NO:5 is reported in SEQ ID NO:122.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vbl4_l should be approximately 2377 bp. The nucleotide sequence disclosed herein for vbl4_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vbl4_l demonstrated at least some similarity with sequences identified as AF007149 (Homo sapiens clone 23568, 23621, 23795, 23873 and 23874 mRNA sequences), AF070612 (Homo sapiens clone 24771 mRNA sequence), T23635 (Human gene signature HUMGS05495; standard; cDNA to mRNA), and W02197 (za57e04.rl Soares fetal liver spleen 1NFLS Homo sapiens cDNA clone 2966705', mRNA sequence). Based upon sequence similarity, vbl4_l proteins and each similar protein or peptide may share at least some activity.
Clone "veil 1"
A polynucleotide of the present invention has been identified as clone "vell_l". vell_l was isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vell_l is a full- length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vell_l protein").
The nucleotide sequence of vell_l as presently determined is reported in SEQ ID NO: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 vell_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:8. Amino acids 1 to 9 of SEQ ID NO:8 are a predicted leader/signal sequence, with the predicted mature amino add sequence beginning at amino acid 10. 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 vell_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vell_l should be approximately 984 bp.
The nucleotide sequence disclosed herein for vell_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vell_l demonstrated at least some similarity with sequences identified as F22745 (H.sapiens EST sequence (LL45/C09) from skeletal muscle, mRNA sequence) and Q60824 (Human brain Expressed Sequence Tag EST00928; standard; DNA). Based upon sequence similarity, vell_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts a potential transmembrane domain within the vell_l protein sequence centered around amino acid 35 of SEQ ID NO:8.
Clone "vf2 1" A polynucleotide of the present invention has been identified as clone "vf2_l". vf2_l was isolated from a human adult heart cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vf2_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vf2_l protein"). The nucleotide sequence of vf2_l as presently determined is reported in SEQ ID
NO: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 vf2_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:10. Amino acids 20 to 32 of SEQ ID NO:10 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, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vf2_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vf2_l should be approximately 1162 bp.
The nucleotide sequence disclosed herein for vf2_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vf2_l demonstrated at least some similarity with sequences identified as AA605037 (no68hl0.sl NCI_CGAP_AA1 Homo sapiens cDNA clone IMAGE: 1112035 similar to contains Alu repetitive element;contains element THR repetitive element; mRNA sequence). Based upon sequence similarity, vf2_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two potential transmembrane domains within the vf2_l protein sequence, one centered around amino acid 30 and another around amino acid 70 of SEQ ID NO:10. The nucleotide sequence of vf2_l indicates that it may contain an Alu repetitive element.
Clone "vg2 1"
A polynucleotide of the present invention has been identified as clone "vg2_l". vg2_l 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. vg2_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vg2_l protein").
The nucleotide sequence of vg2_l as presently determined is reported in SEQ ID
NO:ll, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vg2_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:12. Amino acids 34 to 46 of SEQ ID NO:12 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 vg2_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vg2_l should be approximately 1993 bp. The nucleotide sequence disclosed herein for vg2_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vg2_l demonstrated at least some similarity with sequences identified as AA830272 (oc45gll.sl NCI_CGAP_GCB 1 Homo sapiens cDNA clone IMAGE 13527083' similar to TR Q92853 Q92853 HU-K4; mRNA sequence) and D31740 (Homo sapiens DNA, CpG island). The predicted amino acid sequence disclosed herein for vg2_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vg2_l protein demonstrated at least some similarity to sequences identified as AF026124 (schwannoma- associated protein [Mus museums]) and U60644 (HU-K4 [Homo sapiens]). Based upon sequence similarity, vg2_l proteins and each similar protein or peptide may share at least some activity. Profile hidden markov model analysis (Eddy, S. R., 1996, Curr. Opin. Struct. Biol. 6(3): 361-365; incorporated by reference herein) of the predicted vg2_l protein revealed two phospholipase D active sites (amino acid residues 209 to 236 and 423 to 449 of SEQ ID NO:12). Phospholipase D (PLD) genes are members of a superfamily that is defined by several highly conserved motifs. In mammals, it has been proposed that phospholipase D plays a role in membrane vesicular trafficking and in signal transduction. Using site-directed mutagenesis, twenty-five point mutants have been made in human PLD1 (hPLDl) and then characterized (Sung et al, 1997, EMBO J. 16(15): 4519-4530; which is incorporated by reference herein). Sung et al. found that a motif (HxKxxxxD; see for example amino acids 214-221 of SEQ ID NO:12) and a serine/threonine conserved in all members of the PLD superfamily are critical for PLD biochemical activity, suggesting a possible catalytic mechanism. The vg2_l clone appears to encode a membrane protein that may be a phospholipase related to the phospholipase D family. The TopPredll computer program predicts four potential transmembrane domains within the vg2_l protein sequence, centered around amino acids 40, 305, 330, and 455 of SEQ ID NO:12, respectively. Clone "vjl 1"
A polynucleotide of the present invention has been identified as clone "vjl_l". vjl_l was isolated from a human fetal brain cDNA library (enriched for G-protein-coupled receptors) 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. vjl_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vjl_l protein").
The nucleotide sequence of vjl_l as presently determined is reported in SEQ ID NO:13. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vjl_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:14. Amino acids 1 to 12 of SEQ ID NO:14 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino add 13. 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 vjl_l protein. Another potential vjl_l reading frame and predicted amino acid sequence that could be encoded by basepairs 1795 to 2064 of SEQ ID NO:13 is reported in SEQ ID NO:123.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vjl_l should be approximately 2895 bp. The nucleotide sequence disclosed herein for vjl_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vjl_l demonstrated at least some similarity with sequences identified as AA410352 (zvl lfOl.rl Soares NhHMPu SI Homo sapiens cDNA clone 753337 5', mRNA sequence). Based upon sequence similarity, vjl_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts a potential transmembrane domain within the vjl_l protein sequence centered around arnino acid 70 of SEQ ID NO:14. The nucleotide sequence of vjl_l indicates that it may contain repetitive elements.
Clone "yll 1"
A polynucleotide of the present invention has been identified as clone "vll_l". vll_l was isolated from a human fetal cartilage 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. vll_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vll_l protein").
The nucleotide sequence of vll_l as presently determined is reported in SEQ ID
NO: 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 vll_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:16. Amino acids 187 to
199 of SEQ ID NO:16 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 200. 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 vll_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vll_l should be approximately 1936 bp.
The nucleotide sequence disclosed herein for vll_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vll_l demonstrated at least some similarity with sequences identified as AA464362 (zx81bl2.rl Soares ovary tumor NbHOT Homo sapiens cDNA clone 810143 5', mRNA sequence), M90089 (Mouse inositol 1,4,5-triphosphate receptor mRNA sequence), and T21689 (Human gene signature HUMGS03131; standard; cDNA to mRNA). The predicted amino acid sequence disclosed herein for vll_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vll_l protein demonstrated at least some similarity to the sequence identified as U80846 (partial CDS [Caenorhabditis elegans]). Based upon sequence similarity, vll_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two additional potential transmembrane domains within the vll_l protein sequence, one centered around amino acid 192 and another around amino acid 234 of SEQ ID NO: 16. vll_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 37 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis. Clone "vk2 1"
A polynucleotide of the present invention has been identified as clone "vk2_l". vk2_l was isolated from a human adult brain cDNA library (enriched for G-protein- coupled receptors) 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. vk2_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vk2_l protein").
The nucleotide sequence of vk2_l as presently determined is reported in SEQ ID NO: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 vk2_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:18. Amino acids 10 to 22 of SEQ ID NO:18 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader /signal sequence not be separated from the remainder of the vk2_l protein. Basepairs 416 to 418 of SEQ ID NO:17 may represent the site of an alternatively spliced exon that is not present in clone vk2_l.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vk2_l should be approximately 1284 bp. The nucleotide sequence disclosed herein for vk2_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vk2_l demonstrated at least some similarity with sequences identified as AA152101 (zl49f09.sl Soares pregnant uterus NbHPU Homo sapiens cDNA clone 505289 3', mRNA sequence) and Q78696 (Sequence encoding therapeutic polypeptide from glioblastoma cell line; standard; cDNA to mRNA). The predicted amino add sequence disclosed herein for vk2_l was searched against the GenPept and GeneSeq amino add sequence databases using the BLASTX search protocol. The predicted vk2_l protein demonstrated at least some similarity to the sequence identified as R66278 (Therapeutic polypeptide from glioblastoma cell line). Based upon sequence similarity, vk2_l proteins and each similar protein or peptide may share at least some activity. The
TopPredll computer program predicts two additional potential transmembrane domains within the vk2_l protein sequence, one centered around amino acid 61 and another around amino acid 97 of SEQ ID NO:18. Clone "vb21 1"
A polynucleotide of the present invention has been identified as clone "vb21_l". vb21_l 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. vb21_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb21_l protein").
The nucleotide sequence of vb21_l as presently determined is reported in SEQ ID
NO: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 vb21_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:20. Amino acids 296 to 308 of SEQ ID NO:20 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 309. 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 vb21_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vb21_l should be approximately 4159 bp.
The nucleotide sequence disclosed herein for vb21_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb21_l demonstrated at least some similarity with sequences identified as AA026150 (zj99cl0.sl Soares pregnant uterus NbHPU Homo sapiens cDNA clone 469170 3', mRNA sequence), T72108 (Human semaphorin Z gene; standard; cDNA to mRNA), U52840 (Human semaphorin F homolog), X97817 (M. musculus mRNA for semaphorin F), and X97818 (M. musculus mRNA for semaphorin G). The predicted amino acid sequence disclosed herein for vb21_l was searched against the GenPept and
GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vb21_l protein demonstrated at least some similarity to sequences identified as W19857 (Human semaphorin Z) and X97818 (samaphorin G [Mus musculus]). Semaphorins are important membrane proteins involved in axonal guidance in the embryonic stage, and may also have a role in nerve regeneration after injury. Based upon sequence similarity, vb21_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts four additional potential transmembrane domains within the vb21_l protein sequence, centered around amino acids 237, 523, 769, and 895 of SEQ ID NO:20, respectively. Clone "vc35 1"
A polynucleotide of the present invention has been identified as done "vc35_l". vc35_l 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. vc35_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc35_l protein").
The nucleotide sequence of vc35_l as presently determined is reported in SEQ ID
NO: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 vc35_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:22. Amino acids 38 to 50 of SEQ ID NO:22 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 51. 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 vc35_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vc35_l should be approximately 3042 bp.
The nucleotide sequence disclosed herein for vc35_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc35_l demonstrated at least some similarity with sequences identified as AA532364 (njl2a08.sl NCI_CGAP_Pr22 Homo sapiens cDNA clone EvlAGE:986102, mRNA sequence), AF029343 (human protocadherin 68), and T22263 (Human gene signature HUMGS03835; standard; cDNA to mRNA). The predicted amino acid sequence disdosed herein for vc35_l was searched against the GenPept and GeneSeq amino add sequence databases using the BLASTX search protocol. The predicted vc35_l protein demonstrated at least some similarity to sequences identified as Y08715 (protocadherin-4 [Mus musculus]). Based upon sequence similarity, vc35_l proteins and each similar protein or peptide may share at least some activity.
Clone "vc36 1"
A polynucleotide of the present invention has been identified as clone "vc36_l". vc36_l 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. vc36_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc36_l protein"). The nucleotide sequence of vc36_l as presently determined is reported in SEQ ID NO: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 vc36_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:24. Amino acids 24 to 36 of SEQ ID NO:24 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 37. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc36_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc36_l should be approximately 1395 bp.
The nucleotide sequence disclosed herein for vc36_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc36_l demonstrated at least some similarity with sequences identified as AA259070 (zs33c04.rl NCI_CGAP_GCB1 Homo sapiens cDNA clone IMAGE 6869825', mRNA sequence) and W67508 (zd40fll.sl Soares fetal heart NbHH19W Homo sapiens cDNA clone 3431493', mRNA sequence). Based upon sequence similarity, vc36_l proteins and each similar protein or peptide may share at least some activity. The nucleotide sequence of vc36_l indicates that it may contain repetitive elements.
Clone "vc38 1"
A polynucleotide of the present invention has been identified as clone "vc38_l". vc38_l 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 add sequence of the encoded protein. vc38_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc38_l protein").
The nucleotide sequence of vc38_l as presently determined is reported in SEQ ID NO: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 vc38_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:26.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc38_l should be approximately 2468 bp. The nucleotide sequence disclosed herein for vc38_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc38_l demonstrated at least some similarity with sequences identified as AF037400 (neuropeptide Y/peptide YY receptor Ya [Danio rerio]). Motifs analysis and profile hidden markov model analysis of the predicted vc38_l protein both reveal the presence of the G-protein-coupled receptor signature. G-protein-coupled receptors (also called R7G) are an extensive group of hormones, neurotransmitters, odorants, and light receptors which transduce extracellular signals by interaction with guanine nucleotide-binding (G) proteins. Most G-protein-coupled receptors lack a signal peptide, as does the predicted vc38_l protein. Based upon sequence similarity, vc38_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts seven potential transmembrane domains within the vc38_l protein sequence, centered around amino acids 60, 90, 130, 170, 225, 280, and 318 of SEQ ID NO:26, respectively. vc38_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 71 kDa was detected in conditioned medium using SDS polyacrylamide gel electrophoresis.
Clone "vc39 1" A polynucleotide of the present invention has been identified as clone "vc39_l". vc39_l 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. vc39_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc39_l protein"). The nucleotide sequence of vc39_l as presently determined is reported in SEQ ID
NO:27, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino add sequence of the vc39_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:28. Amino acids 2 to 14 of SEQ ID NO:28 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 vc39_l protein. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc39_l should be approximately 2048 bp.
The nucleotide sequence disclosed herein for vc39_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc39_l demonstrated at least some similarity with sequences identified as AA631722 (np79d04.sl NCI_CGAP_Pr2 Homo sapiens cDNA clone IMAGE:1132519 similar to gb:M21121 T-CELL SPECIFIC RANTES PROTEIN PRECURSOR (HUMAN); contains Alu repetitive element; mRNA sequence). Based upon sequence similarity, vc39_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts an additional potential transmembrane domain within the vc39_l protein sequence centered around amino acid 40 of SEQ ID NO:28. The nucleotide sequence of vc39_l indicates that it may contain an Alu/SVA repetitive element.
Clone "vc40 1"
A polynucleotide of the present invention has been identified as clone "vc40_l". vc40_l 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. vc40_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc40_l protein").
The nudeotide sequence of vc40_l as presently determined is reported in SEQ ID NO:29, and includes a ρoly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino add sequence of the vc40_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:30. Amino acids 19 to 31 of SEQ ID NO:30 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc40_l protein. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc40_l should be approximately 2297 bp.
The nucleotide sequence disclosed herein for vc40_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc40_l demonstrated at least some similarity with sequences 00/11015
identified as AA143014 (zl48g04.rl Soares pregnant uterus NbHPU Homo sapiens cDNA clone 505206 5', mRNA sequence) and T20006 (Human gene signature HUMGS01143; standard; cDNA to mRNA). Based upon sequence similarity, vc40_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts three additional potential transmembrane domains within the vc40_l protein sequence, centered around amino acids 101, 136, and 182 of SEQ ID NO:30, respectively.
Clone "vc46 1" A polynucleotide of the present invention has been identified as clone "vc46_l". vc46_l 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. vc46_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc46_l protein"). The nucleotide sequence of vc46_l as presently determined is reported in SEQ ID
NO: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 vc46_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:32. Amino acids 10 to 22 of SEQ ID NO:32 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc46_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc46_l should be approximately 2938 bp.
The nucleotide sequence disclosed herein for vc46_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc46_l demonstrated at least some similarity with sequences identified as AA029404 (ze94e06.rl Soares fetal heart NbHH19W Homo sapiens cDNA clone 3666585', mRNA sequence) and AQ071029 (human genomic fragment). Based upon sequence similarity, vc46_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two additional potential transmembrane domains within the vc46_l protein sequence, one centered around amino acid 70 and another around amino acid 130 of SEQ ID NO:32. vc46_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 19 kDa was detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vc49 1"
A polynucleotide of the present invention has been identified as clone "vc49_l". vc49_l 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. vc49_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc49_l protein").
The nucleotide sequence of vc49_l as presently determined is reported in SEQ ID
NO: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 vc49_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:34. Amino acids 14 to 26 of SEQ ID NO:34 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 vc49_l protein. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc49_l should be approximately 3471 bp.
The nucleotide sequence disclosed herein for vc49_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc49_l demonstrated at least some similarity with sequences identified as AI075929 (ov46hll.xl Soares_testis_NHT Homo sapiens cDNA clone IMAGE
1640421 3' similar to TR Q63418 Q63418 PROTOCADHERIN-3; mRNA sequence), 179964 (Sequence 109 from patent US 5708143), and T03572 (Human protocadherin pc3 coding sequence; standard; cDNA). The predicted arnino acid sequence disclosed herein for vc49_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc49_l protein demonstrated at least some similarity to sequences identified as L43592 (protocadherin-3 [Rattus norvegicus]) and R86865 (Human protocadherin pc3). Based upon sequence similarity, vc49_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two potential transmembrane domains within the vc49_l protein sequence, one definite transmembrane domain centered around amino acid 700 and another possible transmembrane domain centered around amino acid 260 of SEQ ID NO:34. Profile hidden markov model and motifs analyses of the predicted vc49_l protein sequence have revealed it to contain five cadherin extracellular repeated domain signatures at amino acids 142 to 242, 251 to 347, 356 to 451, 460 to 561, and 576 to 671 of SEQ ID NO:34. Cadherins are a family of animal glyco-proteins responsible for calcium-dependent cell-cell adhesion. Cadherins preferentially interact with themselves in a homophilic manner in connecting cells; thus acting as both receptor and ligand. Structurally, cadherins are built of the following domains: a signal sequence, followed by a propeptide of about 130 residues, then an extracellular domain of around 600 residues, then a transmembrane region, and finally a C-terminal cytoplasmic domain of about 150 residues. The predicted vc49_l protein sequence almost exactly follows this structure (its cytoplasmic domain being approximately 100 amino acids). Clearly, vc49_l protein appears to represent a novel member of the cadherin superfamily.
Clone "vc50 1"
A polynucleotide of the present invention has been identified as clone "vc50_l". vc50_l 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 add sequence of the encoded protein. vc50_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc50_l protein"). The nucleotide sequence of vc50_l as presently determined is reported in SEQ ID NO: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 vc50_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:36. Amino acids 20 to 32 of SEQ ID NO:36 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, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc50_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc50_l should be approximately 3819 bp.
The nucleotide sequence disclosed herein for vc50_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc50_l demonstrated at least some similarity with sequences identified as AA193122 (zr39d05.rl Soares NhHMPu SI Homo sapiens cDNA clone 665769 5', mRNA sequence), T26031 (Human gene signature HUMGS08267; standard; cDNA to mRNA), Z31718 (Hsapiens gene for myelin protein zero), and Z99943 (Human DNA sequence from PAC 313L4 on chromosome lq24). The predicted amino add sequence disclosed herein for vc50_l was searched against the GenPept and GeneSeq arnino acid sequence databases using the BLASTX search protocol. The predicted vc50_l protein demonstrated at least some similarity to the sequence identified as K03242 (rat PO myelin prepeptide), L24893 (myelin protein zero [Homo sapiens]), and M62860 (mouse peripheral myelin protein) . Based upon sequence similarity, vc50_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts an additional potential transmembrane domain within the vc50_l protein sequence centered around amino acid 181 of SEQ ID NO:36. vc50_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 26 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vc51 1"
A polynucleotide of the present invention has been identified as clone "vc51_l". vc51_l 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 arnino add sequence of the encoded protein. vc51_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc51_l protein").
The nucleotide sequence of vc51_l as presently determined is reported in SEQ ID NO:37, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino add sequence of the vc51_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:38. Amino acids 12 to 24 of SEQ ID NO:38 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 25. 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 vc51_l protein. If the "G" residue at position 388 of SEQ ID NO:37 were deleted, two alternative potential vc51_l reading frames and predicted amino acid sequences that could be encoded by basepairs 333 to 1310 of SEQ ID NO:37 and by basepairs 139 to 522 of SEQ ID NO:37 are reported in SEQ ID NO:124 and SEQ ID NO:125, respectively.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc51_l should be approximately 1992 bp. The nucleotide sequence disclosed herein for vc51_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc51_l demonstrated at least some similarity with sequences identified as T21514 (Human gene signature HUMGS02887; standard; cDNA to mRNA) and W52782 (zdl3h06.rl Soares fetal heart NbHH19W Homo sapiens cDNA done 340571 5', mRNA sequence). The predicted arnino add sequence disclosed herein for vc51_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc51_l protein demonstrated at least some similarity to sequences identified as U90716 (human cell surface protein HCAR), Y07593 (coxsackie and adenovirus receptor protein [Homo sapiens]), Y10320 (mouse coxsackie and adenovirus receptor homolog), and W 14146 (Human A33 antigen). Based upon sequence similarity, vc51_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts four additional potential transmembrane domains within the vc51_l protein sequence centered around amino adds 17, 216, 260, and 373 of SEQ ID NO:38, respectively.
Clone "vc52 1"
A polynucleotide of the present invention has been identified as clone "vc52_l". vc52_l 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. vc52_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc52_l protein").
The nucleotide sequence of vc52_l as presently determined is reported in SEQ ID
NO:39, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc52_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:40. Amino acids 19 to 31 of SEQ ID NO:40 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc52_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vc52_l should be approximately 2018 bp. The nucleotide sequence disclosed herein for vc52_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc52_l demonstrated at least some similarity with sequences identified as AA075627 (zm89a01.sl Stratagene ovarian cancer (#937219) Homo sapiens cDNA clone 545064 3', mRNA sequence) and T24879 (Human gene signature HUMGS06985; standard; cDNA to mRNA). The predicted arnino add sequence disclosed herein for vc52_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc52_l protein demonstrated at least some similarity to sequences identified as AL021890 (putative protein [Arabidopsis thaliana]), L47993 (ORF YJR072c [Saccharomyces cerevisiae]), and U10402 (undefined protein [Caenorhabditis elegans]). Based upon sequence similarity, vc52_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts a potential transmembrane domain within the vc52_l protein sequence centered around amino acid 145 of SEQ ID NO:40. vc52_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 44 kDa was detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vc33 1"
A polynucleotide of the present invention has been identified as clone "vc33_l". vc33_l 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 add sequence of the encoded protein. vc33_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc33_l protein").
The nucleotide sequence of vc33_l as presently determined is reported in SEQ ID NO:41, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted arnino acid sequence of the vc33_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:42. Amino acids 99 to 111 of SEQ ID NO:42 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 112. 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 vc33_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vc33_l should be approximately 2877 bp.
The nucleotide sequence disclosed herein for vc33_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc33_l demonstrated at least some similarity with sequences identified as AA846599 (aj97g02.sl Soares parathyroid tumor NbHPA Homo sapiens cDNA clone LMAGE:1404434 3' similar to gb:M95549 SODIUM /GLUCOSE COTRANSPORTER-LIKE (HUMAN); mRNA sequence), M95549 (Homo sapiens sodium /glucose cotransporter-like protein mRNA, complete cds), and Q89779 (Cotransporter protein SNST1 cDNA; standard; cDNA). The predicted amino acid sequence disclosed herein for vc33_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc33_l protein demonstrated at least some similarity to sequences identified as M95549 (sodium/glucose cotransporter-like protein [Homo sapiens]) and R73593 (Cotransporter protein SNST1). Based upon sequence similarity, vc33_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts three additional potential transmembrane domains within the vc33_l protein sequence, centered around amino acids 186, 260, and 324 of SEQ ID NO:42, respectively. vc33_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 45 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vc34 1"
A polynucleotide of the present invention has been identified as clone "vc34_l". vc34_l 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 arnino acid sequence of the encoded protein. vc34_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc34_l protein").
The nucleotide sequence of vc34_l as presently determined is reported in SEQ ID
NO:43, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted arnino acid sequence of the vc34_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:44. Amino acids 4 to 16 of SEQ ID NO:44 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 17. 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 vc34_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc34_l should be approximately 3062 bp.
The nucleotide sequence disclosed herein for vc34_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc34_ l demonstrated at least some similarity with sequences identified as AA927558 (om71e04.sl NCI_CGAP_GC4 Homo sapiens cDNA clone IMAGE 1552638 3', mRNA sequence) and U79281 (Human clone 23588 mRNA sequence). Based upon sequence similarity, vc34_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two additional potential transmembrane domains within the vc34_l protein sequence, one centered around arnino acid 251 and another around amino acid 283 of SEQ ID NO:44. vc34_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 72 kDa was detected in conditioned medium using SDS polyacrylamide gel electrophoresis.
Clone "vc47 1"
A polynucleotide of the present invention has been identified as clone "vc47_l". vc47_l 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. vc47_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc47_l protein").
The nucleotide sequence of vc47_l as presently determined is reported in SEQ ID
NO: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 vc47_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:46. Arnino acids 93 to 105 of SEQ ID NO:46 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 106. 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 vc47_l protein.
Another potential vc47_l reading frame and predicted amino acid sequence that could be encoded by basepairs 1047 to 1322 of SEQ ID NO:45 is reported in SEQ ID NO:126. Amino adds 11 to 23 of SEQ ID NO:126 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of this 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:126. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc47_l should be approximately 3676 bp.
The nucleotide sequence disclosed herein for vc47_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc47_l demonstrated at least some similarity with sequences identified as AA339320 (EST44392 Fetal brain I Homo sapiens cDNA 5' end, mRNA sequence) and R02462 (ye82h04.rl Homo sapiens cDNA clone 124279 5'). Based upon sequence similarity, vc47_l proteins and each similar protein or peptide may share at least some activity. The nucleotide sequence of vc47_l indicates that it may contain one or more of the following repetitive elements: Alu, L1MB7.
Clone "vc54 1"
A polynucleotide of the present invention has been identified as clone "vc54_l". vc54_l 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 add sequence of the encoded protein. vc54_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc54_l protein").
The nudeotide sequence of vc54_l as presently determined is reported in SEQ ID
NO:47, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted arnino add sequence of the vc54_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:48. Amino acids 33 to 45 of SEQ ID NO:48 are a predicted leader/signal sequence, with the predicted mature arnino acid sequence beginning at amino acid 46. 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 vc54_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc54_l should be approximately 2083 bp. The nucleotide sequence disclosed herein for vc54_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc54_l demonstrated at least some similarity with sequences identified as AF007152 (Homo sapiens clone 23649 and 23755 unknown mRNA, partial cds), Q76901 (Human genome fragment (Preferred); standard; DNA), and T46905 (EST014 BL29 Burkitt's lymphoma, Pascalis Sideras Homo sapiens cDNA clone BL29-145', mRNA sequence). The predicted amino add sequence disclosed herein for vc54_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc54_l protein demonstrated at least some similarity to the sequence identified as AF007152 (unknown [Homo sapiens]). Based upon sequence similarity, vc54_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two additional potential transmembrane domains within the vc54_l protein sequence, one centered around amino acid 220 and another around amino acid 247 of SEQ ID NO:48. vc54_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 44 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vc57 1"
A polynucleotide of the present invention has been identified as clone "vc57_l". vc57_l 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 add sequence of the encoded protein. vc57_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc57_l protein").
The nucleotide sequence of vc57_l as presently determined is reported in SEQ ID NO:49, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted arnino acid sequence of the vc57_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:50. Amino acids 15 to 27 of SEQ ID NO:50 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 vc57_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vc57_l should be approximately 2564 bp.
The nucleotide sequence disclosed herein for vc57_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc57_l demonstrated at least some similarity with sequences identified as AA156231 (zl50all.sl Soares pregnant uterus NbHPU Homo sapiens cDNA clone 5053403', mRNA sequence). The predicted amino acid sequence disclosed herein for vc57_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc57_l protein demonstrated at least some similarity to the sequence identified as U41635 (OS-9 precursor [Homo sapiens]). Based upon sequence similarity, vc57_l proteins and each similar protein or peptide may share at least some activity. vc57_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 51 kDa was detected in conditioned medium using SDS polyacrylamide gel electrophoresis.
Clone "ve!3 1"
A polynucleotide of the present invention has been identified as clone "vel3_l". vel3_l was isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino add sequence of the encoded protein. vel3_l is a full- length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vel3_l protein").
The nudeotide sequence of vel3_l as presently determined is reported in SEQ ID NO: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 vel3_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:52. Amino acids 551 to
563 of SEQ ID NO:52 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 564. Due to the hydrophobic nature of the predicted leader /signal sequence, it is likely to act as a transmembrane domain should 00/11015
the predicted leader/signal sequence not be separated from the remainder of the vel3_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vel3_l should be approximately 3046 bp. The nucleotide sequence disclosed herein for vel3_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vel3_l demonstrated at least some similarity with sequences identified as AA587395 (nn82h06.sl NCI_CGAP_Co9 Homo sapiens cDNA clone IMAGE:1090427 similar to contains element THR repetitive element; mRNA sequence) and Q76778 (Human genome fragment (Preferred); standard; DNA). The predicted amino add sequence disclosed herein for vel3_l was searched against the GenPept and GeneSeq arnino acid sequence databases using the BLASTX search protocol. The predicted vel3_l protein demonstrated at least some similarity to the sequence identified as U50828 (sel-1 gene product [Caenorhabditis elegans]). Based upon sequence similarity, vel3_l proteins and each similar protein or peptide may share at least some activity.
Clone "ve!6 1"
A polynucleotide of the present invention has been identified as clone "vel6_l". vel6_l was isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino add sequence of the encoded protein. vel6_l is a full- length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vel6_l protein").
The nucleotide sequence of vel6_l as presently determined is reported in SEQ ID NO:53, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino add sequence of the vel6_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:54. Amino acids 14 to 26 of SEQ ID NO:54 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 vel6_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vel6_l should be approximately 2033 bp. The nucleotide sequence disclosed herein for vel6_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and
FASTA search protocols. No hits were found in the databases. The nucleotide sequence of vel6_l indicates that it may contain one or more of the following repetitive elements: Alu, MER.
Clone "vf3 1"
A polynucleotide of the present invention has been identified as clone "vf3_l". vf3_l was isolated from a human adult heart cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vf3_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vf3_l protein").
The nucleotide sequence of vf3_l as presently determined is reported in SEQ ID
NO:55, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino add sequence of the vf3_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:56. Amino acids 8 to 20 of SEQ ID NO:56 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vf3_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vf3_l should be approximately 2987 bp.
The nucleotide sequence disclosed herein for vf3_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vf3_l demonstrated at least some similarity with sequences identified as Z78394 (H.sapiens mRNA, expressed sequence tag ICRFp507K11187 (5'), mRNA sequence). The predicted amino acid sequence disclosed herein for vf3_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vf3_l protein demonstrated at least some similarity to the sequence identified as U41558 (K02B2.3 gene product [Caenorhabditis elegans]). Based upon sequence similarity, vf3_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two additional potential transmembrane domains within the vf3_l protein sequence, one centered around amino acid 242 and another around amino acid 275 of SEQ ID NO:56. vf3_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 39 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vi2 1"
A polynucleotide of the present invention has been identified as clone "vj2_l". yj2_l was isolated from a human fetal brain (whole brain, enriched for G-protein-coupled receptors) 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. vj2_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vj2_l protein").
The nucleotide sequence of vj2_l as presently determined is reported in SEQ ID NO: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 vj2_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:58. Amino acids 59 to 71 of SEQ ID NO:58 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 72. 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 vj2_l protein.
Another potential vj2_l reading frame and predicted amino acid sequence that could be encoded by basepairs 146 to 400 of SEQ ID NO:57 is reported in SEQ ID NO:127. The TopPredll computer program predicts two potential transmembrane domains within the amino acid sequence of SEQ ID NO: 127.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vj2_l should be approximately 1762 bp.
The nucleotide sequence disclosed herein for vj2_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vj2_l demonstrated at least some similarity with sequences identified as N36445 (yx83c04.rl Homo sapiens cDNA clone 268326 5'). Based upon sequence similarity, yj2_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts three potential transmembrane domains within the vj2_l protein sequence, centered around amino acids 30, 67, and 90 of SEQ ID NO:58, respectively. The nucleotide sequence of vj2_l indicates that it may contain one or more repetitive elements.
Clone "vp7 1"
A polynucleotide of the present invention has been identified as clone "vp7_l". vp7_l 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. vp7_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vp7_l protein").
The nucleotide sequence of vp7_l as presently determined is reported in SEQ ID
NO:59, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted arnino acid sequence of the vp7_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:60. Amino acids 6 to 18 of SEQ ID NO:60 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 19. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vp7_l protein. Another potential vp7_l reading frame and predicted amino acid sequence that could be encoded by basepairs 2071 to 2430 of SEQ ID NO:59 is reported in SEQ ID NO:128.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vp7_l should be approximately 2638 bp.
The nucleotide sequence disclosed herein for vp7_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vp7_l demonstrated at least some similarity with sequences identified as N49433 (yv21el2.rl Homo sapiens cDNA clone 2434065') and Q63862 (AP2 sequence obtained by PCR for tumour specific DNA; standard; cDNA). Based upon sequence similarity, vp7_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts an additional potential transmembrane domain within the vp7_l protein sequence centered around amino acid 75 of SEQ ID NO:60. The nucleotide sequence of vp7_l indicates that it may contain one or more Alu repeat sequences. 00/11015
Clone "vp8 1"
A polynucleotide of the present invention has been identified as clone "vp8_l". vp8_l 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. vp8_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vp8_l protein").
The nucleotide sequence of vp8_l as presently determined is reported in SEQ ID
NO:61, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted arnino add sequence of the vp8_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:62. Amino acids 20 to 32 of SEQ ID NO:62 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, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vp8_l protein. If two insertions of "C" residues were made in the nucleotide sequence of SEQ
ID NO:61, one after the "A" at position 380 and another after the "G" at position 382, the resulting nucleotide sequence would be predicted to encode the amino acid sequence reported in SEQ ID NO:129.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vp8_l should be approximately 1513 bp.
The nucleotide sequence disclosed herein for vp8_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vp8_l demonstrated at least some similarity with sequences identified as AA284421 (zs59cl0.rl NCI_CGAP_GCB1 Homo sapiens cDNA clone IMAGE 701778 5' similar to contains Alu repetitive element; mRNA sequence) and AC002086 (Human PAC clone DJ525N14 from Xq23, complete sequence). Based upon sequence similarity, vp8_l proteins and each similar protein or peptide may share at least some activity. Profile hidden markov model analysis reveals the presence of an SH2 domain in the predicted vρ8_l protein (SEQ ID NO:62). SH2 domains function as regulatory modulators of intra-cellular signalling cascades by interacting with high affinity to phosphotyrosine-containing target peptides in a sequence-specific and strictly phosphorylation-dependent manner. The nucleotide sequence of vp8_l indicates that it may contain one or more Alu repeat sequences. vp8_l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 34 kDa was detected in membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vb22 1"
A polynucleotide of the present invention has been identified as clone "vb22_l". vb22_l 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 arnino add sequence of the encoded protein. vb22_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb22_l protein").
The nucleotide sequence of vb22_l as presently determined is reported in SEQ ID
NO:63, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb22_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:64. Another potential vb22_l reading frame and predicted amino acid sequence is encoded by basepairs 152 to 1006 of SEQ ID NO:63 and is reported in SEQ ID NO:130.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vb22_l should be approximately 4176 bp.
The nucleotide sequence disclosed herein for vb22_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb22_l demonstrated at least some similarity with sequences identified as L10335 (Homo sapiens neuroendocrine-specific protein C (NSP) mRNA, complete cds), N21304 (yx53f07.sl Homo sapiens cDNA clone 265477 3' similar to SP:A60021 A60021 TROPOMYOSIN-RELATED PROTEIN, NEURONAL), and V23695 (Human NSPLP protein A coding sequence; standard; cDNA). The predicted amino acid sequence disclosed herein for vb22_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vb22_l protein demonstrated at least some similarity to sequences identified as L10333 (nueroendocrine-specific protein A [Homo sapiens]) and W53947 (Human NSPLP protein A). Based upon sequence similarity, vb22_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two potential transmembrane domains within the vb22_l protein sequence, one centered around amino add 730 and another around amino acid 846 of SEQ ID NO:64. The nucleotide sequence of vb22_l appears to contain a short simple nucleotide repeat ("GGA") region. Clone "vc48 1"
A polynucleotide of the present invention has been identified as clone "vc48_l". vc48_l 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. vc48_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc48_l protein").
The nucleotide sequence of vc48_l as presently determined is reported in SEQ ID
NO:65, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc48_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:66. Amino acids 7 to 19 of SEQ ID NO:66 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 vc48_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vc48_l should be approximately 3096 bp.
The nucleotide sequence disclosed herein for vc48_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc48_l demonstrated at least some similarity with sequences identified as AA292779 (zt56c06.sl Soares ovary tumor NbHOT Homo sapiens cDNA done 726346 3', mRNA sequence). The predicted amino acid sequence disclosed herein for vc48_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc48_l protein demonstrated at least some similarity to sequences identified as AL031765 (Drosophila genomic product 22E5.z) and Z81058 (FllEό.e [Caenorhabditis elegans]). Based upon sequence similarity, vc48_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts four potential transmembrane domains within the vc48_l protein sequence, one centered around amino acid 39 and others around amino adds 69, 107 and 134 of SEQ ID NO:66, respectively. The nucleotide sequence of vc48_l appears to contain a simple nucleotide repeat ("AC") and one or more of the following repetitive elements: Alu and MIR. Clone "vp3 1"
A polynucleotide of the present invention has been identified as clone "vp3_l". vp3_l 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. vp3_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vp3_l protein").
The nucleotide sequence of vp3_l as presently determined is reported in SEQ ID
NO:67, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vp3_l protein corresponding to the foregoing nudeotide sequence is reported in SEQ ID NO:68. Amino acids 19 to 31 of SEQ ID NO:68 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vp3_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vp3_l should be approximately 552 bp.
The nucleotide sequence disclosed herein for vp3_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vp3_l demonstrated at least some similarity with sequences identified as AA225045 (nc34c06.rl NCI_CGAP_Pr2 Homo sapiens cDNA clone IMAGE 1010026, mRNA sequence), M18157 (Human glandular kallikrein gene, complete cds), and T35868 (Prostate-specific antigen gene partial sequence; standard; DNA). Based upon sequence similarity, vp3_l proteins and each similar protein or peptide may share at least some activity.
Clone "vc61 1"
A polynucleotide of the present invention has been identified as clone "vc61_l". vc61_l 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. vc61_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc61_l protein").
The nucleotide sequence of vc61_l as presently determined is reported in SEQ ID
NO:69, and includes a poly(A) tail. What applicants presently believe to be the proper 00/11015
reading frame and the predicted amino acid sequence of the vc61_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:70. Amino acids 16 to 28 of SEQ ID NO: 70 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 vc61_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vc61_l should be approximately 3199 bp. The nucleotide sequence disclosed herein for vc61_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc61_l demonstrated at least some similarity with sequences identified as AI028115 (ow51d09.xl Soares_parathyroid_tumor_NbHPA Homo sapiens cDNA clone IMAGE 1650353 3' similar to gb S67859 TRANSCRIPTION INITIATION FACTOR IIE-ALPHA CHAIN (HUMAN); mRNA), V20913 (Human induced tumour protein cDNA), and Z99129 (Human DNA sequence from clone 425C14 on chromosome 6q22 Contains the HSF2 gene for Heat Shock Factor 2 (Heat Shock Transcription Factor 2, HSTF 2) and an unknown gene similar to the placental protein DIFF33 gene; Contains ESTs, STSs and GSSs, complete sequence). The predicted amino acid sequence disclosed herein for vc61_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc61_l protein demonstrated at least some similarity to sequences identified as W52812 (Human induced tumour protein) and Z99129 (dJ425C14.2 (Placental protein DIFF33 LIKE) [Homo sapiens]). The deduced vc61_l protein has amino acid similarity to human and mouse diff33 protein. Diff33 is a transmembrane protein which is overexpressed in testicular tumors from polyomavirus large T-antigen transgenic mice. Based upon sequence similarity, vc61_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts nine additional potential transmembrane domains within the vc61_l protein sequence, centered around amino acids 50, 100, 150, 210, 240, 270, 320, 390, and 430 of SEQ ID NO:70, respectively. The nucleotide sequence of vc61_l indicates that it may contain an Alu repetitive element. Clone "vp!5 1"
A polynucleotide of the present invention has been identified as clone "vpl5_l". vpl5_l 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. vpl5_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vpl5_l protein").
The nucleotide sequence of vpl5_l as presently determined is reported in SEQ ID
NO:71, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vpl5_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:72. Arnino acids 4 to 16 of SEQ ID NO:72 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 17. 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 vpl5_l protein. If a "C" residue were inserted between nucleotides 458 and 459 of SEQ
ID NO:71, nucleotides 44 to 568 of the resulting nucleotide sequence would encode a protein having an amino acid sequence reported as SEQ ID NO:131.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vpl5_l should be approximately 2033 bp. The nucleotide sequence disclosed herein for vpl5_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vpl5_l demonstrated at least some similarity with sequences identified as AI033082 (ow97g04.sl Soares_fetal_liver_spleen_lNFLS_Sl Homo sapiens cDNA clone IMAGE 1654806 3', mRNA sequence) and T21877 (Human gene signature HUMGS03418). The predicted amino acid sequence disclosed herein for vpl5_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vpl5_l protein demonstrated at least some similarity to sequences identified as R45335 (Thrombomodulin analogue Q336N, Q365E) and U94333 (ClqR(ρ) [Homo sapiens]). The predicted vpl5_l protein shows some amino acid similarity to multiple thrombomodulin analogues (such as GeneSeq accession number R45335), and shows some end-to-end similairity to GenPept accession number U94333, which is described as a "... human Clq/MBL/SPA receptor that mediates enhanced phagocytosis in vitro" (Nepomuceno et al., 1997, Immunity 6(2): 119-129, which is incorporated by reference herein). Based upon sequence similarity, vpl5_l proteins and each similar protein or peptide may share at least some activity. vpl5_ l protein was expressed in a COS cell expression system, and an expressed protein band of approximately 24 kDa was detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.
Clone "vp!7 1"
A polynucleotide of the present invention has been identified as clone "vpl7_l". vpl7_l 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. vpl7_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vpl7_l protein").
The nucleotide sequence of vpl7_l as presently determined is reported in SEQ ID NO:73, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vpl7_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:74. Amino adds 10 to 22 of SEQ ID NO:74 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader/ signal sequence, it is likely to act as a transmembrane domain should the predicted leader /signal sequence not be separated from the remainder of the vpl7_l protein.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vpl7_l should be approximately 3150 bp.
The nucleotide sequence disclosed herein for vpl7_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vpl7_l demonstrated at least some similarity with sequences identified as AI056890 (oz03g07.xl Soares_fetal_liver_spleen_lNFLS_Sl Homo sapiens cDNA clone IMAGE 1674300 3', mRNA sequence) and T64815 (Tumour suppressor activated pathway gene TSAP6). Based upon sequence similarity, vpl7_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts two additional potential transmembrane domains within the vpl7_l protein sequence, one centered around amino acid 50 and another around amino acid 80 of SEQ ID NO:74. Clone "vp!9 1"
A polynucleotide of the present invention has been identified as clone "vpl9_l". vpl9_l 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. vpl9_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vpl9_l protein").
The nucleotide sequence of vpl9_l as presently determined is reported in SEQ ID
NO:75, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vpl9_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:76.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vpl9_l should be approximately 971 bp.
The nucleotide sequence disclosed herein for vpl9_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vpl9_l demonstrated at least some similarity with sequences identified as AA716408 (zg64b02.sl Soares fetal heart NbHH19W Homo sapiens cDNA clone 398091 3', mRNA sequence) and T20711 (Human gene signature HUMGS01928). Based upon sequence similarity, vpl9_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts a potential transmembrane domain within the vpl9_l protein sequence centered around amino acid
23 of SEQ ID NO:76; due to its hydrophobic nature, this region (amino acids 20 to 32) could also be a leader/signal sequence, with the mature protein beginning at amino acid 33 of SEQ ID NO:76.
Clone "vql 1"
A polynucleotide of the present invention has been identified as clone "vql_l". vql_l 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 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vql_l protein").
The nucleotide sequence of vql_l as presently determined is reported in SEQ ID NO:77, 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 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:78. Amino acids 17 to 29 00/11015
of SEQ ID NO:78 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 30. 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 protein. If a "T" residue were inserted between nucleotides 332 and 333 of SEQ ID NO:77, nucleotides 54 to 496 of the resulting nucleotide sequence would encode a protein having an amino acid sequence reported as SEQ ID NO: 132.
The EcoRI/Notl restriction fragment obtainable from the deposit containing clone vql_l should be approximately 873 bp. The nucleotide sequence disclosed herein for vql_l was searched against the
GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vql_l demonstrated at least some similarity with sequences identified as No hits were found in the databases. The TopPredll computer program predicts an additional potential transmembrane domain within the vql_l protein sequence, extending from about amino acid 36 to about amino acid 76 of SEQ ID NO:78. The nucleotide sequence of vql_l indicates that it may contain an Alu repetitive element.
Clone "vp!4 1" A polynucleotide of the present invention has been identified as clone "vpl4_l". vpl4_l 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 add sequence of the encoded protein. vpl4_l is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vpl4_l protein"). The nucleotide sequence of vpl4_l as presently determined is reported in SEQ ID
NO:79, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vpl4_l protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:80. Arnino adds 5 to 17 of SEQ ID NO:80 are a predided leader/signal sequence, with the predicted mature amino acid sequence beginning at amino add 18. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vpl4_l protein. 00/11015
The EcoRI/Notl restriction fragment obtainable from the deposit containing done vpl4_l should be approximately 1355 bp.
The nucleotide sequence disclosed herein for vpl4_l was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vpl4_l demonstrated at least some similarity with sequences identified as AI052724 (oz27al2.xl Soares_total_fetus_Nb2HF8_9w Homo sapiens cDNA clone IMAGE: 1676542 3' similar to SW:YQJQ_BACSU P54554 HYPOTHETICAL OXIDOREDUCTASE IN GLNQ-ANSR INTERGENIC REGION; mRNA sequence) and T20001 (Human gene signature HUMGS01138). The predicted amino acid sequence disclosed herein for vpl4_l was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vpl4_l protein demonstrated at least some similarity to sequences identified as R61477 (Clavulanic acid dehydrogenase sequence) and Z99116 (similar to ketoacyl reductase [Bacillus subtilis]). The predicted vpl4_l protein shows some amino acid similarity to various dehydrogenases due to the presence of a short-chain alcohol dehydrogenase family signature at amino acids 51 to 240 of SEQ ID NO: 80, as detected by motifs and hidden markov model analysis. Based upon sequence similarity, vpl4_l proteins and each similar protein or peptide may share at least some activity. The TopPredll computer program predicts four additional potential transmembrane domains within the vpl4_l protein sequence, centered around amino acids 55, 195, 230, and 300 of SEQ ID NO:80, respectively.
Deposit of Clones
Clones vbll_l, vbl2_l, vbl4_l, vell_l, vf2_l, vg2_l, vjl_l, and vll_l were deposited on August 20, 1998 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 98846, from which each clone comprising a particular polynucleotide is obtainable.
Clone vk2_l was deposited on August 20, 1998 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 98838, from which the vk2_l clone comprising a particular polynucleotide is obtainable. Clones vb21_l, vc35_l, vc36_l, vc38_l, vc39_l, vc40_l, vc46_l, vc49_l, vc50_l, vc51_l, and vc52_l were deposited on September 2, 1998 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 98862, from which each clone comprising a particular polynucleotide is obtainable.
Clones vc33_l, vc34_l, vc47_l, vc54_l, vc57_l, vel3_l, vel6_l, vf3_l, vj2_l, vp7_l, and vρ8_l were deposited on September 22, 1998 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 98886, from which each clone comprising a particular polynucleotide is obtainable.
Clones vb22_l, vc48_l, and vp3_l were deposited on October 16, 1998 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 98933, from which each clone comprising a particular polynucleotide is obtainable.
Clones vc61_l, vpl5_l, vpl7_l, vpl9_l, and vql_l were deposited on December
23, 1998 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 207012, from which each clone comprising a particular polynucleotide is obtainable.
Clone vpl4_l was deposited on December 23, 1998 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 207011, from which the vpl4_l clone comprising a particular polynucleotide is obtainable.
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. Each clone has been transfected into separate bacterial cells (£. coli) in this composite deposit. Each clone can be removed from the vector in which it was deposited by performing an EcoRI/Notl digestion (5' site, EcoRI; 3' site, Notl) to produce the appropriate fragment for such clone. Each clone was deposited in either the pED6 or pNOTs vector depicted in Figures 1A and IB, respectively. The pED6dpc2 vector ("pED6") was derived from pEDόdpcl 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 Clal 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 Notl. However, Notl 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 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 vbll_l SEQ ID NO:81 vbl2_l SEQ ID NO:82 vbl4_l SEQ ID NO:83 vell_l SEQ ID NO:84 vf2_l SEQ ID NO:85 vg2_l SEQ ID NO:86 vjl_l SEQ ID NO:87 vll_l SEQ ID NO:88 vk2_l SEQ ID NO:89 vb21_l SEQ ID NO:90 vc35_l SEQ ID NO:91 vc36_l SEQ ID NO:92 vc38_l SEQ ID NO:93 vc39_l SEQ ID NO:94 vc40_l SEQ ID NO:95 vc46_l SEQ ID NO:96 vc49_l SEQ ID NO:97 vc50_l SEQ ID NO:98 vc51_l SEQ ID NO:99 vc52_l SEQ ID NO:100 vc33_l SEQ ID NO:101 vc34_l SEQ ID NO:102 vc47_l SEQ ID NO:103 vc54_l SEQ ID NO:104 vc57_l SEQ ID NO:105 vel3_l SEQ ID NO:106 vel6_l SEQ ID NO:107 vf3_l SEQ ID NO:108 vj2_l SEQ ID NO:109 vp7_l SEQ ID NO:110 vp8_l SEQ ID NO:lll vb22_l SEQ ID NO:112 vc48_l SEQ ID NO:113 vp3_l SEQ ID NO:114 vc61_l SEQ ID NO:115 vpl5_l SEQ ID NO:116 vpl7_l SEQ ID NO:117 vpl9_l SEQ ID NO:118 vql_l SEQ ID NO:119 vpl4_l SEQ ID NO:120
In the sequences listed above which include an N at position 2, that position is occupied in preferred probes/primers by a biotinylated phosphoaramidite residue rather than a nucleotide (such as, for example, that produced by use of biotin phosphoramidite (1- dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-O-(2-cyanoethyl)-(N,N- diisopropyl)-phosphoramadite) (Glen Research, cat. no. 10-1953)).
The design of the oligonucleotide probe should preferably follow these parameters: (a) It should be designed to an area of the sequence which has the fewest ambiguous bases ("N's"), if any;
(b) It should be designed to have a Tm 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 γ-32P ATP (specific activity 6000 Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for labeling oligonucleotides. Other labeling techniques can also be used. Unincorporated label should preferably be removed by gel filtration chromatography or other established methods. The amount of radioactivity incorporated into the probe should be quantitated by measurement in a scintillation counter. Preferably, specific activity of the resulting probe should be approximately 4e+6 dpm/pmole.
The bacterial culture containing the pool of full-length clones should preferably be thawed and 100 μl of the stock used to inoculate a sterile culture flask containing 25 ml of sterile L-broth containing ampicillin at 100 μg/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 μg/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 NaCl/liter, 88.2 g Na citrate /liter, adjusted to pH 7.0 with NaOH) containing 0.5% SDS, 100 μg/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 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 0.1X SSC/0.5% SDS at 65°C for 30 minutes to 1 hour is optional. The filter is then preferably dried and subjected to autoradiography for sufficient time to visualize the positives on the X-ray film. Other known hybridization methods can also 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.
Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H.U. Saragovi, et al, Bio/Technology 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 form(s) 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 sequence(s) of the mature form(s) 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 derived and may include contiguous regions of the genome necessary for the regulated expression of such genes. Corresponding genes may therefore include but are not limited to coding sequences, 5' and 3' untranslated regions, alternatively spliced exons, introns, promoters, enhancers, and silencer or suppressor elements. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and /or amplification of genes in appropriate genomic libraries or other sources of genomic materials. An "isolated gene" is a gene that has been separated from the adjacent coding sequences, if any, present in the genome of the organism from which the gene was isolated.
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 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 gene(s) 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 Morris, 1994, Trends Pharmacol Sci. 15(7): 250-254; Lavarosky et al, 1997, Biochem. Mol. Med. 62(1): 11-22; and Hampel, 1998, Prog. Nucleic Acid Res. Mol. Biol. 58: 1- 39; all of which are incorporated by reference herein). The desired change in gene expression can also be achieved through the use of double-stranded ribonucleotide molecules having some 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 gene(s) corresponding to the polynucleotide sequences disclosed herein, preferably produced by transformation of cells with genetic constructs that are stably maintained within the transformed cells and their progeny, are provided. Transgenic animals that have modified genetic control regions that increase or reduce gene expression levels, or that change temporal or spatial patterns of gene expression, are also provided (see European Patent No. 0 649464 Bl, incorporated by reference herein). In addition, organisms are provided in which the gene(s) corresponding to the polynucleotide sequences disclosed herein have been partially or completely inactivated, through insertion of extraneous sequences into the corresponding gene(s) 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. Ac d. 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 product(s) of the corresponding gene(s).
Where the protein of the present invention is membrane-bound (e.g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms, part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information. For example, the TopPredll 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).
Proteins and protein fragments of the present invention include proteins with amino add sequence lengths that are at least 25%(more preferably at least 50%, and most preferably at least 75%) of the length of a disclosed protein and have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 95% identity) with that disclosed protein, where sequence identity is determined by comparing the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Also included in the present invention are proteins and protein fragments that contain a segment preferably comprising 8 or more (more preferably 20 or more, most preferably 30 or more) contiguous amino adds 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 Enz mology 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, TBLASTN and TBLASTX - the gapped alignment routines are integral to the database search itself, and thus yield much better sensitivity and selectivity while producing the more easily interpreted output. Gapping can optionally be turned off in all of these programs, if desired. The default penalty (Q) for a gap of length one is Q=9 for proteins and BLASTP, and Q=10 for BLASTN, but may be changed to any integer value including zero, one through eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. The default per-residue penalty for extending a gap (R) is R=2 for proteins and BLASTP, and R=10 for BLASTN, but may be changed to any integer value including zero, one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. Any combination of values for Q and R can be used in order to align sequences so as to maximize overlap and identity while minimizing sequence gaps. The default amino acid comparison matrix is BLOSUM62, but other amino acid 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. Spedes 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 goήlla, Pongo pygmaeus, Hylobates concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus aethiops, Cebus capucinus, Aotus trivirgatus, Sanguinus oedipus, Microcebus murinus, Mus musculus, Rattus norvegicus,
Cricetulus griseus, Felis catus, Mustek vison, Canisfamiliaris, Oryctolagus cuniculus, Bos taurus, Ovis aries, Sus scrofa, and Equus caballus, for which genetic maps have been created allowing the identification of syntenic relationships between the genomic organization of genes in one species and the genomic organization of the related genes in another species (O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al, 1993, Nature Genetics 3:103-112; Johansson et al, 1995, Genomics 25: 682-690; Lyons et al, 1997, Nature Genetics 15: 47-56; O'Brien et al, 1997, Trends in Genetics 13(10): 393-399; Carver and Stubbs, 1997, Genome Research 7:1123-1137; all of which are incorporated by reference herein).
The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms of the isolated polynucleotides which also encode proteins which are identical or have significantly similar sequences to those encoded by the disclosed polynucleotides. Preferably, allelic variants have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% 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 indudes 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.
00/11015
*: The hybrid length is that anticipated for the hybridized region(s) 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 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 NaH2PGv and 1.25mM EDTA, pH 7.4) can be substituted for SSC (lxSSC is 0.15M NaCI and 15mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes after hybridization is complete.
*TB - TR: The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10°C less than the melting temperature (Tm) of the hybrid, where Tm is determined according to the following equations. For hybrids less than 18 base pairs in length, 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,0[Na+]) + 0.41(%G+C) - (600/N), where N is the number of bases in the hybrid, and [Na+] is the concentration of sodium ions in the hybridization buffer ([Na+] for lxSSC = 0.165 M). Additional examples of stringency conditions for polynucleotide hybridization are provided in Sambrook, J., E.F. Fritsch, and T. Maniatis, 1989, Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, chapters 9 and 11, and Current Protocols in Molecular Biology, 1995, F.M. Ausubel et al., eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, incorporated herein by reference.
Preferably, each such hybridizing polynucleotide has a length that is at least 25%(more preferably at least 50%, and most preferably at least 75%) of the length of the polynucleotide of the present invention to which it hybridizes, and has at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 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 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 (rransfected) 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
Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 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 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 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., Invifrogen, 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 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. 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 Invifrogen Corporation (Carlsbad, CA), respectively. The protein can also be tagged with an epitope and subsequently purified by using a specific antibody directed to such epitope. One such epitope ("Flag") is commercially available from the Eastman Kodak Company (New Haven, CT). Finally, one or more reverse-phase high performance liquid chromatography (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 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 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, 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.
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 stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fmgeφrinting; 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 elidt another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the polynucleotide can also be used in interaction trap assays (such as, for example, those described in Gyuris et al, 1993, Cell 75: 791-803 and in Rossi et al, 1997, Proc. Natl. Acad.
Sci. USA 94: 8405-8410, all of which are incorporated by reference herein) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction. The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high- throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.
Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.
Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E.F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S.L. and A.R. Kimmel eds., 1987.
Nutritional Uses
Polynucleotides and proteins of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino add supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the protein or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured.
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, RB5, DAI, 123, T1165, HT2, CTLL2, TF-1, Mo7e and CMK. The activity of a protein of the invention may, among other means, be measured by the following methods: Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley- Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Bertagnolli et al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., J. Immunol. 149:3778-3783, 1992; Bowman et al, J. Immunol. 152: 1756-1761, 1994.
Assays for cytokine production and /or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a.
Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and
Measurement of mouse and human Interferon γ, Schreiber, R.D. In Current Protocols in
Immunology. J.E.e.a. Coligan eds. Vol 1 pp.6.8.1-6.8.8, John Wiley and Sons, Toronto. 1994.
Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine
Interleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983; Measurement of mouse and human interleukin 6 - Nordan, R. In Current Protocols in
Immunology. J.E.e.a. Coligan eds. Vol 1 pp.6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11 - 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, KJ. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto. 1991.
Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al, Eur. J. Immun. 11:405-411, 1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988.
Immune Stimulating or Suppressing Activity
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 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., HTV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HTV, hepatitis viruses, herpesviruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections such as candidiasis. Of course, in this regard, a protein of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer. Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease. Such a protein of the present invention may also to be useful in the treatment of allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein of the present invention.
Using the proteins of the invention it may also be possible to regulate immune responses in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both. Immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent. Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence of the tolerizing agent.
Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as , for example, B7)), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a soluble, monomeric form of a peptide having B7-2 activity alone or in conjunction with a monomeric form of a peptide having an activity of another B lymphocyte antigen (e.g., B7- 1, B7-3) or blocking antibody), prior to transplantation can lead to the binding of the molecule to the natural ligand(s) on the immune cells without fransmitting 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, Sdence 257:789-792 (1992) and Turka et al, Proc. Natl. Acad. Sci USA, 89:11102-11105 (1992). In addition, murine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of blocking B lymphocyte antigen function in vivo on the development of that disease. Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block costimulation of T cells by disrupting receptoπligand interactions of B lymphocyte antigens can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen-specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/lpr/lpr 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 responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a costimulatory signal to, and thereby activate, T cells in vivo.
In another application, up regulation or enhancement of 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 rumor-specific tolerance in the subject. If desired, the tumor cell can be transfected to express a combination of peptides. For example, tumor cells obtained from a patient can be transfected ex vivo with an expression vector directing the expression of a peptide having B7-2-like activity alone, or in conjunction with a peptide having B7-l-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 antigen(s) 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 β2 microglobulin protein or an MHC class II α chain protein and an MHC class II β chain protein to thereby express MHC class I or MHC class II proteins on the cell surface. Expression of the appropriate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3) induces a T cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Srrober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1- 3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet al., J. Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Brown et al., J. Immunol. 153:3079-3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl/Th2 profiles) include, without limitation, those described in: Maliszewski, J. Immunol. 144:3028-3033, 1990; and Assays for B cell function: In vitro antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto. 1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley- Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al, J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. Immunol. 149:3778-3783, 1992. Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 1995; Porgador et al, Journal of Experimental Medicine 182:255-260, 1995; Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 172:631-640, 1990.
Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in: Darzynkiewicz et al., Cytometry 13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991; Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993; Gorczyca et al., International Journal of Oncology 1:639-648, 1992.
Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et al., Blood 85:2770-2778, 1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.
Hematopoiesis Regulating 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 consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above- mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy. The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.
Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915, 1993.
Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate 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, I.K. and Briddell, R.A. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 23-39,
Wiley-Liss, Inc., New York, NY. 1994; Neben et al., Experimental Hematology 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, 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
A protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, ligament and /or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and in the treatment of burns, incisions and ulcers.
A protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals. Such a preparation employing a protein of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De 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 (coUagenase activity, osteoclast activity, etc.) mediated by inflammatory processes.
Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon/ligament formation. A protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide an environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendinitis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art.
The protein of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, a protein may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, amyofrophic 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, induding without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.
It is expected that a protein of the present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring to allow normal tissue to regenerate. A protein of the invention may also exhibit angiogenic activity.
A protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.
A protein of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for tissue generation activity include, without Umitation, those described in: International Patent Publication No. WO95/ 16035 (bone, cartilage, tendon); International Patent Publication No. WO95/05846 (nerve, neuronal); International Patent Publication No. WO91/07491 (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 follide stimulating hormone (FSH). Thus, a protein of the present invention, alone or in heterodimers with a member of the inhibin α 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- β group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary. See, for example, United States Patent 4,798,885. A protein of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs. The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for activin/inhibin activity include, without limitation, those described in: Vale et al., Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986; Vale et al., Nature 321:776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 83:3091-3095, 1986.
Chemotactic /Chemokinetic 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, 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 indude, without limitation, those described in: Current Protocols in Immunology, Ed by
J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995; Lind et al. APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25: 1744-1748; Gruber et al. J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153: 1762-1768, 1994.
Hemostatic and Thrombolytic Activity A protein of the invention may also exhibit hemostatic or thrombolytic activity.
As a result, such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke).
The activity of a protein of the invention may, among other means, be measured by the following methods: Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al., Thrombosis Res.45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474, 1988.
Receptor /Ligand 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. A protein of the present invention (induding, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.
The activity of a protein of the invention may, among other means, be measured by the following methods: Suitable assays for receptor-ligand activity include without limitation those described in:Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987; Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; Stitt et al., Cell 80:661-670, 1995.
Anti-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 Suppressor Activity
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 expression can lead to changes in cell adhesion properties linked to rumor 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 expression. All members of the superfamily have in common conserved extracellular repeats (cadherin domains), but structural differences are found in other parts of the molecule. The cadherin domains bind calcium to form their tertiary structure and thus calcium is required to mediate their adhesion. Only a few amino acids in the first cadherin domain provide the basis for homophilic adhesion; modification of this recognition site can change the specificity of a cadherin so that instead of recognizing only itself, the mutant molecule can now also bind to a different cadherin. In addition, some cadherins engage in heterophilic adhesion with other cadherins.
E-cadherin, one member of the cadherin superfamily, is expressed in epithelial cell types. Pathologically, if E-cadherin expression is lost in a rumor, the malignant cells become invasive and the cancer metastasizes. Transfection of cancer cell lines with polynucleotides expressing E-cadherin has reversed cancer-associated changes by returning altered cell shapes to normal, restoring cells' adhesiveness to each other and to their substrate, decreasing the cell growth rate, and drastically reducing anchorage- independent cell growth. Thus, reintroducing E-cadherin expression reverts carcinomas to a less advanced stage. It is likely that other cadherins have the same invasion suppressor role in carcinomas derived from other tissue types. Therefore, proteins of the present invention with cadherin activity, and polynucleotides of the present invention 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 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 polypeptide comprising a decapeptide of the cadherin recognition site, and polynucleotides of the present invention encoding such protein fragments, can also be used to block cadherin function by binding to cadherins and preventing them from binding in ways that produce undesirable effects. Additionally, fragments of proteins of the present invention with cadherin activity, preferably truncated soluble cadherin fragments which have been found to be stable in the circulation of cancer patients, and polynucleotides encoding such protein fragments, can be used to disturb proper cell-cell adhesion.
Assays for cadherin adhesive and invasive suppressor activity include, without limitation, those described in: Hortsch et al. J Biol Chem 270 (32): 18809-18817, 1995; Miyaki et al. Oncogene 11: 2547-2552, 1995; Ozawa et al. Cell 63: 1033-1038, 1990.
Tumor Inhibition Activity
In addition to the activities described above for immunological treatment or prevention of tumors, a protein of the invention may exhibit other anti-rumor activities. A protein may inhibit tumor growth directly or indirectly (such as, for example, via antibody-dependent cell-mediated cytotoxidty (ADCQ). 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 fertility of male or female subjects; effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional factors or component(s); effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein.
ADMINISTRATION AND DOSING
A protein of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources) may be used in a pharmaceutical composition when combined with a pharmaceutically acceptable carrier. Such a composition may also contain (in addition to protein and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration. The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IFN, TNFO, TNF1, 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 rninimize side efferts. Conversely, protein of the present invention may be included in formulations of the particular cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent to minimize side effects of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent.
A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multimeric or complexed form.
The pharmaceutical composition of the invention may be in the form of a complex of the protein(s) of present invention along with protein or peptide antigens. The protein and/or peptide antigen will deliver a stimulatory signal to both B and T lymphocytes. B lymphocytes will respond to antigen through their surface immunoglobulin receptor. T lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MHC and structurally related proteins including those encoded by class I and class II MHC genes on host cells will serve to present the peptide antigen(s) 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 carriers, 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, lysoledthin, 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 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 the therapeutic effect, whether administered in combination, serially or simultaneously. In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein of the present invention is administered to a mammal having a condition to be treated. Protein of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors.
Administration of protein of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection. 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, pefroleum, 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 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.
When a therapeutically effective amount of protein of the present invention is administered by intravenous, cutaneous or subcutaneous injection, protein of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution. The preparation of such parenterally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein of the present invention, an isotonic vehide such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art. The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art. The amount of protein of the present invention in the pharmaceutical composition of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone. Ultimately, the attending physician will decide the amount of protein of the present invention with which to treat each individual patient. Initially, the attending physician will administer low doses of protein of the present invention and observe the patient's response. Larger doses of protein of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 μg to about 100 mg (preferably about O.lng to about 10 mg, more preferably about 0.1 μg 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 range of 12 to 24 hours of continuous intravenous administration. Ultimately the attending physidan will dedde 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 polydonal and monoclonal antibodies which specifically react with the protein. As used herein, the term "antibody" includes without limitation a polydonal 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.
Antibodies to a particular protein can be produced by methods well known to those skilled in the art. For example, monoclonal antibodies can be produced by generation of antibody-producing hybridomas in accordance with known methods (see for example, Goding, 1983, Monoclonal antibodies: principles and practice, Academic Press Inc., New York; and Yokoyama, 1992, "Production of Monoclonal Antibodies" in Current Protocols in Immunology, Unit 2.5, Greene Publishing Assoc. and John Wiley & Sons). Polydonal 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 Ixnmunoglobulins" 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 etal, 1997, Nature Genetics 15: 146-156 (erratum Nature Genetics 16: 410); and U.S. Patents 5,877,397 and 5,625,126). Such antibodies maybe obtained using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R.P. Merrifield, J. Amer.Chem.Soc. 85, 2149-2154 (1963); J.L. Krstenansky, et al, FEBS Lett. 21 10 (1987). 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 cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein. For compositions of the present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device. When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen-free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. Therapeutically useful agents other than a protein of the invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods of the invention. Preferably for bone and /or cartilage formation, the composition would include a matrix capable of delivering the protem-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, tricalciumphosphate, hydroxyapatite, polylactic add, 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 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 caldum- aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability. Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns.
In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix.
A preferred family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl- methylcellulose, and carboxymethylcellulose, the most preferred being cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, polyethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and poly(vinyl 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-α and TGF-β), and insuUn-like growth factor (IGF).
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 protem-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering various factors which modify the action of the proteins, e.g., amount of tissue weight desired to be formed, the site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition. For example, the addition of other known growth fartors, such as IGF I (insulin like growth factor I), to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue /bone growth and/or repair, for example, X-rays, histomorphometric determinations and tetracycline labeling.
Polynucleotides of the present invention can also be used for gene therapy. Such polynucleotides can be infroduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynudeotides 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.

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:l;
(b) the nucleotide sequence of SEQ ID NO:l from nucleotide 683 to nucleotide 934;
(c) the nudeotide sequence of the full-length protein coding sequence of clone vbll_l deposited with the ATCC under accession number 98846;
(d) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vbll_l deposited with the ATCC under accession number 98846;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:2;
(f) 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;
(g) the nucleotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(d); and
(h) the nucleotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:l.
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 polynudeotide 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 vbll_l deposited with the ATCC under accession number 98846.
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 vbll_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins.
10. The protein of claim 9, wherein said protein comprises the amino acid sequence of SEQ ID NO:2.
11. A composition comprising the protein of claim 9 and a pharmaceutically acceptable carrier.
12. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:3;
(b) the nucleotide sequence of SEQ ID NO:3 from nucleotide 63 to nucleotide 482;
(c) the nucleotide sequence of SEQ ID NO:3 from nucleotide 201 to nucleotide 482; (d) the nudeotide sequence of the full-length protein coding sequence of clone vbl2_l deposited with the ATCC under accession number 98846;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of clone vbl2_l deposited with the ATCC under accession number 98846;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:4;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight contiguous amino acids of SEQ ID NO:4;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g); and
(k) the nudeotide 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 polynudeotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:3.
13. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:4;
(b) a fragment of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight contiguous amino acids of SEQ ID NO:4; and
(c) the amino acid sequence encoded by the cDNA insert of clone vbl2_l deposited with the ATCC under accession number 98846; 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 1195 to nucleotide 1527;
(c) the nucleotide sequence of SEQ ID NO:5 from nucleotide 1468 to nucleotide 1527;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vbl4_l deposited with the ATCC under accession number 98846;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of done vbl4_l deposited with the ATCC under accession number 98846;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:6;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6, the fragment comprising eight contiguous amino acids of SEQ ID NO:6;
(j) the nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide 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 polynudeotides 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 arnino acid sequence encoded by the cDNA insert of clone vbl4_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins.
16. An isolated polynucleotide comprising a nudeotide 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 82 to nucleotide 294;
(c) the nucleotide sequence of SEQ ID NO:7 from nucleotide 109 to nucleotide 294;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vell_l deposited with the ATCC under accession number 98846;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of clone vell_l deposited with the ATCC under accession number 98846;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vell_l deposited with the ATCC under accession number 98846;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide 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 vell_l deposited with the ATCC under accession number 98846; 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 22 to nucleotide 468;
(c) the nucleotide sequence of SEQ ID NO:9 from nucleotide 118 to nucleotide 468;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vf2_l deposited with the ATCC under accession number 98846;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of done vf2_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of clone vf2_l deposited with the ATCC under accession number 98846;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vf2_l deposited with the ATCC under accession number 98846;
(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 nudeotide 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 add sequence encoded by the cDNA insert of clone v£2_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins.
20. An isolated polynudeotide comprising a nudeotide sequence selerted from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:ll;
(b) the nucleotide sequence of SEQ ID NO:ll from nucleotide 124 to nucleotide 1641;
(c) the nucleotide sequence of SEQ ID NO:ll from nucleotide 262 to nucleotide 1641;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vg2_l deposited with the ATCC under accession number 98846;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of done vg2_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of clone vg2_l deposited with the ATCC under accession number 98846;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vg2_l deposited with the ATCC under accession number 98846;
(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:ll.
21. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO: 12;
(b) a fragment of the amino acid sequence of SEQ ID NO:12, the fragment comprising eight contiguous amino acids of SEQ ID NO:12; and
(c) the amino acid sequence encoded by the cDNA insert of clone vg2_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins.
22. An isolated polynudeotide comprising a nudeotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO: 13;
(b) the nudeotide sequence of SEQ ID NO:13 from nucleotide 380 to nucleotide 892;
(c) the nucleotide sequence of SEQ ID NO:13 from nucleotide 416 to nucleotide 892;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vjl_l deposited with the ATCC under accession number 98846;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vjl_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of clone vjl_l deposited with the ATCC under accession number 98846; (g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vjl_l deposited with the ATCC under accession number 98846;
(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 polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide 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 polynudeotides 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 adds of SEQ ID NO:14; and
(c) the amino add sequence encoded by the cDNA insert of done vjl_l deposited with the ATCC under accession number 98846; the protein being substantially free from other mammalian proteins.
24. An isolated polynucleotide comprising a nudeotide 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 62 to nucleotide 1057;
(c) the nucleotide sequence of SEQ ID NO:15 from nucleotide 659 to nucleotide 1057;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vll_l deposited with the ATCC under accession number 98846; (e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vll_l deposited with the ATCC under accession number 98846;
(f) the nucleotide sequence of a mature protein coding sequence of clone vll_l deposited with the ATCC under accession number 98846;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vll_l deposited with the ATCC under accession number 98846;
(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 nudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nucleotide sequence of a polynudeotide 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 polynudeotides 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 arnino add 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 add sequence encoded by the cDNA insert of done vll_l deposited with the ATCC under accession number 98846; 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 74 to nucleotide 529;
(c) the nucleotide sequence of SEQ ID NO: 17 from nucleotide 140 to nucleotide 529;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vk2_l deposited with the ATCC under accession number 98838;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vk2_l deposited with the ATCC under accession number 98838;
(f) the nucleotide sequence of a mature protein coding sequence of clone vk2_l deposited with the ATCC under accession number 98838;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vk2_l deposited with the ATCC under accession number 98838;
(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 nudeotide sequence of a polynudeotide 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 nudeotide sequence of a polynudeotide 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 polynudeotides 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 add 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 vk2_l deposited with the ATCC under accession number 98838; the protein being substantially free from other mammalian proteins.
28. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:19;
(b) the nucleotide sequence of SEQ ID NO: 19 from nucleotide 174 to nucleotide 3170;
(c) the nucleotide sequence of SEQ ID NO:19 from nucleotide 1098 to nucleotide 3170;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb21_l deposited with the ATCC under accession number 98862;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb21_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb21_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb21_l deposited with the ATCC under accession number 98862;
(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 nudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:19.
29. A protein comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:20;
(b) a fragment of the amino acid sequence of SEQ ID NO:20, the fragment comprising eight contiguous amino acids of SEQ ID NO:20; and
(c) the amino acid sequence encoded by the cDNA insert of clone vb21_l deposited with the ATCC under accession number 98862; 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 74 to nucleotide 1453;
(c) the nucleotide sequence of SEQ ID NO:21 from nucleotide 224 to nucleotide 1453;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc35_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of done vc35_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc35_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc35_l deposited with the ATCC under accession number 98862;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides 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 vc35_l deposited with the ATCC under accession number 98862; 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 135 to nucleotide 368;
(c) the nucleotide sequence of SEQ ID NO:23 from nucleotide 243 to nucleotide 368;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc36_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc36_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc36_l deposited with the ATCC under accession number 98862;
(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 add 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 vc36_l deposited with the ATCC under accession number 98862; 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 370 to nucleotide 1662;
(c) the nudeotide sequence of the full-length protein coding sequence of clone vc38_l deposited with the ATCC under accession number 98862;
(d) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of done vc38_l deposited with the ATCC under accession number 98862;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:26;
(f) 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; (g) the nucleotide sequence of a polynudeotide 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 polynudeotides 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: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 vc38_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
36. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:27;
(b) the nucleotide sequence of SEQ ID NO:27 from nucleotide 105 to nucleotide 365;
(c) the nucleotide sequence of SEQ ID NO:27 from nucleotide 147 to nucleotide 365;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc39_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc39_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc39_l deposited with the ATCC under accession number 98862; (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 nudeotide 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 nudeotide 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 polynudeotides 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;
(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 vc39_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
38. An isolated polynudeotide comprising a nucleotide sequence selerted 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 35 to nucleotide 1066;
(c) the nucleotide sequence of SEQ ID NO:29 from nucleotide 128 to nucleotide 1066;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc40_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862; (f) the nucleotide sequence of a mature protein coding sequence of clone vc40_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862;
(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 nudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide 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 polynudeotides 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 adds of SEQ ID NO:30; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc40_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
40. An isolated polynudeotide comprising a nudeotide sequence selerted 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 553;
(c) the nucleotide sequence of SEQ ID NO:31 from nucleotide 104 to nucleotide 553; (d) the nudeotide sequence of the full-length protein coding sequence of clone vc46_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc46_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc46_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc46_l deposited with the ATCC under accession number 98862;
(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 arnino 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 polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide 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 polynudeotides 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 adds of SEQ ID NO:32; and
(c) the amino acid sequence encoded by the cDNA insert of done vc46_l deposited with the ATCC under accession number 98862; 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 164 to nucleotide 2548;
(c) the nucleotide sequence of SEQ ID NO:33 from nudeotide 242 to nucleotide 2548;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc49_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc49_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of done vc49_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc49_l deposited with the ATCC under accession number 98862;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide 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 polynudeotides 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 vc49_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
44. An isolated polynudeotide comprising a nudeotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:35;
(b) the nucleotide sequence of SEQ ID NO:35 from nucleotide 150 to nucleotide 776;
(c) the nucleotide sequence of SEQ ID NO:35 from nucleotide 246 to nudeotide 776;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc50_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of done vc50_l deposited with the ATCC under accession number 98862;
(f) the nudeotide sequence of a mature protein coding sequence of clone vc50_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:36;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight contiguous amino acids of SEQ ID NO:36;
(j) the nudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:35.
45. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:36;
(b) a fragment of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight contiguous amino acids of SEQ ID NO:36; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc50_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
46. An isolated polynudeotide 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 139 to nucleotide 1308;
(c) the nucleotide sequence of SEQ ID NO:37 from nucleotide 211 to nucleotide 1308;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc51_l deposited with the ATCC under accession number 98862;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc51_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc51_l deposited with the ATCC under accession number 98862;
(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 nudeotide 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 nudeotide 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 vc51_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
48. An isolated polynudeotide comprising a nucleotide sequence selerted 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 21 to nucleotide 1142;
(c) the nucleotide sequence of SEQ ID NO:39 from nucleotide 114 to nucleotide 1142;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc52_l deposited with the ATCC under accession number 98862;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc52_l deposited with the ATCC under accession number 98862;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc52_l deposited with the ATCC under accession number 98862;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc52_l deposited with the ATCC under accession number 98862;
(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 nudeotide 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 polynudeotides 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 vc52_l deposited with the ATCC under accession number 98862; the protein being substantially free from other mammalian proteins.
50. An isolated polynucleotide comprising a nudeotide 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 13 to nucleotide 1416;
(c) the nucleotide sequence of SEQ ID NO:41 from nucleotide 346 to nucleotide 1416;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc33_l deposited with the ATCC under accession number 98886;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc33_l deposited with the ATCC under accession number 98886; (g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc33_l deposited with the ATCC under accession number 98886;
(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 nudeotide 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 nudeotide 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 polynudeotides 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 add 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 vc33_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
52. An isolated polynudeotide comprising a nudeotide sequence selerted from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:43;
(b) the nucleotide sequence of SEQ ID NO:43 from nucleotide 232 to nucleotide 1461;
(c) the nucleotide sequence of SEQ ID NO:43 from nucleotide 280 to nucleotide 1461;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc34_l deposited with the ATCC under accession number 98886; (e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc34_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:43.
53. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:44;
(b) a fragment of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight contiguous amino acids of SEQ ID NO:44; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc34_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
54. An isolated polynudeotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:45; (b) the nudeotide sequence of SEQ ID NO:45 from nucleotide 1922 to nucleotide 2350;
(c) the nudeotide sequence of SEQ ID NO:45 from nucleotide 2237 to nucleotide 2350;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc47_l deposited with the ATCC under accession number 98886;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc47_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc47_l deposited with the ATCC under accession number 98886;
(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 nudeotide 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 nudeotide sequence of a polynudeotide 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 vc47_l deposited with the ATCC under accession number 98886; 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 111 to nucleotide 1337;
(c) the nucleotide sequence of SEQ ID NO:47 from nucleotide 246 to nucleotide 1337;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc54_l deposited with the ATCC under accession number 98886;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc54_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc54_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc54_l deposited with the ATCC under accession number 98886;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide 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 vc54_l deposited with the ATCC under accession number 98886; 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 189 to nucleotide 1637;
(c) the nucleotide sequence of SEQ ID NO:49 from nucleotide 270 to nucleotide 1637;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc57_l deposited with the ATCC under accession number 98886;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of done vc57_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc57_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:50;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50;
(j) the nucleotide sequence of a polynudeotide 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 polynudeotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:49.
59. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:50;
(b) a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc57_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
60. An isolated polynucleotide comprising a nudeotide 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 nudeotide 15 to nucleotide 1934;
(c) the nucleotide sequence of SEQ ID NO:51 from nucleotide 1704 to nucleotide 1934;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vel3_l deposited with the ATCC under accession number 98886;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vel3_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vel3_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vel3_l deposited with the ATCC under accession number 98886;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:52;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:52, the fragment comprising eight contiguous amino acids of SEQ ID NO:52; (j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g); and
(k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynudeotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:51.
61. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:52;
(b) a fragment of the amino acid sequence of SEQ ID NO:52, the fragment comprising eight contiguous amino acids of SEQ ID NO:52; and
(c) the amino acid sequence encoded by the cDNA insert of done vel3_l deposited with the ATCC under accession number 98886; 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 240 to nudeotide 503;
(c) the nucleotide sequence of SEQ ID NO:53 from nucleotide 318 to nucleotide 503;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vel6_l deposited with the ATCC under accession number 98886;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vel6_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vel6_l deposited with the ATCC under accession number 98886; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:54;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54, the fragment comprising eight contiguous amino acids of SEQ ID NO:54;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g); and
(k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:53.
63. A protein comprising an amino acid sequence selected from the group consisting of:
(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 vel6_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
64. An isolated polynudeotide comprising a nucleotide sequence selerted 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 11 to nucleotide 1063;
(c) the nucleotide sequence of SEQ ID NO:55 from nudeotide 71 to nucleotide 1063;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vf3_l deposited with the ATCC under accession number 98886;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of done vf3_l deposited with the ATCC under accession number 98886; (f) the nucleotide sequence of a mature protein coding sequence of clone vf3_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vf3_l deposited with the ATCC under accession number 98886;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:56;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56, the fragment comprising eight contiguous amino acids of SEQ ID NO:56;
(j) the nudeotide sequence of a polynudeotide 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 polynudeotides 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 arnino 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 add sequence encoded by the cDNA insert of done vf3_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
66. An isolated polynudeotide comprising a nudeotide 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 542 to nucleotide 886;
(c) the nucleotide sequence of SEQ ID NO:57 from nucleotide 755 to nucleotide 886; (d) the nucleotide sequence of the full-length protein coding sequence of clone vj2_l deposited with the ATCC under accession number 98886;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vj2_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vj2_l deposited with the ATCC under accession number 98886;
(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 nudeotide sequence of a polynudeotide 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 nudeotide 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 add sequence encoded by the cDNA insert of done vj2_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
68. An isolated polynucleotide comprising a nucleotide sequence selerted 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 30 to nucleotide 344;
(c) the nucleotide sequence of SEQ ID NO:59 from nucleotide 84 to nucleotide 344;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vp7_l deposited with the ATCC under accession number 98886;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886;
(f) the nucleotide sequence of a mature protein coding sequence of clone vp7_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vp7_l deposited with the ATCC under accession number 98886;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide 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 polynudeotides 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 vp7_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
70. An isolated polynucleotide comprising a nucleotide sequence selerted 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 23 to nucleotide 757;
(c) the nucleotide sequence of SEQ ID NO:61 from nucleotide 119 to nucleotide 757;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vp8_l deposited with the ATCC under accession number 98886;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of done vp8_l deposited with the ATCC under accession number 98886;
(f) the nudeotide sequence of a mature protein coding sequence of done vp8_l deposited with the ATCC under accession number 98886;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886;
(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 nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide sequence of a polynudeotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:61.
71. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:62;
(b) a fragment of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight contiguous amino acids of SEQ ID NO:62; and
(c) the amino acid sequence encoded by the cDNA insert of clone vp8_l deposited with the ATCC under accession number 98886; the protein being substantially free from other mammalian proteins.
72. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:63;
(b) the nudeotide sequence of SEQ ID NO:63 from nucleotide 1048 to nucleotide 3726;
(c) the nudeotide sequence of the full-length protein coding sequence of clone vb22_l deposited with the ATCC under accession number 98933;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:64;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64;
(g) the nudeotide 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 polynudeotides specified by (a)-(d); and
(h) the nudeotide 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:63.
73. A protein comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:64;
(b) a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64; and
(c) the amino acid sequence encoded by the cDNA insert of clone vb22_l deposited with the ATCC under accession number 98933; the protein being substantially free from other mammalian proteins.
74. An isolated polynucleotide comprising a nucleotide sequence selerted from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:65;
(b) the nucleotide sequence of SEQ ID NO:65 from nucleotide 134 to nucleotide 667;
(c) the nucleotide sequence of SEQ ID NO:65 from nucleotide 191 to nudeotide 667;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc48_l deposited with the ATCC under accession number 98933;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933;
(f) the nucleotide sequence of a mature protein coding sequence of done vc48_l deposited with the ATCC under accession number 98933;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:66;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66, the fragment comprising eight contiguous amino acids of SEQ ID NO:66;
(j) the nucleotide sequence of a polynudeotide 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 nudeotide 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:65.
75. A protein comprising an arnino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:66;
(b) a fragment of the amino acid sequence of SEQ ID NO:66, the fragment comprising eight contiguous amino acids of SEQ ID NO:66; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc48_l deposited with the ATCC under accession number 98933; the protein being substantially free from other mammalian proteins.
76. An isolated polynudeotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:67;
(b) the nucleotide sequence of SEQ ID NO:67 from nucleotide 65 to nucleotide 457;
(c) the nucleotide sequence of SEQ ID NO:67 from nucleotide 158 to nucleotide 457;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vp3_l deposited with the ATCC under accession number 98933;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933;
(f) the nucleotide sequence of a mature protein coding sequence of clone vp3_l deposited with the ATCC under accession number 98933;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:68;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:68, the fragment comprising eight contiguous amino acids of SEQ ID NO:68; (j) the nucleotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:67.
77. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:68;
(b) a fragment of the amino acid sequence of SEQ ID NO:68, the fragment comprising eight contiguous amino acids of SEQ ID NO:68; and
(c) the amino acid sequence encoded by the cDNA insert of clone vp3_l deposited with the ATCC under accession number 98933; the protein being substantially free from other mammalian proteins.
78. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nudeotide sequence of SEQ ID NO:69;
(b) the nucleotide sequence of SEQ ID NO:69 from nucleotide 29 to nucleotide 1387;
(c) the nucleotide sequence of SEQ ID NO:69 from nucleotide 113 to nucleotide 1387;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vc61_l deposited with the ATCC under accession number 207012;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc61_l deposited with the ATCC under accession number 207012;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:70;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:70, the fragment comprising eight contiguous amino acids of SEQ ID NO:70;
(j) the nudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nudeotide 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:69.
79. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:70;
(b) a fragment of the amino acid sequence of SEQ ID NO:70, the fragment comprising eight contiguous amino acids of SEQ ID NO:70; and
(c) the amino acid sequence encoded by the cDNA insert of clone vc61_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins.
80. An isolated polynucleotide comprising a nudeotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:71;
(b) the nucleotide sequence of SEQ ID NO:71 from nudeotide 44 to nucleotide 1513;
(c) the nucleotide sequence of SEQ ID NO:71 from nucleotide 92 to nucleotide 1513;
(d) the nucleotide sequence of SEQ ID NO:71 from nucleotide 1 to nucleotide 458;
(e) the nudeotide sequence of the full-length protein coding sequence of clone vpl5_l deposited with the ATCC under accession number 207012; (f) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012;
(g) the nucleotide sequence of a mature protein coding sequence of clone vpl5_l deposited with the ATCC under accession number 207012;
(h) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012;
(i) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:72;
(j) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:72, the fragment comprising eight contiguous amino acids of SEQ ID NO:72;
(k) the nudeotide 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 polynudeotides specified by (a)-(h); and
(1) the nucleotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(h), and that has a length that is at least 25% of the length of SEQ ID NO:71.
81. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:72;
(b) the amino add sequence of SEQ ID NO:72 from amino acid 1 to amino acid 139;
(c) a fragment of the amino acid sequence of SEQ ID NO:72, the fragment comprising eight contiguous amino acids of SEQ ID NO:72; and
(d) the amino acid sequence encoded by the cDNA insert of clone vpl5_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins.
82. An isolated polynudeotide comprising a nudeotide sequence selerted from the group consisting of: (a) the nucleotide sequence of SEQ ID NO:73;
(b) the nucleotide sequence of SEQ ID NO:73 from nucleotide 348 to nudeotide 743;
(c) the nucleotide sequence of SEQ ID NO:73 from nucleotide 414 to nucleotide 743;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vpl7_l deposited with the ATCC under accession number 207012;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vpl7_l deposited with the ATCC under accession number 207012;
(f) the nucleotide sequence of a mature protein coding sequence of done vpl7_l deposited with the ATCC under accession number 207012;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vpl7_l deposited with the ATCC under accession number 207012;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:74;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:74, the fragment comprising eight contiguous amino acids of SEQ ID NO:74;
(j) the nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g); and
(k) the nucleotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:73.
83. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:74;
(b) a fragment of the amino acid sequence of SEQ ID NO:74, the fragment comprising eight contiguous amino acids of SEQ ID NO:74; and (c) the amino acid sequence encoded by the cDNA insert of clone vρl7_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins.
84. An isolated polynucleotide comprising a nucleotide sequence selerted from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:75;
(b) the nucleotide sequence of SEQ ID NO:75 from nucleotide 144 to nucleotide 461;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vpl9_l deposited with the ATCC under accession number 207012;
(d) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:76;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:76, the fragment comprising eight contiguous amino acids of SEQ ID NO:76;
(g) the nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(d); and
(h) the nudeotide sequence of a polynudeotide 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 polynudeotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:75.
85. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:76;
(b) a fragment of the amino acid sequence of SEQ ID NO:76, the fragment comprising eight contiguous amino acids of SEQ ID NO:76; and
(c) the amino acid sequence encoded by the cDNA insert of clone vpl9_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins.
86. An isolated polynudeotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:77;
(b) the nucleotide sequence of SEQ ID NO:77 from nucleotide 54 to nucleotide 368;
(c) the nucleotide sequence of SEQ ID NO:77 from nucleotide 141 to nucleotide 368;
(d) the nucleotide sequence of SEQ ID NO:77 from nucleotide 51 to nucleotide 332;
(e) the nudeotide sequence of the full-length protein coding sequence of clone vql_l deposited with the ATCC under accession number 207012;
(f) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of done vql_l deposited with the ATCC under accession number 207012;
(g) the nucleotide sequence of a mature protein coding sequence of clone vql_l deposited with the ATCC under accession number 207012;
(h) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012;
(i) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:78;
(j) a nucleotide sequence encoding a protein comprising a fragment of the amino add sequence of SEQ ID NO:78, the fragment comprising eight contiguous amino acids of SEQ ID NO:78;
(k) the nudeotide sequence of a polynudeotide 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 nudeotide sequence of a polynudeotide 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:77.
87. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:78;
(b) the amino acid sequence of SEQ ID NO:78 from amino acid 1 to amino acid 93;
(c) a fragment of the arnino acid sequence of SEQ ID NO:78, the fragment comprising eight contiguous amino acids of SEQ ID NO:78; and
(d) the amino acid sequence encoded by the cDNA insert of clone vql_l deposited with the ATCC under accession number 207012; the protein being substantially free from other mammalian proteins.
88. An isolated polynucleotide comprising a nucleotide sequence selerted from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:79;
(b) the nucleotide sequence of SEQ ID NO:79 from nucleotide 2 to nucleotide 1018;
(c) the nucleotide sequence of SEQ ID NO:79 from nucleotide 53 to nucleotide 1018;
(d) the nudeotide sequence of the full-length protein coding sequence of clone vpl4_l deposited with the ATCC under accession number 207011;
(e) a nudeotide sequence encoding the full-length protein encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011;
(f) the nucleotide sequence of a mature protein coding sequence of done vpl4_l deposited with the ATCC under accession number 207011;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:80;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:80, the fragment comprising eight contiguous amino acids of SEQ ID NO:80; (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 polynudeotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:79.
89. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:80;
(b) a fragment of the amino acid sequence of SEQ ID NO:80, the fragment comprising eight contiguous amino acids of SEQ ID NO:80; and
(c) the amino acid sequence encoded by the cDNA insert of clone vpl4_l deposited with the ATCC under accession number 207011; the protein being substantially free from other mammalian proteins.
EP99945180A 1998-08-24 1999-08-24 Secreted proteins and polynucleotides encoding them Withdrawn EP1107978A1 (en)

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US9765998P 1998-08-24 1998-08-24
US9763898P 1998-08-24 1998-08-24
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US9961898P 1998-09-09 1998-09-09
US99618P 1998-09-09
US10209298P 1998-09-28 1998-09-28
US102092P 1998-09-28
US10997898P 1998-11-25 1998-11-25
US109978P 1998-11-25
US11364598P 1998-12-23 1998-12-23
US11364698P 1998-12-23 1998-12-23
US113645P 1998-12-23
US113646P 1998-12-23
US37924699A 1999-08-23 1999-08-23
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