CA2327551A1 - Secreted proteins and polynucleotides encoding them - Google Patents
Secreted proteins and polynucleotides encoding them Download PDFInfo
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- CA2327551A1 CA2327551A1 CA002327551A CA2327551A CA2327551A1 CA 2327551 A1 CA2327551 A1 CA 2327551A1 CA 002327551 A CA002327551 A CA 002327551A CA 2327551 A CA2327551 A CA 2327551A CA 2327551 A1 CA2327551 A1 CA 2327551A1
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Abstract
Novel polynucleotides and the proteins encoded thereby are disclosed.
Description
FIELD OF THE INVENTION
The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins.
BACKGROUND QF THE INVENTION
Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques 2 5 clone novel polynucleotides "directly" in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent "indirect" cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader 3 0 sequence motif, as well as various PCR-based or low stringency hybridization cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity by virtue of their secreted nature in the case of leader sequence cloning, or by virtue of the cell or tissue source in the case of PCR-based techniques. It is to these proteins and the 3 5 polynucleotides encoding them that the present invention is directed.
SUMMARY OF THE INVENTION
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:1;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 126 to nucleotide 485;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 207 to nucleotide 485;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb2_1 deposited under accession number ATCC
98804;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
insert of clone vb2_1 deposited under accession number ATCC 98804;
2 0 (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:2;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:2;
2 5 (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a palynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any 3 0 one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:1.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:1 from nucleotide 126 to nucleotide 485; the nucleotide sequence of SEQ ID
NO:1 from nucleotide 207 to nucleotide 485; the nucleotide sequence of the full-length protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:2, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 55 to amino acid 64 of SEQ
ID N0:2.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:1.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i} preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:1, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:1; and (ab) the nucleotide sequence of the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 3 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID NO:1, but excluding the poly(A) tail at the 3' end of SEQ ID N0:1; and (bb) the nucleotide sequence of the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:1, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
NO:1 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:1 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:1. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:1 from nucleotide 126 to nucleotide 485, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of 2 0 SEQ ID N0:1 from nucleotide 126 to nucleotide 485, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:1 from nucleotide 126 to nucleotide 485. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
NO:1 from nucleotide 207 to nucleotide 485, and extending contiguously from a 2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:1 from nucleotide 207 to nucleotide 485, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:1 from nucleotide 207 to nucleotide 485.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:2;
(b) a fragment of the amino acid sequence of SEQ ID N0:2, the fragment comprising eight contiguous amino acids of SEQ ID N0:2; and (c) the amino acid sequence encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:2. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:2, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 55 to amino acid 64 of SEQ ID N0:2.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 130 to nucleotide 2286;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286;
(d) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone vb3_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb3_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:4;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:4;
The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins.
BACKGROUND QF THE INVENTION
Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques 2 5 clone novel polynucleotides "directly" in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent "indirect" cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader 3 0 sequence motif, as well as various PCR-based or low stringency hybridization cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity by virtue of their secreted nature in the case of leader sequence cloning, or by virtue of the cell or tissue source in the case of PCR-based techniques. It is to these proteins and the 3 5 polynucleotides encoding them that the present invention is directed.
SUMMARY OF THE INVENTION
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:1;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 126 to nucleotide 485;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:1 from nucleotide 207 to nucleotide 485;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb2_1 deposited under accession number ATCC
98804;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
insert of clone vb2_1 deposited under accession number ATCC 98804;
2 0 (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:2;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:2;
2 5 (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a palynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any 3 0 one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:1.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:1 from nucleotide 126 to nucleotide 485; the nucleotide sequence of SEQ ID
NO:1 from nucleotide 207 to nucleotide 485; the nucleotide sequence of the full-length protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:2, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 55 to amino acid 64 of SEQ
ID N0:2.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:1.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i} preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID NO:1, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:1; and (ab) the nucleotide sequence of the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 3 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID NO:1, but excluding the poly(A) tail at the 3' end of SEQ ID N0:1; and (bb) the nucleotide sequence of the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:1, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
NO:1 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:1 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:1. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:1 from nucleotide 126 to nucleotide 485, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of 2 0 SEQ ID N0:1 from nucleotide 126 to nucleotide 485, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:1 from nucleotide 126 to nucleotide 485. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
NO:1 from nucleotide 207 to nucleotide 485, and extending contiguously from a 2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:1 from nucleotide 207 to nucleotide 485, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID NO:1 from nucleotide 207 to nucleotide 485.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:2;
(b) a fragment of the amino acid sequence of SEQ ID N0:2, the fragment comprising eight contiguous amino acids of SEQ ID N0:2; and (c) the amino acid sequence encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:2. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:2, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 55 to amino acid 64 of SEQ ID N0:2.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 130 to nucleotide 2286;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286;
(d) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone vb3_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb3_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:4;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:4;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:3.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:3 from nucleotide 130 to nucleotide 2286; the nucleotide sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286; the nucleotide sequence of the full-length protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment 2 0 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:4, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment comprising the amino acid sequence from amino acid 354 to amino acid 363 of SEQ ID N0:4.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:3.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:3, but excluding the poly(A) tail at the 3' end of SEQ ID N0:3; and (ab) the nucleotide sequence of the cDNA insert of done vb3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:3, but excluding the poly(A) tail at the 3' end of SEQ ID N0:3; and (bb) the nucleotide sequence of the cDNA insert of done vb3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynudeotide products of step (b)(iii).
2 0 Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:3, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:3 to a nucleotide sequence cosesponding to the 3' end of SEQ ID N0:3 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:3. Also preferably the polynudeotide isolated 2 5 according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:3 from nucleotide 130 to nucleotide 2286, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:3 from nucleotide 130 to nucleotide 2286, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide 130 to 3 0 nucleotide 2286. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide 214 to nucleotide 2286.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:4;
(b) a fragment of the amino acid sequence of SEQ ID N0:4, the fragment comprising eight contiguous amino acids of SEQ ID N0:4; and (c) the amino acid sequence encoded by the cDNA insert of clone vb3 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:4. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:4, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:4 having biological activity, the fragment comprising the amino acid sequence from amino acid 354 to amino and 363 of SEQ ID N0:4.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 172 to nucleotide 522;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804;
3 0 (e) a polynucleatide encoding the full-length protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb4_1 deposited under accession number ATCC
98804;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:3.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:3 from nucleotide 130 to nucleotide 2286; the nucleotide sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286; the nucleotide sequence of the full-length protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment 2 0 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:4, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment comprising the amino acid sequence from amino acid 354 to amino acid 363 of SEQ ID N0:4.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:3.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:3, but excluding the poly(A) tail at the 3' end of SEQ ID N0:3; and (ab) the nucleotide sequence of the cDNA insert of done vb3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:3, but excluding the poly(A) tail at the 3' end of SEQ ID N0:3; and (bb) the nucleotide sequence of the cDNA insert of done vb3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynudeotide products of step (b)(iii).
2 0 Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:3, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:3 to a nucleotide sequence cosesponding to the 3' end of SEQ ID N0:3 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:3. Also preferably the polynudeotide isolated 2 5 according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:3 from nucleotide 130 to nucleotide 2286, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:3 from nucleotide 130 to nucleotide 2286, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide 130 to 3 0 nucleotide 2286. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:3 from nucleotide 214 to nucleotide 2286, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:3 from nucleotide 214 to nucleotide 2286.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:4;
(b) a fragment of the amino acid sequence of SEQ ID N0:4, the fragment comprising eight contiguous amino acids of SEQ ID N0:4; and (c) the amino acid sequence encoded by the cDNA insert of clone vb3 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:4. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:4 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:4, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:4 having biological activity, the fragment comprising the amino acid sequence from amino acid 354 to amino and 363 of SEQ ID N0:4.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 172 to nucleotide 522;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804;
3 0 (e) a polynucleatide encoding the full-length protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb4_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb4_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:6;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:6;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:5.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:5 from nucleotide 172 to nucleotide 522; the nucleotide sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522; the nucleotide sequence of the full-length protein coding 2 0 sequence of clone vb4_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804. In further preferred embodiments, the 2 5 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:6, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the 3 0 fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ
ID N0:6.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:5.
insert of clone vb4_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:6;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:6;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:5.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:5 from nucleotide 172 to nucleotide 522; the nucleotide sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522; the nucleotide sequence of the full-length protein coding 2 0 sequence of clone vb4_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804. In further preferred embodiments, the 2 5 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:6, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the 3 0 fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ
ID N0:6.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:5.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:5, but excluding the poiy(A) tail at the 3' end of SEQ ID N0:5; and (ab) the nucleotide sequence of the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (ba) SEQ ID N0:5, but excluding the poly(A) tail at the 3' end of SEQ ID N0:5; and (bb) the nucleotide sequence of the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:5, and extending 3 0 contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:5 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:5 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:5. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:5 from nucleotide 214 to nucleotide 522.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:6;
(b) a fragment of the amino acid sequence of SEQ ID N0:6, the fragment comprising eight contiguous amino acids of SEQ ID N0:6; and (c) the amino acid sequence encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:6. In further preferred 2 0 embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:6, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:6 having biological activity, the fragment comprising the amino acid sequence from 2 5 amino acid 53 to amino acid 62 of SEQ ID N0:6.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 119 to nucleotide 502;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the S cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb5_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb5_1 deposited under accession number ATCC 98804;
(h) a polynudeotide encoding a protein comprising the amino acid sequence of SEQ ID N0:8;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:8;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the profiein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 25% of the length of SEQ ID N0:7.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:7 from nucleotide 119 to nucleotide 502; the nucleotide sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502; the nucleotide sequence of the full-length protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb5_1 deposited under 3 0 accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:8, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 59 to amino acid 68 of SEQ
ID N0:8.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:7.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:7, but excluding the poly(A) tail at the 3' end of SEQ ID N0:7; and (ab) the nucleotide sequence of the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that 2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:7, but excluding the poly(A) tail at the 3' end of SEQ ID N0:7; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vb5_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:7, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:7 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:7 , but excluding the poly{A) tail at the 3' end of SEQ ID N0:7. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide 176 to nucleotide 502.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:8;
(b) a fragment of the amino acid sequence of SEQ ID N0:8, the fragment comprising eight contiguous amino acids of SEQ ID N0:8; and (c) the amino acid sequence encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:8. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty} contiguous amino ands 3 0 of SEQ ID N0:8, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 59 to amino acid 68 of SEQ ID N0:8.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a} a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 128 to nucleotide 436;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb6_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb6_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:10;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:10 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:10;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(i); and (m} a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:9.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:9 from nucleotide 128 to nucleotide 436; the nucleotide sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436; the nucleotide sequence of the full-length protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:10 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:10, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:10 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino and 55 of SEQ
ID N0:10.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:9.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:9, but excluding the poly(A) tail at the 3' end of SEQ ID N0:9; and (ab) the nucleotide sequence of the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:9, but excluding the poly(A) tail at the 3' end of SEQ ID N0:9; and (bb) the nucleotide sequence of the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:9, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:9 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:9 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:9. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:9 from nucleotide 203 to nucleotide 436.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID N0:10, the fragment comprising eight contiguous amino acids of SEQ ID N0:10; and {c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vb6_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:10. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:10 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:10, or a protein comprising a fragment of the amino acid sequence of SEQ
ID NO:10 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID NO:10.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:11;
{b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 138 to nucleotide 1250;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb7 1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb7 1 deposited under accession number ATCC
2 0 98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb7 1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:12;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:12;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:11.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:11 from nucleotide 138 to nucleotide 1250; the nucleotide sequence of SEQ
ID NO:11 from nucleotide 279 to nucleotide 1250; the nucleotide sequence of the full-length protein coding sequence of clone vb7_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb7 1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb7_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:12, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment comprising the amino acid sequence from amino acid 180 to amino acid 189 of SEQ ID N0:12.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:11.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:11, but excluding the poly(A) tail at the 3' end of SEQ ID N0:11; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vb7_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:11, but excluding the poly(A) tail at the 3' end of SEQ ID N0:11; and (bb) the nucleotide sequence of the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:11; and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:11 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:11, but excluding the poly(A) tail at the 3' end of SEQ ID N0:11. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:11 from nucleotide 138 to nucleotide 1250, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:11 from nucleotide 138 to nucleotide 1250, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:11 from nucleotide 138 to nucleotide 1250. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:11 from nucleotide 279 to nucleotide 1250.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:12;
(b) a fragment of the amino acid sequence of SEQ ID N0:12, the fragment comprising eight contiguous amino acids of SEQ ID N0:12; and (c) the amino acid sequence encoded by the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:12. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:12, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:12 having biological activity, the fragment comprising the amino acid sequence from amino acid 180 to amino acid 189 of SEQ ID N0:12.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13 from nucleotide 615 to nucleotide 869;
(c) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vb8_1 deposited under accession number ATCC 98804;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(e) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone vb8_1 deposited under accession number ATCC
98804;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb8_1 deposited under accession number ATCC 98804;
(g) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:14;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:14;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h) and that has a length that is at least 25% of the length of SEQ ID N0:13.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:13 from nucleotide 615 to nucleotide 869; the nucleotide sequence of the full-length protein coding sequence of clone vb8_1 deposited under accession number ATCC
98804;
or the nucleotide sequence of a mature protein coding sequence of clone vb8_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of clone vb8_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most 2 0 preferably thirty) contiguous amino acids of SEQ ID N0:14, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment comprising the amino acid sequence from amino acid 37 to amino acid 46 of SEQ ID N0:14.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 5 ID N0:13.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 3 0 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:13, but excluding the poly(A) tail at the 3' end of SEQ ID N0:13; and (ab) the nucleotide sequence of the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:13, but excluding the poly(A) tail at the 3' end of SEQ ID N0:13; and (bb) the nucleotide sequence of the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:13 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:13 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:13. Also preferably the 2 5 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13 fram nucleotide 615 to nucleotide 869, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:13 from nucleotide 615 to nucleotide 869, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:13 from nucleotide 3 0 615 to nucleotide 869.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:14;
(b) a fragment of the amino acid sequence of SEQ ID N0:14, the fragment comprising eight contiguous amino acids of SEQ ID N0:14; and {c) the amino acid sequence encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:14. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:14, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:14 having biological activity, the fragment comprising the amino acid sequence from amino acid 37 to amino acid 46 of SEQ ID N0:14.
In one embodiment, the present invention provides a composition comprising an isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:15;
{b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 148 to nucleotide 1470;
(c) a polynudeotide comprising the nucleotide sequence of SEQ iD
2 0 N0:15 from nucleotide 193 to nucleotide 1470;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the 2 5 cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(f) a polynudeotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb9_1 deposited under accession number ATCC
98804;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
3 0 insert of done vb9_1 deposited under accession number ATCC 98804;
(h) a polynudeotide encoding a protein comprising the amino acid sequence of SEQ ID N0:16;
(i) a polynucleohde encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:16;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:15.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:15 from nucleotide 148 to nucleotide 1470; the nucleotide sequence of SEQ
ID N0:15 from nucleotide 193 to nucleotide 1470; the nucleotide sequence of the full-length protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb9_1 2 0 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:16, or a polynucleotide encoding a protein comprising a 2 5 fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:16.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:15.
3 0 Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:15, but excluding the poly(A) tail at the 3' end of SEQ ID N0:15; and (ab) the nucleotide sequence of the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes} to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:15, but excluding the poly(A) tail at the 3' end of SEQ ID N0:15; and (bb} the nucleotide sequence of the cDNA insert of done 2 0 vb9_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii} amplifying human DNA sequences; and (iv} isolating the polynudeotide products of step (b)(iii).
2 5 Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:15, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:15 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:15 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:15. Also preferably the 3 0 polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:15 from nucleotide 193 to nucleotide 1470, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:15 from nucleotide 193 to nucleotide 1470, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from nucleotide 193 to nucleotide 1470.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:16;
(b) a fragment of the amino acid sequence of SEQ ID N0:16, the fragment comprising eight contiguous amino acids of SEQ ID N0:16; and (c) the amino acid sequence encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:16. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 2 0 of SEQ ID N0:16, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:16 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:16.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
2 5 {a) a polynudeotide comprising the nucleotide sequence of SEQ ID
NO:I7;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 109 to nucleotide 414;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:17 from nucleotide 217 to nucleotide 414;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748;
WO 99/55721 PC'T/US99/08504 (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc3_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc3_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:18;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:18 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:18;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i); and (m) a polynucleotide that hybridizes under stringent conditions to any 2 0 ane of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:17.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:17 from nucleotide 109 to nucleotide 414; the nucleotide sequence of SEQ ID
N0:17 from nucleotide 217 to nucleotide 414; the nucleotide sequence of the full-length protein 2 5 coding sequence of clone vc3_1 deposited under accession number ATCC
98748; or the nucleotide sequence of a mature protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748. In further preferred embodiments, the 3 0 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:18 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:18, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:18 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ
ID N0:18.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:17.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:17, but excluding the poly(A) tail at the 3' end of SEQ ID N0:17; and (ab) the nucleotide sequence of the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and 2 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID NO:17, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:17; and (bb) the nucleotide sequence of the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
3 0 (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:17, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:17 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:17 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:17. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:17 from nucleotide 217 to nucleotide 414, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:17 from nucleotide 217 to nucleotide 414, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from nucleotide 217 to nucleotide 414.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:18;
(b) a fragment of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight contiguous amino acids of SEQ ID N0:18; and 2 0 (c) the amino acid sequence encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:18. In further preferred embodiments, the present invention provides a protein comprising a fragment of the 2 5 amino acid sequence of SEQ ID N0:18 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ 117 N0:18, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:18 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID N0:18.
3 0 In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 169 to nucleotide 840;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc4_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc4_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:20;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:20;
2 0 (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any 2 5 one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:19.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
3 0 N0:19 from nucleotide 169 to nucleotide 840; the nucleotide sequence of SEQ ID N0:19 from nucleotide 211 to nucleotide 840; the nucleotide sequence of the full-length protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:20, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment comprising the amino acid sequence from amino acid 107 to amino acid 116 of SEQ ID N0:20.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:19.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:19, but excluding the poly(A) tail at the 3' end of SEQ ID N0:19; and 2 0 (ab) the nucleotide sequence of the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the 2 5 probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from 3 0 the group consisting of:
(ba) SEQ ID N0:19, but excluding the poly(A) tail at the 3' end of SEQ ID N0:19; and (bb) the nucleotide sequence of the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
wo mssn~ rc~rius99rosso4 (ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:19, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:19 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:19 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:19. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840, to a nucleotide sequence corresponding to the 3' end of 2 0 said sequence of SEQ ID N0:19 from nucleotide 211 to nucleotide 840.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:20;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:20, the fragment comprising eight contiguous amino acids of SEQ ID N0:20; and (c) the amino acld sequence encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such 3 0 protein comprises the amino acid sequence of SEQ ID N0:20. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino atids of SEQ ID N0:20, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:20 having biological activity, the fragment comprising the amino acid sequence from amino acid 107 to amino acid 116 of SEQ ID N0:20.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 508 to nucleotide 951;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc5_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone vc5_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:22;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment 2 5 comprising eight contiguous amino acids of SEQ ID N0:22;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
{k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:21.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:21 from nucleotide 508 to nucleotide 951; the nucleotide sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951; the nucleotide sequence of the full-length protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:22, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment comprising the amino acid sequence from amino acid 69 to amino acid 78 of SEQ
ID N0:22.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:21.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:21, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:21; and (ab) the nucleotide sequence of the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 3 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:21, but excluding the poly(A) tail at the 3' end of SEQ ID N0:21; and (bb) the nucleotide sequence of the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b}(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:21, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:21 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:21, but excluding the poly(A) tail at the 3' end of SEQ ID N0:21. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951, and extending contiguously from a nucleotide sequence corresponding to the 5' end 2 0 of said sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951, and extending contiguously from a 2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from nucleotide 733 to nucleotide 951.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:22;
(b) a fragment of the amino acid sequence of SEQ ID N0:22, the fragment comprising eight contiguous amino acids of SEQ ID N0:22; and (c) the amino acid sequence encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:22. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:22, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:22 having biological activity, the fragment comprising the amino acid sequence from amino acid 69 to amino acid 78 of SEQ ID N0:22.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23 from nucleotide 125 to nucleotide 493;
(c) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc7 1 deposited under accession number ATCC 98748;
2 0 (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc7_1 deposited under accession number ATCC
98748;
2 5 (f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc7_1 deposited under accession number ATCC 98748;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:24;
(h) a polynucleotide encoding a protein comprising a fragment of the 3 0 amino acid sequence of SEQ ID N0:24 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:24;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(h) and that has a length that is at least 25% of the length of SEQ ID N0:23.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:23 from nucleotide 125 to nucleotide 493; the nucleotide sequence of the full-length protein coding sequence of clone vc7_1 deposited under accession number ATCC
98748;
or the nucleotide sequence of a mature protein coding sequence of clone vc7 1 deposited under accession number ATCC 98748. In othex preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of clone vc7_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:24, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24 having 2 0 biological activity, the fragment comprising the amino acid sequence from amino acid 56 to amino acid 65 of SEQ ID N0:24.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:23.
Further embodiments of the invention provide isolated polynucleotides produced 2 5 according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
3 0 (aa) SEQ ID N0:23, but excluding the poly(A) tail at the 3' end of SEQ ID N0:23; and (ab) the nucleotide sequence of the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:23, but excluding the poly(A) tail at the 3' end of SEQ ID N0:23; and (bb) the nucleotide sequence of the cDNA insert of done vc7_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:23, and 2 0 extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:23 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:23 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:23. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 2 5 493, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 493, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 493.
In other embodiments, the present invention provides a composition comprising 3 0 a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:24;
(b) a fragment of the amino acid sequence of SEQ ID N0:24, the fragment comprising eight contiguous amino acids of SEQ ID N0:24; and (c) the amino acid sequence encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:24. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:24, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:24 having biological activity, the fragment comprising the amino acid sequence from amino acid 56 to amino acid 65 of SEQ ID N0:24.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 33 to nucleotide 407;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407;
(d) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone v~ 1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc9_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:26;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:26;
wo mssm pcr~s~rossoa (j} a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:25.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:25 from nucleotide 33 to nucleotide 407; the nucleotide sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407; the nucleotide sequence of the full-length protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone v~ 1 deposited under accession number ATCC 98748. In further preferred embodiments, the presient invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment 2 0 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:26, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ
ID N0:26.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:25.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:25, but excluding the poly(A) tail at the 3' end of SEQ ID N0:25; and WO 99/55721 PC'T/US99/08504 (ab) the nucleotide sequence of the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:25, but excluding the poly(A) tail at the 3' end of SEQ ID N0:25; and (bb) the nucleotide sequence of the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:25, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:25 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:25 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:25. Also preferably the 2 5 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:25 from nucleotide 33 to nucleotide 407, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:25 from nucleotide 33 to nucleotide 407, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from nucleotide 3 0 33 to nucleotide 407. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from nucleotide 99 to nucleotide 407.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) ~ the amino acid sequence of SEQ ID N0:26;
(b) a fragment of the amino acid sequence of SEQ ID N0:26, the fragment comprising eight contiguous amino acids of SEQ ID N0:26; and (c) the amino acid sequence encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:26. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:26, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:26 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ ID N0:26.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27 from nucleotide 176 to nucleotide 871;
2 5 (c) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl0_1 deposited under accession number ATCC 98748;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
3 0 (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl0_1 deposited under accession number ATCC
98748;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl0_1 deposited under accession number ATCC 98748;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:28;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:28;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(h) and that has a length that is at least 25% of the length of SEQ ID N0:27.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:27 from nucleotide 176 to nucleotide 871; the nucleotide sequence of the full-length protein coding sequence of clone vcl0_1 deposited under accession number ATCC
98748;
or the nucleotide sequence of a mature protein coding sequence of clone vcl0_1 deposited under accession number ATCC 98748. In other preferred embodiments, the 2 0 polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most 2 5 preferably thirty) contiguous amino acids of SEQ ID N0:28, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment comprising the amino acid sequence from amino and 111 to amino acid 120 of SEQ ID N0:28.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
3 0 ID N0:27.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:27, but excluding the poly(A) tail at the 3' end of SEQ ID N0:27; and (ab) the nucleotide sequence of the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:27, but excluding the poly(A) tail at the 3' end of SEQ ID N0:27; and (bb) the nucleotide sequence of the cDNA insert of clone 2 0 vcl0_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:27, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:27 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:27 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:27. Also preferably the 3 0 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871, to a nucleotide wo mssm pcTius99rossoa sequence corresponding to the 3' end of said sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:28;
(b) a fragment of the amino acid sequence of SEQ ID N0:28, the fragment comprising eight contiguous amino acids of SEQ ID N0:28; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:28. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:28, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:28 having biological activity, the fragment comprising the amino acid sequence from amino acid 111 to amino acid 120 of SEQ ID N0:28.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 160 to nucleotide 657;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl l_1 deposited under accession number ATCC 98748;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcll_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcll_1 deposited under accession number ATCC
98748;
WO 99/55721 PC1'/US99/08504 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcll 1 deposited under accession number ATCC 98748;
(h} a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:30;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:30;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:29.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:29 from nucleotide 160 to nucleotide 657; the nucleotide sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657; the nucleotide sequence of the full-length protein 2 0 coding sequence of clone vcll_1 deposited under accession number ATCC
98748; or the nucleotide sequence of a mature protein coding sequence of clone vcl l_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcll_1 deposited under accession number ATCC 98748. In further preferred embodiments, the 2 5 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty}
contiguous amino acids of SEQ ID N0:30, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the 3 0 fragment comprising the amino acid sequence from amino and 78 to amino acid 87 of SEQ
ID N0:30.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:29.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:29, but excluding the poly(A) tail at the 3' end of SEQ ID N0:29; and (ab) the nucleotide sequence of the cUNA insert or clone vcll 1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (ba) SEQ ID N0:29, but excluding the poly(A) tail at the 3' end of SEQ ID N0:29; and (bb) the nucleotide sequence of the cDNA insert of clone vcll_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29, and 3 0 extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:29 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:29 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:29. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from nucleotide 214 to nucleotide 657.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:30;
(b) a fragment of the amino acid sequence of SEQ ID N0:30, the fragment comprising eight contiguous amino acids of SEQ ID N0:30; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl l_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:30. In further preferred 2 0 embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty} contiguous amino acids of SEQ ID N0:30, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:30 having biological activity, the fragment comprising the amino acid sequence 2 5 from amino acid 78 to amino acid 87 of SEQ ID N0:30.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 228 to nucleotide 662;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl4_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA _insert of clone vcl4_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl4_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl4_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:32;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:32;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(i); and (m} a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:31.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:31 from nucleotide 228 to nucleotide 662; the nucleotide sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662; the nucleotide sequence of the full-length protein coding sequence of clone vcl4_1 deposited under accession number ATCC 98748;
or the nucleotide sequence of a mature protein coding sequence of clone vcl4_1 deposited under 3 0 accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl4_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:32, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment comprising the amino acid sequence from amino acid 67 to amino acid 76 of SEQ
ID N0:32.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:31.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:31, but excluding the poly(A) tail at the 3' end of SEQ ID N0:31; and (ab) the nucleotide sequence of the cDNA insert of clone vcl4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that 2 5 hybridize in 6X 5SC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:31, but excluding the poly(A) tail at the 3' end of SEQ ID N0:31; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vcl4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:31, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:31 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:31 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:31. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from nucleotide 327 to nucleotide 662.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:32;
(b) a fragment of the amino acid sequence of SEQ ID N0:32, the fragment comprising eight contiguous amino acids of SEQ ID N0:32; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl4_1 deposited under accession number ATCC 98748;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:32. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 3 0 of SEQ ID N0:32, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:32 having biological activity, the fragment comprising the amino acid sequence from amino acid 67 to amino acid 76 of SEQ ID N0:32.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 101 to nucleotide 667;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl6_1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl6_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl6_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:34;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:34 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:34;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:33.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:33 from nucleotide 101 to nucleotide 667; the nucleotide sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667; the nucleotide sequence of the full-length protein coding sequence of clone vcl6_1 deposited under accession number ATCC 98784;
or the nucleotide sequence of a mature protein coding sequence of clone vcl6_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:34, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:34 having biological activity, the fragment comprising the amino acid sequence from amino acid 89 to amino acid 98 of SEQ
ID N0:34.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:33.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:33, but excluding the poly(A) tail at the 3' end of SEQ ID N0:33; and (ab) the nucleotide sequence of the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b} a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:33, but excluding the poly(A) tail at the 3' end of SEQ ID N0:33; and (bb) the nucleotide sequence of the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(ii} hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:33, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:33 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:33 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:33. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from nucleotide 182 to nucleotide 667.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:34;
(b) a fragment of the amino acid sequence of SEQ ID N0:34, the fragment comprising eight contiguous amino acids of SEQ ID N0:34; and (c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vcl6_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:34. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:34 having biological activity, the fragment preferably SS
WO 99/55721 PC'T/US99/08504 comprising eight (more preferably twenty, most preferably thirty) contiguous amino ands of SEQ ID N0:34, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:34 having biological activity, the fragment comprising the amino acid sequence from amino acid 89 to amino acid 98 of SEQ ID N0:34.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 8 to nucleotide 355;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl7 1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl7 1 deposited under accession number ATCC
2 0 98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl7_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:36;
2 5 (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:36;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a}-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i} above ;
(1) a polynudeotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 25% of the length of SEQ ID N0:35.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:35 from nucleotide 8 to nucleotide 355; the nucleotide sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355; the nucleotide sequence of the full-length protein coding sequence of clone vcl7_1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone vcl7_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:36, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ
ID N0:36.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:35.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:35, but excluding the poly(A) tail at the 3' end of SEQ ID N0:35; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vcl7 1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:35, but excluding the poly(A) tail at the 3' end of SEQ ID N0:35; and (bb) the nucleotide sequence of the cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:35, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:35 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:35 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:35. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from nucleotide 134 to nucleotide 355.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:36;
(b) a fragment of the amino acid sequence of SEQ ID N0:36, the fragment comprising eight contiguous amino acids of SEQ ID N0:36; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl7 1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:36. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:36, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:36 having biological activity, the fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ ID N0:36.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37 from nucleotide 1031 to nucleotide 1252;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:37 from nucleotide 1100 to nucleotide 1252;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc21_1 deposited under accession number ATCC 98785;
(e) a polynucleotide encoding the full-length protein encoded by the 2 5 cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(f) a polynucleotlde comprising the nucleotide sequence of a mature protein coding sequence of clone vc21 1 deposited under accession number ATCC
98785;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
3 0 insert of clone vc21 1 deposited under accession number ATCC 98785;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:38;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:38 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:38;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:37.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:37 from nucleotide 1031 to nucleotide 1252; the nucleotide sequence of SEQ
ID N0:37 from nucleotide 1100 to nucleotide 1252; the nucleotide sequence of the full-length protein coding sequence of clone vc21 1 deposited under accession number ATCC
98785;
or the nucleotide sequence of a mature protein coding sequence of clone vc21 1 deposited under accession number ATCC 98785. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert 2 0 of clone vc21 1 deposited under accession number ATCC 98785. In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino acid 74. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38 2 5 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:38, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:38 having biological activity, the fragment comprising the amino acid sequence from amino acid 32 to amino acid 41 of SEQ ID N0:38.
3 0 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:37.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:37, but excluding the poly(A) tail at the 3' end of SEQ ID N0:37; and (ab) the nucleotide sequence of the cDNA insert of done vc21 1 deposited under accession number ATCC 98785;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:37, but excluding the poly(A) tail at the 3' end of SEQ ID N0:37; and (bb) the nucleotide sequence of the cDNA insert of clone 2 0 vc21 1 deposited under accession number ATCC 98785;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:37, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:37 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:37 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:37. Also preferably the 3 0 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA
sequence of SEQ ID N0:37 from nucleotide 1100 to nucleotide 1252, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:37 from nucleotide 1100 to nucleotide 1252, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from nucleotide 1100 to nucleotide 1252.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:38;
(b) the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino acid 74;
(c) a fragment of the amino acid sequence of SEQ ID N0:38, the fragment comprising eight contiguous amino acids of SEQ ID N0:38; and (d) the amino acid sequence encoded by the cDNA insert of clone vc21 1 deposited under accession number ATCC 98785;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:38 or the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino acid 74. In further preferred embodiments, 2 0 the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:38 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:38, or a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38 having biological activity, the fragment comprising the amino acid sequence from amino 2 5 acid 32 to amino acid 41 of SEQ ID N0:38.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 94 to nucleotide 1482;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc23_1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc23_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc23_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:40;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:40;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:39.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:39 from nucleotide 94 to nucleotide 1482; the nucleotide sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482; the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone vc23 1 deposited under 3 0 accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:40, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment comprising the amino acid sequence from amino acid 226 to amino acid 235 of SEQ ID N0:40.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:39.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:39, but excluding the poly(A) tail at the 3' end of SEQ ID N0:39; and (ab) the nucleotide sequence of the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that 2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:39, but excluding the poly(A) tail at the 3' end of SEQ ID N0:39; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vc23_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:39, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:39 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:39 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:39. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from nucleotide 214 to nucleotide 1482.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:40;
(b) a fragment of the amino acid sequence of SEQ ID N0:40, the fragment comprising eight contiguous amino acids of SEQ ID N0:40; and (c) the amino acid sequence encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:40. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 3 0 of SEQ ID N0:40, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:40 having biological activity, the fragment comprising the amino acid sequence from amino acid 226 to amino acid 235 of SEQ ID N0:40.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 153 to nucleotide 413;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc25_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of done vc25_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:42;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:42 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:42;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and {m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:41.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:41 from nucleotide 153 to nucleotide 413; the nucleotide sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413; the nucleotide sequence of the full-length protein coding sequence of clone vc~ 1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:42 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:42, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:42 having biological activity, the fragment comprising the amino acid sequence from amino acid 38 to amino acid 47 of SEQ
ID N0:42.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:41.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:41, but excluding the poly(A) tail at the 3' end of SEQ ID N0:41; and (ab) the nucleotide sequence of the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:41, but excluding the poly(A) tail at the 3' end of SEQ ID N0:41; and (bb) the nucleotide sequence of the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii} amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:41, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
TD N0:41 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:41, but excluding the poly(A) tail at the 3' end of SEQ ID N0:41. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from nucleotide 264 to nucleotide 413.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a} the amino acid sequence of SEQ ID N0:42;
(b) a fragment of the amino acid sequence of SEQ ID N0:42, the fragment comprising eight contiguous amino acids of SEQ ID N0:42; and (c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vc25_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:42. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:42 having biological activity, the fragment preferably WO 99/55721 PC'f/US99/08504 comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:42, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:42 having biological activity, the fragment comprising the amino acid sequence from amino acid 38 to amino acid 47 of SEQ ID N0:42.
In one embodiment, the present invention provides a composition comprising an isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43;
(b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 87 to nucleotide 1409;
(c) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of done vc26_1 deposited under accession number ATCC 98784;
(e) a polynudeotide encoding the full-length protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(f) a polynudeotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc26_1 deposited under accession number ATCC
2 0 98784;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
insert of clone vc26_1 deposited under accession number ATCC 98784;
(h) a polynudeotide encoding a protein comprising the amino acid sequence of SEQ ID N0:44;
2 5 (i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:44;
(j) a polynudeotide which is an allelic variant of a polynudeotide of (a)-(g) above;
3 0 (k) a polynudeotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynudeotide that hybridizes under stringent conditions to any one of the polynudeotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:43.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:43 from nucleotide 87 to nucleotide 1409; the nucleotide sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409; the nucleotide sequence of the full-length protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
or the nucleotide sequence of a mature protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:44, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:44.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:43.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:43, but excluding the poly(A) tail at the 3' end of SEQ ID N0:43; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vc26_1 deposited under accession number ATCC 98784;
{ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:43, but excluding the poly(A) tail at the 3' end of SEQ ID N0:43; and (bb) the nucleotide sequence of the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(ii} hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:43, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:43 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:43 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:43. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from nucleotide 156 to nucleotide 1409.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:44;
(b) a fragment of the amino acid sequence of SEQ ID N0:44, the fragment comprising eight contiguous amino acids of SEQ ID N0:44; and (c) the amino acid sequence encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:44. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:44, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:44 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:44.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 63 to nucleotide 428;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:45 from nucleotide 156 to nucleotide 428;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 356 to nucleotide 1773;
{e) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number 2 5 ATCC 98804;
(f) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc30-1 deposited under accession number ATCC 98804;
(g) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC
3 0 98804;
(h) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc30_1 deposited under accession number ATCC 98804;
(i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:46;
(j) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:46;
(k) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(h) above;
(1) a polynucleotide which encodes a species homologue of the protein of (i) or (j) above ;
(m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j); and (n) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j) and that has a length that is at least 25% of the length of SEQ ID N0:45.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:45 from nucleotide 63 to nucleotide 428; the nucleotide sequence of SEQ ID
N0:45 from nucleotide 156 to nucleotide 428; the nucleotide sequence of SEQ ID N0:45 from nucleotide 356 to nucleotide 1773; the nucleotide sequence of the full-length protein coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
or the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide 2 0 encodes the full-length or a mature protein encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804. In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein 2 5 comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:46, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment comprising the amino acid sequence from amino acid 56 3 0 to amino acid 65 of SEQ ID N0:46.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:45.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa} SEQ ID N0:45, but excluding the poly(A) tail at the 3' end of SEQ ID N0:45; and (ab} the nucleotide sequence of the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:45, but excluding the poly(A) tail at the 3' end of SEQ ID N0:45; and 2 0 (bb) the nucleotide sequence of the cDNA insert of clone vc30_I deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and 2 5 (iv) isolating the polynucleotide products of step (b}(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:45 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:45 , but 3 0 excluding the poly(A) tail at the 3' end of SEQ ID N0:45. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:45 from nucleotide 156 to nucleotide 428, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:45 from nucleotide 156 to nucleotide 428, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from nucleotide 156 to nucleotide 428. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 356 to nucleotide 1773, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:45 from nucleotide 356 to nucleotide 1773, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID
N0:45 from nucleotide 356 to nucleotide 1773.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:46;
(b) the amino acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97;
2 0 (c) a fragment of the amino acid sequence of SEQ ID N0:46, the fragment comprising eight contiguous amino acids of SEQ ID N0:46; and (d) the amino acid sequence encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such 2 5 protein comprises the amino acid sequence of SEQ ID N0:46 or the amino acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
3 0 N0:46, or a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment comprising the amino acid sequence from amino acid 56 to amino acid 65 of SEQ ID N0:46.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 30 to nucleotide 1799;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vdl 1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vdl_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vdl 1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd1 1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:48;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:48 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:48;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k} a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:47.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:47 from nucleotide 30 to nucleotide 1799; the nucleotide sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799; the nucleotide sequence of the full-length protein coding sequence of clone vd1 1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vdl 1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:48, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:48 having biological activity, the fragment comprising the amino acid sequence from amino acid 290 to amino acid 299 of SEQ ID N0:48.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:47.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:47, but excluding the poly(A) tail at the 3' end of SEQ ID N0:47; and (ab) the nucleotide sequence of the cDNA insert of clone vdl_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:47, but excluding the poly(A) tail at the 3' end of SEQ TD N0:47; and (bb) the nucleotide sequence of the cDNA insert of clone vdl 1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:47, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:47 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:47 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:47. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from nucleotide 90 to nucleotide 1799.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:48;
(b) a fragment of the amino acid sequence of SEQ ID N0:48, the fragment comprising eight contiguous amino acids of SEQ ID N0:48; and (c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vd1_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:48. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:48, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:48 having biological activity, the fragment comprising the amino acid sequence from amino acid 290 to amino acid 299 of SEQ ID N0:48.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 69 to nucleotide 443;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vd2_1 deposited under accession number ATCC
2 0 98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd2_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:50;
2 5 (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:50;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein of {h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:49.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:49 from nucleotide 69 to nucleotide 443; the nucleotide sequence of SEQ ID
NO:49 from nucleotide 111 to nucleotide 443; the nucleotide sequence of the full-length protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:50, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ
ID N0:50.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:49.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:49, but excluding the poly(A) tail at the 3' end of SEQ ID N0:49; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vd2 1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:49, but excluding the poly(A) tail at the 3' end of SEQ ID N0:49; and (bb) the nucleotide sequence of the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:49, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:49 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:49 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:49. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from nucleotide 111 to nucleotide 443.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:50;
(b) a fragment of the amino acid sequence of SEQ ID N0:50, the fragment comprising eight contiguous amino acids of SEQ ID N0:50; and (c) the amino acid sequence encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:50. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:50, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:50 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ ID N0:50.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51 from nucleotide 176 to nucleotide 1249;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:51 from nucleotide 227 to nucleotide 1249;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the 2 5 cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vd3_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
3 0 insert of clone vd3_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:52;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:52;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 25% of the length of SEQ ID N0:51.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:51 from nucleotide 176 to nucleotide 1249; the nucleotide sequence of SEQ
ID N0:51 from nucleotide 227 to nucleotide 1249; the nucleoiide sequence of the full-length protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd3_1 2 0 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:52, or a polynucleotide encoding a protein comprising a 2 5 fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment comprising the amino acid sequence from amino acid 174 to amino acid 183 of SEQ ID N0:52.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:51.
3 0 Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:51, but excluding the poly(A) tail at the 3' end of SEQ ID N0:51; and (ab) the nucleotide sequence of the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:51, but excluding the poly(A) tail at the 3' end of SEQ ID N0:51; and (bb) the nucleotide sequence of the cDNA insert of clone 2 0 vd3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:51, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:51 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:51 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:51. Also preferably the 3 0 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:51 from nucleotide 227 to nucleotide 1249, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:51 from nucleotide 227 to nucleotide 1249, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from nucleotide 227 to nucleotide 1249.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:52;
(b) a fragment of the amino and sequence of SEQ ID N0:52, the fragment comprising eight contiguous amino acids of SEQ ID N0:52; and (c) the amino acid sequence encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:52. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 2 0 of SEQ ID N0:52, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:52 having biological activity, the fragment comprising the amino acid sequence from amino acid 174 to amino acid 183 of SEQ ID N0:52.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
2 5 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53 from nucleotide 94 to nucleotide 1530;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:53 from nucleotide 145 to nucleotide 1530;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vd4_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd4_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:54;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:54 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:54;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m} a polynucleotide that hybridizes under stringent conditions to any 2 0 one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:53.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:53 from nucleotide 94 to nucleotide 1530; the nucleotide sequence of SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530; the nucleotide sequence of the full-length protein 2 5 coding sequence of clone vd4_1 deposited under accession number ATCC
98804; or the nucleotide sequence of a mature protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804. In further preferred embodiments, the 3 0 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:54, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:54 having biological activity, the wo mss~z~ pcTiusmossoa fragment comprising the amino acid sequence from amino acid 234 to amino acid 243 of SEQ ID N0:54.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:53.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:53, but excluding the poly(A) tail at the 3' end of SEQ ID N0:53; and (ab) the nucleotide sequence of the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and 2 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) 5EQ ID N0:53, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:53; and (bb) the nucleotide sequence of the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
3 0 (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step {b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:53, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
WO 99/55'121 PGT/US99/08504 ID N0:53 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:53 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:53. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from nucleotide 145 to nucleotide 1530.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:54;
(b) a fragment of the amino acid sequence of SEQ ID N0:54, the fragment comprising eight contiguous amino acids of SEQ ID N0:54; and 2 0 (c) the amino acid sequence encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:54. In further preferred embodiments, the present invention provides a protein comprising a fragment of the 2 5 amino acid sequence of SEQ ID N0:54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:54, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:54 having biological activity, the fragment comprising the amino acid sequence from amino acid 234 to amino acid 243 of SEQ ID N0:54.
3 0 In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 71 to nucleotide 1300;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone ve4_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone ve4_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:56;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:56;
2 0 (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any 2 5 one of the polynucleotides specified in (ar(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:55.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
3 0 N0:55 from nucleotide 71 to nucleotide 1300; the nucleotide sequence of SEQ ID N0:55 from nucleotide 182 to nucleotide 1300; the nucleotide sequence of the full-length protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:56, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 200 to amino acid 209 of SEQ ID N0:56.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:55.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:55, but excluding the poly(A) tail at the 3' end of SEQ ID N0:55; and 2 0 (ab) the nucleotide sequence of the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the 2 5 probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from 3 0 the group consisting of:
{ba) SEQ ID N0:55, but excluding the poly(A) tail at the 3' end of SEQ ID N0:55; and (bb) the nucleotide sequence of the cDNA insert of clone ve4_I deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:55, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:55 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:55 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:55. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300, to a nucleotide sequence corresponding to the 3' end 2 0 of said sequence of SEQ ID N0:55 from nucleotide 182 to nucleotide 1300.
1n other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:56;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:56, the fragment comprising eight contiguous amino acids of SEQ ID N0:56; and (c) the amino acid sequence encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such 3 0 protein comprises the amino acid sequence of SEQ ID N0:56. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:56, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 200 to amino acid 209 of SEQ ID N0:56.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57; ' (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 57 to nucleotide 785;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785;
(d} a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone ve8_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone ve8_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:58;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment 2 5 comprising eight contiguous amino acids of SEQ ID N0:58;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (ar(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-{i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:57.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:57 from nucleotide 57 to nucleotide 785; the nucleotide sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785; the nucleotide sequence of the full-length protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:58, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment comprising the amino acid sequence from amino acid 116 to amino acid 125 of SEQ ID N0:58.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:57.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:57, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:57; and (ab) the nucleotide sequence of the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 3 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:57, but excluding the poly{A) tail at the 3' end of SEQ ID N0:57; and (bb) the nucleotide sequence of the cDNA insert of done ve8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step {b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:57, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:57 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:57 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:57. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785, and extending contiguously from a nucleotide sequence corresponding to the 5' end 2 0 of said sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785, and extending contiguously from a 2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from nucleotide 147 to nucleotide 785.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:58;
(b) a fragment of the amino acid sequence of SEQ ID N0:58, the fragment comprising eight contiguous amino acids of SEQ ID N0:58; and (c) the amino acid sequence encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:58. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:58, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:58 having biological activity, the fragment comprising the amino acid sequence from amino acid 116 to amino acid 125 of SEQ ID N0:58.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 64 to nucleotide 1002;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002;
(d) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vfl 1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vfl 1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone vfl 1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vfl_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:60;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:60;
(j} a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:59.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:59 from nucleotide 64 to nucleotide 1002; the nucleotide sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002; the nucleotide sequence of the full-length protein coding sequence of clone vfl_1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone vfl 1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment 2 0 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:60, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment comprising the amino acid sequence from amino acid 151 to amino acid 160 of SEQ ID N0:60.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:59.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:59, but excluding the poly(A) tail at the 3' end of SEQ ID N0:59; and WO 99/55721 PC"TNS99/08504 (ab) the nucleotide sequence of the cDNA insert of clone vfl 1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:59, but excluding the poly(A) tail at the 3' end of SEQ ID N0:59; and (bb) the nucleotide sequence of the cDNA insert of done vf1 1 deposited under accession number ATCC 98784;
(ii) hybridizing said primer{s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynudeotide products of step (b)(iii).
2 0 Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:59, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:59 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:59 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:59. Also preferably the 2 5 polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:59 from nucleotide 64 to nucleotide 1002, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:59 from nucleotide 64 to nucleotide 1002, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from nucleotide 3 0 64 to nucleotide 1002. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from nucleotide 139 to nucleotide 1002.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID N0:60, the fragment comprising eight contiguous amino acids of SEQ ID N0:60; and (c) the amino acid sequence encoded by the cDNA insert of clone vf1 1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:60. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:60, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:60 having biological activity, the fragment comprising the amino acid sequence from amino acid 151 to amino acid 160 of SEQ ID N0:60.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61;
(b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 588 to nucleotide 995;
2 5 (c) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of done vhf 1 deposited under accession number ATCC 98804;
3 0 (e) a polynudeotide encoding the full-length protein encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(f) a polynudeotide comprising the nucleotide sequence of a mature protein coding sequence of clone vh1_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vhl 1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:62;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:62;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the profiein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:61.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:61 from nucleotide 588 to nucleotide 995; the nucleotide sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995; the nucleotide sequence of the full-length protein 2 0 coding sequence of clone vhl 1 deposited under accession number ATCC
98804; or the nucleotide sequence of a mature protein coding sequence of clone vhl_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vhf 1 deposited under accession number ATCC 98804. In further preferred embodiments, the 2 5 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:62, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the 3 0 fragment comprising the amino acid sequence from amino acid 63 to amino acid 72 of SEQ
ID N0:62.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:61.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:61, but excluding the poly(A) tail at the 3' end of SEQ ID N0:61; and (ab) the nucleotide sequence of the cDNA insert of clone vhl 1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe{s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (ba) SEQ ID N0:61, but excluding the poly(A) tail at the 3' end of SEQ ID N0:61; and (bb) the nucleotide sequence of the cDNA insert of clone vhl 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:61, and 3 0 extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:61 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:61 , but excluding the poly(A} tail at the 3' end of SEQ ID N0:61. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from nucleotide 750 to nucleotide 995.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:62;
(b) a fragment of the amino acid sequence of SEQ ID N0:62, the fragment comprising eight contiguous amino acids of SEQ ID N0:62; and (c) the amino acid sequence encoded by the cDNA insert of clone vhf 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:62. In further preferred 2 0 embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:62, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:62 having biological activity, the fragment comprising the amino acid sequence 2 5 from amino acid 63 to amino acid 72 of SEQ ID N0:62.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 29 to nucleotide 1369;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vi1 1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vil 1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vil 1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vil I deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:64;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:64;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(i); and {m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:63.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:63 from nucleotide 29 to nucleotide 1369; the nucleotide sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369; the nucleotide sequence of the full-length protein coding sequence of clone vi1 1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vil_1 deposited under 3 0 accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activity, the fragment WO 99/55'721 PCTNS99/08504 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:64, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activity, the fragment comprising the amino acid sequence from amino acid 218 to amino acid 227 of SEQ ID N0:64.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:63.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:63, but excluding the poly(A) tail at the 3' end of SEQ ID N0:63; and (ab) the nucleotide sequence of the cDNA insert of clone vi1 1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and {b} a process comprising the steps of:
(i} preparing one or more polynucleotide primers that 2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ 1D N0:63, but excluding the poly(A) tail at the 3' end of SEQ ID N0:63; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vil 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:63, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:63 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:63 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:63. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:63 from nucleotide 104 to nucleotide 1369.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:64;
(b) a fragment of the amino acid sequence of SEQ ID N0:64, the fragment comprising eight contiguous amino acids of SEQ ID N0:64; and (c) the amino acid sequence encoded by the cDNA insert of clone vi1 1 deposited under accession number ATCC 98804;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:64. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activify, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 3 0 of SEQ ID N0:64, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:64 having biological activity, the fragment comprising the amino acid sequence from amino acid 218 to amino acid 227 of SEQ ID N0:64.
In certain preferred embodiments, the polynucleotide is operably linked to an expression control sequence. The invention also provides a host cell, including bacterial, yeast, insect and mammalian cells, transformed with such polynucleotide compositions.
Also provided by the present invention are organisms that have enhanced, reduced, or modified expression of the genes) corresponding to the polynucleotide sequences disclosed herein.
Processes are also provided for producing a protein, which comprise:
(a) growing a culture of the host cell transformed with such polynucleotide compositions in a suitable culture medium; and (b) purifying the protein from the culture.
The protein produced according to such methods is also provided by the present invention.
Protein compositions of the present invention may further comprise a pharmaceutically acceptable Garner. Compositions comprising an antibody which specifically reacts with such protein are also provided by the present invention.
Methods are also provided for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein of the present invention and a pharmaceutically acceptable carrier.
BRIEF DESCRIPTION OF THE DRAWINGS
2 0 Figures 1A and 1B are schematic representations of the pED6 and pNOTs vectors, respectively, used for deposit of clones disclosed herein.
DETAILED DESCRIPTION
ISOLATED PROTEINS AND POLYNUCLEOTIDES
2 5 Nucleotide and amino acid sequences, as presently determined, are reported below for each clone and protein disclosed in the present application. The nucleotide sequence of each clone can readily be determined by sequencing of the deposited clone in accordance with known methods. The predicted amino acid sequence (both full-length and mature forms) can then be determined from such nucleotide sequence. The amino 3 0 acid sequence of the protein encoded by a particular clone can also be determined by expression of the clone in a suitable host cell, collecting the protein and determining its sequence. For each disclosed protein applicants have identified what they have determined to be the reading frame best identifiable with sequence information available at the time of filing.
As used herein a "secreted" protein is one which, when expressed in a suitable host cell, is transported across or through a membrane, including transport as a result of signal sequences in its amino acid sequence. "Secreted" proteins include without limitation proteins secreted wholly (e.g., soluble proteins) or partially (e.g. , receptors) from the cell in which they are expressed. "Secreted" proteins also include without limitation proteins which are transported across the membrane of the endoplasmic reticulum.
Clone"vb2 1"
A polynucleotide of the present invention has been identified as clone "vb2_1".
vb2_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb2_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb2_1 protein").
The nucleotide sequence of vb2_1 as presently determined is reported in SEQ ID
NO:1, and includes a poly(A} tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb2_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:2. Amino acids 15 to 27 of SEQ ID N0:2 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature of the predicted 2 0 leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb2_1 protein.
If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:1 by deleting one of the adenine residues at positions 315 and 316, another potential vb2_1 reading frame and predicted amino acid sequence could be encoded by basepairs 126 to 2 5 381 of SEQ ID N0:1 and is reported in SEQ ID N0:97. Amino acids 15 to 27 of SEQID
N0:97 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28 of SEQ ID N0:97, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb2_1 should be approximately 2342 bp.
3 0 The nucleotide sequence disclosed herein for vb2_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb2_1 demonstrated at least some similarity with sequences identified as AA308563 (EST179381 HCC cell line (matastasis to liver in mouse) II Homo Sapiens cDNA 5' end, mRNA sequence). Based upon sequence similarity, vb2_1 proteins and each similar protein or peptide may share at least some activity.
Clone "vb3 1"
A polynucleotide of the present invention has been identified as clone "vb3_1".
vb3_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb3_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb3_1 protein").
The nucleotide sequence of vb3 1 as presently determined is reported in SEQ ID
N0:3, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb3_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:4. Amino acids 16 to 28 of SEQ ID N0:4 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 29. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb3_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb3_1 should be approximately 2498 bp.
2 0 The nucleotide sequence disclosed herein for vb3_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb3_1 demonstrated at least some similarity with sequences identified as AA098874 (zn45f I l .s 1 Stratagene HeLa cell s3 937216 Homo sapiens cDNA
clone 550413 3', mRNA sequence) and T26482 (Human gene signature HUMGS08724).
2 5 Based upon sequence similarity, vb3_1 proteins and each similar protein or peptide may share at least some activity.
Clone "vb4 1"
A polynucleotide of the present invention has been identified as clone "vb4_1".
3 0 vb4_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb4_1 protein").
The nucleotide sequence of vb4_1 as presently determined is reported in SEQ ID
N0:5, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:6. Amino acids 2 to 14 of SEQ ID N0:6 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb4_1 should be approximately 2161 bp.
The nucleotide sequence disclosed herein for vb4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb4_1 demonstrated at least some similarity with sequences identified as D88035 (Rat mRNA for glycoprotein specific UDP-glucuronyltransferase, complete cds), N49234 (yy83b10.s1 Homo Sapiens cDNA clone 280123 3'), and (Human brain Expressed Sequence Tag EST00765). Based upon sequence similarity, vb4_1 proteins and each similar protein or peptide may share at least some activity. The TopPredlI computer program predicts two additional potential transmembrane domains within the vb4_1 protein sequence, one centered around amino acid 40 and another 2 0 around amino acid 80 of SEQ ID N0:6.
Clone "vb5 1"
A polynucleotide of the present invention has been identified as clone "vb5_1".
vb5_1 was isolated from a human fetal brain cDNA library and was identified as encoding 2 5 a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb5_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb5_1 protein").
The nucleotide sequence of vb5_1 as presently determined is reported in SEQ ID
N0:7, and includes a poly(A} tail. What applicants presently believe to be the proper 3 0 reading frame and the predicted amino acid sequence of the vb5_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:8. Amino acids 7 to 19 of SEQ ID N0:8 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 20. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb5_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb5_1 should be approximately 724 bp.
The nucleotide sequence disclosed herein for vb5_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb5_7 demonstrated at least some similarity with sequences identified as AA835218 (ak65a05.s1 Barstead pancreas HPLRBI Homo sapiens cDNA
clone IMAGE:1412720 3', mRNA sequence). Based upon sequence similarity, vb5_1 proteins and each similar protein or peptide may share at least some activity.
Clone "vb6 1"
A polynucleotide of the present invention has been identified as clone "vb6_1".
vb6_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb6_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb6_1 protein").
The nucleotide sequence of vb6_1 as presently determined is reported in SEQ ID
N0:9, and includes a poly(A) tail. What applicants presently believe to be the proper 2 0 reading frame and the predicted amino acid sequence of the vb6_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:10. Amino acids 13 to 25 of SEQ ID NO:10 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 5 the predicted leader/signal sequence not be separated from the remainder of the vb6_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb6_1 should be approximately 2685 bp.
The nucleotide sequence disclosed herein for vb6_1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb6_1 demonstrated at least some similarity with sequences identified as AA478801 (zv20fn5.s 1 Soares NhHMPu S 1 Homo sapiens cDNA clone 754209 3', mRNA sequence). Based upon sequence similarity, vb6_1 proteins and each similar protein or peptide may share at least some activity.
done "vb7 1"
A polynucleotide of the present invention has been identified as clone "vb7 1".
vb7 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb7 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb7 1 protein').
The nucleotide sequence of vb7_1 as presently determined is reported in SEQ ID
N0:11, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb7 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:12. Amino acids 35 to 47 of SEQ ID N0:12 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 48. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb7 1 protein.
Another potential vb7 1 reading frame and predicted amino acid sequence that 2 0 could be encoded by basepairs 1093 to 1577 of SEQ ID N0:11 is reported in SEQ ID
N0:98. Amino acids 11 to 23 of SEQ ID N0:98 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24 of SEQ ID
N0:98, or are a transmembrane domain. The TapPredII computer program predicts another potential transmembrane domain within the protein sequence of SEQ ID
N0:98 2 5 centered around amino acid 86 of SEQ ID N0:98. If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:11 approximately between position 1090 and position 1253, the open reading frame of SEQ ID N0:12 could be joined to the open reading frame of SEQ ID N0:98.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 3 0 vb7 1 should be approximately 1730 bp.
The nucleotide sequence disclosed herein for vb7 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb7 1 demonstrated at least some similarity with sequences identified as D 13748 {human eukaryotic initiation factor 4A)], M22873 (Mus musculus protein synthesis initiation factor 4A (e1F-4A) gene, exon 1), and N36589 (yx86fO8.r1 Homo sapiens cDNA clone 268647 S'). The predicted amino acid sequence disclosed herein for vb7_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLAST7C search protocol. The predicted vb7 1 protein demonstrated at least some similarity to the sequence identified as AL021839 (hypothetical protein [Schizosaccharomyces pombe]). Based upon sequence similarity, vb7 1 proteins and each similar protein or peptide may share at least some activity.
vb7_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 45 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vb8 1"
A polynucleotide of the present invention has been identified as clone "vb8_1".
vb8_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb8_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb8_1 protein").
The nucleotide sequence of vb8_1 as presently determined is reported in SEQ ID
N0:13, and includes a poly(A) tail. What applicants presently believe to be the proper 2 0 reading frame and the predicted amino acid sequence of the vb8_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:14.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb8_1 should be approximately 1363 bp.
The nucleotide sequence disclosed herein for vb8_1 was searched against the 2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb8_1 demonstrated at least some similarity with sequences identified as N57252 (yw93dll.rl Homo sapiens cDNA clone 259797 5'). The predicted amino acid sequence disclosed herein for vb8_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The 3 0 predicted vb8_1 protein demonstrated at least some similarity to sequences identified as AF51239 (probable ubiquitin activating enzyme 2 [Picea mariana]). Based upon sequence similarity, vb8_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain WO 99/55?21 PCT/US99/08504 within the vb8_1 protein sequence centered around amino acid 30 of SEQ ID
N0:14. Both the CodonPreference and Testcode computer programs indicate that frameshifts in the nucleotide sequence of SEQ ID N0:13, resulting in the joining of the open reading frame of SEQ ID N0:14 with open reading frames that are more 5' to that of SEQ ID
N0:14, are likely.
vb8_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 23 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vb9 1"
A polynudeotide of the present invention has been identified as clone "vb9_1".
vb9_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb9_1 is a full-length done, including the entire coding sequence of a secreted protein (also referred to herein as "vb9_1 protein").
The nucleotide sequence of vb9_1 as presently determined is reported in SEQ ID
N0:15, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb9_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:16. Amino acids 3 to 15 2 0 of SEQ ID N0:16 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 16. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb9_1 protein.
2 5 The EcoRI/NotI restriction fragment obtainable from the deposit containing done vb9_1 should be approximately 2996 bp.
The nucleotide sequence disclosed herein for vb9_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and PASTA search protocols. vb9_1 demonstrated at least some similarity with sequences 3 0 identified as AA446380 (zw58b09.r1 Soares total fetus Nb2HF8 9w Homo sapiens cDNA
clone 774233 5', mRNA sequence) and L48440 (Rattus norvegicus collagen type II
mRNA, complete cds). The predicted amino add sequence disclosed herein for vb9_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vb9_1 protein demonstrated at least some similarity to the sequence identified as 278279 (Collagen alphal [Rattus norvegicus]).
Based upon sequence similarity, vb9_1 proteins and each similar protein or peptide may share at least some activity.
vb9_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 58 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vc3 1"
A polynucleotide of the present invention has been identified as clone "v~ 1".
vc3_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc3_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc3_1 protein").
The nucleotide sequence of vc3_1 as presently determined is reported in SEQ ID
N0:17, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc3_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:18. Amino acids 24 to 36 of SEQ ID N0:18 are a predicted leader/signal sequence, with the predicted mature 2 0 amino acid sequence beginning at amino acid 37. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc3_1 protein.
Another potential vc3_1 reading frame and predicted amino acid sequence is 2 5 encoded by basepairs 227 to 703 of SEQ TD N0:17 and is reported in SEQ ID
N0:99.
Amino acids 83 to 95 of SEQ ID N0:99 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 96, or are a transmembrane domain, and the TopPredII computer program predicts two additional transmembrane domains within the SEQ ID N0:99 amino acid sequence. A
frameshift in 3 0 the nucleotide sequence of SEQ ID N0:17 between about nucleotide 109 to about nucleotide 417 could join together portions of the overlapping reading frames of SEQ ID
N0:18 and SEQ ID N0:99.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc3_1 should be approximately 950 bp.
The nucleotide sequence disclosed herein for vc3_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc3_1 demonstrated at least some similarity with sequences identified as AA669665 (ac18h12.s1 Stratagene ovary (#937217) Homo sapiens cDNA clone 856871 3'). Based upon sequence similarity, vc3_1 proteins and each similar protein or peptide may share at least some activity.
vc3_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 19 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vc4 1"
A polynucleotide of the present invention has been identified as clone "vc4_1".
vc4_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc4_1 protein").
The nucleotide sequence of vc4 1 as presently determined is reported in SEQ ID
2 0 N0:19, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:20. Amino acids 2 to 14 of SEQ ID N0:20 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc4_1 should be approximately 1200 bp.
3 0 The nucleotide sequence disclosed herein for vc4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc4_1 demonstrated at least some similarity with sequences identified as Q40970 (Human skeletal muscle ADP-ribosyltransferase gene), U60881 (Mus musculus Yac-2 NAD:arginine ADP-ribosyltransferase mRNA, complete cds), and W12489 (ma57b11.r1 Soares mouse p3NMF19.5 Mus musculus cDNA clone 314781 5' similar to SW RT61_RAT P17982 ALLOANTIGEN RT6.1 PRECURSOR). The predicted amino acid sequence disclosed herein for vc4_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc4_1 protein demonstrated at least some similarity to sequences identified as 837572 (Rabbit skeletal muscle ADP-ribosyltransferase) and U60881 (Yac-2 NAD
arginine ADP-ribosyltransferase [Mus musculus]). ADP-ribosyltransferases are localized to the plasma membrane and are involved in "post-translational modification of proteins in which the ADP-ribose moiety of NAD is transferred to proteins", which is "responsible for the toxicity of some bacterial toxins (e.g. cholera toxin and pertussis toxin)". Based upon sequence similarity, vc4_1 proteins and each similar protein or peptide may share at least some activity.
vc4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 26 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vc5 1"
A polynucleotide of the present invention has been identified as clone "v~ 1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as encoding 2 0 a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc5_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc5_1 protein").
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:21, and includes a poly(A) tail. What applicants presently believe to be the proper 2 5 reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:22. Amino acids 63 to 75 of SEQ ID N0:22 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 76. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 3 0 the predicted leader/signal sequence not be separated from the remainder of the vc5_1 protein.
Another potential vc5_1 reading frame and predicted amino acid sequence is encoded by basepairs 215-376 of SEQ ID N0:21 and is reported in SEQ ID NO:100.
Amino acids 4 to 16 of SEQ ID NO:10(? are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 17 of SEQ ID N0:100.
The EcoRI/NotI restriction fragment obtainable from the deposit containing done vc5_1 should be approximately 1650 bp.
The nucleotide sequence disclosed herein for vc5_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc5_1 demonstrated at least some similarity with sequences identified as AA002211 (zh81h07.s1 Soares fetal liver spleen 1NFLS S1 Homo sapiens cDNA clone 4277413'}. Based upon sequence similarity, vc5_1 proteins and each similar protein or peptide may share at least some activity.
vc5_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 28 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vc7 1"
A polynucleotide of the present invention has been identified as clone "vc7 1".
vc7 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc7 1 is a full-length clone, including the entire coding 2 0 sequence of a secreted protein (also referred to herein as "vc7 1 protein").
The nucleotide sequence of vc7_1 as presently determined is reported in SEQ ID
N0:23, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc7_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:24. Amino acids 11 to 23 2 5 of SEQ ID N0:24 are a possible leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc7 1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vc7 1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. No hits were found in the database.
Clone"vc9 1"
A polynucleotide of the present invention has been identified as clone "vc9_1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc9_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "v~ 1 protein').
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:25, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:26. Amino acids 10 to 22 of SEQ ID N0:26 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the v~ 1 protein.
Another potential v~ 1 reading frame and predicted amino acid sequence is encoded by basepairs 1981 to 2619 of SEQ ID N0:25 and is reported in SEQ ID
N0:101.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone v~ 1 should be approximately 4500 bp.
2 0 The nucleotide sequence disclosed herein for v~ 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using B1.,ASTN/BLASTX and FASTA search protocols. vc9_1 demonstrated at least some similarity with sequences identified as N66453 (yz41a08.s1 Homo Sapiens cDNA clone 285590 3') and 275407 (Human DNA sequence from cosmid N128A12 on chromosome 22q12-qter contains ESTs, 2 5 CpG island). Based upon sequence similarity, v~ 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the v~ 1 protein sequence at the extreme C-terminus of SEQ ID N0:26.
3 0 Clone "vcl0 1"
A polynucleotide of the present invention has been identified as clone "vcl0_1".
vcl0_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl0_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl0_1 protein").
The nucleotide sequence of vcl0_1 as presently determined is reported in SEQ
ID
N0:27, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl0_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:28. Amino acids 21 to 33 of SEQ ID N0:28 are a possible leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 34.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcl0_1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vcl0_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcl0_1 demonstrated at least some similarity with sequences identified as AA398711 (zt75a05.s1 Soares testis NHT Homo sapiens cDNA clone 3') and T24621 {Human gene signature HUMGS06681). Based upon sequence similarity, vcl0_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the vcl0_1 protein sequence centered around amino acid 74 of SEQ ID N0:28.
Nuclotides 1103 to 1191 of SEQ ID N0:27 represent a possible intron in the predicted 3' untranslated 2 0 region of the vcl0_1 mRNA molecule.
Clone"vcll 1"
A polynucleotide of the present invention has been identified as clone "vcll_1".
vcll_1 was isolated from a human fetal brain cDNA library and was identified as 2 5 encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl l 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcll_1 protein').
The nucleotide sequence of vcll 1 as presently determined is reported in SEQ
ID
N0:29, and includes a poly(A) tail. What applicants presently believe to be the proper 3 0 reading frame and the predicted amino acid sequence of the vcll 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:30. Amino acids 6 to 18 of SEQ ID N0:30 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 19. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcll_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcll_1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vcll 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcll_1 demonstrated at Least some similarity with sequences identified as AA193348 (zr41c08.r1 Soares NhHMPu S1 Homo Sapiens cDNA clone 5') and T23590 (Human gene signature HIJMGS05443). Based upon sequence similarity, vcll 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the vcll 1 protein sequence centered around amino acid 32 of SEQ ID N0:30.
Clone"vcl4 1"
A polynucleotide of the present invention has been identified as clone "vcl4_1".
vcl4_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl4_1 protein").
2 0 The nucleotide sequence of vcl4_1 as presently determined is reported in SEQ ID
N0:31, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:32. Amino acids 21 to 33 of SEQ ID N0:32 are a predicted leader/signal sequence, with the predicted mature 2 5 amino acid sequence beginning at amino acid 34. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcl4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 3 0 vcl4_1 should be approximately 1300 bp.
The nucleotide sequence disclosed herein for vcl4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcl4_1 demonstrated at least some similarity with sequences identified as AA258182 (zs35f09.s1 NCI_CGAP_GCB1 Homo sapiens cDNA clone IMAGE
687209 3'). The predicted amino acid sequence disclosed herein for vcl4_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vcl4 1 protein demonstrated at least some similarity to sequences identified as AC002339 (BAC T11A7 (Arabidopsis thaliana]) and 271266 (R06C7.6 [Caenorhabditis elegans]). Based upon sequence similarity, vcl4_1 proteins and each similar protein or peptide may share at least some activity.
vcl4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 22 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vcl6 1"
A polynucleotide of the present invention has been identified as clone "vcl6_1".
vcl6_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl6_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl6_1 protein"}.
The nucleotide sequence of vcl6_1 as presently determined is reported in SEQ
ID
N0:33, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl6_1 protein corresponding 2 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:34. Amino acids 15 to 27 of SEQ ID N0:34 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcl6_1 2 5 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcl6_1 should be approximately 1256 bp.
The nucleotide sequence disclosed herein for vcl6_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and 3 0 FASTA search protocols. vcl6_1 demonstrated at least some similarity with sequences identified as AA776882 (ac40a09.s1 Stratagene hNT neuron (#937233) Homo sapiens cDNA clone 858904 3' similar to SW XB3_XENLA Q09004 STATHMIN-LIKE
PROTEIN XB3, mRNA sequence), AF026528 (Rattus norvegicus stathmin-like-protein RB3 mRNA, complete cds), and AF026529 (Rattus norvegicus stathmin-like-protein splice variant RB3' mRNA, complete cds). The predicted amino acid sequence disclosed herein for vcl6_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vcl6_1 protein demonstrated at least some siirularity to sequences identified as AF026528 (stathmin-like-protein RB3 [Rattus norvegicus]). While stathmin itself is intracellular, stathmin-related protein RB3 (as well as related proteins SCG10 in rat and XB3 in Xenopus) is membrane-associated and has been isolated in the membrane fraction from cell cultures. RB3 is expressed in neural tissue and may be involved in the expression of differentiated neuronal function. Based upon sequence similarity, vcl6_1 proteins and each similar protein or peptide may share at least some activity.
vcl6_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 89 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vcl7 1"
A polynucleotide of the present invention has been identified as clone "vcl7 1".
vcl7 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the 2 0 amino acid sequence of the encoded protein. vcl7 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl7 1 protein").
The nucleotide sequence of vcl7 1 as presently determined is reported in SEQ
ID
N0:35, and includes a poly{A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl7 1 protein corresponding 2 5 to the foregoing nucleotide sequence is reported in SEQ ID N0:36. Amino acids 30 to 42 of SEQ ID N0:36 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 43. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcl7 1 3 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcl7_1 should be approximately 1783 bp.
The nucleotide sequence disclosed herein for vcl7_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcl7_1 demonstrated at least some similarity with sequences identified as N73805 (yz80g02.s 1 Homo sapiens cDNA clone 289394 3'), and (Human gene signature HLTMGS06471). Based upon sequence similarity, vcl7 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII
computer program predicts an additional potential transmembrane domain within the vcl7 1 protein sequence centered around amino acid 60 of SEQ ID N0:36.
Clone "vc21 1"
A polynucleotide of the present invention has been identified as clone "vc21 1".
vc21 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc21 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc21_1 protein").
The nucleotide sequence of vc21_1 as presently determined is reported in SEQ
ID
N0:37, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc21 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:38. Amino acids 11 to 23 2 0 of SEQ ID N0:38 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc21_1 protein.
2 5 Another potential vc21 1 reading frame and predicted amino acid sequence is encoded by basepairs 796 to 1014 of SEQ ID N0:37 and is reported in SEQ ID
N0:102.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc21 1 should be approximately 1773 bp.
The nucleotide sequence disclosed herein for vc21 1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc21 1 demonstrated at least some similarity with sequences identified as W85910 (zh52b10.s1 Soares fetal liver spleen 1NFLS S1 Homo sapiens cDNA clone 415675 3', mRNA sequence) and T24609 (Human gene signature HUMGS06668). Based upon sequence similarity, vc21 1 proteins and each similar protein or peptide may share at least some activity.
Gone "vc23 1"
A polynucleotide of the present invention has been identified as clone "vc23_1".
vc23_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc23_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc23_2 protein").
The nucleotide sequence of vc23_1 as presently determined is reported in SEQ
ID
N0:39, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:40. Amino acids 28 to 40 of SEQ ID N0:40 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 41. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc23_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 2 0 vc23_1 should be approximately 1998 bp.
The nucleotide sequence disclosed herein for vc23_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc23_1 demonstrated at least some similarity with sequences identified as AA580484 (nn22a05.s 1 NCI CGAP_Co 12 Homo sapiens cDNA clone 2 5 IMAGE:1084592 similar to TR:G 1209718 G 1209718 HYPOTHETICAL 50.1 KD
PROTEIN, mRNA sequence), T25530 (Human gene signature HUMGS07700), U41293 (Saccharomyces cerevisiae putative serine/threonine protein kinase gene, putative ribosomal protein L25 gene, and malate dehydrogenase (MDH2) gene, complete cds), and 274866 (S.cerevisiae chromosome XV reading frame ORF YOL124c). The predicted 3 0 amino acid sequence disclosed herein for vc23_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc23_1 protein demonstrated at least some similarity to sequences identified as U41293 (unknown [Saccharomyces cerevisiae]) and 274866 (ORF YOL124c [Saccharo-myces cerevisiae]). Based upon sequence similarity, vc23_1 proteins and each similar protein or peptide may share at least some activity. The vc23_1 protein contains a "N-6 adenine-specific DNA methylases signature" motif. The TopPredII computer program predicts a potential transmembrane domain within the vc23_I protein sequence centered around amino acid 232 of SEQ ID N0:40.
vc23_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 51 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vc25 1"
A polynucleotide of the present invention has been identified as clone "vc25_1".
vc25_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc25_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc25_1 protein").
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:41, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:42. Amino acids 25 to 37 2 0 of SEQ ID N0:42 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 38. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc25_1 protein.
2 5 The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc25_1 should be approximately 1653 bp.
The nucleotide sequence disclosed herein for v~ 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc25_1 demonstrated at least some similarity with sequences 3 0 identified as N21690 (yx63h08.s1 Soares melanocyte 2NbHM Homo Sapiens cDNA
clone 266463 3', mRNA sequence) and T25257 (Human gene signature HUMGS07418). Based upon sequence similarity, vc25_1 proteins and each similar protein or peptide may share at least some activity.
vc25_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 15 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vc26 1"
A polynucleotide of the present invention has been identified as clone "vc26_1".
vc26_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc26_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc26_1 protein").
The nucleotide sequence of vc26_1 as presently determined is reported in SEQ
ID
N0:43, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc26_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:44. Amino acids 11 to 23 of SEQ ID N0:44 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc26_1 protein.
2 0 If the "G" residue at position 669 of SEQ ID N0:43 were deleted to create a frameshft, another potential vc26_1 reading frame and predicted amino acid sequence could be encoded by what would then be basepairs 87 to 992 of the deletion-containing version of SEQ ID N0:43. This potential vc26_1 reading frame and predicted amino acid sequence is reported in SEQ ID N0:103. Amino acids 11 to 23 of both SEQ ID
N0:44 and 2 5 SEQ ID N0:103 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc26_1 should be approximately 1982 bp.
The nucleotide sequence disclosed herein for vc26_1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc26_1 demonstrated at least some similarity with sequences identified as AA877534 (nrO1g08.s 1 NCI CGAP_Co 10 Homo sapiens cDNA clone IMAGE:1160606 3', mRNA sequence) and T25645 (Human gene signature HUMGS07835). The predicted vc26_1 protein of SEQ ID NO:10 contains an immuno-globulins and major histocompatibility complex proteins signature at amino acid 131.
Based upon sequence similarity, vc26_1 proteins and each similar protein or peptide may share at least some activity. The TopPredlI computer program predicts seven additional potential transmembrane domains within the vc26_1 protein sequence, centered around amino acids 60,100,120,160, 210, 250, and 290 of SEQ ID N0:44, respectively.
Clone"vc30 1"
A polynucleotide of the present invention has been identified as clone "vc30_1".
vc30_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc30_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc30_1 protein").
The nucleotide sequence of vc30_l as presently determined is reported in SEQ
ID
N0:45, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc30_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:46. Amino acids 19 to 31 of SEQ ID N0:46 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vc30_1 protein.
If a frameshift were introduced in the nucleotide sequence of SEQ ID N0:45 by deleting the cytosine residue at position 1393, another potential vc30_1 reading frame and predicted amino acid sequence could be encoded by what would then be basepairs 2 5 to 1659 of SEQ ID N0:45 and is reported in SEQ ID N0:104.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc30_1 should be approximately 1887 bp.
The nucleotide sequence disclosed herein for vc30_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and 3 0 FASTA search protocols. vc30_1 demonstrated at least some similarity with sequences identified as AA496421 (zv37c04.r1 Soares ovary tumor NbHOT Homo sapiens cDNA
clone 755814 5', mRNA sequence). The predicted amino acid sequence disclosed herein for vc30_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc30_l protein demonstrated at least some similarity to sequences identified as AF047760 (phosphatidic acid phosphohydrolase type 2c [Homo sapiens]). Based upon sequence similarity, vc3a_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII
computer program predicts an additional potential transmembrane domain within the vc30_1 protein sequence centered around amino acid 55 of SEQ ID N0:46.
Clone "vdl 1"
A polynucleotide of the present invention has been identified as clone "vd1 1".
vdl 1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vdl_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vdl 1 protein").
The nucleotide sequence of vdl_1 as presently determined is reported in SEQ ID
N0:47, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd1 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:48. Amino acids 8 to 20 of SEQ ID N0:48 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vd1_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vd1 1 should be approximately 2000 bp.
The nucleotide sequence disclosed herein for vdl 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vdl_1 demonstrated at least some similarity with sequences identified as AA582963 (nn72e02.s1 NCI_CGAP_Larl Homo sapiens cDNA clone IMAGE
1089434) and AC002389 (Human DNA from chromosome 19 specific cosmid 828461, genomic sequence, complete sequence). Based upon sequence similarity, vdl 1 proteins 3 0 and each similar protein or peptide may share at least some activity.
There is an 18-residue amino acid stretch (with an approximate consensus sequence shown in SEQ ID
N0:105 {HHAAGQAGNEAGRFGQG~) that is almost tandemly repeated 25 times in the vd1 1 protein. Nucleotides 406-1668 of SEQ ID N0:47, which encode a region of SEQ ID
WO 99/SS'I21 PCT/US99/08504 N0:48 that includes the 18-residue amino acid repeats, may represent an alternatively spliced region in mRNA molecules transcribed from the vdl 1 gene.
vdl_protein was expressed in a COS cell expression system, and an expressed protein band of approximately 55 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vd2 1"
A polynucleotide of the present invention has been identified as clone "vd2_1".
vd2_1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vd2_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vd2_1 protein') The nucleotide sequence of vd2_1 as presently determined is reported in SEQ ID
N0:49, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd2_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:50. Amino acids 2 to 14 of SEQ ID N0:50 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vd2_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing done vd2_1 should be approximately 900 bp.
The nucleotide sequence disclosed herein for vd2_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vd2_1 demonstrated at least some similarity with sequences identified as H03945 (yj44c02.s1 Homo sapiens cDNA clone 151586 3'). Based upon sequence similarity, vd2_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane 3 0 domain within the vd2_1 protein sequence centered around amino acid 115 of SEQ ID
N0:50.
Clone "vd3 1"
A polynudeotide of the present invention has been identified as clone "vd3_1".
vd3_1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vd3_1 is a full-length done, including the entire coding sequence of a secreted protein (also referred to herein as "vd3_1 protein').
The nucleotide sequence of vd3_1 as presently determined is reported in SEQ ID
N0:51, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd3_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:52. Amino acids 5 to 17 of SEQ ID N0:52 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vd3_1 protein.
If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:19 by inserting an adenine or thymine residue at position 1132 or 1133, another potential vd3_1 reading frame and predicted amino acid sequence could be encoded by basepairs 176 to 1281 of SEQ ID N0:51 and is reported in SEQ ID N0:106. Amino acids 5 to 17 of SEQID
2 0 N0:106 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18 of SEQ ID N0:106, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing done vd3_1 should be approximately 1537 bp.
The nucleotide sequence disclosed herein for vd3_1 was searched against the 2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vd3_1 demonstrated at least some similarity with sequences identified as AA873028 (ob11e05.s1 NCI CGAP_Kid3 Homo sapiens cDNA clone IMAGE 1323392 3', mRNA sequence), AC002389 (Human DNA from chromosome 19 specific cosmid 828461, genomic sequence, complete sequence), and AD001502 (Homo 3 0 sapiens DNA from chromosome 19-cosmid (21246, genomic sequence). Based upon sequence similarity, vd3_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts an additional possible transmembrane domain within the vd3_1 protein sequence centered around amino acid 290 of SEQ ID N0:52. The vd3_1 protein is apparently a splice variant of the vd4 1 protein described below.
vd3_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 42 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vd4 1"
A polynucleotide of the present invention has been identified as clone "vd4_1".
vd4_1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vd4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vd4_1 protein").
The nucleotide sequence of vd4_1 as presently determined is reported in SEQ ID
N0:53, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:54. Amino acids 5 to 17 of SEQ ID N0:54 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vd4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vd4_1 should be approximately 1897 bp.
The nucleotide sequence disclosed herein for vd4 1 was searched against the 2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vd4_2 demonstrated at least some similarity with sequences identified as AA706316 (ah28e1l.sl Soares parathyroid tumor NbHPA Homo sapiens cDNA clone 1240172 3', mRNA sequence), AC002389 (Human DNA from chromosome 19 specific cosmid 828461, genomic sequence, complete sequence), and AD001502 3 0 (Homo sapiens DNA from chromosome 19-cosmid f21246, genomic sequence).
Based upon sequence similarity, vd4_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts an additional possible transmembrane domain within the vd4_1 protein sequence centered around amino acid 290 of SEQ ID N0:54. The vd4_1 protein is apparently a splice variant of the vd3_1 protein described above.
vd4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 54 kDa was detected in conditioned medium using SDS
polyacxylamide gel electrophoresis.
Clone "ve4 1"
A polynucleotide of the present invention has been identified as clone "ve4_1".
ve4_1 was isolated from a human adult brain (Alzheimer s hippocampus level 7) cDNA
library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. ve4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "ve4_1 protein").
The nucleotide sequence of ve4_1 as presently determined is reported in SEQ ID
N0:55, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the ve4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:56. Amino acids 25 to 37 of SEQ ID N0:56 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 38. Due to the hydrophobic nature of the 2 0 predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the ve4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone ve4_1 should be approximately 1578 bp.
2 5 The nucleotide sequence disclosed herein for ve4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. ve4_1 demonstrated at least some similarity with sequences identified as AA707153 (zj33f10.s1 Soares fetal liver spleen 1NFT.S S1 Homo sapiens cDNA clone 452107 3' similar to TR P70295 P70295 AUP1 PRECURSOR, mRNA
3 0 sequence} and U41736 (Mus musculus ancient ubiquitous 46 kDa protein AUP1 precursor (Aup 1 ) mRNA, complete cds). The predicted amino acid sequence disclosed herein for ve4_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted ve4_1 protein demonstrated at least some similarity to the sequence identified as U41736 (ancient ubiquitous 46 kDa protein AUP46 precursor [Mus musculus]). Based upon sequence similarity, ve4_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts two additional potential transmembrane domains within the ve4_ 1 protein sequence, one centered around amino acid 110 and another around amino acid 210 of SEQ m N0:56.
ve4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 41 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "ve8 1"
A polynucleotide of the present invention has been identified as clone "ve8_1".
ve8_1 was isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA
library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. ve8_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "ve8_1 protein").
The nucleoside sequence of ve8_i as presently determined is reported in SEQ ID
N0:57, and includes a poly(A) tail. What applicants presently believe to be the proper 2 0 reading frame and the predicted amino acid sequence of the ve8_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:58. Amino acids 18 to 30 of SEQ ID N0:58 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 31. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 5 the predicted leader/signal sequence not be separated from the remainder of the ve8_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone ve8_1 should be approximately 2093 bp.
The nucleotide sequence disclosed herein for ve8_1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. ve8_1 demonstrated at least some similarity with sequences identified as AC004126 (Homo Sapiens Chromosome l 1q12 pac pDJ606g6; HTGS
phase 1, 17 unordered pieces). Based upon sequence similarity, ve8_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts four additional potential transmembrane domains within the ve8_1 protein sequence, centered around amino acids 94, 147, 150, and 193 of SEQ ID N0:58, respectively.
Clone "vf1 1"
A polynucleotide of the present invention has been identified as clone "vf1_1".
vfl 1 was isolated from a human adult heart cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vfl 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vf1_1 protein").
The nucleotide sequence of vfl 1 as presently determined is reported in SEQ ID
N0:59, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vf1 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:60. Amino acids 13 to 25 of SEQ ID N0:60 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vf1_1 2 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vfl 1 should be approximately 1382 bp.
The nucleotide sequence disclosed herein for vfl_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and 2 5 FASTA search protocols. vfl_1 demonstrated at least some similarity with sequences identified as AA349531 (EST56314 Infant brain Homo sapiens cDNA 5' end, mRNA
sequence) and AA532642 (nj17c07.s1 NCI_CGAP Pr22 Homo sapiens cDNA clone IMAGE 986604, mRNA sequence). Based upon sequence similarity, vfl 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer 3 0 program predicts an additional potential transmembrane domain within the vfl_1 protein sequence centered around amino acid 138 of SEQ ID N0:60.
vf1 1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 40 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vhl 1"
A polynucleotide of the present invention has been identified as clone "vhl 1".
vhl_1 was isolated from a human adult thymus cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vhl 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vhf 1 protein').
The nucleotide sequence of vh1_1 as presently determined is reported in SEQ ID
N0:61, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vhl_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:62. Amino acids 42 to 54 of SEQ ID N0:62 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 55. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vh1_1 protein.
2 0 Another potential vhl_1 reading frame and predicted amino acid sequence that could be encoded by basepairs 833 to 1054 of SEQ ID N0:61 is reported in SEQ
ID
N0:107. Amino aclds 22 to 34 of SEQ ID N0:107 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 35 of SEQ ID
N0:107, or are a transmembrane domain. If a frameshift were introduced into the 2 5 nucleotide sequence of SEQ ID N0:61 approximately between position 830 and position 998, the open reading frame of SEQ ID N0:62 could be joined to the open reading frame of SEQ ID N0:107.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vhl 1 should be approximately 1529 bp.
3 0 The nucleotide sequence disclosed herein for vhl 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vhl_1 demonstrated at least some similarity with sequences identified as AA927736 (om72h10.s1 NCI CGAP_GC4 Homo sapiens cDNA clone IMAGE:1552771 3', mRNA sequence). Based upon sequence similarity, vhf 1 proteins and each similar protein or peptide may share at least some activity.
Clone "vil 1"
A polynucleotide of the present invention has been identified as clone "vi1_1".
vi1_1 was isolated from a human adult aorta cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vil 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "viI 1 protein").
The nucleotide sequence of vi1_1 as presently determined is reported in SEQ ID
N0:63, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vi1 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:64. Amino acids 13 to 25 of SEQ ID N0:64 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vi1_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 2 0 vil 1 should be approximately 2348 bp.
The nucleotide sequence disclosed herein for vi1 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vil_1 demonstrated at least some similarity with sequences identified as AA411541 (zv30a03.r1 Soares ovary tumor NbHOT Homo sapiens cDNA
2 5 clone 755116 S' similar to WP:F07H5.1 I CE03160) and T21484 (Human gene signature HUMGS02856). The predicted amino acid sequence disclosed herein for vil_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted viI_1 protein demonstrated at least some similarity to the sequence identified as 268314 (F46C5.9 [Caenorhabditis elegans]). The 3 0 amino acid sequence of the predicted vil_1 protein indicates that it may contain a beta-transducin family Trp-Asp repeat signature (WD-40} motif centered around residue 300 of SEQ ID N0:28. The WD-40 motif is thought to be a widely distributed protein-protein interaction domain. Based upon sequence similarity, vil_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts two additional possible transmembrane domains within the vi 1_ 1 protein sequence, one centered around amino acid 200 and another around amino acid 340 of SEQ
m N0:64.
vi 1 _ 1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 45 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Deposit of Clones Clones vc3_l, vc4_l, v~ 1, vc7 1, vc9_1, vcl0_1, vcll 1, vcl4_1, vd1_l, and vd2_1 were deposited on April 24,1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98748, from which each clone comprising a particular polynucleotide is obtainable.
Clone vc21_1 was deposited on June 10, 1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and was given the accession number ATCC
98785, from which each clone comprising a particular polynucleotide is obtainable.
Clones vcl6_1, vcl7 1, v~ 1, vc25_1, vc26_1, ve4_l, and vfl 1 were deposited 2 0 on June 10,1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98784, from which each clone comprising a particular polynucleotide is obtainable.
Clones vb2_1, vb3_l, vb4_l, vb5_l, vb6_l, vb7_l, vb8_1, vb9_l, vc30_l, vd3_l, 2 5 vd4_l, ve8_l, vhl_l, and vil 1 were deposited on July 1,1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98804, from which each clone comprising a particular polynucleotide is obtainable.
All restrictions on the availability to the public of the deposited material will be 3 0 irrevocably removed upon the granting of the patent, except for the requirements specified in 37 C.F.R. ~ 1.808(b), and the term of the deposit will comply with 37 C.F.R.
~ 1.806.
Each clone has been transfected into separate bacterial cells (E. coli) in these composite deposits. Each clone can be removed from the vector in which it was deposited by performing an EcoRI/NotI digestion (5' site, EcoRI; 3' site, NotI) to produce the appropriate fragment for such clone. Each clone was deposited in either the pED6 or pNOTs vector depicted in Figures lA and 1B, respectively. The pED6dpc2 vector ("pED6") was derived from pED6dpc1 by insertion of a new polylinker to facilitate cDNA cloning (Kaufman et al.,1991, Nucleic Acids Res.19: 4485-4490); the pNOTs vector was derived from pMT2 (Kaufman et al.,1989, Mol. Cell. Biol. 9: 946-958) by deletion of the DHFR sequences, insertion of a new polylinker, and insertion of the M13 origin of replication in the CIaI site. In some instances, the deposited clone can become "flipped"
(i.e., in the reverse orientation) in the deposited isolate. In such instances, the cDNA insert can still be isolated by digestion with EcoRI and NotI. However, NotI will then produce the 5' site and EcoRI will produce the 3' site for placement of the cDNA in proper orientation for expression in a suitable vector. The cDNA may also be expressed from the vectors in which they were deposited.
Bacterial cells containing a particular clone can be obtained from the composite deposit as follows:
An oligonucleotide probe or probes should be designed to the sequence that is known for that particular clone. This sequence can be derived from the sequences 2 0 provided herein, or from a combination of those sequences. The sequence of an oligonucleotide probe that was used to isolate or to sequence each full-length clone is identified below, and should be most reliable in isolating the clone of interest.
Clone Probe uence 2 5 vb2_1 SEQ ID N0:65 vb3_i SEQ ID N0:66 vb4_1 SEQ ID N0:67 vb5_1 SEQ ID N0:68 vb6_1 SEQ ID N0:69 3 0 vb7_1 SEQ ID N0:70 vb8 1 SEQ ID N0:71 vb9_1 SEQ ID N0:72 vc3_1 SEQ ID N0:73 vc4_1 SEQ ID N0:74 vc5_1 SEQ ID N0:75 vc7 1 SEQ ID N0:76 vc9_1 SEQ ID N0:77 vcl0_1 SEQ ID N0:78 vcll_1 SEQ ID N0:79 vcl4_1 SEQ ID N0:80 vcl6_1 SEQ ID N0:81 vcl7_1 SEQ ID N0:82 vc21_1 SEQ ID N0:83 vc23_1 SEQ ID N0:84 vc25_1 SEQ ID N0:85 vc26_1 SEQ ID N0:86 vc30_1 SEQ ID N0:87 vd1 1 SEQ ID N0:88 vd2_1 SEQ ID N0:89 vd3_1 ~ SEQ ID N0:90 vd4_1 SEQ ID N0:91 ve4_1 SEQ ID N0:92 ve8_1 SEQ ID N0:93 2 0 vfl_1 SEQ ID N0:94 vhf 1 SEQ ID N0:95 vil_1 SEQ ID N0:96 In the sequences listed above which include an N at position 2, that position is occupied in preferred probes/primers by a biotinylated phosphoaramidite residue rather than a nucleotide (such as, for example, that produced by use of biotin phosphoramidite (1-dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-O-(2-cyanoethyl)-(N,N-diisopropyl)-phosphoramadite) (Glen Research, cat. no.10-1953)).
The design of the oligonucleotide probe should preferably follow these 3 0 parameters:
(a) It should be designed to an area of the sequence which has the fewest ambiguous bases ("N's"), if any;
(b) It should be designed to have a T," of approx. 80 ° C (assuming 2° for each A or T and 4 degrees for each G or C).
The oligonucleotide should preferably be labeled with y 32P ATP (specific activity 6000 Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for labeling oligonucleotides. Other labeling techniques can also be used.
Unincorporated label should preferably be removed by gel filtration chromatography or other established methods. The amount of radioactivity incorporated into the probe should be quantitated by measurement in a scintillation counter. Preferably, specific activity of the resulting probe should be approximately 4e+6 dpm/pmole.
The bacterial culture containing the pool of full-length clones should preferably be thawed and 100 lxl of the stock used to inoculate a sterile culture flask containing 25 ml of sterile L-broth containing ampicillin at 100 pg/ml. The culture should preferably be grown to saturation at 37°C, and the saturated culture should preferably be diluted in fresh L broth. Aliquots of these dilutions should preferably be plated to determine the dilution and volume which will yield approximately 5000 distinct and well-separated colonies on solid bacteriological media containing L-broth containing ampicillin at 100 ug/ml and agar at 1.5% in a 150 mm petri dish when grown overnight at 37°C. Other known methods of obtaining distinct, well-separated colonies can also be employed.
Standard colony hybridization procedures should then be used to transfer the colonies to nitrocellulose filters and lyse, denature and bake them.
The filter is then preferably incubated at 65°C for 1 hour with gentle agitation in 2 0 6X SSC (20X stock is 175.3 g NaCI/liter, 88.2 g Na citrate/liter, adjusted to pH 7.0 with NaOH) containing 0.5% SDS,100 pg/ml of yeast RNA, and 10 mM EDTA
(approximately 10 mL per 150 mm filter). Preferably, the probe is then added to the hybridization mix at a concentration greater than or equal to 1e+6 dpm/mL. The filter is then preferably incubated at 65°C with gentle agitation overnight. The filter is then preferably washed in 2 5 500 mL of 2X SSC/0.5% SDS at room temperature without agitation, preferably followed by 500 mL of 2X SSC/0.1% SDS at room temperature with gentle shaking for 15 minutes.
A third wash with O.1X SSC/0.5% SDS at 65°C for 30 minutes to 1 hour is optional. The filter is then preferably dried and subjected to autoradiography for sufficient time to visualize the positives on the X-ray film. Other known hybridization methods can also 3 0 be employed.
The positive colonies are picked, grown in culture, and plasmid DNA isolated using standard procedures. The clones can then be verified by restriction analysis, hybridization analysis, or DNA sequencing.
Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H.U. Saragovi, et al., Bio/Technology 1~,0 773-778 (1992) and in R.S.
McDowell, et al., J. Amer. Chem. Soc.114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may be fused to earner molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites. For example, fragments of the protein may be fused through "linker"
sequences to the Fc portion of an immunoglobulin. For a bivalent form of the protein, such a fusion could be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes may also be used to generate such fusions. For example, a protein - IgM fusion would generate a decavalent form of the protein of the invention.
The present invention also provides both full-length and mature forms of the disclosed proteins. The full-length form of the such proteins is identified in the sequence 25 listing by translation of the nucleotide sequence of each disclosed clone.
The mature forms) of such protein may be obtained by expression of the disclosed full-length polynucleotide (preferably those deposited with ATCC) in a suitable mammalian cell or other host cell. The sequences) of the mature forms) of the protein may also be determinable from the amino acid sequence of the full-length form.
2 0 The present invention also provides genes corresponding to the polynucleotide sequences disclosed herein. "Corresponding genes" are the regions of the genome that are transcribed to produce the mRNAs from which cDNA polynucleotide sequences are derived and may include contiguous regions of the genome necessary for the regulated expression of such genes. Corresponding genes may therefore include but are not limited 2 5 to coding sequences, 5' and 3' untranslated regions, alternatively spliced exons, introns, promoters, enhancers, and silencer or suppressor elements. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate 3 0 genomic libraries or other sources of genomic materials. An "isolated gene" is a gene that has been separated from the adjacent coding sequences, if any, present in the genome of the organism from which the gene was isolated.
The chromosomal location corresponding to the polynucleotide sequences disclosed herein may also be determined, for example by hybridizing appropriately labeled polynucleotides of the present invention to chromosomes in situ. It may also be possible to determine the corresponding chromosomal location for a disclosed polynucleotide by identifying significantly similar nucleotide sequences in public databases, such as expressed sequence tags (ESTs), that have already been mapped to particular chromosomal locations. For at least some of the polynucleotide sequences disclosed herein, public database sequences having at least some similarity to the polynucleotide of the present invention have been listed by database accession number.
Searches using the GenBank accession numbers of these public database sequences can then be performed at an Internet site provided by the National Center for Biotechnology Information having the address http://www.ncbi.nlin.nih.gov/UruGene/, in order to identify "UniGene clusters" of overlapping sequences. Many of the "UniGene clusters"
so identified will already have been mapped to particular chromosomal sites.
Organisms that have enhanced, reduced, or modified expression of the genes) corresponding to the polynucleotide sequences disclosed herein are provided.
The desired change in gene expression can be achieved through the use of antisense polynucleotides or ribozymes that bind and/or cleave the mItNA transcribed from the gene (Albert and Morris,1994, Trends Pharmacol. Sci.15(7): 250-254; Lavarosky et al.,1997, Biochem. Mol. Med. 62(1):11-22; and Hampel,1998, Prog. Nucleic Acid Res. Mol.
Biol. 58:1-39; all of which are incorporated by reference herein). Transgenic animals that have 2 0 multiple copies of the genes) corresponding to the polynucleotide sequences disclosed herein, preferably produced by transformation of cells with genetic constructs that are stably maintained within the transformed cells and their progeny, are provided.
Transgenic animals that have modified genetic control regions that increase or reduce gene expression levels, or that change temporal or spatial patterns of gene expression, are 2 5 also provided (see European Patent No. 0 649 464 Bl, incorporated by reference herein).
In addition, organisms are provided in which the genes) corresponding to the polynucleotide sequences disclosed herein have been partially or completely inactivated, through insertion of extraneous sequences into the corresponding genes) or through deletion of all or part of the corresponding gene(s). Partial or complete gene inactivation 3 0 can be accomplished through insertion, preferably followed by imprecise excision, of transposable elements (Plasterk,1992, Bioessays 14(9): 629-633; Zwaal et al.,1993, Proc. Natl.
Acad. Sci. USA 90(16): 7431-79:35; Clark et aL,1994, Proc. Natl. Acad. Sci.
LISA 91(2): 719-722;
all of which are incorporated by reference herein), or through homologous recombination, preferably detected by positive/negative genetic selection strategies (Mansour et aL,1988, Nature 336: 348-352; U.S. Patent Nos. 5,464,764; 5,487,992; 5,627,059;
5,631,153; 5,614, 396;
5,616,491; and 5,679,523; all of which are incorporated by reference herein).
These organisms with altered gene expression are preferably eukaryotes and more preferably are mammals. Such organisms are useful for the development of non-human models for the study of disorders involving the corresponding gene(s), and for the development of assay systems for the identification of molecules that interact with the protein products) of the corresponding gene(s).
Where the protein of the present invention is membrane-bound (e.g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms, part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information.
For example, the TopPredII computer program can be used to predict the location of transmembrane domains in an amino and sequence, domains which are described by the location of the center of the transmsmbrane domain, with at least ten transmembrane amino acids on each side of the reported central residue(s).
Proteins and protein fragments of the present invention include proteins with amino acid sequence lengths that are at least 25%(more preferably at least 50%, and most 2 0 preferably at least 75%) of the length of a disclosed protein and have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90%
or 95%
identity) with that disclosed protein, where sequence identity is determined by comparing the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Also included in the present invention are 2 5 proteins and protein fragments that contain a segment preferably comprising 8 or more (more preferably 20 or more, most preferably 30 or more) contiguous amino acids that shares at least 75% sequence identity (more preferably, at least 85% identity;
most preferably at least 95% identity) with any such segment of any of the disclosed proteins.
In particular, sequence identity may be determined using WU-BLAST
3 0 (Washington University BLAST) version 2.0 software, which builds upon WU-BLAST
version 1.4, which in turn is based on the public domain NCBI-BLAST version 1.4 (Altschul and Gish, 1996, Local alignment statistics, Doolittle ed., Methods in Enzymology 266: 460-480; Altschul et al., 1990, Basic local alignment search tool, Journal of Molecular Biology 215: 403-410; Gish and States, 1993, Identification of protein coding regions by database similarity search, Nature Genetics 3: 266-272; Karlin and Altschul, 1993, Applications and statistics for multiple high-scoring segments in molecular sequences, Proc. Natl. Acad. Sci. USA 90: 5873-5877; all of which are incorporated by reference herein). WU-BLAST version 2.0 executable programs for several UNIX
platforms can be downloaded from ftp://blast.wustl.edu/blasdexecutables. The complete suite of search programs (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) is provided at that site, in addition to several support programs. WU-BLAST 2.0 is copyrighted and may not be sold or redistributed in any form or manner without the express written consent of the author; but the posted executables may otherwise be freely used for commercial, nonprofit, or academic purposes. In all search programs in the suite -- BLASTP, BLASTN, BLASTX, TBLASTN and TBLASTX -- the gapped alignment routines are integral to the database search itself, and thus yield much better sensitivity and selectivity while producing the more easily interpreted output. Gapping can optionally be turned off in all of these programs, if desired. The default penalty (Q) for a gap of length one is Q=9 for proteins and BLASTP, and Q=10 for BLASTN, but may be changed to any integer value including zero, one through eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. The default per-residue penalty for extending a gap (R) is R=2 for proteins and BLASTP, and R=10 for BLASTN, 2 0 but may be changed to any integer value including zero, one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. Any combination of values for Q and R can be used in order to align sequences so as to maximize overlap and identity while minimizing sequence gaps.
The default amino acid comparison matrix is BLOSUM62, but other amino acid 2 5 comparison matrices such as PAM can be utilized.
Species homologues of the disclosed polynucleotides and proteins are also provided by the present invention. As used herein, a "species homologue" is a protein or polynucleotide with a different species of origin from that of a given protein or polynucleotide, but with significant sequence similarity to the given protein or 3 0 polynucleotide. Preferably, polynucleotide species homologues have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90%
identity) with the given polynucleotide, and protein species homologues have at least 30%
sequence identity (more preferably, at least 45% identity; most preferably at least 60%
identity) with the given protein, where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides or the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps.
Species homologues may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species. Preferably, species homologues are those isolated from mammalian species. Most preferably, species homologues are those isolated from certain mammalian species such as, for example, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, HyIobates concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus aethiops, Cebus capucinus, Aotus trivirgatus, Sanguinus Oedipus, Microcebus murinus, Mus musculus, Rattus norvegicus, Cricetulus griseus, Fells catus, Mustela vison, Canis familiaris, Oryctolagus cuniculus, Bos taurus, Ovis aries, Sus scrofa, and Eguus caballus, for which genetic maps have been created allowing the identification of syntenic relationships between the genomic organization of genes in one species and the genomic organization of the related genes in another species (O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al., 1993, Nature Genetics 3:103-112; Johansson et al.,1995, Genomics 25: 682-690; Lyons et al.,1997, Nature Genetics 15: 47 56; O'Brien et al.,1997, Trends in Genetics 13(10): 393-399;
Carver and Stubbs, 1997, Genome Research 7:1123-1137; all of which are incorporated by reference herein).
2 0 The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms of the isolated polynucleotides which also encode proteins which are identical or have significantly similar sequences to those encoded by the disclosed polynucleotides. Preferably, allelic variants have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90%
2 5 identity) with the given polynucleotide, where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides when aligned so as to maximize overlap and identity while minimizing sequence gaps. Allelic variants may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from individuals of the appropriate species.
3 0 The invention also includes polynucleotides with sequences complementary to those of the polynucleotides disclosed herein.
The present invention also includes polynucleotides that hybridize under reduced stringency conditions, more preferably stringent conditions, and most preferably highly stringent conditions, to polynucleotides described herein. Examples of stringency conditions are shown in the table below: highly stringent conditions are those that are at least as stringent as, for example, conditions A-F; stringent conditions are at least as stringent as, for example, conditions G-L; and reduced stringency conditions are at least as stringent as, for example, conditions M-R.
StringencyPolynucleotideHybrid Hybridization TemperatureWash ConditionHybrid Length and Temperature (bp)= Buffer' and Buffers A DNA:DNA 2 50 65C; lxSSC -or- 65C; 0.3xSSC
42C; lxSSC, 50% formamide B DNA:DNA <50 TB*; lxSSC TB*; lxSSC
C DNA:RNA 2 50 67C; lxSSC -or- 67C; 0.3xSSC
45C; lxSSC, 50% formamide D DNA:RNA <50 Tp*; lxSSC Tp*; lxSSC
E RNA:RNA 2 50 70C; lxSSC -or- 70C; 0.3xSSC
50C; lxSSC, 50% formamide F RNA:RNA <50 TF*; lxSSC TF*; lxSSC
G DNA:DNA 2 50 65C; 4xSSC -or- 65C; lxSSC
42C; 4xSSC, 50% formamide H DNA:DNA <50 TH*; 4xSSC TH*; 4xSSC
I DNA:RNA x 50 67C; 4xSSC -or- 67C; lxSSC
45C; 4xSSC, 50% formamide J DNA:RNA <50 TJ*; 4xSSC T~*; 4xSSC
K RNA:RNA 2 50 70C; 4xSSC -or- 67C; lxSSC
50C; 4xSSC, 50% formamide L RNA:RNA <50 T,,*; 2xSSC T~*; 2xSSC
2 M DNA:DNA 2 50 SOC; 4xSSC -or- 50C; 2xSSC
0 40C; 6xSSC, 50% formamide N DNA:DNA <50 TN*; 6xSSC T~,*; 6xSSC
O DNA:RNA 2 50 55C; 4xSSC -or- 55C; 2xSSC
42C; 6xSSC, 50% formamide P DNA:RNA <50 TP*; 6xSSC Tp*; 6xSSC
Q RNA:RNA 2 50 60C; 4xSSC -or- 60C; 2xSSC
45C; 6xSSC, SO~o formamide 2 R RNA:RNA <50 TR*; 4xSSC TR*; 4xSSC
t: The hybrid length is that anticipated for the hybridized regions) of the hybridizing polynucleotides. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is assumed to be that of the hybridizing polynucleotide. When polynucleotides of known sequence are hybridized, the 3 0 hybrid length can be determined by aligning the sequences of the polynudeotides and identifying the region or regions of optimal sequence complementarity.
t: SSPE (lxSSPE is 0.15M NaCI, lOmM NaHiPO,, and 1.25mM EDTA, pH 7.4) can be substituted for SSC
(lxSSC is 0.15M NaCI and l5mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes after hybridization is complete.
"TB - TR: The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10°C less than the melting temperature (Tm) of the hybrid, where Tm is determined according to the following equations. For hybrids less than 18 base pairs in length, T°,(°C) = 2(# of A + T bases) + 4(# of G +
C bases). For hybrids between 18 and 49 base pairs in length, T,°(°C) = 81.5 + 16.6(log,o[Na*]) + 0.41(%G+C) (600/N), where N is the number of bases in the hybrid, and [Na*] is the concentration of sodium ions in the hybridization buffer ([Na*] for lxSSC = 0.165 M).
Additional examples of stringency conditions for polynucleotide hybridization are provided in Sambrook, J., E.F. Fritsch, and T. Maniatis, 1989, Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, chapters 9 and 11, and Current Protocols in Molecular Biology,1995, F.M.
Ausubel et al., eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, incorporated herein by reference.
Preferably, each such hybridizing polynucleotide has a length that is at least 25%(more preferably at least 50%, and most preferably at least 75%) of the length of the polynucleotide of the present invention to which it hybridizes, and has at least 60%
sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 2 0 95% identity) with the polynucleotide of the present invention to which it hybridizes, where sequence identity is determined by comparing the sequences of the hybridizing polynucleotides when aligned so as to maximize overlap and identity while minimizing sequence gaps.
The isolated polynucleotide of the invention may be operably linked to an 2 5 expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufman et aL, Nucleic Acids Res. ~ 4485-4490 (1991), in order to produce the protein recombinantly. Many suitable expression control sequences are known in the art. General methods of expressing recombinant proteins are also known and are exemplified in R.
Kaufman, Methods in Enzymology ~, 537-566 (1990). As defined herein "operably 3 0 linked" means that the isolated polynucleotide of the invention and an expression control sequence are situated within a vector or cell in such a way that the protein is expressed by a host cell which has been transformed (transfected) with the ligated polynucleotide/expression control sequence.
A number of types of cells may act as suitable host cells for expression of the 3 5 protein. Mammalian host cells include, for example, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Co1o205 cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid cells, cell strains derived from in yitro culture of primary tissue, primary explants, HeLa cells, mouse L cells, BHK, HL-60, U937, HaK or jurkat cells.
Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or in prokaryotes such as bacteria. Potentially suitable yeast strains include Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains, Canriida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium, or any bacterial strain capable of expressing heterologous proteins. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation of the appropriate sites, in order to obtain the functional protein. Such covalent attachments may be accomplished using known chemical or enzymatic methods.
The protein may also be produced by operably linking the isolated polynucleotide of the invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system. Materials and methods for baculovirus/insect cell expression systems are commercially available in kit form from, e.g., Invitrogen, San Diego, California, U.S.A. (the MaxBac~ kit), and such methods are well known in the art, as described in Summers and Smith, Texas Aericultural Experiment Station Bulletin No. 1555 (1987), incorporated herein by reference. As used herein, an 2 0 insect cell capable of expressing a polynucleotide of the present invention is "transformed."
The protein of the invention may be prepared by culturing transformed host cells under culture conditions suitable to express the recombinant protein. The resulting expressed protein may then be purified from such culture (i.e., from culture medium or 2 5 cell extracts) using known purification processes, such as gel filtration and ion exchange chromatography. The purification of the protein may also include an affinity column containing agents which will bind to the protein; one or more column steps over such affinity resins as concanavalin A-agarose, heparin-toyopearl~ or Cibacrom blue Sepharose~; one or more steps involving hydrophobic interaction chromatography using 3 0 such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffiruty chromatography.
Alternatively, the protein of the invention may also be expressed in a form which will facilitate purification. For example, it may be expressed as a fusion protein, such as those of maltose binding protein (MBP), glutathione-S-transferase (GST) or thioredoxin (TR7~. Kits for expression and purification of such fusion proteins are commercially available from New England BioLabs (Beverly, MA), Pharmacia (Piscataway, Nj) and Invitrogen Corporation (Carlsbad, CA), respectively. The protein can also be tagged with an epitope and subsequently purified by using a specific antibody directed to such epitope. One such epitope ("Flag") is commercially available from the Eastman Kodak Company (New Haven, CT).
Finally, one or more reverse-phase high performance liquid chromatography (lZl'-HPLC) steps employing hydrophobic 1ZP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify the protein. Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined in accordance with the present invention as an "isolated protein."
The protein of the invention may also be expressed as a product of transgeruc animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or sheep which are characterized by somatic or germ cells containing a nucleotide sequence encoding the protein.
The protein may also be produced by known conventional chemical synthesis.
Methods for constructing the proteins of the present invention by synthetic means are 2 0 known to those skilled in the art. The synthetically-constructed protein sequences, by virtue of sharing primary, secondary or tertiary structural and/or conformational characteristics with proteins may possess biological properties in common therewith, including protein activity. Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic 2 5 compounds and in immunological processes for the development of antibodies.
The proteins provided herein also include proteins characterized by amino acid sequences similar to those of purified proteins but into which modification are naturally provided or deliberately engineered. For example, modifications in the peptide or DNA
sequences can be made by those skilled in the art using known techniques.
Modifications 3 0 of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence.
For example, one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S. Patent No. 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein.
Other fragments and derivatives of the sequences of proteins which would be expected to retain protein activity in whole or in part and may thus be useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are believed to be encompassed by the presentinvention.
USES AND BIOLOGICAL ACTIVITY
The polynucleotides and proteins of the present invention are expected to exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA).
Research Uses and Utilities The polynucleotides provided by the present invention can be used by the research community for various purposes. The polynucleotides can be used to express 2 0 recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare 2 5 with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to "subtract-out"
known sequences in the process of discovering other novel polynucleotides; for selecting and making oligomers for attachment to a "gene chip" or other support, including for 3 0 examination of expression patterns; to raise anti-protein antibodies using DNA
immunization techniques; and as an antigen to raise anti-DNA antibodies or elicit another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction}, the polynucleotide can also be used in interaction trap assays (such as, for example, those described in Gyuris et al.,1993, Cell 75: 791-803 and in Rossi et al.,1997, Proc. Natl. Acad.
Sci. USA 94: 8405-8410, all of which are incorporated by reference herein) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction.
The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor} in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.
Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.
2 0 Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E.F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S.L. and A.R. ICimmel eds.,1987.
Nutritional Uses Polynucleotides and proteins of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a 3 0 source of carbohydrate. In such cases the protein or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured.
~,ytokine and Cell Proliferation/Differentiation Activity A protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor-dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a protein of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+ (preB M+), 2E8, RBS, DA1,123, T1165, HT2, CTLL2, TF 1, Mole and CMK.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986;
Bertagnolli et al., J. Lmmunol.145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., J. Immunol. 149:3778-3783,1992; Bowman et al., J.
2 0 Immunol. 152: 1756-1761,1994.
Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in:
Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a.
Coligan eds. Vol 1 pp. 3.12.1-3.12.14, john Wiley and Sons, Toronto. 1994; and 2 5 Measurement of mouse and human Interferon y, Schreiber, R.D. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons, Toronto.1994.
Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine lnterleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In Current 3 0 Protocols in Immunology. j.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983;
Measurement of mouse and human interleukin 6 - Nordan, R. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto.1991;
Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11- Bennett, F., Giannotti, J., Clark, S.C. and Turner, K. J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.15.1 john Wiley and Sons, Toronto.1991;
Measurement of mouse and human Interleukin 9 - Ciarletta, A., Giannotti, J., Clark, S.C.
and Turner, K.J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto.1991.
Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in:
Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans);
Weinberger et al., Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al., Eur. J.
Immun.
11:405-411,1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol.
140:508-5I2, 1988.
Immune Stimulating or Sup rn essin Activi , A protein of the present invention may also exhibit immune stimulating or 2 0 immune suppressing activity, including without limitation the activities for which assays are described herein. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SCID)), e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations.
These immune 2 5 deficiencies may be genetic or be caused by viral (e.g., HIV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, herpesviruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections 3 0 such as candidiasis. Of course, in this regard, a protein of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer.
Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease.
Such a protein of the present invention may also to be useful in the treatment of allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein of the present invention.
Using the proteins of the invention it may also be possible to regulate immune responses in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both.
Immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent.
Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the 2 0 absence of the tolerizing agent.
Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as , for example, B~), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, 2 5 blockage of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a soluble, 3 0 monomeric form of a peptide having B7-2 activity alone or in conjunction with a monomeric form of a peptide having an activity of another B lymphocyte antigen (e.g., B7-1, B7-3) or blocking antibody), prior to transplantation can lead to the binding of the molecule to the natural ligand(s) on the immune cells without transmitting the corresponding costimulatory signal. Blocking B lymphocyte antigen function in this matter prevents cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, the lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens.
The efficacy of particular blocking reagents in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et aL, Proc. Natl. Acad.
Sci USA, 89:11102-11105 (1992). In addition, marine models of GVI-iD {see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of blocking B lymphocyte antigen function in vivo on the development of that disease.
Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate 2 0 activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases.
Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms.
Administration of reagents which block costimulation of T cells by disrupting receptor:ligand interactions of B lymphocyte antigens can be used to inhibit T
cell 2 5 activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of 3 0 human autoimmune diseases. Examples include marine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/Ipr/lpr mice or NZB hybrid mice, marine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB
rats, and marine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York,1989, pp. 840-856).
Upregulation of an antigen function (preferably a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy.
Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response through stimulating B lymphocyte antigen function may be useful in cases of viral infection. In addition, systemic viral diseases such as influenza, the common cold, and encephalitis might be alleviated by the administration of stimulatory forms of B
lymphocyte antigens systemically.
Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducing the in vitro activated T cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a castimulatory signal to, and thereby activate, T cells in vivo.
In another application, up regulation or enhancement of antigen function 2 0 (preferably B lymphocyte antigen function) may be useful in the induction of tumor immunity. Tumor cells (e.g., sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, carcinoma) transfected with a nucleic acid encoding at least one peptide of the present invention can be administered to a subject to overcome tumor-specific tolerance in the subject. If desired, the tumor cell can be transfected to express a combination of peptides.
2 5 For example, tumor cells obtained from a patient can be transfected ex vivo with an expression vector directing the expression of a peptide having B7-2-like activity alone, or in conjunction with a peptide having B71-like activity and/or B7-3-like activity. The transfected tumor cells are returned to the patient to result in expression of the peptides on the surface of the transfected cell. Alternatively, gene therapy techniques can be used 3 0 to target a tumor cell for transfection in vivo.
The presence of the peptide of the present invention having the activity of a B
lymphocyte antigens) on the surface of the tumor cell provides the necessary costimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells. In addition, tumor cells which lack MHC class I or MHC class II
molecules, or which fail to reexpress sufficient amounts of MHC class I or MHC
class II
molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytoplasmic-domain truncated portion) of an MHC class I a chain protein and (32 microglobulin protein or an MHC class II a chain protein and an MHC class II
~i chain protein to thereby express MHC class I or MHC class II proteins on the cell surface.
Expression of the appropriate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3} induces a T
cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E.
Coligan, A.M.
ICruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates 2 0 and Wiley-lnterscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl.
Acad. Sci.
USA 78:2488-2492,1981; Herrmann et al., J. Immunol.128:1968-1974,1982; Handa et al., J. Immunol.135:1564-1572,1985; Takai et al., J. Immunol.137:3494-3500,1986;
Takai et al., J. Immunol.140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA
78:2488-2492, 2 5 1981; Herrmann et al., J. l:mmunol. 128:1968-1974, 1982; Handa et al., J.
l:mmunol.
235:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet al., J.
Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988;
Bertagnolli et al., Cellular Immunology 133:327-341,1991; Brown et al., J. Immunol.153:3079-3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching 3 0 (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl /Th2 profiles) include, without limitation, those described in: Maliszewski, J. Immunol.144:3028-3033,1990; and Assays for B cell function: In vitro antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto.1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M.
Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., j. Immunol.137:3494-3500,1986; Takai et al., J. Immunol.140:508-512, 1988; Bertagnolli et al., j. Immunol.149:3778-3783,1992.
Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., journal of Immunology 154:5071-5079,1995; Porgador et al., Journal of Experimental Medicine 182:255-260,1995;
Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264,1989;
Bhardwaj et al., Journal of Clinical Investigation 94:797 807, 1994; and Inaba et al., journal of Experimental Medicine 172:631-640,1990.
Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in:
Darzynkiewicz 2 0 et al., Cytometry 13:795-808,1992; Gorczyca et al., Leukemia 7:659-670,1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991;
Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993;
Gorczyca et al., International Journal of Oncology 1:639-648,1992.
Assays for proteins that influence early steps of T-cell commitment and 2 5 development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122,1994; Galy et al., Blood 85:2770-2778,1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551,1991.
Hematopoiesis Re atin A ' i , 3 0 A protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies.
Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction with irradiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF
activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferatian of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal ~
cells or genetically manipulated for gene therapy.
The activity of a protein of the invention may, among other means, be measured by the following methods:
2 0 Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.
Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 2995; Kelley et 2 5 al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915,1993.
Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those described in: Methylcellulose colony forming assays, Freshney, M.G. In Culture of 3 0 Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, NY. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992;
Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, LK. and Briddell, R.A. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds.
Vol pp. 23-39, Wiley-Liss, Inc., New York, NY.1994; Neben et al., Experimental Hematology 22:353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. l-21, Wiley-Liss, Inc.., New York, NY.1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, NY.1994; Long term culture initiating cell assay, Sutherland, H.J. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp.139-162, Wiley-Liss, Inc., New York, NY.1994.
Tissue Growth Activit3r A protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and in the treatment of burns, incisions and ulcers.
A protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals.
Such a preparation employing a protein of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De rcovo bone formation induced by an osteogenic agent contributes to the repair of 2 0 congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery.
A protein of this invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone-forming cells, stimulate growth of bone-forming cells or induce 2 5 differentiation of progenitors of bone-forming cells. A protein of the invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes.
3 0 Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon/ligament formation. A protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide an environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendirutis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art.
The protein of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve 2 0 tissue. More specifically, a protein may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson s disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present 2 5 invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a protein of the invention.
Proteins of the invention may also be useful to promote better or faster closure of 3 0 non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.
It is expected that a protein of the present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring to allow normal tissue to regenerate. A protein of the invention may also exhibit angiogenic activity.
A protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.
A protein of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for tissue generation activity include, without limitation, those described in: International Patent Publication No. W095/16035 (bone, cartilage, tendon);
International Patent Publication No. W095/05846 (nerve, neuronal);
International Patent Publication No. W091/07491 (skin, endothelium ).
Assays for wound healing activity include, without limitation, those described in:
Winter, epidermal Wound Healing, pps. 71-112 (Maibach, HI and Rovee, DT, eds.), Year Book Medical Publishers, lnc., Chicago, as modified by Eaglstein and Mertz, J.
Invest.
2 0 Dermatol 71:382-84 (1978).
~ctivin/Inhibin Activity A protein of the present invention may also exhibit activin- or inhibin-related activities. Inhibins are characterized by their ability to inhibit the release of follicle 2 5 stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a protein of the present invention, alone or in heterodimers with a member of the inhibin a family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts 3 0 of other inhibins can induce infertility in these mammals. Alternatively, the protein of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin-~i group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary.
See, for example, United States Patent 4,798,885. A protein of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for activin/inhibin activity include, without limitation, those described in:
Vale et al., Endocrinology 91:562-572,1972; Ling et al., Nature 321:779-782,1986; Vale et al., Nature 321:776-779,1986; Mason et al., Nature 318:659-663,1985; Forage et al., Proc.
Natl. Acad. Sci. USA 83:3091-3095,1986.
Chemotactic/Chemokinetic Activit<r A protein of the present invention may have chemotactic or chemokinetic activity (e.g., act as a chemokine) for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells.
Chemotactic and chemokinetic proteins can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent.
2 0 A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known 2 5 assay for cell chemotaxis.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis) consist of assays that measure the ability of a protein to induce the migration 3 0 of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in: Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub.
Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376,1995; Lind et al.
APMIS 103:140-146,1995; Muller et al Eur. J. Immunol. 25:1744-1748; Gruber et al. J. of Immunol.152:5860-5867,1994; Johnston et al. J. of Immunol.153:1762-1768,1994.
Hemostatic and Thrombol3rtic Activ'~
A protein of the invention may also exhibit hemostatic or thrombolytic activity.
As a result, such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke).
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140,1986; Burdick et al., Thrombosis Res. 45:413-419,1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474,1988.
Rece~tor/Lig~nd Activit3~
A protein of the present invention may also demonstrate activity as receptors, receptor ligands or inhibitors or agonists of receptor/ligand interactions.
Examples of such receptors and ligands include, without limitation, cytokine receptors and their 2 5 ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selectins, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses). Receptors and ligands are also 3 0 useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.
WO 99/55721 PC"TNS99/08504 The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for receptor-ligand activity include without limitation those described in:Current Protocols in Immunology, Ed by J.E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987;
Bierer et al., J. Exp. Med.168:I145-1156, 1988; Rosenstein et al., J. Exp.
Med.169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68,1994; Stitt et al., Cell 80:661-670, 1995.
Anti-Inflammatory Act Proteins of the present invention may also exhibit anti-inflammatory activity.
The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Proteins exhibiting such ?ctivities can be used to treat 2 0 inflammatory conditions including chronic or acute conditions), including without limitation inflammation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting 2 5 from over production of cytokines such as TNF or IL-1. Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.
Cadherin/Tumor Invasion Suppressor Activit3r Cadherins are calcium-dependent adhesion molecules that appear to play major 3 0 roles during development, particularly in defining specific cell types.
Loss or alteration of normal cadherin expression can lead to changes in cell adhesion properties linked to tumor growth and metastasis. Cadherin malfunction is also implicated in other human diseases, such as pemphigus vulgaris and pemphigus foliaceus (auto-immune blistering skin diseases), Crohn's disease, and some developmental abnormalities.
The cadherin superfamily includes well over forty members, each with a distinct pattern of expression. All members of the superfamily have in common conserved extracellular repeats (cadherin domains), but structural differences are found in other parts of the molecule. The cadherin domains bind calcium to form their tertiary structure and thus calcium is required to mediate their adhesion. Only a few amino acids in the first cadherin domain provide the basis for homophilic adhesion; modification of this recognition site can change the specificity of a cadherin so that instead of recognizing only itself, the mutant molecule can now also bind to a different cadherin. In addition, some cadherins engage in heterophilic adhesion with other cadherins.
E-cadherin, one member of the cadherin superfamily, is expressed in epithelial cell types. Pathologically, if E-cadherin expression is lost in a tumor, the malignant cells become invasive and the cancer metastasizes. Transfection of cancer cell lines with polynucleotides expressing E-cadherin has reversed cancer-associated changes by returning altered cell shapes to normal, restoring cells' adhesiveness to each other and to their substrate, decreasing the cell growth rate, and drastically reducing anchorage-independent cell growth. Thus, reintroducing E-cadherin expression reverts carcinomas to a less advanced stage. It is likely that other cadherins have the same invasion suppressor role in carcinomas derived from other tissue types. Therefore, proteins of the present invention with cadherin activity, and polynucleotides of the present invention 2 0 encoding such proteins, can be used to treat cancer. Introducing such proteins or polynucleotides into cancer cells can reduce or eliminate the cancerous changes observed in these cells by providing normal cadherin expression.
Cancer cells have also been shown to express cadherins of a different tissue type than their origin, thus allowing these cells to invade and metastasize in a different tissue 2 5 in the body. Proteins of the present invention with cadherin activity, and polynucleotides of the present invention encoding such proteins, can be substituted in these cells for the inappropriately expressed cadherins, restoring normal cell adhesive properties and reducing or eliminating the tendency of the cells to metastasize.
Additionally, proteins of the present invention with cadherin activity, and 3 0 polynucleotides of the present invention encoding such proteins, can used to generate antibodies recognizing and binding to cadherins. Such antibodies can be used to block the adhesion of inappropriately expressed tumor-cell cadherins, preventing the cells from forming a tumor elsewhere. Such an anti-cadherin antibody can also be used as a marker for the grade, pathological type, and prognosis of a cancer, i.e. the more progressed the WO 99/55721 PCTlUS99/08504 cancer, the less cadherin expression there will be, and this decrease in cadherin expression can be detected by the use of a cadherin-binding antibody.
Fragments of proteins of the present invention with cadherin activity, preferably a polypeptide comprising a decapeptide of the cadherin recognition site, and poly-nucleotides of the present invention encoding such protein fragments, can also be used to block cadherin function by binding to cadherins and preventing them from binding in ways that produce undesirable effects. Additionally, fragments of proteins of the present invention with cadherin activity, preferably truncated soluble cadherin fragments which have been found to be stable in the circulation of cancer patients, and polynucleotides encoding such protein fragments, can be used to disturb proper cell-cell adhesion.
Assays for cadherin adhesive and invasive suppressor activity include, without limitation, those described in: Hortsch et al. J Biol Chem 270 (32): 18809-18817, 1995;
Miyaki et al. Oncogene 11: 2547-2552,1995; Ozawa et al. Cell 63: 1033-1038,1990.
Tumor Inhibition Activitar In addition to the activities described above for immunological treatment or prevention of tumors, a protein of the invention may exhibit other anti-tumor activities.
A protein may inhibit tumor growth directly or indirectly (such as, for example, via antibody-dependent cell-mediated cytotoxicity (ADCC)). A protein may exhibit its tumor 2 0 inhibitory activity by acting on tumor tissue or tumor precursor tissue, by inhibiting formation of tissues necessary to support tumor growth (such as, for example, by inhibiting angiogenesis), by causing production of other factors, agents or cell types which inhibit tumor growth, or by suppressing, eliminating or inhibiting factors, agents or cell types which promote tumor growth.
Other Activities A protein of the invention may also exhibit one or more of the following additional activities or effects: inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites; effecting 3 0 (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape); effecting biorhythms or caricadic cycles or rhythms;
effecting the fertility of male or female subjects; effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional factors or component(s);
effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects;
promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein.
ADMINISTRATION AND DOSING
A protein of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources) may be used in a pharmaceutical composition when combined with a pharmaceutically acceptable carrier.
Such a composition may also contain (in addition to protein and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term 2 0 "pharmaceutically acceptable" means a non toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration. The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, ILr6, ILr7, IIr8, ILr9, ILrlO, ILrl l, 2 5 IL-12, IL-13, IL-14, IL-15,1FN, TNFO, TNFl, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin. The pharmaceutical composition may further contain other agents which either enhance the activity of the protein or compliment its activity or use in treatment. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein of the invention, 3 0 or to minimize side effects. Conversely, protein of the present invention may be included in formulations of the particular cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent to minimize side effects of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent.
A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multimeric or complexed form.
The pharmaceutical composition of the invention may be in the form of a complex of the proteins) of present invention along with protein or peptide antigens.
The protein and/or peptide antigen will deliver a stimulatory signal to both B and T
lymphocytes. B
lymphocytes will respond to antigen through their surface immunoglobulin receptor. T
lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MI~iC and structurally related proteins including those encoded by class I and class II MHC genes on host cells will serve to present the peptide antigens) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunolgobulin and other molecules on B cells as well as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition of the invention.
The pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other 2 0 pharmaceutically acceptable earners, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the 2 5 art, as disclosed, for example, in U.S. Patent No. 4,235,871; U.S. Patent No. 4,501,728; U.S.
Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are incorporated herein by reference.
As used herein, the term "therapeutically effective amount" means the total amount of each active component of the pharmaceutical composition or method that is 3 0 sufficient to show a meaningful patient benefit, i.e., treatment, healing, prevention or amelioration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously.
In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein of the present invention is administered to a mammal having a condition to be treated. Protein of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors.
Administration of protein of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection.
2 0 Intravenous administration to the patient is preferred.
When a therapeutically effective amount of protein of the present invention is administered orally, protein of the present invention will be in the form of a tablet, capsule, powder, solution or elixir. When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as a gelatin or 2 5 an adjuvant. The tablet, capsule, and powder contain from about 5 to 95%
protein of the present invention, and preferably from about 25 to 90% protein of the present invention.
When administered in liquid form, a liquid carrier such as water, petroleum, oils of animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic ails may be added. The liquid form of the pharmaceutical composition may further contain 3 0 physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of protein of the present invention, and preferably from about 1 to 50% protein of the present invention.
When a therapeutically effective amount of protein of the present invention is administered by intravenous, cutaneous or subcutaneous injection; protein of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution.
The preparation of such parenterally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A
preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein of the present invention, an isotonic vehicle such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art.
The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art.
The amount of protein of the present invention in the pharmaceutical composition of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone.
Ultimately, the attending physician will decide the amount of protein of the present invention with which to treat each individual patient. Initially, the attending physician will administer low doses of protein of the present invention and observe the patient's response. Larger doses of protein of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not 2 0 increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 pg to about 100 mg (preferably about 0.lng to about 10 mg, more preferably about 0.1 ug to about 1 mg) of protein of the present invention per kg body weight.
The duration of intravenous therapy using the pharmaceutical composition of the 2 5 present invention will vary, depending on the severity of the disease being treated and the condition and potential idiosyncratic response of each individual patient.
It is contemplated that the duration of each application of the protein of the present invention will be in the range of 12 to 24 hours of continuous intravenous administration.
Ultimately the attending physician will decide on the appropriate duration of intravenous 3 0 therapy using the pharmaceutical composition of the present invention.
Protein of the invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protein. As used herein, the term "antibody" includes without limitation a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-grafted antibody, a humanized antibody, or fragments thereof which bind to the indicated protein.
Such term also includes any other species derived from an antibody or antibody sequence which is capable of binding the indicated protein.
Antibodies to a particular protein can be produced by methods well known to those skilled in the art. For example, monoclonal antibodies can be produced by generation of antibody-producing hybridomas in accordance with known methods (see for example, Goding, 1983, Monoclonal antibodies: principles and practice, Academic Press Inc., New York; and Yokoyama, 1992, "Production of Monoclonal Antibodies" in Current Protocols in Immunology, Unit 2.5, Greene Publishing Assoc. and John Wiley & Sons).
Polyclonal sera and antibodies can be produced by inoculation of a mammalian subject with the relevant protein or fragments thereof in accordance with known methods.
Fragments of antibodies, receptors, or other reactive peptides can be produced from the corresponding antibodies by cleavage of and collection of the desired fragments in accordance with known methods (see for example, Goding, supra; and Andrew et al., 1992, "Fragmentation of Immunoglobulins" in Current Protocols in Immunology, Unit 2.8, Greene Publishing Assoc. and John Wiley & Sons). Chimeric antibodies and single chain antibodies can also be produced in accordance with known recombinant methods (see for example, 5,169,939, 5,194,594, and 5,576,184). Humanized antibodies can also be made from corresponding marine antibodies in accordance with well known methods (see for example, U.S.
Patent 2 0 Nos. 5,530,101, 5,585,089, and 5,693,762). Additionally, human antibodies may be produced in non-human animals such as mice that have been genetically altered to express human antibody molecules (see for example Fishwild et al., 1996, Nature Biotechnology 14: 845-851; Mendez et al., 1997, Nature Genetics 15: 146-156 (erratum Nature Genetics 16: 410); and U.S. Patents 5,877,397 and 5,625,126). Such antibodies may be obtained 2 5 using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R.P.
Merrifield, J.
Amer.Chem.Soc. $5, 2149-2154 (1963); J.L. ICrstenansky, et al., FEBS Lett.
211,10 (198.
3 0 Monoclonal antibodies binding to the protein of the invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression of the protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein.
For compositions of the present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device.
When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. Therapeutically useful agents other than a protein of the invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods of the invention. Preferably for bone and/or cartilage formation, the composition would include a matrix capable of delivering the protein-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body.
2 0 Such matrices may be formed of materials presently in use for other implanted medical applications.
The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application of the compositions will define the appropriate formulation.
Potential 2 5 matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydrides. Other potential materials are biodegradable and biologically well-defined, such as bone or dermal collagen. Further matrices are comprised of pure proteins or extracellular matrix components. Other potential matrices are nonbiodegradable and 3 0 chemically defined, such as sintered hydroxapatite, bioglass, aluminates, or other ceramics. Matrices may be comprised of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tricalciumphosphate. The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability.
Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns.
In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix.
A preferred family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, and carboxymethylcellulose, the most preferred being cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, polyethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and polyvinyl alcohol). The amount of sequestering agent useful herein is 0.5-20 wt%, preferably 1-10 wt% based on total formulation weight, which represents the amount necessary to prevent desorbtion of the protein from the polymer matrix and to provide appropriate handling of the composition, yet not so much that the progenitor cells are prevented from infiltrating the matrix, thereby providing the protein the opportunity to assist the osteogenic activity of the progenitor cells.
2 0 In further compositions, proteins of the invention may be combined with other agents beneficial to the treatment of the bone and/or cartilage defect, wound, or tissue in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-a and TGR~3), and insulin-like growth factor (IGF).
2 5 The therapeutic compositions are also presently valuable for veterinary applications. Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins of the present invention.
The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering 3 0 various factors which modify the action of the proteins, e.g., amount of tissue weight desired to be formed, the site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition. For example, the addition of other known growth factors, such as IGF I (insulin like growth factor I}, to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue/bone growth and/or repair, for example, X-rays, histomorphometric determinations and tetracycline labeling.
Polynucleotides of the present invention can also be used for gene therapy.
Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynucleotides of the invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA).
Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells.
Treated cells can then be introduced in vivo for therapeutic purposes.
Patent and literature references cited herein are incorporated by reference as if fully set forth.
SEQUENCE LISTING
<110> Valenzuela, Dario Yuan, Olive Hoffman, Heidi Hall, Jeff Rapiejko, Peter AlphaGene, Inc.
<120> SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
<130> GI 6900X
<140>
<141>
<160> 107 <170> PatentIn Ver. 2.0 <210> 1 <211> 2201 <212> DNA
<213> Homo sapiens <400> 1 tccttcgcct cctgcacctt gggagccctg ggctactctt tcacggcccc tgttgccctg 60 tgatctgtag gtccttgggg acgcacagtt aaggtgccag gacatcctgg aagctgggaa 120 atgatatgta ttcatttcct accaccgtag tggaagagat actatcccta tctttacaac 180 tgatagcatt tccaacagta agctgtgaga ttctgcttga aatcacctct caaacaaata 240 aaaaacagac ccgggagaca tgctacgctc attctgctga agaaataggc atcatagctg 300 ggaaacggat tcacaagacc caggctgttc cctacatatg tttcctcctc cgacatcagt 360 tcatcagtca atcaagccat gtgagagtgg aggccttgta ttccctatta ttcttgggca 420 ctctactcca agtaggaaaa ggccaggagg tcctgttaaa ggatgcactc agagcccggg 480 ctccctaaca tatgagagtg ctaaccagca ggtgtagact tttcaggagt gaagaatgag 540 gcaggcattc caaacctgga ccttcatcac cttttgtttc atctcaagac aattctgagg 600 gactgttttg gagcgtgtct ggaaggtgaa ccttgaagaa gagtgtgggc tttgatgtga 660 ctcagttgag atctttcatg gggaggcagg aattcaatgc ccagaatctg ggctggtgtc 720 tttgaggtca gtaggttgcg tctttgtatc caagtccatt gttactaggt tggaggctgg 780 agattctaaa tggcttccag accatctctc tgattctctt tgggagatgg ggtctgaaag 840 acaatatcag tagttttggg aaattctaga aagtgtgctt ggaaacgtgg gaagagctct 900 tgcctagtgc ctaaatgctc catttgcagc tctagccaag tagatacttg gtaggtatag 960 agccgggttt gcgtttatat cagcaaaacc tatatcagag ttgaagaagt agtcaggaaa 1020 aagcgtcttg gtcgcaggcc ggggaacatc ttaaaagcaa acttctagcc tgctgactct 1080 tggcaatgag tgttggatcc tggctaaagt gccttgaatg cagcatgagg ccaatccatg 1140 aatccaactt ctcatggaga aatgttaata ttttttcagt ttgaatcaat cagggtgaaa 1200 ctaccatgct attggtttgc ttacttttta ttatttcatg taaaatctaa gacaaaatac 1260 attaaatgct tattgacata tgtatttatt cttcaccagg ctgataatat ctgcctaatt 1320 ttaaactttc ttccattttg taggtttcaa cttattctat tgtaagatac tgttaaatct 1380 aatagaggca ttgtcacttt tacgtataat tttattttat ttcatatatt tcctattggc 1440 tttttacatt taaattatgg agcacttcat catataaaaa acttcaatta tatttaaaca 1500 gtaagtcttt ggattttttt gccttgtaat ttccatatta cataataatg agataaacat 1560 taatgttttc agggtacttt aaattttaga taattactca ttgtattcat gtgaaatttg 1620 ttttactgc atgtgtgggt tggaggactg ttttcacttc tgattcatct ttactcttat 1680 ~ctcatcagag ctcatacctc ttgtagttgg gggattgcag tttataattc caataaatgg 1740 'ggcaaattca ataataacat aatacaaatg agtttgaatg caggacaggt cttcaaagca 1800 tacacaacat gggcctacat atgtacaaca ataataattt ataagttact gtttggatgg 1860 aaagtaaaag tacagaaaat ttgttaaagg aaattaaaat ggagatcatg tctcaataat 1920 ctctgagcag acaaaattag ttaggtctca taagtgatct caacctcgct tgatttgcaa 1980 atacaaacaa aacttacatt atttcttgta gctgcatatt gaaaaaagag aaatgaagct 2040 caaccagtca gaagtagcca acaaccttat ataaatagaa actgtccaac aaggtaaaca 2100 gacaaacaaa aaacaataaa aaaagttgtg ctaccaccaa aaaaaaaaaa aaaaaaaaaa 2160 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 2201 <210> 2 <211> 120 <212> PRT
<213> Homo sapiens <400> 2 Met Tyr Ser Phe Pro Thr Thr Val Val Glu Glu Ile Leu Ser Leu Ser Leu Gln Leu Ile Ala Phe Pro Thr Val Ser Cys Glu Ile Leu Leu Glu Ile Thr Ser Gln Thr Asn Lys Lys Gln Thr Arg Glu Thr Cys Tyr Ala His Ser Ala Glu Glu Ile Gly Ile Ile Ala Gly Lys Arg Ile His Lys Thr Gln Ala Val Pro Tyr Ile Cys Phe Leu Leu Arg His Gln Phe Ile Ser Gln Ser Ser His Val Arg Val Glu Ala Leu Tyr Ser Leu Leu Phe Leu Gly Thr Leu Leu Gln Val Gly Lys Gly Gln Glu Val Leu Leu Lys Asp Ala Leu Arg Ala Arg Ala Pro <210> 3 <211> 2498 <212> DNA
<213> Homo sapiens <400> 3 ggtcgtttgg atagtgatga acagaaaatt cagaatgata tcattgatat tttactgact 60 tttacacaag gagttaatga aaaactcaca atctcagaag agactctggc caataatact 120 tggtctttaa tgttaaaaga agttctttct tcaatcttga aggttcctga aggatttttt 180 tctggactca tactcctttc agagctgctg cctcttccat tgcccatgca aacaactcag 240 gttattgagc cacatgatat atcagtggca ctcaacaccc gaaaattgtg gagcatgcac 300 cttcatgttc aagcaaagtt gctccaagaa atagttcgct ctttctctgg cacaacctgc 360 cagcccattc aacatatgtt acggcgtatt tgtgttcaat tgtgtgacct tgcctcacca 420 actgcacttc tgattatgag aactgtgttg gatttgattg tagaagactt gcaaagcact 480 tcagaagata aagaaaaaca gtatactagc caaaccacca ggttgcttgc tcttcttgat 540 gctctggctt cacacaaagc ttgtaaatta gctattttgc atctaattaa tggaactatt 600 aaaggtgatg aaagatatgc agagatattc caggatcttt tagctttggt gcggtctcct 660 ggagacagtg ttattcgcca acagtgtgtt gaatatgtca catccatttt gcagtctctc 720 tgtgatcagg acattgcact tatcttacca agctcttctg aaggttctat ttctgaactg 780 gagcagctct ccaattctct accaaataaa gaattgatga cctcaatctg tgactgtctg 840 ttggctacgc tagctaactc tgagagcagt tacaactgtt tactgacatg tgtcagaaca 900 atgatgtttc ttgcagagca tgattatgga ttatttcatt taaaaagttc tttaaggaaa 960 aacagtagtg ctctgcatag tttactgaaa cgagtggtca gcacatttag taaggacaca 1020 ggagagcttg catcttcatt tttagaattt atgagacaaa ttcttaactc tgacacaatt 1080 ggatgctgtg gagatgataa tggtctcatg gaagtagagg gagctcatac atcacggacg 1140 atgagtatta atgctgcaga gttaaaacag cttctacaaa gcaaagaaga aagtccagaa 1200 aatttgttcc ttgaactaga gaagcttgtt ttggaacatt caaaagatga tgacaatctg 1260 gattctttgt tggacagtgt agttggactt aagcagatgc tggagtcatc aggtgaccct 1320 ttacctctca gtgaccagga tgtagaacca gtactttcag ctccagaatc tcttcagaat 1380 ctgtttaaca ataggactgc ctatgtgctt gctgatgtca tggatgatca gttgaaatct 1440 atgtggttca ctccatttca ggctgaagag atagatacag atctggattt ggtaaaggtt 1500 gacttaattg aactctctga aaaatgctgt agtgactttg atttgcactc agaattagag 1560 cgctcatttt tgtcagaacc atcatctcca ggaagaacca agactactaa aggattcaaa 1620 cttgggaagc acaagcatga gacctttata acgtcaagtg gaaaatctga atacattgaa 1680 cctgccaaaa gagctcatgt tgtgccacca ccaagaggaa ggggcagggg aggatttgga 1740 cagggtatac gacctcatga tatttttcgt cagagaaaac agaacacaag tagaccacca 1800 tctatgcatg tggatgactt tgttgctgct gaaagtaaag aagtggttcc tcaagatgga 1860 atacctccac caaaacggcc actcaaagca tcacagaaga tttcttcccg tggtgggttt 1920 tcaggcaata gaggaggacg gggtgctttc cacagtcaga ataggttttt cacaccacct 1980 gcttcaaaag gaaactacag tcgtcgggaa ggaacaagag gctccagttg gagtgctcag 2040 aatactcctc gaggaaatta caatgaaagt cgtggaggcc agagcaattt taacagaggc 2100 cctcttccac cattacgacc ccttagttct acaggttacc gcccaagtcc tcgggaccgt 2160 gcttctagag gtcgtggggg acttggacct tcctgggcta gtgcaaatag cggcagtgga 2220 ggctcaagag gaaagtttgt tagtggaggc agtggtagag gtcgtcatgt acgctccttt 2280 acacgataaa aatccttttg ggaacatctt aactgtatat gaacatttca cgaggacaat 2340 aaaaataaga cattgaagga ccaatttaga cttagcagtt atctggagac atctgagaga 2400 atatttttat ctgaagaaag cagaatttgt ttgataccta acaagatttc aataaaaatc 2460 caaactttgt atgtaaaaaa aaaaaaaaaa aaaaaaaa 2498 <210> 4 <211> 719 <212> PRT
<213> Homo sapiens <400> 4 Met Leu Lys Glu Val Leu Ser Ser Ile Leu Lys Val Pro Glu Gly Phe Phe Ser Gly Leu Ile Leu Leu Ser Glu Leu Leu Pro Leu Pro Leu Pro Met Gln Thr Thr Gln Val Ile Glu Pro His Asp Ile Ser Val Ala Leu Asn Thr Arg Lys Leu Trp Ser Met His Leu His Val Gln Ala Lys Leu Leu Gln Glu Ile Val Arg Ser Phe Ser Gly Thr Thr Cys Gln Pro Ile Gln His Met Leu Arg Arg Ile Cys Val Gln Leu Cys Asp Leu Ala Ser Pro Thr Ala Leu Leu Ile Met Arg Thr Val Leu Asp Leu Ile Val Glu Asp Leu Gln Ser Thr Ser Glu Asp Lys Glu Lys Gln Tyr Thr Ser Gln Thr Thr Arg Leu Leu Ala Leu Leu Asp Ala Leu Ala Ser His Lys Ala Cys Lys Leu Ala Ile Leu His Leu Ile Asn Gly Thr Ile Lys Gly Asp Glu Arg Tyr Ala Glu Ile Phe Gln Asp Leu Leu Ala Leu Val Arg Ser Pro Gly Asp Ser Val Ile Arg Gln Gln Cys Val Glu Tyr Val Thr Ser Ile Leu Gln Ser Leu Cys Asp Gln Asp Ile Ala Leu Ile Leu Pro Ser Ser Ser Glu Gly Ser Ile Ser Glu Leu Glu Gln Leu Ser Asn Ser Leu Pro Asn Lys Glu Leu Met Thr Ser Ile Cys Asp Cys Leu Leu Ala Thr Leu Ala Asn Ser Glu Ser Ser Tyr Asn Cys Leu Leu Thr Cys Val Arg Thr Met Met Phe Leu Ala Glu His Asp Tyr Gly Leu Phe His Leu Lys Ser Ser Leu Arg Lys Asn Ser Ser Ala Leu His Ser Leu Leu Lys Arg Val Val Ser Thr Phe Ser Lys Asp Thr Gly Glu Leu Ala Ser Ser Phe Leu Glu Phe Met Arg Gln Ile Leu Asn Ser Asp Thr Ile Gly Cys Cys Gly Asp Asp Asn Gly Leu Met Glu Val Glu Gly Ala His Thr Ser Arg Thr Met Ser Ile Asn Ala Ala Glu Leu Lys Gln Leu Leu Gln Ser Lys Glu Glu Ser Pro Glu Asn Leu Phe Leu Glu Leu Glu Lys Leu Val Leu Glu His Ser Lys Asp Asp Asp Asn Leu Asp Ser Leu Leu Asp Ser Val Val Gly Leu Lys Gln Met Leu Glu Ser Ser Gly Asp Pro Leu Pro Leu Ser Asp Gln Asp Val Glu Pro Val Leu Ser Ala Pro Glu Ser Leu Gln Asn Leu Phe Asn Asn Arg Thr Ala Tyr Val Leu Ala Asp Val Met Asp Asp Gln Leu Lys Ser Met Trp Phe Thr Pro Phe Gln Ala Glu Glu Ile Asp Thr Asp Leu Asp Leu Val Lys Val Asp Leu Ile Glu Leu Ser Glu Lys Cys Cys Ser Asp Phe Asp Leu His Ser Glu Leu Glu Arg Ser Phe Leu Ser Glu Pro Ser Ser Pro Gly Arg Thr Lys Thr Thr Lys Gly Phe Lys Leu Gly Lys His Lys His Glu Thr Phe Ile Thr Ser Ser Gly Lys Ser Glu Tyr Ile Glu Pro Ala Lys Arg Ala His Val Val Pro Pro Pro Arg Gly Arg Gly Arg Gly Gly Phe Gly Gln Gly Ile Arg Pro His Asp Ile Phe Arg Gln Arg Lys Gln Asn Thr Ser Arg Pro Pro Ser Met His Val Asp Asp Phe Val Ala Ala Glu Ser Lys Glu Val Val Pro Gln Asp Gly Ile Pro Pro Pro Lys Arg Pro Leu Lys Ala Ser Gln Lys Ile Ser Ser Arg Gly Gly Phe Ser Gly Asn Arg Gly Gly Arg Gly Ala Phe His Ser Gln Asn Arg Phe Phe Thr Pro Pro Ala Ser Lys Gly Asn Tyr Ser Arg Arg Glu Gly Thr Arg Gly Ser Ser Trp Ser Ala Gln Asn Thr Pro Arg Gly Asn Tyr Asn Glu Ser Arg Gly Gly Gln Ser Asn Phe Asn Arg Gly Pro Leu Pro Pro Leu Arg Pro Leu Ser Ser Thr Gly Tyr Arg Pro Ser Pro Arg Asp Arg Ala Ser Arg Gly Arg Gly Gly Leu Gly Pro Ser Trp Ala Ser Ala Asn Ser Gly Ser Gly Gly Ser Arg Gly Lys Phe Val Ser Gly Gly Ser Gly Arg Gly Arg His Val Arg Ser Phe Thr Arg <210> 5 <211> 2054 <212> DNA
<213> Homo sapiens <400> 5 tgcagggcca gggtggggtg tccagcacca gccaagctgg tgctccagcg cacctcccca 60 gagctccccg cactgacggg gctgcaggag caggtgcagt gggcgcccac actggccctg 120 cagtgatgca gggcgggagg gagataagaa gaccccgcag tcaagtggag catggccctc 180 cctggctccc tgtccctggg ctcagcacga ccacacagga cacccagcca gggaattctg 240 aagaccagag agcagcccac gggcatcacg agcgctctgc tcctctcctg ggcccctgct 300 cttcccgaga gctgccccca aatcagacat acctctgtgg ctctcctctg gttcacgttt 360 acagagcata aggctgtctt ggatcccaac aggcacccag ccctgcatgg ggggagcctg 420 ggcctaatag gcaccccctg tacctcaggc tgtggcggga gcagagtccc cccctccggc 480 ccctcttcct ttaccccttc tcctccagca gtggcaaagg ggtaggctct agagccagca 540 caggtcactg cctgacctgg actaagaacc ccacggcccc actgtccaca cactgcctcc 600 ccaccgccca cctcggctgc taggcccctc gcctggactg gactggggag ggaaagcgcc 660 ttttcctgca gctcttcaga gccacagacc tcagggtgga gtgagcccat ggtgggcagt 720 gggcaaggcg gtgggtggtg ggcaaggtgg gacctcctgc agcctggaaa gaggagggag 780 gccaaggcca ttccctaact ccctcctgcc cctggtctga ggaggaggga ctctggagta 840 gcagaggggc tgggaaagag ggggcagggg ctgctgggac actgagcagg agggaggcct 900 gagcacactg ctttggaaat tattctaaac acaaaaaagg gaaagaaaat gttatttctc 960 cctaagtcag gagcatgcag agctagccca cctcatgtcc agctgtccac tttccatcct 1020 ggagaaagaa cagtgtgcct caaactcctg ccctccccag gcctctgggg cccgctggaa 1080 agggctctga ccccctggcc cggccgggct ctctagtggt gatccggctc attctcctgc 1140 aagttggaag cacaattttc cccccaagtg gaggaaaagg aaagggcccc agcctactga 1200 agaggtgttt attttttaac taacagcctc ccaccccatt aagactcacc aggagaggtc 1260 tgagggccat tcagaaccca ctcctgagtg ggtgggtggg tgggactcag tccagagacc 1320 taacattcag aatatagcat tggttgccta ttttgagatg gatttaatct cccacagtat 1380 tcatgagacc atctgatgga atcagatccc tgagccacct tgcaggacgt tttccccaac 1440 ctcttacacc ctggatgtca ctttggaaac caagcccttg gaagcaagtg gggtggcatg 1500 ggagagaagg gaggaggtgg gcacaggtgg tgagcttatg tgtgggcact ctactgcctc 1560 acagaagcca gccaagtgcc aaggtcagct tggctggtct gaggccacct tcttagccaa 1620 aaacctaggg ttcattttca ggactttgat aatgaacaac aaaatgggga cttctttggg 1680 cagatgctag gtcagttgtt ttcacctaat atcctctttt agctgcatgt atatttattt 1740 ataattataa ccctggtgga ctgcagcctt catctttatt gggaatgagt ttgttataaa 1800 tcagaaatgg gtccatgatg accactgttt tccaaaccca gtctgttccc tgctccctcg 1860 ctggcaagcc ccaccacaca ggagtgaggc caggggctag gagttctaag aacagaggct 1920 ggggtgaggg tggcacccag gcagctgcat ctggtctgtt ttaatttaac tgtatttaat 1980 ttgctttcaa aattaaaagt caaatacagt ttttaacagt ectaaaaaaa aaaaaaaaaa 2040 aaaaaaaaaa aaaa 2054 <210> 6 <211> 117 <212> PRT
<213> Homo Sapiens <400> 6 Met Ala Leu Pro Gly Ser Leu Ser Leu Gly Ser Ala Arg Pro His Arg Thr Pro Ser Gln Gly Ile Leu Lys Thr Arg Glu Gln Pro Thr Gly Ile Thr Ser Ala Leu Leu Leu Ser Trp Ala Pro Ala Leu Pro Glu Ser Cys Pro Gln Ile Arg His Thr Ser Val Ala Leu Leu Trp Phe Thr Phe Thr Glu His Lys Ala Val Leu Asp Pro Asn Arg His Pro Ala Leu His Gly Gly Ser Leu Gly Leu Ile Gly Thr Pro Cys Thr Ser Gly Cys Gly Gly Ser Arg Val Pro Pro Ser Gly Pro Ser Ser Phe Thr Pro Ser Pro Pro Ala Val Ala Lys Gly <210> 7 <211> 724 <212> DNA
<213> Homo Sapiens <400> 7 gtggacctgt gctgtctcag tttgctctgg ggtctgggca gtcctgtggt ttgggcagag 60 gcctcagagg gccctaggga cagactgacc caggtctgag cctcttggga gcgtgcggat 120 ggccggcctc agacaggcct ggttgtgggt ttgtcttcca aggggcacac gcgcactctg 180 gtgcttcctg gcattcagaa gagaatgggg aatccagaca tcaggccttc cttctccctg 240 ggaaggatgg caggtgcttg gagccaggcc tgtcttgaga gccagggctc tgggtcttcc 300 tcctccagtg ccctgttcca cgccttcagt gcacaaagca ctcccctcct gggatctctt 360 cagggatccc cgggatgcaa actggccagg gattagaatt ccacatttga gcaaacagac 420 tgagagtgga gaagcaccca gctggacatc ctctaggtgt tcctggcaga ggcccttgct 480 acttgtctgt gcccaaaggc cctagagggt cctagatgtg ggacaaggtc tcagcagggc 540 tccagtccca ggcctggaaa cagctggggg tgggggaagc tggctgggtg ggtgtggtta 600 tcttttccca gcttgtggct ccgaggtgac agaaccaatc tcaggaggct ttgtttggtt 660 aataaaatct actgaatggt ttaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720 aaaa 724 <210> B
<211> 128 <212> PRT
<213> Homo Sapiens <400> 8 Met Ala Gly Leu Arg Gln Ala Trp Leu Trp Val Cys Leu Pro Arg Gly Thr Arg Ala Leu Trp Cys Phe Leu Ala Phe Arg Arg Glu Trp Gly Ile Gln Thr Ser Gly Leu Pro Ser Pro Trp Glu Gly Trp Gln Val Leu Gly Ala Arg Pro Val Leu Arg Ala Arg Ala Leu Gly Leu Pro Pro Pro Val Pro Cys Ser Thr Pro Ser Val His Lys Ala Leu Pro Ser Trp Asp Leu Phe Arg Asp Pro Arg Asp Ala Asn Trp Pro Gly Ile Arg Ile Pro His Leu Ser Lys Gln Thr Glu Ser Gly Glu Ala Pro Ser Trp Thr Ser Ser Arg Cys Ser Trp Gln Arg Pro Leu Leu Leu Val Cys Ala Gln Arg Pro <210> 9 <211> 2685 <212> DNA
<213> Homo sapiens <400> 9 acaccagctg ccacttcttt tgcctcatga agaactcttg ggccagccaa actgggaacc 60 taggtgtctg ggtcttgtga caaccaaagc actttgacac taccccctgc cgagagaaga 120 ggagtggatg agcctgcggg tttgcctcaa gaaacttcat gagggtctct tactaactcc 180 attacactct ctctcctgga gcctcatctc catgtcaagc aggagggtaa agaagggaac 240 taagagcagg tctttcaagc cacaccccca cctgcggatg gatgggtttc tctgtaggcc 300 atgcaggcct ttgtcgcagc aaaccttccc agcagccctt gagccaagta aaaccagcac 360 aaccagccac cagtggttgg tgaggcagtg cccacaaggc tcatgttgta tgcctttgat 420 aaggccatct tggctttgag tagcagtgtt cctcgtcacc catttccccc tcaggattac 480 aacacctgct atcaaatcat ctaagctgaa aacatgagat gcgcttggaa aggcctagtc 540 agaagccatt tcctcttatc atttccctct cctatgcacc agtaaggccc gtccagagcc 600 ccagcaggga gtgggccctg agtccacact gtccctgagt gatccaggag gctgcccaca 660 tccccacatg tgcactgtgg ttccagtgta gctgctgtga gcccactgcc actgcctcag 720 aagggagcca ctgtgaacct ctcgagtggc tccaaagagc agtggctttt tgagaatggc 780 ccatacttct ggcccggctg gatgaaggga atgccgaccc tttggcctct ccccctcctt 840 ccatctcttc tctctcttgc cctatctctc tttctacttc agaaaaaaaa aaaaaaaaaa 900 agcctgtcat tcacttttta acactttatc ccaaataaga tccctgtgta attctgaagc 960 tggtgatcca cttggaattg tagatagttt caggaagctc ctgcagggct gtccaccgtt 1020 ggtgtgtgcc tcagtatttg gacttccgaa actgaaagtg aasgtgtctt tataggagag 1080 aaacgcatgc tgctctttgg ctctttctgt ccaacttttc tagaaatgac tcaaagtcca 1140 ttaagatttg tgaatattgt ataaattagc tatggaaagt agcaggtcag atggaaaatt 1200 cttttccaca gccctgctct ccgcctccct ccatcttagg agcgcctgcc tcaattcctc 1260 gtcaactgct ttgctccact ccatcccaca ggtgtgagtg ggggaagttt ttcattagga 1320 atacagtctg cgtgacatgg agaatggatg gagggagctt tgctactctg ctcttggcat 1380 gactccagga tttttttctg gaatccaacc tctgtcctct taggagaagg aacctgtcct 1940 tggttcagat ggctgggcat gaggaggaaa atttccatta gtgtagaaaa gtgctggaca 1500 gaatccggtt tggaaaatta caaatccagt tggtcasaat aggccatttc ctatgtgtga 1560 cctattcgtg gtatgccaac tggactgctt cctaaacagg acgaggaaag tgaggaatat 1620 ttttatatga aagccttagc ctgtctggca cccatgaaaa aaactattta tgcactccta 1680 ctttcaccgt ctttttgcat tctctatttg tagcacaaca gagttgaatg ccacaaaaca 1740 ccccgtttat agtgagctgt tttcagtgac caatatcaga aggaggcttg cttctggact 1800 agcctcacta attgccagca gccaccattt tccatggaat ggccttggga cagatgtcac 1860 ctctgttatg gggctctaat aggaaagaga atgttttttc ccttcctatg atcaatactg 1920 caaattattg ctgctcacag cttttatagg attctcccaa ctgaaagttg cagcattttt 1980 ctgtccctgt gcatcagtac taacaaaaga cagcctcacc aagtctgtat atttgaacag 2040 aggcaagtta attcatcccc ccgtgtcaga gccacaggca tgttgagggg gttgatacgt 2100 agcactggac cagggcgcaa agcccagata gttccagcca tgagaggaga gcacaagaat 2160 gctctgcact ctgcactcag caccatcttg ggtctgcttt gcccagatga gggaccacta 2220 acaaccttct cagcacatgt gaatgtggac tgattttaaa atgcattcat tctgctagga 2280 ttgggctgga agctggaaca gtgagagtac tttttctgct cctagtcatc tccctttctc 2340 agcgtgacat cctcctgcag caagcctagt atcactagca gtagttcctg cgactcttag 2400 caacacaacc cgaatatttg ctccctgcat ctgggtcctc caccaggatg ggcctgcgca 2460 tctgcattgc tgtacagaca ascaggcctt ttaatttaca tcctccttta attctcatta 2520 aaatcgcagg gtttttgttt gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2580 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2685 <210> 10 <211> 103 <212> PRT
<213> Homo Sapiens <400> 10 Met Ser Leu Arg Val Cys Leu Lys Lys Leu His Glu Gly Leu Leu Leu Thr Pro Leu His Ser Leu Ser Trp Ser Leu Ile Ser Met Ser Ser Arg Arg Val Lys Lys Gly Thr Lys Ser Arg Ser Phe Lys Pro His Pro His Leu Arg Met Asp Gly Phe Leu Cys Arg Pro Cys Arg Pro Leu Ser Gln g Gln Thr Phe Pro Ala Ala Leu Glu Pro Ser Lys Thr Ser Thr Thr Ser His Gln Trp Leu Val Arg Gln Cys Pro Gln Gly Ser Cys Cys Met Pro Leu Ile Arg Pro Ser Trp Leu <210> 11 <211> 1760 <212> DNA
<213> Homo sapiens <400> 11 ggcggggcct cgcacacccc aagaaccatc tttcacccca gcaagggggt gcgacgccac 60 aggtgccatc cccctgttgt cgttttgact ccccccgggg gccacctcca ccccggctgg 120 gtctgctagg tgctctcatg gctgaggatg gggtgagagg gtctccacca gtgccctctg 180 ggccccccat ggaggaagat ggactcaggt ggactccaaa gtctcctctg gaccctgact 240 cgggcctcct ttcatgtact ctgcccaacg gttttggggg acaatctggg ccagaagggg 300 agcgcagctt ggcaccccct gatgccagca tcctcatcag caatgtgtgc agcatcgggg 360 accatgtggc ccaggagctt tttcagggct cagatttggg catggcagaa gaggcagaga 420 ggcctgggga gaaagccggc cagcacagcc ccctgcgaga ggagcatgtg acctgcgtac 480 agagcatctt ggacgaattc cttcaaacgt atggcagcct catacccctc agcactgatg 540 aggtagtaga gaagctggag gacattttcc agcaggagtt ttccacccct tccaggaagg 600 gcctggtgtt gcagctgatc cagtcttacc agcggatgcc aggcaatgcc atggtgaggg 660 gcttccgagt ggcttataag cggcacgtgc tgaccatgga tgacttgggg accttgtatg 720 gacagaactg gctcaatgac caggtgatga acatgtatgg agacctggtc atggacacag 780 tccctgaaaa ggtgcatttc ttcaatagtt tcttctatga taaactccgt accsagggtt 840 atgatggggt gaaaaggtgg accaaaaacg tggacatctt caataaggag ctactgctaa 900 tccccatcca cctggaggtg cattggtccc tcatctctgt tgatgtgagg cgacgcacca 960 tcacctattt tgactcgcag cgtaccctaa accgccgctg ccctaagcat attgccaagt 1020 atctacaggc agaggcggta aagaaagacc gactggattt ccaccagggc tggaaaggtt 1080 acttcaaaat gaatgtggcc aggcagaata atgacagtga ctgtggtgct tttgtgttgc 1140 agtactgcaa gcatctggcc ctgtctcagc cattcagctt cacccagcag gacatgccca 1200 aacttcgtcg gcagatctac aaggagctgt gtcactgcaa actcactgtg tgagcctcgt 1260 accccagacc ccaagcccat aaatgggaag ggagacatgg gagtcccttc ccaagaaact 1320 ccagttcctt tcctctcttg cctcttccca ctcacttccc tttggttttt catatttaaa 1380 tgtttcaatt tctgtatttt tttttctttg agagaatact tgttgatttc tgatgtgcag 1440 ggggtggcta cagaaaagcc cctttcttcc tctgtttgca ggggagtgtg gccctgtggc 1500 ctgggtggag cagtcatcct cccccttccc cgtgcaggga gcaggaaatc agtgctgggg 1560 gtggtgggcg gacaatagga tcactgcctg ccagatcttc aaacttttat atatatatat 1620 atatatatat atatatatat atatatatat atatatatat ataaaaatgc cacggtcctg 1680 ctctggtcaa taaaggatcc tttgttgata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1740 aaaaaaaaaa aaaaaaaaaa 1760 <210> 12 <211> 371 <212> PRT
<213> Homo Sapiens <400> 12 Met Ala Glu Asp Gly Val Arg Gly Ser Pro Pro Val Pro Ser Gly Pro Pro Met Glu Glu Asp Gly Leu Arg Trp Thr Pro Lys Ser Pro Leu Asp Pro Asp Ser Gly Leu Leu Ser Cys Thr Leu Pro Asn Gly Phe Gly Gly Gln Ser Gly Pro Glu Gly Glu Arg Ser Leu Ala Pro Pro Asp Ala Ser Ile Leu Ile 5er Asn Val Cys Ser Ile Gly Asp His Val Ala Gln Glu Leu Phe Gln Gly Ser Asp Leu Gly Met Ala Glu Glu Ala Glu Arg Pro Gly Glu Lys Ala Gly Gln His Ser Pro Leu Arg Glu Glu His Val Thr Cys Val Gln Ser Ile Leu Asp Glu Phe Leu Gln Thr Tyr Gly Ser Leu Ile Pro Leu Ser Thr Asp Glu Val Val Glu Lys Leu Glu Asp Ile Phe Gln Gln Glu Phe Ser Thr Pro Ser Arg Lys Gly Leu Val Leu Gln Leu Ile Gln Ser Tyr Gln Arg Met Pro Gly Asn Ala Met Val Arg Gly Phe Arg Val Ala Tyr Lys Arg His Val Leu Thr Met Asp Asp Leu Gly Thr Leu Tyr Gly Gln Asn Trp Leu Asn Asp Gln Val Met Asn Met Tyr Gly Asp Leu Val Met Asp Thr Val Pro Glu Lys Val His Phe Phe Asn Ser Phe Phe Tyr Asp Lys Leu Arg Thr Lys Gly Tyr Asp Gly Val Lys Arg Trp Thr Lys Asn Val Asp Ile Phe Asn Lys Glu Leu Leu Leu Ile Pro Ile His Leu Glu Val His Trp Ser Leu Ile Ser Val Asp Val Arg Arg Arg Thr Ile Thr Tyr Phe Asp Ser Gln Arg Thr Leu Asn Arg Arg Cys Pro Lys His Ile Ala Lys Tyr Leu Gln Ala Glu Ala Val Lys Lys Asp Arg Leu Asp Phe His Gln Gly Trp Lys Gly Tyr Phe Lys Met Asn Val Ala Arg Gln Asn Asn Asp Ser Asp Cys Gly Ala Phe Val Leu Gln Tyr Cys Lys His Leu Ala Leu Ser Gln Pro Phe Ser Phe Thr Gln Gln Asp Met Pro Lys Leu Arg Arg Gln Ile Tyr Lys Glu Leu Cys His Cys Lys 1~
Leu Thr Val <210> 13 <211> 1299 <212> DNA
<213> Homo Sapiens <400> 13 agtgctctta aagttccgta cagataaagg aagagatccc agttctgata catatgagga 60 agattctgag ttgttgctcc agatacgaaa tgatgtgctt gactcactgg gtattagtcc 120 tgacctgctt cctgaggact ttgtcaggta ctgcttctcc gagatggccc cagtgtgtgc 180 ggtggttgga gggattttgg cacaggaaat tgtgaaggcc ctgtctcagc gggaccctcc 240 tcacaacaac ttcttcttct tcgatggcat gaaggggaat gggattgtgg agtgccttgg 300 ccccaagtga actcaagatt tggcagcccc agagatgcca actgcagcat gcccacctgt 360 attccctgtc cccttccttc atgaaggcat ctccaggcaa ggaaaactga agtcattggc 420 ccgatacaaa acatttcctg caacgaagga ggtggtgccg acgtgctgct tcccatcacc 480 agcagctgct cgacaagggg cgcagggtgg ctgtctttgt tccagcactg ttcaggctgc 540 ctgtcatccc gggcctgcca gctcccctga gtgatgagca cttccaagca cccctctgcc 600 ctttctctgt ccttatgctg tcccggctcg ccagccctct ggggcattgt gggagatgcc 660 tgccaggaat gagcaagctc tgttgctcgg gagcctcttg tcaccttctt ggacttattc 720 cccacctgat accttataga gaaaagtgtg aattcaggtg gagagtaggc ccaggcccca 780 tgaggcacca gtggaagcac agctccaagt tcagacaggt gcccttagag aggaaaacca 840 tgacaggcaa atgcatttcc tctggagttt gagaccctga caaacaacag gtggcatctg 900 gtgtgctgtt cttgagtttt cgtttaggat tagttgagtt ccagctgggt tttgggagaa 960 aggagatgct accaagtctt ggatgttagg gcgagaccct gcaagttgag tattagagag 1020 cttgtctttc aaggcaggtt cctggggctC cagggctagg agggaggagc ctgccctttt 1080 aacagaaccc cagtcacatg cggctcaagt cactcagagg ctgttgcatt tcagggctat 1140 gttggtcctt tgtttacctc ctaaaccaca gctgtttgtg tttcacatat gttgtgaatt 1200 ttccttggtt ctttttaaag gaatgataat aaagttactt gctttaggaa aaaaaaaaaa 1260 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1299 <210> 14 <211> 85 <212> PRT
<213> Homo Sapiens <400> 14 Met Leu Ser Arg Leu Ala Ser Pro Leu Gly His Cys Gly Arg Cys Leu Pro Gly Met Ser Lys Leu Cys Cys Ser Gly Ala Ser Cys His Leu Leu Gly Leu Ile Pro His Leu Ile Pro Tyr Arg Glu Lys Cys Glu Phe Arg Trp Arg Val Gly Pro Gly Pro Met Arg His Gln Trp Lys His Ser Ser Lys Phe Arg Gln Val Pro Leu Glu Arg Lys Thr Met Thr Gly Lys Cys Ile Ser Ser Gly Val <210> 15 <211> 2996 <212> DNA
<213> Homo Sapiens <400> 15 atttccagct cgcacccggg ctccgatcgc tcgccccgct cctctcgctc tgctcctggc 60 cggggctgcg ggttcggtcc gggcgccggt gcgctcctgc cggtcctcgt gcccgggact 120 ccgggtcccc gcgggctgct gcgcacgatg aagctggccc tgctcctgcc ctgggcgtgt 180 tgctgcctct gcgggtcggc gctggccact ggctttctct atcccttctc ggccgcagct 240 ctgcagcagc acggctaccc cgagcccggc gccggctccc ctggcagcgg ctacgcgagc 300 cgccggcact ggtgccatca cacagtgaca cggacggtgt cctgccaggt gcagaatggc 360 tcggagacgg tggtccagcg cgtgtaccag agctgccggt ggccggggcc ctgcgccaac 420 ctcgtaagtt acaggactct gatcagaccc acctacagag tgtcctaccg cacggtgacg 480 gtgctggagt ggagatgctg ccctggcttc accgggagca actgtgatga ggaatgcatg 540 aactgcaccc ggctcagtga catgagtgag cgactgacca cactggaggc caaggtcctc 600 ctgctagaag cagcagaacg gccctccagc ccggacaacg acctgccagc ccccgagagc 660 actccgccga cctggaatga ggacttcctc cccgacgcca tccctcttgc tcaccctgtg 720 ccacgacaga gaaggcccac gggcccagcc gggcccccgg ggcagacagg accaccaggg 780 cctgcaggcc cccccgggtc tasaggtgac cgaggccaga caggagagaa gggtccagcg 840 gggccgcctg ggctcctggg gcctccaggg ccccgtgggc ttcctggaga gatggggcgc 900 cccggccccc caggaccacc cggcccagca ggcaacccag gcccctcacc aaacagcccc 960 cagggcgccc tctactccct gcagccgcct acagacaaag acaatggaga ctcaaggctg 1020 gcctctgcca tcgtggacac agtgctggca ggtgtcccag gaccccgggg tccccctggt 1080 ccaccaggtc cccctgggcc tcgaggtccc ccaggacccc caggaacacc tggatcccag 1140 ggcctggctg gagagcgagg cacagtgggg ccgtctggtg aacctggcgt gaagggggaa 1200 gaaggagaga sagccgccac tgcagagggc gagggggtgc agcagctgag agaggccctg 1260 aagatcctgg cagsgcgagt cctcatcctg gagcacatga ttgggatcca cgatcccctg 1320 gcctccccag agggaggttc tggccaggat gctgccctga gagccaacct caagatgaag 1380 aggggtggcg cccaacccga tggggtcctt gctgccctgc ttgggcccga ccctggacag 1440 aagagcgtgg accaggccag cagcaggaag tgagagccca ctgctccagg acaccctgtc 1500 ctggctagag acccagcccc agaggcctga gccgccgctg tttcctaaag atgcccccag 1560 gggaactggg ctccaggcgt ggatgattgt gaggacatgg ggggctttgg ggacagataa 1620 tgtctccagg ggcagggtct ggaggggcca acaccctcat cagagccctc ctctggcctg 1680 tcccctcccc tacccccact cccggctgga gacggggtct gggtgggctg ggtgctggga 1740 atgagaataa tcctaatacc catcatttat tgagtccctg ctgtaactgg ccctgtccag 1800 ggaactttcg ttacgttgtc tcattattta acccttagga ggtaagctta ttatccccac 1860 ttcacaaggg gaccgaggct cagacggtag aaataaccct ctcttggcca ccagatcacg 1920 ggtggcaggg gcaggatttg aacccaggac cctcagttcc tgaagccatg ttctcttgac 1980 cctgccagct tcccctcttc gagagaaaac tcagacaggg agggcgcagg gccagaacgg 2040 ctccttaagg caggcagggc tgcggggagg ctgggccagc cagcctgagg gggtaggcag 2100 ggtcctgcag ggcctggggc ttcccttcct catccccctt ccccactggc tcggggagca 2160 gcctggactg cagctctcag aggccaggga gaccctgaat aaatcactgc cagccatacg 2220 gacttgagga ccttgagaga gaagcattgg gggtgcaagg gtcccccaaa ccagataggc 2280 atccctggcc actgcctccc agtcttgctg agcccacccg ctctctctgg gtccatccca 2340 tccctgagcc aggggaggca gcatttcatg ggcatgtcta tcagaggtgg gacttgcagc 2400 ctctgcccca cgagtttgtc tctcagtgga ctctataggt ttgctacttt tgcatgacac 2460 agcaagccca gtgtcccctt tgcaagctgc agagagggaa acagagtccc aggcctgctg 2520 ggaagagatg ctcctgcctc ccaccttcca gagttggggg cctggcaggc tccatggcag 2580 gcaccaggtc cctagcagcc cagaacagct ctgactggag ccctcaaggc ctctggggcc 2640 agggtctccg tgatcagctc agccctggtg ttcctctctt gctgggctgg gacctgggac 2700 acagccacgg cagcaaactc agagaattga aggtgctggc gccaccctgg ggcactctgt 2760 cttcacagca ggagtgactg tctccagtgc tcttggtact cctgtttggc tgtggcctgg 2820 tccctctggg ccctgggatc ttcttctggc ccttgaggca ggtctggaga ggcagtctct 2880 gtcttcatgg aggggtggtc agaggcgggc gggaccacca gcctgtagcg ttattattat 2940 atgtgacaat aaaggtgctc tccccacaaa aaaaaaaaaa aaaaasaaaa aaaaaa 2996 <210> 16 <211> 441 <212> PRT
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:5, but excluding the poiy(A) tail at the 3' end of SEQ ID N0:5; and (ab) the nucleotide sequence of the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (ba) SEQ ID N0:5, but excluding the poly(A) tail at the 3' end of SEQ ID N0:5; and (bb) the nucleotide sequence of the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:5, and extending 3 0 contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:5 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:5 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:5. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:5 from nucleotide 172 to nucleotide 522. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:5 from nucleotide 214 to nucleotide 522, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:5 from nucleotide 214 to nucleotide 522.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:6;
(b) a fragment of the amino acid sequence of SEQ ID N0:6, the fragment comprising eight contiguous amino acids of SEQ ID N0:6; and (c) the amino acid sequence encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:6. In further preferred 2 0 embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:6, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:6 having biological activity, the fragment comprising the amino acid sequence from 2 5 amino acid 53 to amino acid 62 of SEQ ID N0:6.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 119 to nucleotide 502;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the S cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb5_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb5_1 deposited under accession number ATCC 98804;
(h) a polynudeotide encoding a protein comprising the amino acid sequence of SEQ ID N0:8;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:8;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the profiein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 25% of the length of SEQ ID N0:7.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:7 from nucleotide 119 to nucleotide 502; the nucleotide sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502; the nucleotide sequence of the full-length protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb5_1 deposited under 3 0 accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:8, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 59 to amino acid 68 of SEQ
ID N0:8.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:7.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:7, but excluding the poly(A) tail at the 3' end of SEQ ID N0:7; and (ab) the nucleotide sequence of the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that 2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:7, but excluding the poly(A) tail at the 3' end of SEQ ID N0:7; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vb5_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:7, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:7 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:7 , but excluding the poly{A) tail at the 3' end of SEQ ID N0:7. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide 119 to nucleotide 502. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:7 from nucleotide 176 to nucleotide 502, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:7 from nucleotide 176 to nucleotide 502.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:8;
(b) a fragment of the amino acid sequence of SEQ ID N0:8, the fragment comprising eight contiguous amino acids of SEQ ID N0:8; and (c) the amino acid sequence encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:8. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty} contiguous amino ands 3 0 of SEQ ID N0:8, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 59 to amino acid 68 of SEQ ID N0:8.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a} a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 128 to nucleotide 436;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb6_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb6_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:10;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:10 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID NO:10;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(i); and (m} a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:9.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:9 from nucleotide 128 to nucleotide 436; the nucleotide sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436; the nucleotide sequence of the full-length protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:10 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:10, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:10 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino and 55 of SEQ
ID N0:10.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:9.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:9, but excluding the poly(A) tail at the 3' end of SEQ ID N0:9; and (ab) the nucleotide sequence of the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:9, but excluding the poly(A) tail at the 3' end of SEQ ID N0:9; and (bb) the nucleotide sequence of the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:9, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ ID
N0:9 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:9 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:9. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:9 from nucleotide 128 to nucleotide 436. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:9 from nucleotide 203 to nucleotide 436, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:9 from nucleotide 203 to nucleotide 436.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID N0:10, the fragment comprising eight contiguous amino acids of SEQ ID N0:10; and {c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vb6_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:10. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:10 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:10, or a protein comprising a fragment of the amino acid sequence of SEQ
ID NO:10 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID NO:10.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
NO:11;
{b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 138 to nucleotide 1250;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb7 1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb7 1 deposited under accession number ATCC
2 0 98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb7 1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:12;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:12;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:11.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
NO:11 from nucleotide 138 to nucleotide 1250; the nucleotide sequence of SEQ
ID NO:11 from nucleotide 279 to nucleotide 1250; the nucleotide sequence of the full-length protein coding sequence of clone vb7_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb7 1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb7_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:12, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment comprising the amino acid sequence from amino acid 180 to amino acid 189 of SEQ ID N0:12.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:11.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:11, but excluding the poly(A) tail at the 3' end of SEQ ID N0:11; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vb7_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:11, but excluding the poly(A) tail at the 3' end of SEQ ID N0:11; and (bb) the nucleotide sequence of the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:11; and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:11 to a nucleotide sequence corresponding to the 3' end of SEQ ID NO:11, but excluding the poly(A) tail at the 3' end of SEQ ID N0:11. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:11 from nucleotide 138 to nucleotide 1250, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID NO:11 from nucleotide 138 to nucleotide 1250, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:11 from nucleotide 138 to nucleotide 1250. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:11 from nucleotide 279 to nucleotide 1250, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:11 from nucleotide 279 to nucleotide 1250.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:12;
(b) a fragment of the amino acid sequence of SEQ ID N0:12, the fragment comprising eight contiguous amino acids of SEQ ID N0:12; and (c) the amino acid sequence encoded by the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:12. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:12 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:12, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:12 having biological activity, the fragment comprising the amino acid sequence from amino acid 180 to amino acid 189 of SEQ ID N0:12.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:13 from nucleotide 615 to nucleotide 869;
(c) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vb8_1 deposited under accession number ATCC 98804;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(e) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone vb8_1 deposited under accession number ATCC
98804;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vb8_1 deposited under accession number ATCC 98804;
(g) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:14;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:14;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h) and that has a length that is at least 25% of the length of SEQ ID N0:13.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:13 from nucleotide 615 to nucleotide 869; the nucleotide sequence of the full-length protein coding sequence of clone vb8_1 deposited under accession number ATCC
98804;
or the nucleotide sequence of a mature protein coding sequence of clone vb8_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of clone vb8_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most 2 0 preferably thirty) contiguous amino acids of SEQ ID N0:14, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment comprising the amino acid sequence from amino acid 37 to amino acid 46 of SEQ ID N0:14.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 5 ID N0:13.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 3 0 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:13, but excluding the poly(A) tail at the 3' end of SEQ ID N0:13; and (ab) the nucleotide sequence of the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:13, but excluding the poly(A) tail at the 3' end of SEQ ID N0:13; and (bb) the nucleotide sequence of the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:13 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:13 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:13. Also preferably the 2 5 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:13 fram nucleotide 615 to nucleotide 869, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:13 from nucleotide 615 to nucleotide 869, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:13 from nucleotide 3 0 615 to nucleotide 869.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:14;
(b) a fragment of the amino acid sequence of SEQ ID N0:14, the fragment comprising eight contiguous amino acids of SEQ ID N0:14; and {c) the amino acid sequence encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:14. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:14, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:14 having biological activity, the fragment comprising the amino acid sequence from amino acid 37 to amino acid 46 of SEQ ID N0:14.
In one embodiment, the present invention provides a composition comprising an isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:15;
{b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:15 from nucleotide 148 to nucleotide 1470;
(c) a polynudeotide comprising the nucleotide sequence of SEQ iD
2 0 N0:15 from nucleotide 193 to nucleotide 1470;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the 2 5 cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(f) a polynudeotide comprising the nucleotide sequence of a mature protein coding sequence of clone vb9_1 deposited under accession number ATCC
98804;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
3 0 insert of done vb9_1 deposited under accession number ATCC 98804;
(h) a polynudeotide encoding a protein comprising the amino acid sequence of SEQ ID N0:16;
(i) a polynucleohde encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:16;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:15.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:15 from nucleotide 148 to nucleotide 1470; the nucleotide sequence of SEQ
ID N0:15 from nucleotide 193 to nucleotide 1470; the nucleotide sequence of the full-length protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vb9_1 2 0 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:16, or a polynucleotide encoding a protein comprising a 2 5 fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:16.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:15.
3 0 Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:15, but excluding the poly(A) tail at the 3' end of SEQ ID N0:15; and (ab) the nucleotide sequence of the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes} to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:15, but excluding the poly(A) tail at the 3' end of SEQ ID N0:15; and (bb} the nucleotide sequence of the cDNA insert of done 2 0 vb9_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii} amplifying human DNA sequences; and (iv} isolating the polynudeotide products of step (b)(iii).
2 5 Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:15, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:15 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:15 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:15. Also preferably the 3 0 polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from nucleotide 148 to nucleotide 1470. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:15 from nucleotide 193 to nucleotide 1470, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:15 from nucleotide 193 to nucleotide 1470, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:15 from nucleotide 193 to nucleotide 1470.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:16;
(b) a fragment of the amino acid sequence of SEQ ID N0:16, the fragment comprising eight contiguous amino acids of SEQ ID N0:16; and (c) the amino acid sequence encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:16. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 2 0 of SEQ ID N0:16, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:16 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:16.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
2 5 {a) a polynudeotide comprising the nucleotide sequence of SEQ ID
NO:I7;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:17 from nucleotide 109 to nucleotide 414;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:17 from nucleotide 217 to nucleotide 414;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748;
WO 99/55721 PC'T/US99/08504 (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc3_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc3_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:18;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:18 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:18;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i); and (m) a polynucleotide that hybridizes under stringent conditions to any 2 0 ane of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:17.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:17 from nucleotide 109 to nucleotide 414; the nucleotide sequence of SEQ ID
N0:17 from nucleotide 217 to nucleotide 414; the nucleotide sequence of the full-length protein 2 5 coding sequence of clone vc3_1 deposited under accession number ATCC
98748; or the nucleotide sequence of a mature protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748. In further preferred embodiments, the 3 0 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:18 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:18, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:18 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ
ID N0:18.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:17.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:17, but excluding the poly(A) tail at the 3' end of SEQ ID N0:17; and (ab) the nucleotide sequence of the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and 2 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID NO:17, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:17; and (bb) the nucleotide sequence of the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
3 0 (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:17, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:17 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:17 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:17. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from nucleotide 109 to nucleotide 414. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:17 from nucleotide 217 to nucleotide 414, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:17 from nucleotide 217 to nucleotide 414, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:17 from nucleotide 217 to nucleotide 414.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:18;
(b) a fragment of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight contiguous amino acids of SEQ ID N0:18; and 2 0 (c) the amino acid sequence encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:18. In further preferred embodiments, the present invention provides a protein comprising a fragment of the 2 5 amino acid sequence of SEQ ID N0:18 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ 117 N0:18, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:18 having biological activity, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID N0:18.
3 0 In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 169 to nucleotide 840;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc4_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc4_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:20;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:20;
2 0 (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any 2 5 one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:19.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
3 0 N0:19 from nucleotide 169 to nucleotide 840; the nucleotide sequence of SEQ ID N0:19 from nucleotide 211 to nucleotide 840; the nucleotide sequence of the full-length protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:20, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment comprising the amino acid sequence from amino acid 107 to amino acid 116 of SEQ ID N0:20.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:19.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:19, but excluding the poly(A) tail at the 3' end of SEQ ID N0:19; and 2 0 (ab) the nucleotide sequence of the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the 2 5 probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from 3 0 the group consisting of:
(ba) SEQ ID N0:19, but excluding the poly(A) tail at the 3' end of SEQ ID N0:19; and (bb) the nucleotide sequence of the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
wo mssn~ rc~rius99rosso4 (ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:19, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:19 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:19 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:19. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:19 from nucleotide 169 to nucleotide 840. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:19 from nucleotide 211 to nucleotide 840, to a nucleotide sequence corresponding to the 3' end of 2 0 said sequence of SEQ ID N0:19 from nucleotide 211 to nucleotide 840.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:20;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:20, the fragment comprising eight contiguous amino acids of SEQ ID N0:20; and (c) the amino acld sequence encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such 3 0 protein comprises the amino acid sequence of SEQ ID N0:20. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:20 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino atids of SEQ ID N0:20, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:20 having biological activity, the fragment comprising the amino acid sequence from amino acid 107 to amino acid 116 of SEQ ID N0:20.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 508 to nucleotide 951;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc5_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone vc5_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:22;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment 2 5 comprising eight contiguous amino acids of SEQ ID N0:22;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
{k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:21.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:21 from nucleotide 508 to nucleotide 951; the nucleotide sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951; the nucleotide sequence of the full-length protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:22, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment comprising the amino acid sequence from amino acid 69 to amino acid 78 of SEQ
ID N0:22.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:21.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:21, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:21; and (ab) the nucleotide sequence of the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 3 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:21, but excluding the poly(A) tail at the 3' end of SEQ ID N0:21; and (bb) the nucleotide sequence of the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b}(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:21, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:21 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:21, but excluding the poly(A) tail at the 3' end of SEQ ID N0:21. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951, and extending contiguously from a nucleotide sequence corresponding to the 5' end 2 0 of said sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from nucleotide 508 to nucleotide 951. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951, and extending contiguously from a 2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:21 from nucleotide 733 to nucleotide 951, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:21 from nucleotide 733 to nucleotide 951.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:22;
(b) a fragment of the amino acid sequence of SEQ ID N0:22, the fragment comprising eight contiguous amino acids of SEQ ID N0:22; and (c) the amino acid sequence encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:22. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:22, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:22 having biological activity, the fragment comprising the amino acid sequence from amino acid 69 to amino acid 78 of SEQ ID N0:22.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:23 from nucleotide 125 to nucleotide 493;
(c) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc7 1 deposited under accession number ATCC 98748;
2 0 (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc7_1 deposited under accession number ATCC
98748;
2 5 (f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc7_1 deposited under accession number ATCC 98748;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:24;
(h) a polynucleotide encoding a protein comprising a fragment of the 3 0 amino acid sequence of SEQ ID N0:24 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:24;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(h) and that has a length that is at least 25% of the length of SEQ ID N0:23.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:23 from nucleotide 125 to nucleotide 493; the nucleotide sequence of the full-length protein coding sequence of clone vc7_1 deposited under accession number ATCC
98748;
or the nucleotide sequence of a mature protein coding sequence of clone vc7 1 deposited under accession number ATCC 98748. In othex preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert of clone vc7_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:24, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24 having 2 0 biological activity, the fragment comprising the amino acid sequence from amino acid 56 to amino acid 65 of SEQ ID N0:24.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:23.
Further embodiments of the invention provide isolated polynucleotides produced 2 5 according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
3 0 (aa) SEQ ID N0:23, but excluding the poly(A) tail at the 3' end of SEQ ID N0:23; and (ab) the nucleotide sequence of the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:23, but excluding the poly(A) tail at the 3' end of SEQ ID N0:23; and (bb) the nucleotide sequence of the cDNA insert of done vc7_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:23, and 2 0 extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:23 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:23 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:23. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 2 5 493, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 493, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:23 from nucleotide 125 to nucleotide 493.
In other embodiments, the present invention provides a composition comprising 3 0 a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:24;
(b) a fragment of the amino acid sequence of SEQ ID N0:24, the fragment comprising eight contiguous amino acids of SEQ ID N0:24; and (c) the amino acid sequence encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:24. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:24, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:24 having biological activity, the fragment comprising the amino acid sequence from amino acid 56 to amino acid 65 of SEQ ID N0:24.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 33 to nucleotide 407;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407;
(d) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone v~ 1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc9_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:26;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:26;
wo mssm pcr~s~rossoa (j} a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:25.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:25 from nucleotide 33 to nucleotide 407; the nucleotide sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407; the nucleotide sequence of the full-length protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone v~ 1 deposited under accession number ATCC 98748. In further preferred embodiments, the presient invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment 2 0 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:26, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ
ID N0:26.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:25.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:25, but excluding the poly(A) tail at the 3' end of SEQ ID N0:25; and WO 99/55721 PC'T/US99/08504 (ab) the nucleotide sequence of the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:25, but excluding the poly(A) tail at the 3' end of SEQ ID N0:25; and (bb) the nucleotide sequence of the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 0 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:25, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:25 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:25 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:25. Also preferably the 2 5 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:25 from nucleotide 33 to nucleotide 407, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:25 from nucleotide 33 to nucleotide 407, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from nucleotide 3 0 33 to nucleotide 407. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:25 from nucleotide 99 to nucleotide 407, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:25 from nucleotide 99 to nucleotide 407.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) ~ the amino acid sequence of SEQ ID N0:26;
(b) a fragment of the amino acid sequence of SEQ ID N0:26, the fragment comprising eight contiguous amino acids of SEQ ID N0:26; and (c) the amino acid sequence encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:26. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:26 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:26, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:26 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ ID N0:26.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:27 from nucleotide 176 to nucleotide 871;
2 5 (c) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl0_1 deposited under accession number ATCC 98748;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
3 0 (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl0_1 deposited under accession number ATCC
98748;
(f) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl0_1 deposited under accession number ATCC 98748;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:28;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:28;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above;
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above ;
(k) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(h) and that has a length that is at least 25% of the length of SEQ ID N0:27.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:27 from nucleotide 176 to nucleotide 871; the nucleotide sequence of the full-length protein coding sequence of clone vcl0_1 deposited under accession number ATCC
98748;
or the nucleotide sequence of a mature protein coding sequence of clone vcl0_1 deposited under accession number ATCC 98748. In other preferred embodiments, the 2 0 polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most 2 5 preferably thirty) contiguous amino acids of SEQ ID N0:28, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment comprising the amino acid sequence from amino and 111 to amino acid 120 of SEQ ID N0:28.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
3 0 ID N0:27.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:27, but excluding the poly(A) tail at the 3' end of SEQ ID N0:27; and (ab) the nucleotide sequence of the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:27, but excluding the poly(A) tail at the 3' end of SEQ ID N0:27; and (bb) the nucleotide sequence of the cDNA insert of clone 2 0 vcl0_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:27, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:27 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:27 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:27. Also preferably the 3 0 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871, to a nucleotide wo mssm pcTius99rossoa sequence corresponding to the 3' end of said sequence of SEQ ID N0:27 from nucleotide 176 to nucleotide 871.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:28;
(b) a fragment of the amino acid sequence of SEQ ID N0:28, the fragment comprising eight contiguous amino acids of SEQ ID N0:28; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl0_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:28. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:28, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:28 having biological activity, the fragment comprising the amino acid sequence from amino acid 111 to amino acid 120 of SEQ ID N0:28.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 160 to nucleotide 657;
2 5 (c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl l_1 deposited under accession number ATCC 98748;
3 0 (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcll_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcll_1 deposited under accession number ATCC
98748;
WO 99/55721 PC1'/US99/08504 (g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcll 1 deposited under accession number ATCC 98748;
(h} a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:30;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:30;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:29.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:29 from nucleotide 160 to nucleotide 657; the nucleotide sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657; the nucleotide sequence of the full-length protein 2 0 coding sequence of clone vcll_1 deposited under accession number ATCC
98748; or the nucleotide sequence of a mature protein coding sequence of clone vcl l_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcll_1 deposited under accession number ATCC 98748. In further preferred embodiments, the 2 5 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty}
contiguous amino acids of SEQ ID N0:30, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the 3 0 fragment comprising the amino acid sequence from amino and 78 to amino acid 87 of SEQ
ID N0:30.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:29.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:29, but excluding the poly(A) tail at the 3' end of SEQ ID N0:29; and (ab) the nucleotide sequence of the cUNA insert or clone vcll 1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (ba) SEQ ID N0:29, but excluding the poly(A) tail at the 3' end of SEQ ID N0:29; and (bb) the nucleotide sequence of the cDNA insert of clone vcll_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29, and 3 0 extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:29 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:29 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:29. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from nucleotide 160 to nucleotide 657. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:29 from nucleotide 214 to nucleotide 657, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:29 from nucleotide 214 to nucleotide 657.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:30;
(b) a fragment of the amino acid sequence of SEQ ID N0:30, the fragment comprising eight contiguous amino acids of SEQ ID N0:30; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl l_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:30. In further preferred 2 0 embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:30 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty} contiguous amino acids of SEQ ID N0:30, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:30 having biological activity, the fragment comprising the amino acid sequence 2 5 from amino acid 78 to amino acid 87 of SEQ ID N0:30.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 228 to nucleotide 662;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl4_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA _insert of clone vcl4_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl4_1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl4_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:32;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:32;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(i); and (m} a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:31.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:31 from nucleotide 228 to nucleotide 662; the nucleotide sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662; the nucleotide sequence of the full-length protein coding sequence of clone vcl4_1 deposited under accession number ATCC 98748;
or the nucleotide sequence of a mature protein coding sequence of clone vcl4_1 deposited under 3 0 accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl4_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:32, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment comprising the amino acid sequence from amino acid 67 to amino acid 76 of SEQ
ID N0:32.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:31.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:31, but excluding the poly(A) tail at the 3' end of SEQ ID N0:31; and (ab) the nucleotide sequence of the cDNA insert of clone vcl4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that 2 5 hybridize in 6X 5SC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:31, but excluding the poly(A) tail at the 3' end of SEQ ID N0:31; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vcl4_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:31, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:31 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:31 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:31. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from nucleotide 228 to nucleotide 662. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:31 from nucleotide 327 to nucleotide 662, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:31 from nucleotide 327 to nucleotide 662.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:32;
(b) a fragment of the amino acid sequence of SEQ ID N0:32, the fragment comprising eight contiguous amino acids of SEQ ID N0:32; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl4_1 deposited under accession number ATCC 98748;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:32. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:32 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 3 0 of SEQ ID N0:32, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:32 having biological activity, the fragment comprising the amino acid sequence from amino acid 67 to amino acid 76 of SEQ ID N0:32.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 101 to nucleotide 667;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl6_1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl6_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl6_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:34;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:34 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:34;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:33.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:33 from nucleotide 101 to nucleotide 667; the nucleotide sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667; the nucleotide sequence of the full-length protein coding sequence of clone vcl6_1 deposited under accession number ATCC 98784;
or the nucleotide sequence of a mature protein coding sequence of clone vcl6_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:34, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:34 having biological activity, the fragment comprising the amino acid sequence from amino acid 89 to amino acid 98 of SEQ
ID N0:34.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:33.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:33, but excluding the poly(A) tail at the 3' end of SEQ ID N0:33; and (ab) the nucleotide sequence of the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b} a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:33, but excluding the poly(A) tail at the 3' end of SEQ ID N0:33; and (bb) the nucleotide sequence of the cDNA insert of clone vcl6_1 deposited under accession number ATCC 98784;
(ii} hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:33, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:33 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:33 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:33. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from nucleotide 101 to nucleotide 667. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:33 from nucleotide 182 to nucleotide 667, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:33 from nucleotide 182 to nucleotide 667.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:34;
(b) a fragment of the amino acid sequence of SEQ ID N0:34, the fragment comprising eight contiguous amino acids of SEQ ID N0:34; and (c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vcl6_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:34. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:34 having biological activity, the fragment preferably SS
WO 99/55721 PC'T/US99/08504 comprising eight (more preferably twenty, most preferably thirty) contiguous amino ands of SEQ ID N0:34, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:34 having biological activity, the fragment comprising the amino acid sequence from amino acid 89 to amino acid 98 of SEQ ID N0:34.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 8 to nucleotide 355;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vcl7 1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vcl7 1 deposited under accession number ATCC
2 0 98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vcl7_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:36;
2 5 (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:36;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a}-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i} above ;
(1) a polynudeotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 25% of the length of SEQ ID N0:35.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:35 from nucleotide 8 to nucleotide 355; the nucleotide sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355; the nucleotide sequence of the full-length protein coding sequence of clone vcl7_1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone vcl7_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:36, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ
ID N0:36.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:35.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:35, but excluding the poly(A) tail at the 3' end of SEQ ID N0:35; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vcl7 1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:35, but excluding the poly(A) tail at the 3' end of SEQ ID N0:35; and (bb) the nucleotide sequence of the cDNA insert of clone vcl7_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:35, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:35 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:35 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:35. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from nucleotide 8 to nucleotide 355. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:35 from nucleotide 134 to nucleotide 355, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:35 from nucleotide 134 to nucleotide 355.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:36;
(b) a fragment of the amino acid sequence of SEQ ID N0:36, the fragment comprising eight contiguous amino acids of SEQ ID N0:36; and (c) the amino acid sequence encoded by the cDNA insert of clone vcl7 1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:36. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:36, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:36 having biological activity, the fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ ID N0:36.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:37 from nucleotide 1031 to nucleotide 1252;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:37 from nucleotide 1100 to nucleotide 1252;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc21_1 deposited under accession number ATCC 98785;
(e) a polynucleotide encoding the full-length protein encoded by the 2 5 cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(f) a polynucleotlde comprising the nucleotide sequence of a mature protein coding sequence of clone vc21 1 deposited under accession number ATCC
98785;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
3 0 insert of clone vc21 1 deposited under accession number ATCC 98785;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:38;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:38 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:38;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:37.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:37 from nucleotide 1031 to nucleotide 1252; the nucleotide sequence of SEQ
ID N0:37 from nucleotide 1100 to nucleotide 1252; the nucleotide sequence of the full-length protein coding sequence of clone vc21 1 deposited under accession number ATCC
98785;
or the nucleotide sequence of a mature protein coding sequence of clone vc21 1 deposited under accession number ATCC 98785. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA
insert 2 0 of clone vc21 1 deposited under accession number ATCC 98785. In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino acid 74. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38 2 5 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:38, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:38 having biological activity, the fragment comprising the amino acid sequence from amino acid 32 to amino acid 41 of SEQ ID N0:38.
3 0 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:37.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:37, but excluding the poly(A) tail at the 3' end of SEQ ID N0:37; and (ab) the nucleotide sequence of the cDNA insert of done vc21 1 deposited under accession number ATCC 98785;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:37, but excluding the poly(A) tail at the 3' end of SEQ ID N0:37; and (bb) the nucleotide sequence of the cDNA insert of clone 2 0 vc21 1 deposited under accession number ATCC 98785;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:37, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:37 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:37 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:37. Also preferably the 3 0 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from nucleotide 1031 to nucleotide 1252. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA
sequence of SEQ ID N0:37 from nucleotide 1100 to nucleotide 1252, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:37 from nucleotide 1100 to nucleotide 1252, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:37 from nucleotide 1100 to nucleotide 1252.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:38;
(b) the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino acid 74;
(c) a fragment of the amino acid sequence of SEQ ID N0:38, the fragment comprising eight contiguous amino acids of SEQ ID N0:38; and (d) the amino acid sequence encoded by the cDNA insert of clone vc21 1 deposited under accession number ATCC 98785;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:38 or the amino acid sequence of SEQ ID N0:38 from amino acid 29 to amino acid 74. In further preferred embodiments, 2 0 the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:38 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
N0:38, or a protein comprising a fragment of the amino acid sequence of SEQ ID
N0:38 having biological activity, the fragment comprising the amino acid sequence from amino 2 5 acid 32 to amino acid 41 of SEQ ID N0:38.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 94 to nucleotide 1482;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc23_1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc23_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc23_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:40;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:40;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:39.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:39 from nucleotide 94 to nucleotide 1482; the nucleotide sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482; the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone vc23 1 deposited under 3 0 accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:40, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment comprising the amino acid sequence from amino acid 226 to amino acid 235 of SEQ ID N0:40.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:39.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:39, but excluding the poly(A) tail at the 3' end of SEQ ID N0:39; and (ab) the nucleotide sequence of the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that 2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:39, but excluding the poly(A) tail at the 3' end of SEQ ID N0:39; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vc23_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:39, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:39 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:39 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:39. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from nucleotide 94 to nucleotide 1482. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:39 from nucleotide 214 to nucleotide 1482, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:39 from nucleotide 214 to nucleotide 1482.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:40;
(b) a fragment of the amino acid sequence of SEQ ID N0:40, the fragment comprising eight contiguous amino acids of SEQ ID N0:40; and (c) the amino acid sequence encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:40. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 3 0 of SEQ ID N0:40, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:40 having biological activity, the fragment comprising the amino acid sequence from amino acid 226 to amino acid 235 of SEQ ID N0:40.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 153 to nucleotide 413;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc25_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of done vc25_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:42;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:42 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:42;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and {m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:41.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:41 from nucleotide 153 to nucleotide 413; the nucleotide sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413; the nucleotide sequence of the full-length protein coding sequence of clone vc~ 1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:42 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:42, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:42 having biological activity, the fragment comprising the amino acid sequence from amino acid 38 to amino acid 47 of SEQ
ID N0:42.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:41.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:41, but excluding the poly(A) tail at the 3' end of SEQ ID N0:41; and (ab) the nucleotide sequence of the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:41, but excluding the poly(A) tail at the 3' end of SEQ ID N0:41; and (bb) the nucleotide sequence of the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii} amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:41, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
TD N0:41 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:41, but excluding the poly(A) tail at the 3' end of SEQ ID N0:41. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from nucleotide 153 to nucleotide 413. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:41 from nucleotide 264 to nucleotide 413, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:41 from nucleotide 264 to nucleotide 413.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a} the amino acid sequence of SEQ ID N0:42;
(b) a fragment of the amino acid sequence of SEQ ID N0:42, the fragment comprising eight contiguous amino acids of SEQ ID N0:42; and (c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vc25_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:42. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:42 having biological activity, the fragment preferably WO 99/55721 PC'f/US99/08504 comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:42, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:42 having biological activity, the fragment comprising the amino acid sequence from amino acid 38 to amino acid 47 of SEQ ID N0:42.
In one embodiment, the present invention provides a composition comprising an isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43;
(b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 87 to nucleotide 1409;
(c) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of done vc26_1 deposited under accession number ATCC 98784;
(e) a polynudeotide encoding the full-length protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(f) a polynudeotide comprising the nucleotide sequence of a mature protein coding sequence of clone vc26_1 deposited under accession number ATCC
2 0 98784;
(g) a polynudeotide encoding a mature protein encoded by the cDNA
insert of clone vc26_1 deposited under accession number ATCC 98784;
(h) a polynudeotide encoding a protein comprising the amino acid sequence of SEQ ID N0:44;
2 5 (i) a polynudeotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:44;
(j) a polynudeotide which is an allelic variant of a polynudeotide of (a)-(g) above;
3 0 (k) a polynudeotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynudeotide that hybridizes under stringent conditions to any one of the polynudeotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:43.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:43 from nucleotide 87 to nucleotide 1409; the nucleotide sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409; the nucleotide sequence of the full-length protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
or the nucleotide sequence of a mature protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:44, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:44.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:43.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:43, but excluding the poly(A) tail at the 3' end of SEQ ID N0:43; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vc26_1 deposited under accession number ATCC 98784;
{ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:43, but excluding the poly(A) tail at the 3' end of SEQ ID N0:43; and (bb) the nucleotide sequence of the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(ii} hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:43, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:43 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:43 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:43. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from nucleotide 87 to nucleotide 1409. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:43 from nucleotide 156 to nucleotide 1409, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:43 from nucleotide 156 to nucleotide 1409.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:44;
(b) a fragment of the amino acid sequence of SEQ ID N0:44, the fragment comprising eight contiguous amino acids of SEQ ID N0:44; and (c) the amino acid sequence encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:44. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:44 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:44, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:44 having biological activity, the fragment comprising the amino acid sequence from amino acid 215 to amino acid 224 of SEQ ID N0:44.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 63 to nucleotide 428;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:45 from nucleotide 156 to nucleotide 428;
(d) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:45 from nucleotide 356 to nucleotide 1773;
{e) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone v~ 1 deposited under accession number 2 5 ATCC 98804;
(f) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc30-1 deposited under accession number ATCC 98804;
(g) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC
3 0 98804;
(h) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vc30_1 deposited under accession number ATCC 98804;
(i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:46;
(j) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:46;
(k) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(h) above;
(1) a polynucleotide which encodes a species homologue of the protein of (i) or (j) above ;
(m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j); and (n) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(j) and that has a length that is at least 25% of the length of SEQ ID N0:45.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:45 from nucleotide 63 to nucleotide 428; the nucleotide sequence of SEQ ID
N0:45 from nucleotide 156 to nucleotide 428; the nucleotide sequence of SEQ ID N0:45 from nucleotide 356 to nucleotide 1773; the nucleotide sequence of the full-length protein coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
or the nucleotide sequence of a mature protein coding sequence of clone v~ 1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide 2 0 encodes the full-length or a mature protein encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804. In yet other preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein 2 5 comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:46, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment comprising the amino acid sequence from amino acid 56 3 0 to amino acid 65 of SEQ ID N0:46.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:45.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa} SEQ ID N0:45, but excluding the poly(A) tail at the 3' end of SEQ ID N0:45; and (ab} the nucleotide sequence of the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:45, but excluding the poly(A) tail at the 3' end of SEQ ID N0:45; and 2 0 (bb) the nucleotide sequence of the cDNA insert of clone vc30_I deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and 2 5 (iv) isolating the polynucleotide products of step (b}(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:45 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:45 , but 3 0 excluding the poly(A) tail at the 3' end of SEQ ID N0:45. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from nucleotide 63 to nucleotide 428. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:45 from nucleotide 156 to nucleotide 428, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:45 from nucleotide 156 to nucleotide 428, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:45 from nucleotide 156 to nucleotide 428. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:45 from nucleotide 356 to nucleotide 1773, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:45 from nucleotide 356 to nucleotide 1773, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID
N0:45 from nucleotide 356 to nucleotide 1773.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:46;
(b) the amino acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97;
2 0 (c) a fragment of the amino acid sequence of SEQ ID N0:46, the fragment comprising eight contiguous amino acids of SEQ ID N0:46; and (d) the amino acid sequence encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such 2 5 protein comprises the amino acid sequence of SEQ ID N0:46 or the amino acid sequence of SEQ ID N0:46 from amino acid 1 to amino acid 97. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID
3 0 N0:46, or a protein comprising a fragment of the amino acid sequence of SEQ ID N0:46 having biological activity, the fragment comprising the amino acid sequence from amino acid 56 to amino acid 65 of SEQ ID N0:46.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 30 to nucleotide 1799;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vdl 1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vdl_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vdl 1 deposited under accession number ATCC
98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd1 1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:48;
(i) a polynucleotide encoding a protein comprising a fragment of the 2 0 amino acid sequence of SEQ ID N0:48 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:48;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k} a polynucleotide which encodes a species homologue of the protein 2 5 of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 3 0 25% of the length of SEQ ID N0:47.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:47 from nucleotide 30 to nucleotide 1799; the nucleotide sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799; the nucleotide sequence of the full-length protein coding sequence of clone vd1 1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vdl 1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:48, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:48 having biological activity, the fragment comprising the amino acid sequence from amino acid 290 to amino acid 299 of SEQ ID N0:48.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:47.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (aa) SEQ ID N0:47, but excluding the poly(A) tail at the 3' end of SEQ ID N0:47; and (ab) the nucleotide sequence of the cDNA insert of clone vdl_1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:47, but excluding the poly(A) tail at the 3' end of SEQ TD N0:47; and (bb) the nucleotide sequence of the cDNA insert of clone vdl 1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:47, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:47 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:47 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:47. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from nucleotide 30 to nucleotide 1799. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799, and extending contiguously from a 2 0 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:47 from nucleotide 90 to nucleotide 1799, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:47 from nucleotide 90 to nucleotide 1799.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 2 5 consisting of:
(a) the amino acid sequence of SEQ ID N0:48;
(b) a fragment of the amino acid sequence of SEQ ID N0:48, the fragment comprising eight contiguous amino acids of SEQ ID N0:48; and (c) the amino acid sequence encoded by the cDNA insert of clone 3 0 vd1_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:48. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID NO:48, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:48 having biological activity, the fragment comprising the amino acid sequence from amino acid 290 to amino acid 299 of SEQ ID N0:48.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 69 to nucleotide 443;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vd2_1 deposited under accession number ATCC
2 0 98748;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd2_1 deposited under accession number ATCC 98748;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:50;
2 5 (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:50;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
3 0 (k) a polynucleotide which encodes a species homologue of the protein of {h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:49.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:49 from nucleotide 69 to nucleotide 443; the nucleotide sequence of SEQ ID
NO:49 from nucleotide 111 to nucleotide 443; the nucleotide sequence of the full-length protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748; or the nucleotide sequence of a mature protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:50, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ
ID N0:50.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
2 0 ID N0:49.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize 2 5 in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:49, but excluding the poly(A) tail at the 3' end of SEQ ID N0:49; and (ab) the nucleotide sequence of the cDNA insert of clone 3 0 vd2 1 deposited under accession number ATCC 98748;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:49, but excluding the poly(A) tail at the 3' end of SEQ ID N0:49; and (bb) the nucleotide sequence of the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:49, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:49 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:49 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:49. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence 2 0 corresponding to the cDNA sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from nucleotide 69 to nucleotide 443. Also preferably the polynucleotide isolated according to the above 2 5 process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:49 from nucleotide 111 to nucleotide 443, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:49 from nucleotide 111 to nucleotide 443.
3 0 In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:50;
(b) a fragment of the amino acid sequence of SEQ ID N0:50, the fragment comprising eight contiguous amino acids of SEQ ID N0:50; and (c) the amino acid sequence encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:50. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:50 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:50, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:50 having biological activity, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ ID N0:50.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:51 from nucleotide 176 to nucleotide 1249;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
2 0 N0:51 from nucleotide 227 to nucleotide 1249;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the 2 5 cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vd3_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
3 0 insert of clone vd3_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:52;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:52;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a}-(i) and that has a length that is at least 25% of the length of SEQ ID N0:51.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:51 from nucleotide 176 to nucleotide 1249; the nucleotide sequence of SEQ
ID N0:51 from nucleotide 227 to nucleotide 1249; the nucleoiide sequence of the full-length protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd3_1 2 0 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:52, or a polynucleotide encoding a protein comprising a 2 5 fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment comprising the amino acid sequence from amino acid 174 to amino acid 183 of SEQ ID N0:52.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:51.
3 0 Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:51, but excluding the poly(A) tail at the 3' end of SEQ ID N0:51; and (ab) the nucleotide sequence of the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:51, but excluding the poly(A) tail at the 3' end of SEQ ID N0:51; and (bb) the nucleotide sequence of the cDNA insert of clone 2 0 vd3_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
2 5 Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:51, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:51 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:51 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:51. Also preferably the 3 0 polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from nucleotide 176 to nucleotide 1249. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:51 from nucleotide 227 to nucleotide 1249, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:51 from nucleotide 227 to nucleotide 1249, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:51 from nucleotide 227 to nucleotide 1249.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:52;
(b) a fragment of the amino and sequence of SEQ ID N0:52, the fragment comprising eight contiguous amino acids of SEQ ID N0:52; and (c) the amino acid sequence encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:52. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:52 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 2 0 of SEQ ID N0:52, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:52 having biological activity, the fragment comprising the amino acid sequence from amino acid 174 to amino acid 183 of SEQ ID N0:52.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
2 5 (a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:53 from nucleotide 94 to nucleotide 1530;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
3 0 N0:53 from nucleotide 145 to nucleotide 1530;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vd4_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vd4_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:54;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:54 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:54;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m} a polynucleotide that hybridizes under stringent conditions to any 2 0 one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:53.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:53 from nucleotide 94 to nucleotide 1530; the nucleotide sequence of SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530; the nucleotide sequence of the full-length protein 2 5 coding sequence of clone vd4_1 deposited under accession number ATCC
98804; or the nucleotide sequence of a mature protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804. In further preferred embodiments, the 3 0 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:54, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:54 having biological activity, the wo mss~z~ pcTiusmossoa fragment comprising the amino acid sequence from amino acid 234 to amino acid 243 of SEQ ID N0:54.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:53.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynudeotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:53, but excluding the poly(A) tail at the 3' end of SEQ ID N0:53; and (ab) the nucleotide sequence of the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe(s);
and 2 0 (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) 5EQ ID N0:53, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:53; and (bb) the nucleotide sequence of the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
3 0 (iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step {b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:53, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
WO 99/55'121 PGT/US99/08504 ID N0:53 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:53 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:53. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from nucleotide 94 to nucleotide 1530. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:53 from nucleotide 145 to nucleotide 1530, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:53 from nucleotide 145 to nucleotide 1530.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:54;
(b) a fragment of the amino acid sequence of SEQ ID N0:54, the fragment comprising eight contiguous amino acids of SEQ ID N0:54; and 2 0 (c) the amino acid sequence encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:54. In further preferred embodiments, the present invention provides a protein comprising a fragment of the 2 5 amino acid sequence of SEQ ID N0:54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:54, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:54 having biological activity, the fragment comprising the amino acid sequence from amino acid 234 to amino acid 243 of SEQ ID N0:54.
3 0 In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 71 to nucleotide 1300;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone ve4_1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone ve4_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:56;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:56;
2 0 (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any 2 5 one of the polynucleotides specified in (ar(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:55.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
3 0 N0:55 from nucleotide 71 to nucleotide 1300; the nucleotide sequence of SEQ ID N0:55 from nucleotide 182 to nucleotide 1300; the nucleotide sequence of the full-length protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:56, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 200 to amino acid 209 of SEQ ID N0:56.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:55.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:55, but excluding the poly(A) tail at the 3' end of SEQ ID N0:55; and 2 0 (ab) the nucleotide sequence of the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the 2 5 probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from 3 0 the group consisting of:
{ba) SEQ ID N0:55, but excluding the poly(A) tail at the 3' end of SEQ ID N0:55; and (bb) the nucleotide sequence of the cDNA insert of clone ve4_I deposited under accession number ATCC 98784;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:55, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:55 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:55 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:55. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:55 from nucleotide 71 to nucleotide 1300. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:55 from nucleotide 182 to nucleotide 1300, to a nucleotide sequence corresponding to the 3' end 2 0 of said sequence of SEQ ID N0:55 from nucleotide 182 to nucleotide 1300.
1n other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:56;
2 5 (b) a fragment of the amino acid sequence of SEQ ID N0:56, the fragment comprising eight contiguous amino acids of SEQ ID N0:56; and (c) the amino acid sequence encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such 3 0 protein comprises the amino acid sequence of SEQ ID N0:56. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:56, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 200 to amino acid 209 of SEQ ID N0:56.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57; ' (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 57 to nucleotide 785;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785;
(d} a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone ve8_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
2 0 insert of clone ve8_1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:58;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment 2 5 comprising eight contiguous amino acids of SEQ ID N0:58;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (ar(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
3 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-{i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:57.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:57 from nucleotide 57 to nucleotide 785; the nucleotide sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785; the nucleotide sequence of the full-length protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:58, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment comprising the amino acid sequence from amino acid 116 to amino acid 125 of SEQ ID N0:58.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:57.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
2 0 (a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:57, but excluding the poly(A) tail at the 2 5 3' end of SEQ ID N0:57; and (ab) the nucleotide sequence of the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 3 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:57, but excluding the poly{A) tail at the 3' end of SEQ ID N0:57; and (bb) the nucleotide sequence of the cDNA insert of done ve8_1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step {b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:57, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:57 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:57 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:57. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785, and extending contiguously from a nucleotide sequence corresponding to the 5' end 2 0 of said sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from nucleotide 57 to nucleotide 785. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785, and extending contiguously from a 2 5 nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:57 from nucleotide 147 to nucleotide 785, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:57 from nucleotide 147 to nucleotide 785.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group 3 0 consisting of:
(a) the amino acid sequence of SEQ ID N0:58;
(b) a fragment of the amino acid sequence of SEQ ID N0:58, the fragment comprising eight contiguous amino acids of SEQ ID N0:58; and (c) the amino acid sequence encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:58. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:58 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:58, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:58 having biological activity, the fragment comprising the amino acid sequence from amino acid 116 to amino acid 125 of SEQ ID N0:58.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 64 to nucleotide 1002;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002;
(d) a polynucleotide comprising the nucleotide sequence of the full-2 0 length protein coding sequence of clone vfl 1 deposited under accession number ATCC 98784;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vfl 1 deposited under accession number ATCC 98784;
(f) a polynucleotide comprising the nucleotide sequence of a mature 2 5 protein coding sequence of clone vfl 1 deposited under accession number ATCC
98784;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vfl_1 deposited under accession number ATCC 98784;
(h) a polynucleotide encoding a protein comprising the amino acid 3 0 sequence of SEQ ID N0:60;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:60;
(j} a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:59.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:59 from nucleotide 64 to nucleotide 1002; the nucleotide sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002; the nucleotide sequence of the full-length protein coding sequence of clone vfl_1 deposited under accession number ATCC 98784; or the nucleotide sequence of a mature protein coding sequence of clone vfl 1 deposited under accession number ATCC 98784. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment 2 0 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:60, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment comprising the amino acid sequence from amino acid 151 to amino acid 160 of SEQ ID N0:60.
2 5 Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:59.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
3 0 (i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:59, but excluding the poly(A) tail at the 3' end of SEQ ID N0:59; and WO 99/55721 PC"TNS99/08504 (ab) the nucleotide sequence of the cDNA insert of clone vfl 1 deposited under accession number ATCC 98784;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynudeotides detected with the probe(s);
and (b) a process comprising the steps of:
(i) preparing one or more polynudeotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ ID N0:59, but excluding the poly(A) tail at the 3' end of SEQ ID N0:59; and (bb) the nucleotide sequence of the cDNA insert of done vf1 1 deposited under accession number ATCC 98784;
(ii) hybridizing said primer{s) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynudeotide products of step (b)(iii).
2 0 Preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:59, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:59 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:59 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:59. Also preferably the 2 5 polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:59 from nucleotide 64 to nucleotide 1002, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:59 from nucleotide 64 to nucleotide 1002, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from nucleotide 3 0 64 to nucleotide 1002. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:59 from nucleotide 139 to nucleotide 1002, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:59 from nucleotide 139 to nucleotide 1002.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID N0:60, the fragment comprising eight contiguous amino acids of SEQ ID N0:60; and (c) the amino acid sequence encoded by the cDNA insert of clone vf1 1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:60. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:60 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:60, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:60 having biological activity, the fragment comprising the amino acid sequence from amino acid 151 to amino acid 160 of SEQ ID N0:60.
In one embodiment, the present invention provides a composition comprising an 2 0 isolated polynudeotide selected from the group consisting of:
(a) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61;
(b) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 588 to nucleotide 995;
2 5 (c) a polynudeotide comprising the nucleotide sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995;
(d) a polynudeotide comprising the nucleotide sequence of the full-length protein coding sequence of done vhf 1 deposited under accession number ATCC 98804;
3 0 (e) a polynudeotide encoding the full-length protein encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(f) a polynudeotide comprising the nucleotide sequence of a mature protein coding sequence of clone vh1_1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vhl 1 deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:62;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:62;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the profiein of (h) or (i) above ;
(1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a~(i) and that has a length that is at least 25% of the length of SEQ ID N0:61.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID
N0:61 from nucleotide 588 to nucleotide 995; the nucleotide sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995; the nucleotide sequence of the full-length protein 2 0 coding sequence of clone vhl 1 deposited under accession number ATCC
98804; or the nucleotide sequence of a mature protein coding sequence of clone vhl_1 deposited under accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vhf 1 deposited under accession number ATCC 98804. In further preferred embodiments, the 2 5 present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:62, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the 3 0 fragment comprising the amino acid sequence from amino acid 63 to amino acid 72 of SEQ
ID N0:62.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:61.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:61, but excluding the poly(A) tail at the 3' end of SEQ ID N0:61; and (ab) the nucleotide sequence of the cDNA insert of clone vhl 1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and (iii) isolating the DNA polynucleotides detected with the probe{s);
and (b) a process comprising the steps of:
(i) preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
2 0 (ba) SEQ ID N0:61, but excluding the poly(A) tail at the 3' end of SEQ ID N0:61; and (bb) the nucleotide sequence of the cDNA insert of clone vhl 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in 2 5 conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:61, and 3 0 extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:61 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:61 , but excluding the poly(A} tail at the 3' end of SEQ ID N0:61. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from nucleotide 588 to nucleotide 995. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:61 from nucleotide 750 to nucleotide 995, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:61 from nucleotide 750 to nucleotide 995.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID N0:62;
(b) a fragment of the amino acid sequence of SEQ ID N0:62, the fragment comprising eight contiguous amino acids of SEQ ID N0:62; and (c) the amino acid sequence encoded by the cDNA insert of clone vhf 1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID N0:62. In further preferred 2 0 embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:62 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:62, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:62 having biological activity, the fragment comprising the amino acid sequence 2 5 from amino acid 63 to amino acid 72 of SEQ ID N0:62.
In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63;
3 0 (b) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 29 to nucleotide 1369;
(c) a polynucleotide comprising the nucleotide sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369;
(d) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vi1 1 deposited under accession number ATCC 98804;
(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vil 1 deposited under accession number ATCC 98804;
(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone vil 1 deposited under accession number ATCC
98804;
(g) a polynucleotide encoding a mature protein encoded by the cDNA
insert of clone vil I deposited under accession number ATCC 98804;
(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID N0:64;
(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activity, the fragment comprising eight contiguous amino acids of SEQ ID N0:64;
(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above;
(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above ;
2 0 (1) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (ar(i); and {m) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i) and that has a length that is at least 25% of the length of SEQ ID N0:63.
2 5 Preferably, such polynucleotide comprises the nucleotide sequence of SEQ
ID
N0:63 from nucleotide 29 to nucleotide 1369; the nucleotide sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369; the nucleotide sequence of the full-length protein coding sequence of clone vi1 1 deposited under accession number ATCC 98804; or the nucleotide sequence of a mature protein coding sequence of clone vil_1 deposited under 3 0 accession number ATCC 98804. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activity, the fragment WO 99/55'721 PCTNS99/08504 preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids of SEQ ID N0:64, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activity, the fragment comprising the amino acid sequence from amino acid 218 to amino acid 227 of SEQ ID N0:64.
Other embodiments provide the gene corresponding to the cDNA sequence of SEQ
ID N0:63.
Further embodiments of the invention provide isolated polynucleotides produced according to a process selected from the group consisting of:
(a) a process comprising the steps of:
(i) preparing one or more polynucleotide probes that hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(aa) SEQ ID N0:63, but excluding the poly(A) tail at the 3' end of SEQ ID N0:63; and (ab) the nucleotide sequence of the cDNA insert of clone vi1 1 deposited under accession number ATCC 98804;
(ii) hybridizing said probes) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C; and 2 0 (iii) isolating the DNA polynucleotides detected with the probe(s);
and {b} a process comprising the steps of:
(i} preparing one or more polynucleotide primers that 2 5 hybridize in 6X SSC at 65 degrees C to a nucleotide sequence selected from the group consisting of:
(ba) SEQ 1D N0:63, but excluding the poly(A) tail at the 3' end of SEQ ID N0:63; and (bb) the nucleotide sequence of the cDNA insert of clone 3 0 vil 1 deposited under accession number ATCC 98804;
(ii) hybridizing said primers) to human genomic DNA in conditions at least as stringent as 4X SSC at 50 degrees C;
(iii) amplifying human DNA sequences; and (iv) isolating the polynucleotide products of step (b)(iii).
Preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:63, and extending contiguously from a nucleotide sequence corresponding to the 5' end of SEQ
ID N0:63 to a nucleotide sequence corresponding to the 3' end of SEQ ID N0:63 , but excluding the poly(A) tail at the 3' end of SEQ ID N0:63. Also preferably the polynucleotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:63 from nucleotide 29 to nucleotide 1369. Also preferably the polynudeotide isolated according to the above process comprises a nucleotide sequence corresponding to the cDNA sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369, and extending contiguously from a nucleotide sequence corresponding to the 5' end of said sequence of SEQ ID
N0:63 from nucleotide 104 to nucleotide 1369, to a nucleotide sequence corresponding to the 3' end of said sequence of SEQ ID N0:63 from nucleotide 104 to nucleotide 1369.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
2 0 (a) the amino acid sequence of SEQ ID N0:64;
(b) a fragment of the amino acid sequence of SEQ ID N0:64, the fragment comprising eight contiguous amino acids of SEQ ID N0:64; and (c) the amino acid sequence encoded by the cDNA insert of clone vi1 1 deposited under accession number ATCC 98804;
2 5 the protein being substantially free from other mammalian proteins.
Preferably such protein comprises the amino acid sequence of SEQ ID N0:64. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID N0:64 having biological activify, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) contiguous amino acids 3 0 of SEQ ID N0:64, or a protein comprising a fragment of the amino acid sequence of SEQ
ID N0:64 having biological activity, the fragment comprising the amino acid sequence from amino acid 218 to amino acid 227 of SEQ ID N0:64.
In certain preferred embodiments, the polynucleotide is operably linked to an expression control sequence. The invention also provides a host cell, including bacterial, yeast, insect and mammalian cells, transformed with such polynucleotide compositions.
Also provided by the present invention are organisms that have enhanced, reduced, or modified expression of the genes) corresponding to the polynucleotide sequences disclosed herein.
Processes are also provided for producing a protein, which comprise:
(a) growing a culture of the host cell transformed with such polynucleotide compositions in a suitable culture medium; and (b) purifying the protein from the culture.
The protein produced according to such methods is also provided by the present invention.
Protein compositions of the present invention may further comprise a pharmaceutically acceptable Garner. Compositions comprising an antibody which specifically reacts with such protein are also provided by the present invention.
Methods are also provided for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein of the present invention and a pharmaceutically acceptable carrier.
BRIEF DESCRIPTION OF THE DRAWINGS
2 0 Figures 1A and 1B are schematic representations of the pED6 and pNOTs vectors, respectively, used for deposit of clones disclosed herein.
DETAILED DESCRIPTION
ISOLATED PROTEINS AND POLYNUCLEOTIDES
2 5 Nucleotide and amino acid sequences, as presently determined, are reported below for each clone and protein disclosed in the present application. The nucleotide sequence of each clone can readily be determined by sequencing of the deposited clone in accordance with known methods. The predicted amino acid sequence (both full-length and mature forms) can then be determined from such nucleotide sequence. The amino 3 0 acid sequence of the protein encoded by a particular clone can also be determined by expression of the clone in a suitable host cell, collecting the protein and determining its sequence. For each disclosed protein applicants have identified what they have determined to be the reading frame best identifiable with sequence information available at the time of filing.
As used herein a "secreted" protein is one which, when expressed in a suitable host cell, is transported across or through a membrane, including transport as a result of signal sequences in its amino acid sequence. "Secreted" proteins include without limitation proteins secreted wholly (e.g., soluble proteins) or partially (e.g. , receptors) from the cell in which they are expressed. "Secreted" proteins also include without limitation proteins which are transported across the membrane of the endoplasmic reticulum.
Clone"vb2 1"
A polynucleotide of the present invention has been identified as clone "vb2_1".
vb2_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb2_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb2_1 protein").
The nucleotide sequence of vb2_1 as presently determined is reported in SEQ ID
NO:1, and includes a poly(A} tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb2_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:2. Amino acids 15 to 27 of SEQ ID N0:2 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature of the predicted 2 0 leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb2_1 protein.
If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:1 by deleting one of the adenine residues at positions 315 and 316, another potential vb2_1 reading frame and predicted amino acid sequence could be encoded by basepairs 126 to 2 5 381 of SEQ ID N0:1 and is reported in SEQ ID N0:97. Amino acids 15 to 27 of SEQID
N0:97 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28 of SEQ ID N0:97, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb2_1 should be approximately 2342 bp.
3 0 The nucleotide sequence disclosed herein for vb2_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb2_1 demonstrated at least some similarity with sequences identified as AA308563 (EST179381 HCC cell line (matastasis to liver in mouse) II Homo Sapiens cDNA 5' end, mRNA sequence). Based upon sequence similarity, vb2_1 proteins and each similar protein or peptide may share at least some activity.
Clone "vb3 1"
A polynucleotide of the present invention has been identified as clone "vb3_1".
vb3_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb3_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb3_1 protein").
The nucleotide sequence of vb3 1 as presently determined is reported in SEQ ID
N0:3, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb3_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:4. Amino acids 16 to 28 of SEQ ID N0:4 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 29. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb3_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb3_1 should be approximately 2498 bp.
2 0 The nucleotide sequence disclosed herein for vb3_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb3_1 demonstrated at least some similarity with sequences identified as AA098874 (zn45f I l .s 1 Stratagene HeLa cell s3 937216 Homo sapiens cDNA
clone 550413 3', mRNA sequence) and T26482 (Human gene signature HUMGS08724).
2 5 Based upon sequence similarity, vb3_1 proteins and each similar protein or peptide may share at least some activity.
Clone "vb4 1"
A polynucleotide of the present invention has been identified as clone "vb4_1".
3 0 vb4_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb4_1 protein").
The nucleotide sequence of vb4_1 as presently determined is reported in SEQ ID
N0:5, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:6. Amino acids 2 to 14 of SEQ ID N0:6 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb4_1 should be approximately 2161 bp.
The nucleotide sequence disclosed herein for vb4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb4_1 demonstrated at least some similarity with sequences identified as D88035 (Rat mRNA for glycoprotein specific UDP-glucuronyltransferase, complete cds), N49234 (yy83b10.s1 Homo Sapiens cDNA clone 280123 3'), and (Human brain Expressed Sequence Tag EST00765). Based upon sequence similarity, vb4_1 proteins and each similar protein or peptide may share at least some activity. The TopPredlI computer program predicts two additional potential transmembrane domains within the vb4_1 protein sequence, one centered around amino acid 40 and another 2 0 around amino acid 80 of SEQ ID N0:6.
Clone "vb5 1"
A polynucleotide of the present invention has been identified as clone "vb5_1".
vb5_1 was isolated from a human fetal brain cDNA library and was identified as encoding 2 5 a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb5_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb5_1 protein").
The nucleotide sequence of vb5_1 as presently determined is reported in SEQ ID
N0:7, and includes a poly(A} tail. What applicants presently believe to be the proper 3 0 reading frame and the predicted amino acid sequence of the vb5_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:8. Amino acids 7 to 19 of SEQ ID N0:8 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 20. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb5_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb5_1 should be approximately 724 bp.
The nucleotide sequence disclosed herein for vb5_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb5_7 demonstrated at least some similarity with sequences identified as AA835218 (ak65a05.s1 Barstead pancreas HPLRBI Homo sapiens cDNA
clone IMAGE:1412720 3', mRNA sequence). Based upon sequence similarity, vb5_1 proteins and each similar protein or peptide may share at least some activity.
Clone "vb6 1"
A polynucleotide of the present invention has been identified as clone "vb6_1".
vb6_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb6_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb6_1 protein").
The nucleotide sequence of vb6_1 as presently determined is reported in SEQ ID
N0:9, and includes a poly(A) tail. What applicants presently believe to be the proper 2 0 reading frame and the predicted amino acid sequence of the vb6_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:10. Amino acids 13 to 25 of SEQ ID NO:10 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 5 the predicted leader/signal sequence not be separated from the remainder of the vb6_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb6_1 should be approximately 2685 bp.
The nucleotide sequence disclosed herein for vb6_1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb6_1 demonstrated at least some similarity with sequences identified as AA478801 (zv20fn5.s 1 Soares NhHMPu S 1 Homo sapiens cDNA clone 754209 3', mRNA sequence). Based upon sequence similarity, vb6_1 proteins and each similar protein or peptide may share at least some activity.
done "vb7 1"
A polynucleotide of the present invention has been identified as clone "vb7 1".
vb7 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb7 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb7 1 protein').
The nucleotide sequence of vb7_1 as presently determined is reported in SEQ ID
N0:11, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb7 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:12. Amino acids 35 to 47 of SEQ ID N0:12 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 48. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb7 1 protein.
Another potential vb7 1 reading frame and predicted amino acid sequence that 2 0 could be encoded by basepairs 1093 to 1577 of SEQ ID N0:11 is reported in SEQ ID
N0:98. Amino acids 11 to 23 of SEQ ID N0:98 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24 of SEQ ID
N0:98, or are a transmembrane domain. The TapPredII computer program predicts another potential transmembrane domain within the protein sequence of SEQ ID
N0:98 2 5 centered around amino acid 86 of SEQ ID N0:98. If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:11 approximately between position 1090 and position 1253, the open reading frame of SEQ ID N0:12 could be joined to the open reading frame of SEQ ID N0:98.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 3 0 vb7 1 should be approximately 1730 bp.
The nucleotide sequence disclosed herein for vb7 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb7 1 demonstrated at least some similarity with sequences identified as D 13748 {human eukaryotic initiation factor 4A)], M22873 (Mus musculus protein synthesis initiation factor 4A (e1F-4A) gene, exon 1), and N36589 (yx86fO8.r1 Homo sapiens cDNA clone 268647 S'). The predicted amino acid sequence disclosed herein for vb7_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLAST7C search protocol. The predicted vb7 1 protein demonstrated at least some similarity to the sequence identified as AL021839 (hypothetical protein [Schizosaccharomyces pombe]). Based upon sequence similarity, vb7 1 proteins and each similar protein or peptide may share at least some activity.
vb7_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 45 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vb8 1"
A polynucleotide of the present invention has been identified as clone "vb8_1".
vb8_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb8_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vb8_1 protein").
The nucleotide sequence of vb8_1 as presently determined is reported in SEQ ID
N0:13, and includes a poly(A) tail. What applicants presently believe to be the proper 2 0 reading frame and the predicted amino acid sequence of the vb8_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:14.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vb8_1 should be approximately 1363 bp.
The nucleotide sequence disclosed herein for vb8_1 was searched against the 2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vb8_1 demonstrated at least some similarity with sequences identified as N57252 (yw93dll.rl Homo sapiens cDNA clone 259797 5'). The predicted amino acid sequence disclosed herein for vb8_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The 3 0 predicted vb8_1 protein demonstrated at least some similarity to sequences identified as AF51239 (probable ubiquitin activating enzyme 2 [Picea mariana]). Based upon sequence similarity, vb8_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain WO 99/55?21 PCT/US99/08504 within the vb8_1 protein sequence centered around amino acid 30 of SEQ ID
N0:14. Both the CodonPreference and Testcode computer programs indicate that frameshifts in the nucleotide sequence of SEQ ID N0:13, resulting in the joining of the open reading frame of SEQ ID N0:14 with open reading frames that are more 5' to that of SEQ ID
N0:14, are likely.
vb8_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 23 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vb9 1"
A polynudeotide of the present invention has been identified as clone "vb9_1".
vb9_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vb9_1 is a full-length done, including the entire coding sequence of a secreted protein (also referred to herein as "vb9_1 protein").
The nucleotide sequence of vb9_1 as presently determined is reported in SEQ ID
N0:15, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vb9_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:16. Amino acids 3 to 15 2 0 of SEQ ID N0:16 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 16. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vb9_1 protein.
2 5 The EcoRI/NotI restriction fragment obtainable from the deposit containing done vb9_1 should be approximately 2996 bp.
The nucleotide sequence disclosed herein for vb9_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and PASTA search protocols. vb9_1 demonstrated at least some similarity with sequences 3 0 identified as AA446380 (zw58b09.r1 Soares total fetus Nb2HF8 9w Homo sapiens cDNA
clone 774233 5', mRNA sequence) and L48440 (Rattus norvegicus collagen type II
mRNA, complete cds). The predicted amino add sequence disclosed herein for vb9_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vb9_1 protein demonstrated at least some similarity to the sequence identified as 278279 (Collagen alphal [Rattus norvegicus]).
Based upon sequence similarity, vb9_1 proteins and each similar protein or peptide may share at least some activity.
vb9_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 58 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vc3 1"
A polynucleotide of the present invention has been identified as clone "v~ 1".
vc3_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc3_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc3_1 protein").
The nucleotide sequence of vc3_1 as presently determined is reported in SEQ ID
N0:17, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc3_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:18. Amino acids 24 to 36 of SEQ ID N0:18 are a predicted leader/signal sequence, with the predicted mature 2 0 amino acid sequence beginning at amino acid 37. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc3_1 protein.
Another potential vc3_1 reading frame and predicted amino acid sequence is 2 5 encoded by basepairs 227 to 703 of SEQ TD N0:17 and is reported in SEQ ID
N0:99.
Amino acids 83 to 95 of SEQ ID N0:99 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 96, or are a transmembrane domain, and the TopPredII computer program predicts two additional transmembrane domains within the SEQ ID N0:99 amino acid sequence. A
frameshift in 3 0 the nucleotide sequence of SEQ ID N0:17 between about nucleotide 109 to about nucleotide 417 could join together portions of the overlapping reading frames of SEQ ID
N0:18 and SEQ ID N0:99.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc3_1 should be approximately 950 bp.
The nucleotide sequence disclosed herein for vc3_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc3_1 demonstrated at least some similarity with sequences identified as AA669665 (ac18h12.s1 Stratagene ovary (#937217) Homo sapiens cDNA clone 856871 3'). Based upon sequence similarity, vc3_1 proteins and each similar protein or peptide may share at least some activity.
vc3_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 19 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vc4 1"
A polynucleotide of the present invention has been identified as clone "vc4_1".
vc4_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc4_1 protein").
The nucleotide sequence of vc4 1 as presently determined is reported in SEQ ID
2 0 N0:19, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:20. Amino acids 2 to 14 of SEQ ID N0:20 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc4_1 should be approximately 1200 bp.
3 0 The nucleotide sequence disclosed herein for vc4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc4_1 demonstrated at least some similarity with sequences identified as Q40970 (Human skeletal muscle ADP-ribosyltransferase gene), U60881 (Mus musculus Yac-2 NAD:arginine ADP-ribosyltransferase mRNA, complete cds), and W12489 (ma57b11.r1 Soares mouse p3NMF19.5 Mus musculus cDNA clone 314781 5' similar to SW RT61_RAT P17982 ALLOANTIGEN RT6.1 PRECURSOR). The predicted amino acid sequence disclosed herein for vc4_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc4_1 protein demonstrated at least some similarity to sequences identified as 837572 (Rabbit skeletal muscle ADP-ribosyltransferase) and U60881 (Yac-2 NAD
arginine ADP-ribosyltransferase [Mus musculus]). ADP-ribosyltransferases are localized to the plasma membrane and are involved in "post-translational modification of proteins in which the ADP-ribose moiety of NAD is transferred to proteins", which is "responsible for the toxicity of some bacterial toxins (e.g. cholera toxin and pertussis toxin)". Based upon sequence similarity, vc4_1 proteins and each similar protein or peptide may share at least some activity.
vc4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 26 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vc5 1"
A polynucleotide of the present invention has been identified as clone "v~ 1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as encoding 2 0 a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc5_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc5_1 protein").
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:21, and includes a poly(A) tail. What applicants presently believe to be the proper 2 5 reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:22. Amino acids 63 to 75 of SEQ ID N0:22 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 76. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 3 0 the predicted leader/signal sequence not be separated from the remainder of the vc5_1 protein.
Another potential vc5_1 reading frame and predicted amino acid sequence is encoded by basepairs 215-376 of SEQ ID N0:21 and is reported in SEQ ID NO:100.
Amino acids 4 to 16 of SEQ ID NO:10(? are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 17 of SEQ ID N0:100.
The EcoRI/NotI restriction fragment obtainable from the deposit containing done vc5_1 should be approximately 1650 bp.
The nucleotide sequence disclosed herein for vc5_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc5_1 demonstrated at least some similarity with sequences identified as AA002211 (zh81h07.s1 Soares fetal liver spleen 1NFLS S1 Homo sapiens cDNA clone 4277413'}. Based upon sequence similarity, vc5_1 proteins and each similar protein or peptide may share at least some activity.
vc5_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 28 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vc7 1"
A polynucleotide of the present invention has been identified as clone "vc7 1".
vc7 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc7 1 is a full-length clone, including the entire coding 2 0 sequence of a secreted protein (also referred to herein as "vc7 1 protein").
The nucleotide sequence of vc7_1 as presently determined is reported in SEQ ID
N0:23, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc7_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:24. Amino acids 11 to 23 2 5 of SEQ ID N0:24 are a possible leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc7 1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vc7 1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. No hits were found in the database.
Clone"vc9 1"
A polynucleotide of the present invention has been identified as clone "vc9_1".
v~ 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc9_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "v~ 1 protein').
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:25, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:26. Amino acids 10 to 22 of SEQ ID N0:26 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the v~ 1 protein.
Another potential v~ 1 reading frame and predicted amino acid sequence is encoded by basepairs 1981 to 2619 of SEQ ID N0:25 and is reported in SEQ ID
N0:101.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone v~ 1 should be approximately 4500 bp.
2 0 The nucleotide sequence disclosed herein for v~ 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using B1.,ASTN/BLASTX and FASTA search protocols. vc9_1 demonstrated at least some similarity with sequences identified as N66453 (yz41a08.s1 Homo Sapiens cDNA clone 285590 3') and 275407 (Human DNA sequence from cosmid N128A12 on chromosome 22q12-qter contains ESTs, 2 5 CpG island). Based upon sequence similarity, v~ 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the v~ 1 protein sequence at the extreme C-terminus of SEQ ID N0:26.
3 0 Clone "vcl0 1"
A polynucleotide of the present invention has been identified as clone "vcl0_1".
vcl0_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl0_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl0_1 protein").
The nucleotide sequence of vcl0_1 as presently determined is reported in SEQ
ID
N0:27, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl0_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:28. Amino acids 21 to 33 of SEQ ID N0:28 are a possible leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 34.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcl0_1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vcl0_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcl0_1 demonstrated at least some similarity with sequences identified as AA398711 (zt75a05.s1 Soares testis NHT Homo sapiens cDNA clone 3') and T24621 {Human gene signature HUMGS06681). Based upon sequence similarity, vcl0_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the vcl0_1 protein sequence centered around amino acid 74 of SEQ ID N0:28.
Nuclotides 1103 to 1191 of SEQ ID N0:27 represent a possible intron in the predicted 3' untranslated 2 0 region of the vcl0_1 mRNA molecule.
Clone"vcll 1"
A polynucleotide of the present invention has been identified as clone "vcll_1".
vcll_1 was isolated from a human fetal brain cDNA library and was identified as 2 5 encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl l 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcll_1 protein').
The nucleotide sequence of vcll 1 as presently determined is reported in SEQ
ID
N0:29, and includes a poly(A) tail. What applicants presently believe to be the proper 3 0 reading frame and the predicted amino acid sequence of the vcll 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:30. Amino acids 6 to 18 of SEQ ID N0:30 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 19. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcll_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcll_1 should be approximately 2600 bp.
The nucleotide sequence disclosed herein for vcll 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcll_1 demonstrated at Least some similarity with sequences identified as AA193348 (zr41c08.r1 Soares NhHMPu S1 Homo Sapiens cDNA clone 5') and T23590 (Human gene signature HIJMGS05443). Based upon sequence similarity, vcll 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the vcll 1 protein sequence centered around amino acid 32 of SEQ ID N0:30.
Clone"vcl4 1"
A polynucleotide of the present invention has been identified as clone "vcl4_1".
vcl4_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl4_1 protein").
2 0 The nucleotide sequence of vcl4_1 as presently determined is reported in SEQ ID
N0:31, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:32. Amino acids 21 to 33 of SEQ ID N0:32 are a predicted leader/signal sequence, with the predicted mature 2 5 amino acid sequence beginning at amino acid 34. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcl4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 3 0 vcl4_1 should be approximately 1300 bp.
The nucleotide sequence disclosed herein for vcl4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcl4_1 demonstrated at least some similarity with sequences identified as AA258182 (zs35f09.s1 NCI_CGAP_GCB1 Homo sapiens cDNA clone IMAGE
687209 3'). The predicted amino acid sequence disclosed herein for vcl4_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX
search protocol. The predicted vcl4 1 protein demonstrated at least some similarity to sequences identified as AC002339 (BAC T11A7 (Arabidopsis thaliana]) and 271266 (R06C7.6 [Caenorhabditis elegans]). Based upon sequence similarity, vcl4_1 proteins and each similar protein or peptide may share at least some activity.
vcl4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 22 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone"vcl6 1"
A polynucleotide of the present invention has been identified as clone "vcl6_1".
vcl6_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vcl6_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl6_1 protein"}.
The nucleotide sequence of vcl6_1 as presently determined is reported in SEQ
ID
N0:33, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl6_1 protein corresponding 2 0 to the foregoing nucleotide sequence is reported in SEQ ID N0:34. Amino acids 15 to 27 of SEQ ID N0:34 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcl6_1 2 5 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcl6_1 should be approximately 1256 bp.
The nucleotide sequence disclosed herein for vcl6_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and 3 0 FASTA search protocols. vcl6_1 demonstrated at least some similarity with sequences identified as AA776882 (ac40a09.s1 Stratagene hNT neuron (#937233) Homo sapiens cDNA clone 858904 3' similar to SW XB3_XENLA Q09004 STATHMIN-LIKE
PROTEIN XB3, mRNA sequence), AF026528 (Rattus norvegicus stathmin-like-protein RB3 mRNA, complete cds), and AF026529 (Rattus norvegicus stathmin-like-protein splice variant RB3' mRNA, complete cds). The predicted amino acid sequence disclosed herein for vcl6_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vcl6_1 protein demonstrated at least some siirularity to sequences identified as AF026528 (stathmin-like-protein RB3 [Rattus norvegicus]). While stathmin itself is intracellular, stathmin-related protein RB3 (as well as related proteins SCG10 in rat and XB3 in Xenopus) is membrane-associated and has been isolated in the membrane fraction from cell cultures. RB3 is expressed in neural tissue and may be involved in the expression of differentiated neuronal function. Based upon sequence similarity, vcl6_1 proteins and each similar protein or peptide may share at least some activity.
vcl6_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 89 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vcl7 1"
A polynucleotide of the present invention has been identified as clone "vcl7 1".
vcl7 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the 2 0 amino acid sequence of the encoded protein. vcl7 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vcl7 1 protein").
The nucleotide sequence of vcl7 1 as presently determined is reported in SEQ
ID
N0:35, and includes a poly{A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vcl7 1 protein corresponding 2 5 to the foregoing nucleotide sequence is reported in SEQ ID N0:36. Amino acids 30 to 42 of SEQ ID N0:36 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 43. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vcl7 1 3 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vcl7_1 should be approximately 1783 bp.
The nucleotide sequence disclosed herein for vcl7_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vcl7_1 demonstrated at least some similarity with sequences identified as N73805 (yz80g02.s 1 Homo sapiens cDNA clone 289394 3'), and (Human gene signature HLTMGS06471). Based upon sequence similarity, vcl7 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII
computer program predicts an additional potential transmembrane domain within the vcl7 1 protein sequence centered around amino acid 60 of SEQ ID N0:36.
Clone "vc21 1"
A polynucleotide of the present invention has been identified as clone "vc21 1".
vc21 1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc21 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc21_1 protein").
The nucleotide sequence of vc21_1 as presently determined is reported in SEQ
ID
N0:37, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc21 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:38. Amino acids 11 to 23 2 0 of SEQ ID N0:38 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc21_1 protein.
2 5 Another potential vc21 1 reading frame and predicted amino acid sequence is encoded by basepairs 796 to 1014 of SEQ ID N0:37 and is reported in SEQ ID
N0:102.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc21 1 should be approximately 1773 bp.
The nucleotide sequence disclosed herein for vc21 1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc21 1 demonstrated at least some similarity with sequences identified as W85910 (zh52b10.s1 Soares fetal liver spleen 1NFLS S1 Homo sapiens cDNA clone 415675 3', mRNA sequence) and T24609 (Human gene signature HUMGS06668). Based upon sequence similarity, vc21 1 proteins and each similar protein or peptide may share at least some activity.
Gone "vc23 1"
A polynucleotide of the present invention has been identified as clone "vc23_1".
vc23_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc23_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc23_2 protein").
The nucleotide sequence of vc23_1 as presently determined is reported in SEQ
ID
N0:39, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:40. Amino acids 28 to 40 of SEQ ID N0:40 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 41. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc23_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 2 0 vc23_1 should be approximately 1998 bp.
The nucleotide sequence disclosed herein for vc23_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc23_1 demonstrated at least some similarity with sequences identified as AA580484 (nn22a05.s 1 NCI CGAP_Co 12 Homo sapiens cDNA clone 2 5 IMAGE:1084592 similar to TR:G 1209718 G 1209718 HYPOTHETICAL 50.1 KD
PROTEIN, mRNA sequence), T25530 (Human gene signature HUMGS07700), U41293 (Saccharomyces cerevisiae putative serine/threonine protein kinase gene, putative ribosomal protein L25 gene, and malate dehydrogenase (MDH2) gene, complete cds), and 274866 (S.cerevisiae chromosome XV reading frame ORF YOL124c). The predicted 3 0 amino acid sequence disclosed herein for vc23_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc23_1 protein demonstrated at least some similarity to sequences identified as U41293 (unknown [Saccharomyces cerevisiae]) and 274866 (ORF YOL124c [Saccharo-myces cerevisiae]). Based upon sequence similarity, vc23_1 proteins and each similar protein or peptide may share at least some activity. The vc23_1 protein contains a "N-6 adenine-specific DNA methylases signature" motif. The TopPredII computer program predicts a potential transmembrane domain within the vc23_I protein sequence centered around amino acid 232 of SEQ ID N0:40.
vc23_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 51 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vc25 1"
A polynucleotide of the present invention has been identified as clone "vc25_1".
vc25_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc25_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc25_1 protein").
The nucleotide sequence of v~ 1 as presently determined is reported in SEQ ID
N0:41, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the v~ 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:42. Amino acids 25 to 37 2 0 of SEQ ID N0:42 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 38. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc25_1 protein.
2 5 The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc25_1 should be approximately 1653 bp.
The nucleotide sequence disclosed herein for v~ 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc25_1 demonstrated at least some similarity with sequences 3 0 identified as N21690 (yx63h08.s1 Soares melanocyte 2NbHM Homo Sapiens cDNA
clone 266463 3', mRNA sequence) and T25257 (Human gene signature HUMGS07418). Based upon sequence similarity, vc25_1 proteins and each similar protein or peptide may share at least some activity.
vc25_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 15 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vc26 1"
A polynucleotide of the present invention has been identified as clone "vc26_1".
vc26_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc26_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc26_1 protein").
The nucleotide sequence of vc26_1 as presently determined is reported in SEQ
ID
N0:43, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc26_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:44. Amino acids 11 to 23 of SEQ ID N0:44 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vc26_1 protein.
2 0 If the "G" residue at position 669 of SEQ ID N0:43 were deleted to create a frameshft, another potential vc26_1 reading frame and predicted amino acid sequence could be encoded by what would then be basepairs 87 to 992 of the deletion-containing version of SEQ ID N0:43. This potential vc26_1 reading frame and predicted amino acid sequence is reported in SEQ ID N0:103. Amino acids 11 to 23 of both SEQ ID
N0:44 and 2 5 SEQ ID N0:103 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc26_1 should be approximately 1982 bp.
The nucleotide sequence disclosed herein for vc26_1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vc26_1 demonstrated at least some similarity with sequences identified as AA877534 (nrO1g08.s 1 NCI CGAP_Co 10 Homo sapiens cDNA clone IMAGE:1160606 3', mRNA sequence) and T25645 (Human gene signature HUMGS07835). The predicted vc26_1 protein of SEQ ID NO:10 contains an immuno-globulins and major histocompatibility complex proteins signature at amino acid 131.
Based upon sequence similarity, vc26_1 proteins and each similar protein or peptide may share at least some activity. The TopPredlI computer program predicts seven additional potential transmembrane domains within the vc26_1 protein sequence, centered around amino acids 60,100,120,160, 210, 250, and 290 of SEQ ID N0:44, respectively.
Clone"vc30 1"
A polynucleotide of the present invention has been identified as clone "vc30_1".
vc30_1 was isolated from a human fetal brain cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vc30_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vc30_1 protein").
The nucleotide sequence of vc30_l as presently determined is reported in SEQ
ID
N0:45, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vc30_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:46. Amino acids 19 to 31 of SEQ ID N0:46 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vc30_1 protein.
If a frameshift were introduced in the nucleotide sequence of SEQ ID N0:45 by deleting the cytosine residue at position 1393, another potential vc30_1 reading frame and predicted amino acid sequence could be encoded by what would then be basepairs 2 5 to 1659 of SEQ ID N0:45 and is reported in SEQ ID N0:104.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vc30_1 should be approximately 1887 bp.
The nucleotide sequence disclosed herein for vc30_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and 3 0 FASTA search protocols. vc30_1 demonstrated at least some similarity with sequences identified as AA496421 (zv37c04.r1 Soares ovary tumor NbHOT Homo sapiens cDNA
clone 755814 5', mRNA sequence). The predicted amino acid sequence disclosed herein for vc30_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc30_l protein demonstrated at least some similarity to sequences identified as AF047760 (phosphatidic acid phosphohydrolase type 2c [Homo sapiens]). Based upon sequence similarity, vc3a_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII
computer program predicts an additional potential transmembrane domain within the vc30_1 protein sequence centered around amino acid 55 of SEQ ID N0:46.
Clone "vdl 1"
A polynucleotide of the present invention has been identified as clone "vd1 1".
vdl 1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vdl_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vdl 1 protein").
The nucleotide sequence of vdl_1 as presently determined is reported in SEQ ID
N0:47, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd1 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:48. Amino acids 8 to 20 of SEQ ID N0:48 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vd1_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vd1 1 should be approximately 2000 bp.
The nucleotide sequence disclosed herein for vdl 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vdl_1 demonstrated at least some similarity with sequences identified as AA582963 (nn72e02.s1 NCI_CGAP_Larl Homo sapiens cDNA clone IMAGE
1089434) and AC002389 (Human DNA from chromosome 19 specific cosmid 828461, genomic sequence, complete sequence). Based upon sequence similarity, vdl 1 proteins 3 0 and each similar protein or peptide may share at least some activity.
There is an 18-residue amino acid stretch (with an approximate consensus sequence shown in SEQ ID
N0:105 {HHAAGQAGNEAGRFGQG~) that is almost tandemly repeated 25 times in the vd1 1 protein. Nucleotides 406-1668 of SEQ ID N0:47, which encode a region of SEQ ID
WO 99/SS'I21 PCT/US99/08504 N0:48 that includes the 18-residue amino acid repeats, may represent an alternatively spliced region in mRNA molecules transcribed from the vdl 1 gene.
vdl_protein was expressed in a COS cell expression system, and an expressed protein band of approximately 55 kDa was detected in conditioned medium using SDS
polyacrylamide gel electrophoresis.
Clone "vd2 1"
A polynucleotide of the present invention has been identified as clone "vd2_1".
vd2_1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vd2_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vd2_1 protein') The nucleotide sequence of vd2_1 as presently determined is reported in SEQ ID
N0:49, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd2_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:50. Amino acids 2 to 14 of SEQ ID N0:50 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vd2_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing done vd2_1 should be approximately 900 bp.
The nucleotide sequence disclosed herein for vd2_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vd2_1 demonstrated at least some similarity with sequences identified as H03945 (yj44c02.s1 Homo sapiens cDNA clone 151586 3'). Based upon sequence similarity, vd2_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts a potential transmembrane 3 0 domain within the vd2_1 protein sequence centered around amino acid 115 of SEQ ID
N0:50.
Clone "vd3 1"
A polynudeotide of the present invention has been identified as clone "vd3_1".
vd3_1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vd3_1 is a full-length done, including the entire coding sequence of a secreted protein (also referred to herein as "vd3_1 protein').
The nucleotide sequence of vd3_1 as presently determined is reported in SEQ ID
N0:51, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd3_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:52. Amino acids 5 to 17 of SEQ ID N0:52 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vd3_1 protein.
If a frameshift were introduced into the nucleotide sequence of SEQ ID N0:19 by inserting an adenine or thymine residue at position 1132 or 1133, another potential vd3_1 reading frame and predicted amino acid sequence could be encoded by basepairs 176 to 1281 of SEQ ID N0:51 and is reported in SEQ ID N0:106. Amino acids 5 to 17 of SEQID
2 0 N0:106 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18 of SEQ ID N0:106, or are a transmembrane domain.
The EcoRI/NotI restriction fragment obtainable from the deposit containing done vd3_1 should be approximately 1537 bp.
The nucleotide sequence disclosed herein for vd3_1 was searched against the 2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vd3_1 demonstrated at least some similarity with sequences identified as AA873028 (ob11e05.s1 NCI CGAP_Kid3 Homo sapiens cDNA clone IMAGE 1323392 3', mRNA sequence), AC002389 (Human DNA from chromosome 19 specific cosmid 828461, genomic sequence, complete sequence), and AD001502 (Homo 3 0 sapiens DNA from chromosome 19-cosmid (21246, genomic sequence). Based upon sequence similarity, vd3_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts an additional possible transmembrane domain within the vd3_1 protein sequence centered around amino acid 290 of SEQ ID N0:52. The vd3_1 protein is apparently a splice variant of the vd4 1 protein described below.
vd3_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 42 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vd4 1"
A polynucleotide of the present invention has been identified as clone "vd4_1".
vd4_1 was isolated from a human adult skin cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vd4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vd4_1 protein").
The nucleotide sequence of vd4_1 as presently determined is reported in SEQ ID
N0:53, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vd4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:54. Amino acids 5 to 17 of SEQ ID N0:54 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 0 the predicted leader/signal sequence not be separated from the remainder of the vd4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vd4_1 should be approximately 1897 bp.
The nucleotide sequence disclosed herein for vd4 1 was searched against the 2 5 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vd4_2 demonstrated at least some similarity with sequences identified as AA706316 (ah28e1l.sl Soares parathyroid tumor NbHPA Homo sapiens cDNA clone 1240172 3', mRNA sequence), AC002389 (Human DNA from chromosome 19 specific cosmid 828461, genomic sequence, complete sequence), and AD001502 3 0 (Homo sapiens DNA from chromosome 19-cosmid f21246, genomic sequence).
Based upon sequence similarity, vd4_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts an additional possible transmembrane domain within the vd4_1 protein sequence centered around amino acid 290 of SEQ ID N0:54. The vd4_1 protein is apparently a splice variant of the vd3_1 protein described above.
vd4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 54 kDa was detected in conditioned medium using SDS
polyacxylamide gel electrophoresis.
Clone "ve4 1"
A polynucleotide of the present invention has been identified as clone "ve4_1".
ve4_1 was isolated from a human adult brain (Alzheimer s hippocampus level 7) cDNA
library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. ve4_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "ve4_1 protein").
The nucleotide sequence of ve4_1 as presently determined is reported in SEQ ID
N0:55, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the ve4_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:56. Amino acids 25 to 37 of SEQ ID N0:56 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 38. Due to the hydrophobic nature of the 2 0 predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the ve4_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone ve4_1 should be approximately 1578 bp.
2 5 The nucleotide sequence disclosed herein for ve4_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. ve4_1 demonstrated at least some similarity with sequences identified as AA707153 (zj33f10.s1 Soares fetal liver spleen 1NFT.S S1 Homo sapiens cDNA clone 452107 3' similar to TR P70295 P70295 AUP1 PRECURSOR, mRNA
3 0 sequence} and U41736 (Mus musculus ancient ubiquitous 46 kDa protein AUP1 precursor (Aup 1 ) mRNA, complete cds). The predicted amino acid sequence disclosed herein for ve4_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted ve4_1 protein demonstrated at least some similarity to the sequence identified as U41736 (ancient ubiquitous 46 kDa protein AUP46 precursor [Mus musculus]). Based upon sequence similarity, ve4_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts two additional potential transmembrane domains within the ve4_ 1 protein sequence, one centered around amino acid 110 and another around amino acid 210 of SEQ m N0:56.
ve4_1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 41 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "ve8 1"
A polynucleotide of the present invention has been identified as clone "ve8_1".
ve8_1 was isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA
library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. ve8_1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "ve8_1 protein").
The nucleoside sequence of ve8_i as presently determined is reported in SEQ ID
N0:57, and includes a poly(A) tail. What applicants presently believe to be the proper 2 0 reading frame and the predicted amino acid sequence of the ve8_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:58. Amino acids 18 to 30 of SEQ ID N0:58 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 31. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should 2 5 the predicted leader/signal sequence not be separated from the remainder of the ve8_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone ve8_1 should be approximately 2093 bp.
The nucleotide sequence disclosed herein for ve8_1 was searched against the 3 0 GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. ve8_1 demonstrated at least some similarity with sequences identified as AC004126 (Homo Sapiens Chromosome l 1q12 pac pDJ606g6; HTGS
phase 1, 17 unordered pieces). Based upon sequence similarity, ve8_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts four additional potential transmembrane domains within the ve8_1 protein sequence, centered around amino acids 94, 147, 150, and 193 of SEQ ID N0:58, respectively.
Clone "vf1 1"
A polynucleotide of the present invention has been identified as clone "vf1_1".
vfl 1 was isolated from a human adult heart cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vfl 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vf1_1 protein").
The nucleotide sequence of vfl 1 as presently determined is reported in SEQ ID
N0:59, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vf1 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:60. Amino acids 13 to 25 of SEQ ID N0:60 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vf1_1 2 0 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vfl 1 should be approximately 1382 bp.
The nucleotide sequence disclosed herein for vfl_1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and 2 5 FASTA search protocols. vfl_1 demonstrated at least some similarity with sequences identified as AA349531 (EST56314 Infant brain Homo sapiens cDNA 5' end, mRNA
sequence) and AA532642 (nj17c07.s1 NCI_CGAP Pr22 Homo sapiens cDNA clone IMAGE 986604, mRNA sequence). Based upon sequence similarity, vfl 1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer 3 0 program predicts an additional potential transmembrane domain within the vfl_1 protein sequence centered around amino acid 138 of SEQ ID N0:60.
vf1 1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 40 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Clone "vhl 1"
A polynucleotide of the present invention has been identified as clone "vhl 1".
vhl_1 was isolated from a human adult thymus cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vhl 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "vhf 1 protein').
The nucleotide sequence of vh1_1 as presently determined is reported in SEQ ID
N0:61, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vhl_1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:62. Amino acids 42 to 54 of SEQ ID N0:62 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 55. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vh1_1 protein.
2 0 Another potential vhl_1 reading frame and predicted amino acid sequence that could be encoded by basepairs 833 to 1054 of SEQ ID N0:61 is reported in SEQ
ID
N0:107. Amino aclds 22 to 34 of SEQ ID N0:107 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 35 of SEQ ID
N0:107, or are a transmembrane domain. If a frameshift were introduced into the 2 5 nucleotide sequence of SEQ ID N0:61 approximately between position 830 and position 998, the open reading frame of SEQ ID N0:62 could be joined to the open reading frame of SEQ ID N0:107.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone vhl 1 should be approximately 1529 bp.
3 0 The nucleotide sequence disclosed herein for vhl 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vhl_1 demonstrated at least some similarity with sequences identified as AA927736 (om72h10.s1 NCI CGAP_GC4 Homo sapiens cDNA clone IMAGE:1552771 3', mRNA sequence). Based upon sequence similarity, vhf 1 proteins and each similar protein or peptide may share at least some activity.
Clone "vil 1"
A polynucleotide of the present invention has been identified as clone "vi1_1".
vi1_1 was isolated from a human adult aorta cDNA library and was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. vil 1 is a full-length clone, including the entire coding sequence of a secreted protein (also referred to herein as "viI 1 protein").
The nucleotide sequence of vi1_1 as presently determined is reported in SEQ ID
N0:63, and includes a poly(A) tail. What applicants presently believe to be the proper reading frame and the predicted amino acid sequence of the vi1 1 protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID N0:64. Amino acids 13 to 25 of SEQ ID N0:64 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the vi1_1 protein.
The EcoRI/NotI restriction fragment obtainable from the deposit containing clone 2 0 vil 1 should be approximately 2348 bp.
The nucleotide sequence disclosed herein for vi1 1 was searched against the GenBank and GeneSeq nucleotide sequence databases using BLASTN/BLASTX and FASTA search protocols. vil_1 demonstrated at least some similarity with sequences identified as AA411541 (zv30a03.r1 Soares ovary tumor NbHOT Homo sapiens cDNA
2 5 clone 755116 S' similar to WP:F07H5.1 I CE03160) and T21484 (Human gene signature HUMGS02856). The predicted amino acid sequence disclosed herein for vil_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted viI_1 protein demonstrated at least some similarity to the sequence identified as 268314 (F46C5.9 [Caenorhabditis elegans]). The 3 0 amino acid sequence of the predicted vil_1 protein indicates that it may contain a beta-transducin family Trp-Asp repeat signature (WD-40} motif centered around residue 300 of SEQ ID N0:28. The WD-40 motif is thought to be a widely distributed protein-protein interaction domain. Based upon sequence similarity, vil_1 proteins and each similar protein or peptide may share at least some activity. The TopPredII computer program predicts two additional possible transmembrane domains within the vi 1_ 1 protein sequence, one centered around amino acid 200 and another around amino acid 340 of SEQ
m N0:64.
vi 1 _ 1 protein was expressed in a COS cell expression system, and an expressed protein band of approximately 45 kDa was detected in membrane fractions using SDS
polyacrylamide gel electrophoresis.
Deposit of Clones Clones vc3_l, vc4_l, v~ 1, vc7 1, vc9_1, vcl0_1, vcll 1, vcl4_1, vd1_l, and vd2_1 were deposited on April 24,1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98748, from which each clone comprising a particular polynucleotide is obtainable.
Clone vc21_1 was deposited on June 10, 1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and was given the accession number ATCC
98785, from which each clone comprising a particular polynucleotide is obtainable.
Clones vcl6_1, vcl7 1, v~ 1, vc25_1, vc26_1, ve4_l, and vfl 1 were deposited 2 0 on June 10,1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98784, from which each clone comprising a particular polynucleotide is obtainable.
Clones vb2_1, vb3_l, vb4_l, vb5_l, vb6_l, vb7_l, vb8_1, vb9_l, vc30_l, vd3_l, 2 5 vd4_l, ve8_l, vhl_l, and vil 1 were deposited on July 1,1998 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98804, from which each clone comprising a particular polynucleotide is obtainable.
All restrictions on the availability to the public of the deposited material will be 3 0 irrevocably removed upon the granting of the patent, except for the requirements specified in 37 C.F.R. ~ 1.808(b), and the term of the deposit will comply with 37 C.F.R.
~ 1.806.
Each clone has been transfected into separate bacterial cells (E. coli) in these composite deposits. Each clone can be removed from the vector in which it was deposited by performing an EcoRI/NotI digestion (5' site, EcoRI; 3' site, NotI) to produce the appropriate fragment for such clone. Each clone was deposited in either the pED6 or pNOTs vector depicted in Figures lA and 1B, respectively. The pED6dpc2 vector ("pED6") was derived from pED6dpc1 by insertion of a new polylinker to facilitate cDNA cloning (Kaufman et al.,1991, Nucleic Acids Res.19: 4485-4490); the pNOTs vector was derived from pMT2 (Kaufman et al.,1989, Mol. Cell. Biol. 9: 946-958) by deletion of the DHFR sequences, insertion of a new polylinker, and insertion of the M13 origin of replication in the CIaI site. In some instances, the deposited clone can become "flipped"
(i.e., in the reverse orientation) in the deposited isolate. In such instances, the cDNA insert can still be isolated by digestion with EcoRI and NotI. However, NotI will then produce the 5' site and EcoRI will produce the 3' site for placement of the cDNA in proper orientation for expression in a suitable vector. The cDNA may also be expressed from the vectors in which they were deposited.
Bacterial cells containing a particular clone can be obtained from the composite deposit as follows:
An oligonucleotide probe or probes should be designed to the sequence that is known for that particular clone. This sequence can be derived from the sequences 2 0 provided herein, or from a combination of those sequences. The sequence of an oligonucleotide probe that was used to isolate or to sequence each full-length clone is identified below, and should be most reliable in isolating the clone of interest.
Clone Probe uence 2 5 vb2_1 SEQ ID N0:65 vb3_i SEQ ID N0:66 vb4_1 SEQ ID N0:67 vb5_1 SEQ ID N0:68 vb6_1 SEQ ID N0:69 3 0 vb7_1 SEQ ID N0:70 vb8 1 SEQ ID N0:71 vb9_1 SEQ ID N0:72 vc3_1 SEQ ID N0:73 vc4_1 SEQ ID N0:74 vc5_1 SEQ ID N0:75 vc7 1 SEQ ID N0:76 vc9_1 SEQ ID N0:77 vcl0_1 SEQ ID N0:78 vcll_1 SEQ ID N0:79 vcl4_1 SEQ ID N0:80 vcl6_1 SEQ ID N0:81 vcl7_1 SEQ ID N0:82 vc21_1 SEQ ID N0:83 vc23_1 SEQ ID N0:84 vc25_1 SEQ ID N0:85 vc26_1 SEQ ID N0:86 vc30_1 SEQ ID N0:87 vd1 1 SEQ ID N0:88 vd2_1 SEQ ID N0:89 vd3_1 ~ SEQ ID N0:90 vd4_1 SEQ ID N0:91 ve4_1 SEQ ID N0:92 ve8_1 SEQ ID N0:93 2 0 vfl_1 SEQ ID N0:94 vhf 1 SEQ ID N0:95 vil_1 SEQ ID N0:96 In the sequences listed above which include an N at position 2, that position is occupied in preferred probes/primers by a biotinylated phosphoaramidite residue rather than a nucleotide (such as, for example, that produced by use of biotin phosphoramidite (1-dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-O-(2-cyanoethyl)-(N,N-diisopropyl)-phosphoramadite) (Glen Research, cat. no.10-1953)).
The design of the oligonucleotide probe should preferably follow these 3 0 parameters:
(a) It should be designed to an area of the sequence which has the fewest ambiguous bases ("N's"), if any;
(b) It should be designed to have a T," of approx. 80 ° C (assuming 2° for each A or T and 4 degrees for each G or C).
The oligonucleotide should preferably be labeled with y 32P ATP (specific activity 6000 Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for labeling oligonucleotides. Other labeling techniques can also be used.
Unincorporated label should preferably be removed by gel filtration chromatography or other established methods. The amount of radioactivity incorporated into the probe should be quantitated by measurement in a scintillation counter. Preferably, specific activity of the resulting probe should be approximately 4e+6 dpm/pmole.
The bacterial culture containing the pool of full-length clones should preferably be thawed and 100 lxl of the stock used to inoculate a sterile culture flask containing 25 ml of sterile L-broth containing ampicillin at 100 pg/ml. The culture should preferably be grown to saturation at 37°C, and the saturated culture should preferably be diluted in fresh L broth. Aliquots of these dilutions should preferably be plated to determine the dilution and volume which will yield approximately 5000 distinct and well-separated colonies on solid bacteriological media containing L-broth containing ampicillin at 100 ug/ml and agar at 1.5% in a 150 mm petri dish when grown overnight at 37°C. Other known methods of obtaining distinct, well-separated colonies can also be employed.
Standard colony hybridization procedures should then be used to transfer the colonies to nitrocellulose filters and lyse, denature and bake them.
The filter is then preferably incubated at 65°C for 1 hour with gentle agitation in 2 0 6X SSC (20X stock is 175.3 g NaCI/liter, 88.2 g Na citrate/liter, adjusted to pH 7.0 with NaOH) containing 0.5% SDS,100 pg/ml of yeast RNA, and 10 mM EDTA
(approximately 10 mL per 150 mm filter). Preferably, the probe is then added to the hybridization mix at a concentration greater than or equal to 1e+6 dpm/mL. The filter is then preferably incubated at 65°C with gentle agitation overnight. The filter is then preferably washed in 2 5 500 mL of 2X SSC/0.5% SDS at room temperature without agitation, preferably followed by 500 mL of 2X SSC/0.1% SDS at room temperature with gentle shaking for 15 minutes.
A third wash with O.1X SSC/0.5% SDS at 65°C for 30 minutes to 1 hour is optional. The filter is then preferably dried and subjected to autoradiography for sufficient time to visualize the positives on the X-ray film. Other known hybridization methods can also 3 0 be employed.
The positive colonies are picked, grown in culture, and plasmid DNA isolated using standard procedures. The clones can then be verified by restriction analysis, hybridization analysis, or DNA sequencing.
Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H.U. Saragovi, et al., Bio/Technology 1~,0 773-778 (1992) and in R.S.
McDowell, et al., J. Amer. Chem. Soc.114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may be fused to earner molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites. For example, fragments of the protein may be fused through "linker"
sequences to the Fc portion of an immunoglobulin. For a bivalent form of the protein, such a fusion could be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes may also be used to generate such fusions. For example, a protein - IgM fusion would generate a decavalent form of the protein of the invention.
The present invention also provides both full-length and mature forms of the disclosed proteins. The full-length form of the such proteins is identified in the sequence 25 listing by translation of the nucleotide sequence of each disclosed clone.
The mature forms) of such protein may be obtained by expression of the disclosed full-length polynucleotide (preferably those deposited with ATCC) in a suitable mammalian cell or other host cell. The sequences) of the mature forms) of the protein may also be determinable from the amino acid sequence of the full-length form.
2 0 The present invention also provides genes corresponding to the polynucleotide sequences disclosed herein. "Corresponding genes" are the regions of the genome that are transcribed to produce the mRNAs from which cDNA polynucleotide sequences are derived and may include contiguous regions of the genome necessary for the regulated expression of such genes. Corresponding genes may therefore include but are not limited 2 5 to coding sequences, 5' and 3' untranslated regions, alternatively spliced exons, introns, promoters, enhancers, and silencer or suppressor elements. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate 3 0 genomic libraries or other sources of genomic materials. An "isolated gene" is a gene that has been separated from the adjacent coding sequences, if any, present in the genome of the organism from which the gene was isolated.
The chromosomal location corresponding to the polynucleotide sequences disclosed herein may also be determined, for example by hybridizing appropriately labeled polynucleotides of the present invention to chromosomes in situ. It may also be possible to determine the corresponding chromosomal location for a disclosed polynucleotide by identifying significantly similar nucleotide sequences in public databases, such as expressed sequence tags (ESTs), that have already been mapped to particular chromosomal locations. For at least some of the polynucleotide sequences disclosed herein, public database sequences having at least some similarity to the polynucleotide of the present invention have been listed by database accession number.
Searches using the GenBank accession numbers of these public database sequences can then be performed at an Internet site provided by the National Center for Biotechnology Information having the address http://www.ncbi.nlin.nih.gov/UruGene/, in order to identify "UniGene clusters" of overlapping sequences. Many of the "UniGene clusters"
so identified will already have been mapped to particular chromosomal sites.
Organisms that have enhanced, reduced, or modified expression of the genes) corresponding to the polynucleotide sequences disclosed herein are provided.
The desired change in gene expression can be achieved through the use of antisense polynucleotides or ribozymes that bind and/or cleave the mItNA transcribed from the gene (Albert and Morris,1994, Trends Pharmacol. Sci.15(7): 250-254; Lavarosky et al.,1997, Biochem. Mol. Med. 62(1):11-22; and Hampel,1998, Prog. Nucleic Acid Res. Mol.
Biol. 58:1-39; all of which are incorporated by reference herein). Transgenic animals that have 2 0 multiple copies of the genes) corresponding to the polynucleotide sequences disclosed herein, preferably produced by transformation of cells with genetic constructs that are stably maintained within the transformed cells and their progeny, are provided.
Transgenic animals that have modified genetic control regions that increase or reduce gene expression levels, or that change temporal or spatial patterns of gene expression, are 2 5 also provided (see European Patent No. 0 649 464 Bl, incorporated by reference herein).
In addition, organisms are provided in which the genes) corresponding to the polynucleotide sequences disclosed herein have been partially or completely inactivated, through insertion of extraneous sequences into the corresponding genes) or through deletion of all or part of the corresponding gene(s). Partial or complete gene inactivation 3 0 can be accomplished through insertion, preferably followed by imprecise excision, of transposable elements (Plasterk,1992, Bioessays 14(9): 629-633; Zwaal et al.,1993, Proc. Natl.
Acad. Sci. USA 90(16): 7431-79:35; Clark et aL,1994, Proc. Natl. Acad. Sci.
LISA 91(2): 719-722;
all of which are incorporated by reference herein), or through homologous recombination, preferably detected by positive/negative genetic selection strategies (Mansour et aL,1988, Nature 336: 348-352; U.S. Patent Nos. 5,464,764; 5,487,992; 5,627,059;
5,631,153; 5,614, 396;
5,616,491; and 5,679,523; all of which are incorporated by reference herein).
These organisms with altered gene expression are preferably eukaryotes and more preferably are mammals. Such organisms are useful for the development of non-human models for the study of disorders involving the corresponding gene(s), and for the development of assay systems for the identification of molecules that interact with the protein products) of the corresponding gene(s).
Where the protein of the present invention is membrane-bound (e.g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms, part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information.
For example, the TopPredII computer program can be used to predict the location of transmembrane domains in an amino and sequence, domains which are described by the location of the center of the transmsmbrane domain, with at least ten transmembrane amino acids on each side of the reported central residue(s).
Proteins and protein fragments of the present invention include proteins with amino acid sequence lengths that are at least 25%(more preferably at least 50%, and most 2 0 preferably at least 75%) of the length of a disclosed protein and have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90%
or 95%
identity) with that disclosed protein, where sequence identity is determined by comparing the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Also included in the present invention are 2 5 proteins and protein fragments that contain a segment preferably comprising 8 or more (more preferably 20 or more, most preferably 30 or more) contiguous amino acids that shares at least 75% sequence identity (more preferably, at least 85% identity;
most preferably at least 95% identity) with any such segment of any of the disclosed proteins.
In particular, sequence identity may be determined using WU-BLAST
3 0 (Washington University BLAST) version 2.0 software, which builds upon WU-BLAST
version 1.4, which in turn is based on the public domain NCBI-BLAST version 1.4 (Altschul and Gish, 1996, Local alignment statistics, Doolittle ed., Methods in Enzymology 266: 460-480; Altschul et al., 1990, Basic local alignment search tool, Journal of Molecular Biology 215: 403-410; Gish and States, 1993, Identification of protein coding regions by database similarity search, Nature Genetics 3: 266-272; Karlin and Altschul, 1993, Applications and statistics for multiple high-scoring segments in molecular sequences, Proc. Natl. Acad. Sci. USA 90: 5873-5877; all of which are incorporated by reference herein). WU-BLAST version 2.0 executable programs for several UNIX
platforms can be downloaded from ftp://blast.wustl.edu/blasdexecutables. The complete suite of search programs (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) is provided at that site, in addition to several support programs. WU-BLAST 2.0 is copyrighted and may not be sold or redistributed in any form or manner without the express written consent of the author; but the posted executables may otherwise be freely used for commercial, nonprofit, or academic purposes. In all search programs in the suite -- BLASTP, BLASTN, BLASTX, TBLASTN and TBLASTX -- the gapped alignment routines are integral to the database search itself, and thus yield much better sensitivity and selectivity while producing the more easily interpreted output. Gapping can optionally be turned off in all of these programs, if desired. The default penalty (Q) for a gap of length one is Q=9 for proteins and BLASTP, and Q=10 for BLASTN, but may be changed to any integer value including zero, one through eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. The default per-residue penalty for extending a gap (R) is R=2 for proteins and BLASTP, and R=10 for BLASTN, 2 0 but may be changed to any integer value including zero, one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. Any combination of values for Q and R can be used in order to align sequences so as to maximize overlap and identity while minimizing sequence gaps.
The default amino acid comparison matrix is BLOSUM62, but other amino acid 2 5 comparison matrices such as PAM can be utilized.
Species homologues of the disclosed polynucleotides and proteins are also provided by the present invention. As used herein, a "species homologue" is a protein or polynucleotide with a different species of origin from that of a given protein or polynucleotide, but with significant sequence similarity to the given protein or 3 0 polynucleotide. Preferably, polynucleotide species homologues have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90%
identity) with the given polynucleotide, and protein species homologues have at least 30%
sequence identity (more preferably, at least 45% identity; most preferably at least 60%
identity) with the given protein, where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides or the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps.
Species homologues may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species. Preferably, species homologues are those isolated from mammalian species. Most preferably, species homologues are those isolated from certain mammalian species such as, for example, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, HyIobates concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus aethiops, Cebus capucinus, Aotus trivirgatus, Sanguinus Oedipus, Microcebus murinus, Mus musculus, Rattus norvegicus, Cricetulus griseus, Fells catus, Mustela vison, Canis familiaris, Oryctolagus cuniculus, Bos taurus, Ovis aries, Sus scrofa, and Eguus caballus, for which genetic maps have been created allowing the identification of syntenic relationships between the genomic organization of genes in one species and the genomic organization of the related genes in another species (O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al., 1993, Nature Genetics 3:103-112; Johansson et al.,1995, Genomics 25: 682-690; Lyons et al.,1997, Nature Genetics 15: 47 56; O'Brien et al.,1997, Trends in Genetics 13(10): 393-399;
Carver and Stubbs, 1997, Genome Research 7:1123-1137; all of which are incorporated by reference herein).
2 0 The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms of the isolated polynucleotides which also encode proteins which are identical or have significantly similar sequences to those encoded by the disclosed polynucleotides. Preferably, allelic variants have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90%
2 5 identity) with the given polynucleotide, where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides when aligned so as to maximize overlap and identity while minimizing sequence gaps. Allelic variants may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from individuals of the appropriate species.
3 0 The invention also includes polynucleotides with sequences complementary to those of the polynucleotides disclosed herein.
The present invention also includes polynucleotides that hybridize under reduced stringency conditions, more preferably stringent conditions, and most preferably highly stringent conditions, to polynucleotides described herein. Examples of stringency conditions are shown in the table below: highly stringent conditions are those that are at least as stringent as, for example, conditions A-F; stringent conditions are at least as stringent as, for example, conditions G-L; and reduced stringency conditions are at least as stringent as, for example, conditions M-R.
StringencyPolynucleotideHybrid Hybridization TemperatureWash ConditionHybrid Length and Temperature (bp)= Buffer' and Buffers A DNA:DNA 2 50 65C; lxSSC -or- 65C; 0.3xSSC
42C; lxSSC, 50% formamide B DNA:DNA <50 TB*; lxSSC TB*; lxSSC
C DNA:RNA 2 50 67C; lxSSC -or- 67C; 0.3xSSC
45C; lxSSC, 50% formamide D DNA:RNA <50 Tp*; lxSSC Tp*; lxSSC
E RNA:RNA 2 50 70C; lxSSC -or- 70C; 0.3xSSC
50C; lxSSC, 50% formamide F RNA:RNA <50 TF*; lxSSC TF*; lxSSC
G DNA:DNA 2 50 65C; 4xSSC -or- 65C; lxSSC
42C; 4xSSC, 50% formamide H DNA:DNA <50 TH*; 4xSSC TH*; 4xSSC
I DNA:RNA x 50 67C; 4xSSC -or- 67C; lxSSC
45C; 4xSSC, 50% formamide J DNA:RNA <50 TJ*; 4xSSC T~*; 4xSSC
K RNA:RNA 2 50 70C; 4xSSC -or- 67C; lxSSC
50C; 4xSSC, 50% formamide L RNA:RNA <50 T,,*; 2xSSC T~*; 2xSSC
2 M DNA:DNA 2 50 SOC; 4xSSC -or- 50C; 2xSSC
0 40C; 6xSSC, 50% formamide N DNA:DNA <50 TN*; 6xSSC T~,*; 6xSSC
O DNA:RNA 2 50 55C; 4xSSC -or- 55C; 2xSSC
42C; 6xSSC, 50% formamide P DNA:RNA <50 TP*; 6xSSC Tp*; 6xSSC
Q RNA:RNA 2 50 60C; 4xSSC -or- 60C; 2xSSC
45C; 6xSSC, SO~o formamide 2 R RNA:RNA <50 TR*; 4xSSC TR*; 4xSSC
t: The hybrid length is that anticipated for the hybridized regions) of the hybridizing polynucleotides. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is assumed to be that of the hybridizing polynucleotide. When polynucleotides of known sequence are hybridized, the 3 0 hybrid length can be determined by aligning the sequences of the polynudeotides and identifying the region or regions of optimal sequence complementarity.
t: SSPE (lxSSPE is 0.15M NaCI, lOmM NaHiPO,, and 1.25mM EDTA, pH 7.4) can be substituted for SSC
(lxSSC is 0.15M NaCI and l5mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes after hybridization is complete.
"TB - TR: The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10°C less than the melting temperature (Tm) of the hybrid, where Tm is determined according to the following equations. For hybrids less than 18 base pairs in length, T°,(°C) = 2(# of A + T bases) + 4(# of G +
C bases). For hybrids between 18 and 49 base pairs in length, T,°(°C) = 81.5 + 16.6(log,o[Na*]) + 0.41(%G+C) (600/N), where N is the number of bases in the hybrid, and [Na*] is the concentration of sodium ions in the hybridization buffer ([Na*] for lxSSC = 0.165 M).
Additional examples of stringency conditions for polynucleotide hybridization are provided in Sambrook, J., E.F. Fritsch, and T. Maniatis, 1989, Molecular Cloning: A
Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, chapters 9 and 11, and Current Protocols in Molecular Biology,1995, F.M.
Ausubel et al., eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, incorporated herein by reference.
Preferably, each such hybridizing polynucleotide has a length that is at least 25%(more preferably at least 50%, and most preferably at least 75%) of the length of the polynucleotide of the present invention to which it hybridizes, and has at least 60%
sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 2 0 95% identity) with the polynucleotide of the present invention to which it hybridizes, where sequence identity is determined by comparing the sequences of the hybridizing polynucleotides when aligned so as to maximize overlap and identity while minimizing sequence gaps.
The isolated polynucleotide of the invention may be operably linked to an 2 5 expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufman et aL, Nucleic Acids Res. ~ 4485-4490 (1991), in order to produce the protein recombinantly. Many suitable expression control sequences are known in the art. General methods of expressing recombinant proteins are also known and are exemplified in R.
Kaufman, Methods in Enzymology ~, 537-566 (1990). As defined herein "operably 3 0 linked" means that the isolated polynucleotide of the invention and an expression control sequence are situated within a vector or cell in such a way that the protein is expressed by a host cell which has been transformed (transfected) with the ligated polynucleotide/expression control sequence.
A number of types of cells may act as suitable host cells for expression of the 3 5 protein. Mammalian host cells include, for example, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Co1o205 cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid cells, cell strains derived from in yitro culture of primary tissue, primary explants, HeLa cells, mouse L cells, BHK, HL-60, U937, HaK or jurkat cells.
Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or in prokaryotes such as bacteria. Potentially suitable yeast strains include Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains, Canriida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium, or any bacterial strain capable of expressing heterologous proteins. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation of the appropriate sites, in order to obtain the functional protein. Such covalent attachments may be accomplished using known chemical or enzymatic methods.
The protein may also be produced by operably linking the isolated polynucleotide of the invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system. Materials and methods for baculovirus/insect cell expression systems are commercially available in kit form from, e.g., Invitrogen, San Diego, California, U.S.A. (the MaxBac~ kit), and such methods are well known in the art, as described in Summers and Smith, Texas Aericultural Experiment Station Bulletin No. 1555 (1987), incorporated herein by reference. As used herein, an 2 0 insect cell capable of expressing a polynucleotide of the present invention is "transformed."
The protein of the invention may be prepared by culturing transformed host cells under culture conditions suitable to express the recombinant protein. The resulting expressed protein may then be purified from such culture (i.e., from culture medium or 2 5 cell extracts) using known purification processes, such as gel filtration and ion exchange chromatography. The purification of the protein may also include an affinity column containing agents which will bind to the protein; one or more column steps over such affinity resins as concanavalin A-agarose, heparin-toyopearl~ or Cibacrom blue Sepharose~; one or more steps involving hydrophobic interaction chromatography using 3 0 such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffiruty chromatography.
Alternatively, the protein of the invention may also be expressed in a form which will facilitate purification. For example, it may be expressed as a fusion protein, such as those of maltose binding protein (MBP), glutathione-S-transferase (GST) or thioredoxin (TR7~. Kits for expression and purification of such fusion proteins are commercially available from New England BioLabs (Beverly, MA), Pharmacia (Piscataway, Nj) and Invitrogen Corporation (Carlsbad, CA), respectively. The protein can also be tagged with an epitope and subsequently purified by using a specific antibody directed to such epitope. One such epitope ("Flag") is commercially available from the Eastman Kodak Company (New Haven, CT).
Finally, one or more reverse-phase high performance liquid chromatography (lZl'-HPLC) steps employing hydrophobic 1ZP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify the protein. Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined in accordance with the present invention as an "isolated protein."
The protein of the invention may also be expressed as a product of transgeruc animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or sheep which are characterized by somatic or germ cells containing a nucleotide sequence encoding the protein.
The protein may also be produced by known conventional chemical synthesis.
Methods for constructing the proteins of the present invention by synthetic means are 2 0 known to those skilled in the art. The synthetically-constructed protein sequences, by virtue of sharing primary, secondary or tertiary structural and/or conformational characteristics with proteins may possess biological properties in common therewith, including protein activity. Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic 2 5 compounds and in immunological processes for the development of antibodies.
The proteins provided herein also include proteins characterized by amino acid sequences similar to those of purified proteins but into which modification are naturally provided or deliberately engineered. For example, modifications in the peptide or DNA
sequences can be made by those skilled in the art using known techniques.
Modifications 3 0 of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence.
For example, one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S. Patent No. 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein.
Other fragments and derivatives of the sequences of proteins which would be expected to retain protein activity in whole or in part and may thus be useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are believed to be encompassed by the presentinvention.
USES AND BIOLOGICAL ACTIVITY
The polynucleotides and proteins of the present invention are expected to exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA).
Research Uses and Utilities The polynucleotides provided by the present invention can be used by the research community for various purposes. The polynucleotides can be used to express 2 0 recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare 2 5 with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to "subtract-out"
known sequences in the process of discovering other novel polynucleotides; for selecting and making oligomers for attachment to a "gene chip" or other support, including for 3 0 examination of expression patterns; to raise anti-protein antibodies using DNA
immunization techniques; and as an antigen to raise anti-DNA antibodies or elicit another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction}, the polynucleotide can also be used in interaction trap assays (such as, for example, those described in Gyuris et al.,1993, Cell 75: 791-803 and in Rossi et al.,1997, Proc. Natl. Acad.
Sci. USA 94: 8405-8410, all of which are incorporated by reference herein) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction.
The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor} in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.
Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.
2 0 Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E.F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S.L. and A.R. ICimmel eds.,1987.
Nutritional Uses Polynucleotides and proteins of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a 3 0 source of carbohydrate. In such cases the protein or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured.
~,ytokine and Cell Proliferation/Differentiation Activity A protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor-dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a protein of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+ (preB M+), 2E8, RBS, DA1,123, T1165, HT2, CTLL2, TF 1, Mole and CMK.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986;
Bertagnolli et al., J. Lmmunol.145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., J. Immunol. 149:3778-3783,1992; Bowman et al., J.
2 0 Immunol. 152: 1756-1761,1994.
Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in:
Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a.
Coligan eds. Vol 1 pp. 3.12.1-3.12.14, john Wiley and Sons, Toronto. 1994; and 2 5 Measurement of mouse and human Interferon y, Schreiber, R.D. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons, Toronto.1994.
Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine lnterleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In Current 3 0 Protocols in Immunology. j.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983;
Measurement of mouse and human interleukin 6 - Nordan, R. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto.1991;
Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11- Bennett, F., Giannotti, J., Clark, S.C. and Turner, K. J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.15.1 john Wiley and Sons, Toronto.1991;
Measurement of mouse and human Interleukin 9 - Ciarletta, A., Giannotti, J., Clark, S.C.
and Turner, K.J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto.1991.
Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in:
Current Protocols in Immunology, Ed by J. E. Coligan, A.M. Kruisbeek, D.H.
Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans);
Weinberger et al., Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al., Eur. J.
Immun.
11:405-411,1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol.
140:508-5I2, 1988.
Immune Stimulating or Sup rn essin Activi , A protein of the present invention may also exhibit immune stimulating or 2 0 immune suppressing activity, including without limitation the activities for which assays are described herein. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SCID)), e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations.
These immune 2 5 deficiencies may be genetic or be caused by viral (e.g., HIV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, herpesviruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections 3 0 such as candidiasis. Of course, in this regard, a protein of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer.
Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease.
Such a protein of the present invention may also to be useful in the treatment of allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein of the present invention.
Using the proteins of the invention it may also be possible to regulate immune responses in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both.
Immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent.
Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the 2 0 absence of the tolerizing agent.
Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as , for example, B~), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, 2 5 blockage of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a soluble, 3 0 monomeric form of a peptide having B7-2 activity alone or in conjunction with a monomeric form of a peptide having an activity of another B lymphocyte antigen (e.g., B7-1, B7-3) or blocking antibody), prior to transplantation can lead to the binding of the molecule to the natural ligand(s) on the immune cells without transmitting the corresponding costimulatory signal. Blocking B lymphocyte antigen function in this matter prevents cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, the lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens.
The efficacy of particular blocking reagents in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et aL, Proc. Natl. Acad.
Sci USA, 89:11102-11105 (1992). In addition, marine models of GVI-iD {see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of blocking B lymphocyte antigen function in vivo on the development of that disease.
Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate 2 0 activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases.
Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms.
Administration of reagents which block costimulation of T cells by disrupting receptor:ligand interactions of B lymphocyte antigens can be used to inhibit T
cell 2 5 activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of 3 0 human autoimmune diseases. Examples include marine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/Ipr/lpr mice or NZB hybrid mice, marine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB
rats, and marine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York,1989, pp. 840-856).
Upregulation of an antigen function (preferably a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy.
Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response through stimulating B lymphocyte antigen function may be useful in cases of viral infection. In addition, systemic viral diseases such as influenza, the common cold, and encephalitis might be alleviated by the administration of stimulatory forms of B
lymphocyte antigens systemically.
Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducing the in vitro activated T cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a castimulatory signal to, and thereby activate, T cells in vivo.
In another application, up regulation or enhancement of antigen function 2 0 (preferably B lymphocyte antigen function) may be useful in the induction of tumor immunity. Tumor cells (e.g., sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, carcinoma) transfected with a nucleic acid encoding at least one peptide of the present invention can be administered to a subject to overcome tumor-specific tolerance in the subject. If desired, the tumor cell can be transfected to express a combination of peptides.
2 5 For example, tumor cells obtained from a patient can be transfected ex vivo with an expression vector directing the expression of a peptide having B7-2-like activity alone, or in conjunction with a peptide having B71-like activity and/or B7-3-like activity. The transfected tumor cells are returned to the patient to result in expression of the peptides on the surface of the transfected cell. Alternatively, gene therapy techniques can be used 3 0 to target a tumor cell for transfection in vivo.
The presence of the peptide of the present invention having the activity of a B
lymphocyte antigens) on the surface of the tumor cell provides the necessary costimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells. In addition, tumor cells which lack MHC class I or MHC class II
molecules, or which fail to reexpress sufficient amounts of MHC class I or MHC
class II
molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytoplasmic-domain truncated portion) of an MHC class I a chain protein and (32 microglobulin protein or an MHC class II a chain protein and an MHC class II
~i chain protein to thereby express MHC class I or MHC class II proteins on the cell surface.
Expression of the appropriate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3} induces a T
cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E.
Coligan, A.M.
ICruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates 2 0 and Wiley-lnterscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl.
Acad. Sci.
USA 78:2488-2492,1981; Herrmann et al., J. Immunol.128:1968-1974,1982; Handa et al., J. Immunol.135:1564-1572,1985; Takai et al., J. Immunol.137:3494-3500,1986;
Takai et al., J. Immunol.140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA
78:2488-2492, 2 5 1981; Herrmann et al., J. l:mmunol. 128:1968-1974, 1982; Handa et al., J.
l:mmunol.
235:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet al., J.
Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988;
Bertagnolli et al., Cellular Immunology 133:327-341,1991; Brown et al., J. Immunol.153:3079-3092, 1994.
Assays for T-cell-dependent immunoglobulin responses and isotype switching 3 0 (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Thl /Th2 profiles) include, without limitation, those described in: Maliszewski, J. Immunol.144:3028-3033,1990; and Assays for B cell function: In vitro antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in Immunology.
J.E.e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto.1994.
Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A.M.
Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., j. Immunol.137:3494-3500,1986; Takai et al., J. Immunol.140:508-512, 1988; Bertagnolli et al., j. Immunol.149:3778-3783,1992.
Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., journal of Immunology 154:5071-5079,1995; Porgador et al., Journal of Experimental Medicine 182:255-260,1995;
Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264,1989;
Bhardwaj et al., Journal of Clinical Investigation 94:797 807, 1994; and Inaba et al., journal of Experimental Medicine 172:631-640,1990.
Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in:
Darzynkiewicz 2 0 et al., Cytometry 13:795-808,1992; Gorczyca et al., Leukemia 7:659-670,1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991;
Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993;
Gorczyca et al., International Journal of Oncology 1:639-648,1992.
Assays for proteins that influence early steps of T-cell commitment and 2 5 development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122,1994; Galy et al., Blood 85:2770-2778,1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551,1991.
Hematopoiesis Re atin A ' i , 3 0 A protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies.
Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction with irradiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF
activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferatian of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal ~
cells or genetically manipulated for gene therapy.
The activity of a protein of the invention may, among other means, be measured by the following methods:
2 0 Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.
Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 2995; Kelley et 2 5 al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915,1993.
Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those described in: Methylcellulose colony forming assays, Freshney, M.G. In Culture of 3 0 Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, NY. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992;
Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, LK. and Briddell, R.A. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds.
Vol pp. 23-39, Wiley-Liss, Inc., New York, NY.1994; Neben et al., Experimental Hematology 22:353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. l-21, Wiley-Liss, Inc.., New York, NY.1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, NY.1994; Long term culture initiating cell assay, Sutherland, H.J. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp.139-162, Wiley-Liss, Inc., New York, NY.1994.
Tissue Growth Activit3r A protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and in the treatment of burns, incisions and ulcers.
A protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals.
Such a preparation employing a protein of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De rcovo bone formation induced by an osteogenic agent contributes to the repair of 2 0 congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery.
A protein of this invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone-forming cells, stimulate growth of bone-forming cells or induce 2 5 differentiation of progenitors of bone-forming cells. A protein of the invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes.
3 0 Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon/ligament formation. A protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide an environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendirutis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art.
The protein of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve 2 0 tissue. More specifically, a protein may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson s disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present 2 5 invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a protein of the invention.
Proteins of the invention may also be useful to promote better or faster closure of 3 0 non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.
It is expected that a protein of the present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring to allow normal tissue to regenerate. A protein of the invention may also exhibit angiogenic activity.
A protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.
A protein of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for tissue generation activity include, without limitation, those described in: International Patent Publication No. W095/16035 (bone, cartilage, tendon);
International Patent Publication No. W095/05846 (nerve, neuronal);
International Patent Publication No. W091/07491 (skin, endothelium ).
Assays for wound healing activity include, without limitation, those described in:
Winter, epidermal Wound Healing, pps. 71-112 (Maibach, HI and Rovee, DT, eds.), Year Book Medical Publishers, lnc., Chicago, as modified by Eaglstein and Mertz, J.
Invest.
2 0 Dermatol 71:382-84 (1978).
~ctivin/Inhibin Activity A protein of the present invention may also exhibit activin- or inhibin-related activities. Inhibins are characterized by their ability to inhibit the release of follicle 2 5 stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a protein of the present invention, alone or in heterodimers with a member of the inhibin a family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts 3 0 of other inhibins can induce infertility in these mammals. Alternatively, the protein of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin-~i group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary.
See, for example, United States Patent 4,798,885. A protein of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for activin/inhibin activity include, without limitation, those described in:
Vale et al., Endocrinology 91:562-572,1972; Ling et al., Nature 321:779-782,1986; Vale et al., Nature 321:776-779,1986; Mason et al., Nature 318:659-663,1985; Forage et al., Proc.
Natl. Acad. Sci. USA 83:3091-3095,1986.
Chemotactic/Chemokinetic Activit<r A protein of the present invention may have chemotactic or chemokinetic activity (e.g., act as a chemokine) for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells.
Chemotactic and chemokinetic proteins can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent.
2 0 A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known 2 5 assay for cell chemotaxis.
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis) consist of assays that measure the ability of a protein to induce the migration 3 0 of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in: Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub.
Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376,1995; Lind et al.
APMIS 103:140-146,1995; Muller et al Eur. J. Immunol. 25:1744-1748; Gruber et al. J. of Immunol.152:5860-5867,1994; Johnston et al. J. of Immunol.153:1762-1768,1994.
Hemostatic and Thrombol3rtic Activ'~
A protein of the invention may also exhibit hemostatic or thrombolytic activity.
As a result, such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke).
The activity of a protein of the invention may, among other means, be measured by the following methods:
Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140,1986; Burdick et al., Thrombosis Res. 45:413-419,1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474,1988.
Rece~tor/Lig~nd Activit3~
A protein of the present invention may also demonstrate activity as receptors, receptor ligands or inhibitors or agonists of receptor/ligand interactions.
Examples of such receptors and ligands include, without limitation, cytokine receptors and their 2 5 ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selectins, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses). Receptors and ligands are also 3 0 useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.
WO 99/55721 PC"TNS99/08504 The activity of a protein of the invention may, among other means, be measured by the following methods:
Suitable assays for receptor-ligand activity include without limitation those described in:Current Protocols in Immunology, Ed by J.E. Coligan, A.M.
Kruisbeek, D.H.
Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987;
Bierer et al., J. Exp. Med.168:I145-1156, 1988; Rosenstein et al., J. Exp.
Med.169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68,1994; Stitt et al., Cell 80:661-670, 1995.
Anti-Inflammatory Act Proteins of the present invention may also exhibit anti-inflammatory activity.
The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Proteins exhibiting such ?ctivities can be used to treat 2 0 inflammatory conditions including chronic or acute conditions), including without limitation inflammation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting 2 5 from over production of cytokines such as TNF or IL-1. Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.
Cadherin/Tumor Invasion Suppressor Activit3r Cadherins are calcium-dependent adhesion molecules that appear to play major 3 0 roles during development, particularly in defining specific cell types.
Loss or alteration of normal cadherin expression can lead to changes in cell adhesion properties linked to tumor growth and metastasis. Cadherin malfunction is also implicated in other human diseases, such as pemphigus vulgaris and pemphigus foliaceus (auto-immune blistering skin diseases), Crohn's disease, and some developmental abnormalities.
The cadherin superfamily includes well over forty members, each with a distinct pattern of expression. All members of the superfamily have in common conserved extracellular repeats (cadherin domains), but structural differences are found in other parts of the molecule. The cadherin domains bind calcium to form their tertiary structure and thus calcium is required to mediate their adhesion. Only a few amino acids in the first cadherin domain provide the basis for homophilic adhesion; modification of this recognition site can change the specificity of a cadherin so that instead of recognizing only itself, the mutant molecule can now also bind to a different cadherin. In addition, some cadherins engage in heterophilic adhesion with other cadherins.
E-cadherin, one member of the cadherin superfamily, is expressed in epithelial cell types. Pathologically, if E-cadherin expression is lost in a tumor, the malignant cells become invasive and the cancer metastasizes. Transfection of cancer cell lines with polynucleotides expressing E-cadherin has reversed cancer-associated changes by returning altered cell shapes to normal, restoring cells' adhesiveness to each other and to their substrate, decreasing the cell growth rate, and drastically reducing anchorage-independent cell growth. Thus, reintroducing E-cadherin expression reverts carcinomas to a less advanced stage. It is likely that other cadherins have the same invasion suppressor role in carcinomas derived from other tissue types. Therefore, proteins of the present invention with cadherin activity, and polynucleotides of the present invention 2 0 encoding such proteins, can be used to treat cancer. Introducing such proteins or polynucleotides into cancer cells can reduce or eliminate the cancerous changes observed in these cells by providing normal cadherin expression.
Cancer cells have also been shown to express cadherins of a different tissue type than their origin, thus allowing these cells to invade and metastasize in a different tissue 2 5 in the body. Proteins of the present invention with cadherin activity, and polynucleotides of the present invention encoding such proteins, can be substituted in these cells for the inappropriately expressed cadherins, restoring normal cell adhesive properties and reducing or eliminating the tendency of the cells to metastasize.
Additionally, proteins of the present invention with cadherin activity, and 3 0 polynucleotides of the present invention encoding such proteins, can used to generate antibodies recognizing and binding to cadherins. Such antibodies can be used to block the adhesion of inappropriately expressed tumor-cell cadherins, preventing the cells from forming a tumor elsewhere. Such an anti-cadherin antibody can also be used as a marker for the grade, pathological type, and prognosis of a cancer, i.e. the more progressed the WO 99/55721 PCTlUS99/08504 cancer, the less cadherin expression there will be, and this decrease in cadherin expression can be detected by the use of a cadherin-binding antibody.
Fragments of proteins of the present invention with cadherin activity, preferably a polypeptide comprising a decapeptide of the cadherin recognition site, and poly-nucleotides of the present invention encoding such protein fragments, can also be used to block cadherin function by binding to cadherins and preventing them from binding in ways that produce undesirable effects. Additionally, fragments of proteins of the present invention with cadherin activity, preferably truncated soluble cadherin fragments which have been found to be stable in the circulation of cancer patients, and polynucleotides encoding such protein fragments, can be used to disturb proper cell-cell adhesion.
Assays for cadherin adhesive and invasive suppressor activity include, without limitation, those described in: Hortsch et al. J Biol Chem 270 (32): 18809-18817, 1995;
Miyaki et al. Oncogene 11: 2547-2552,1995; Ozawa et al. Cell 63: 1033-1038,1990.
Tumor Inhibition Activitar In addition to the activities described above for immunological treatment or prevention of tumors, a protein of the invention may exhibit other anti-tumor activities.
A protein may inhibit tumor growth directly or indirectly (such as, for example, via antibody-dependent cell-mediated cytotoxicity (ADCC)). A protein may exhibit its tumor 2 0 inhibitory activity by acting on tumor tissue or tumor precursor tissue, by inhibiting formation of tissues necessary to support tumor growth (such as, for example, by inhibiting angiogenesis), by causing production of other factors, agents or cell types which inhibit tumor growth, or by suppressing, eliminating or inhibiting factors, agents or cell types which promote tumor growth.
Other Activities A protein of the invention may also exhibit one or more of the following additional activities or effects: inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites; effecting 3 0 (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape); effecting biorhythms or caricadic cycles or rhythms;
effecting the fertility of male or female subjects; effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional factors or component(s);
effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects;
promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein.
ADMINISTRATION AND DOSING
A protein of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources) may be used in a pharmaceutical composition when combined with a pharmaceutically acceptable carrier.
Such a composition may also contain (in addition to protein and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term 2 0 "pharmaceutically acceptable" means a non toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration. The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, ILr6, ILr7, IIr8, ILr9, ILrlO, ILrl l, 2 5 IL-12, IL-13, IL-14, IL-15,1FN, TNFO, TNFl, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin. The pharmaceutical composition may further contain other agents which either enhance the activity of the protein or compliment its activity or use in treatment. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein of the invention, 3 0 or to minimize side effects. Conversely, protein of the present invention may be included in formulations of the particular cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent to minimize side effects of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent.
A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multimeric or complexed form.
The pharmaceutical composition of the invention may be in the form of a complex of the proteins) of present invention along with protein or peptide antigens.
The protein and/or peptide antigen will deliver a stimulatory signal to both B and T
lymphocytes. B
lymphocytes will respond to antigen through their surface immunoglobulin receptor. T
lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MI~iC and structurally related proteins including those encoded by class I and class II MHC genes on host cells will serve to present the peptide antigens) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunolgobulin and other molecules on B cells as well as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition of the invention.
The pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other 2 0 pharmaceutically acceptable earners, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the 2 5 art, as disclosed, for example, in U.S. Patent No. 4,235,871; U.S. Patent No. 4,501,728; U.S.
Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are incorporated herein by reference.
As used herein, the term "therapeutically effective amount" means the total amount of each active component of the pharmaceutical composition or method that is 3 0 sufficient to show a meaningful patient benefit, i.e., treatment, healing, prevention or amelioration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously.
In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein of the present invention is administered to a mammal having a condition to be treated. Protein of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors.
Administration of protein of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection.
2 0 Intravenous administration to the patient is preferred.
When a therapeutically effective amount of protein of the present invention is administered orally, protein of the present invention will be in the form of a tablet, capsule, powder, solution or elixir. When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as a gelatin or 2 5 an adjuvant. The tablet, capsule, and powder contain from about 5 to 95%
protein of the present invention, and preferably from about 25 to 90% protein of the present invention.
When administered in liquid form, a liquid carrier such as water, petroleum, oils of animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic ails may be added. The liquid form of the pharmaceutical composition may further contain 3 0 physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of protein of the present invention, and preferably from about 1 to 50% protein of the present invention.
When a therapeutically effective amount of protein of the present invention is administered by intravenous, cutaneous or subcutaneous injection; protein of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution.
The preparation of such parenterally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A
preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein of the present invention, an isotonic vehicle such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art.
The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art.
The amount of protein of the present invention in the pharmaceutical composition of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone.
Ultimately, the attending physician will decide the amount of protein of the present invention with which to treat each individual patient. Initially, the attending physician will administer low doses of protein of the present invention and observe the patient's response. Larger doses of protein of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not 2 0 increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 pg to about 100 mg (preferably about 0.lng to about 10 mg, more preferably about 0.1 ug to about 1 mg) of protein of the present invention per kg body weight.
The duration of intravenous therapy using the pharmaceutical composition of the 2 5 present invention will vary, depending on the severity of the disease being treated and the condition and potential idiosyncratic response of each individual patient.
It is contemplated that the duration of each application of the protein of the present invention will be in the range of 12 to 24 hours of continuous intravenous administration.
Ultimately the attending physician will decide on the appropriate duration of intravenous 3 0 therapy using the pharmaceutical composition of the present invention.
Protein of the invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protein. As used herein, the term "antibody" includes without limitation a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a single-chain antibody, a CDR-grafted antibody, a humanized antibody, or fragments thereof which bind to the indicated protein.
Such term also includes any other species derived from an antibody or antibody sequence which is capable of binding the indicated protein.
Antibodies to a particular protein can be produced by methods well known to those skilled in the art. For example, monoclonal antibodies can be produced by generation of antibody-producing hybridomas in accordance with known methods (see for example, Goding, 1983, Monoclonal antibodies: principles and practice, Academic Press Inc., New York; and Yokoyama, 1992, "Production of Monoclonal Antibodies" in Current Protocols in Immunology, Unit 2.5, Greene Publishing Assoc. and John Wiley & Sons).
Polyclonal sera and antibodies can be produced by inoculation of a mammalian subject with the relevant protein or fragments thereof in accordance with known methods.
Fragments of antibodies, receptors, or other reactive peptides can be produced from the corresponding antibodies by cleavage of and collection of the desired fragments in accordance with known methods (see for example, Goding, supra; and Andrew et al., 1992, "Fragmentation of Immunoglobulins" in Current Protocols in Immunology, Unit 2.8, Greene Publishing Assoc. and John Wiley & Sons). Chimeric antibodies and single chain antibodies can also be produced in accordance with known recombinant methods (see for example, 5,169,939, 5,194,594, and 5,576,184). Humanized antibodies can also be made from corresponding marine antibodies in accordance with well known methods (see for example, U.S.
Patent 2 0 Nos. 5,530,101, 5,585,089, and 5,693,762). Additionally, human antibodies may be produced in non-human animals such as mice that have been genetically altered to express human antibody molecules (see for example Fishwild et al., 1996, Nature Biotechnology 14: 845-851; Mendez et al., 1997, Nature Genetics 15: 146-156 (erratum Nature Genetics 16: 410); and U.S. Patents 5,877,397 and 5,625,126). Such antibodies may be obtained 2 5 using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R.P.
Merrifield, J.
Amer.Chem.Soc. $5, 2149-2154 (1963); J.L. ICrstenansky, et al., FEBS Lett.
211,10 (198.
3 0 Monoclonal antibodies binding to the protein of the invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression of the protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein.
For compositions of the present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device.
When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. Therapeutically useful agents other than a protein of the invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods of the invention. Preferably for bone and/or cartilage formation, the composition would include a matrix capable of delivering the protein-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body.
2 0 Such matrices may be formed of materials presently in use for other implanted medical applications.
The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application of the compositions will define the appropriate formulation.
Potential 2 5 matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydrides. Other potential materials are biodegradable and biologically well-defined, such as bone or dermal collagen. Further matrices are comprised of pure proteins or extracellular matrix components. Other potential matrices are nonbiodegradable and 3 0 chemically defined, such as sintered hydroxapatite, bioglass, aluminates, or other ceramics. Matrices may be comprised of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tricalciumphosphate. The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability.
Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns.
In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix.
A preferred family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, and carboxymethylcellulose, the most preferred being cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, polyethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and polyvinyl alcohol). The amount of sequestering agent useful herein is 0.5-20 wt%, preferably 1-10 wt% based on total formulation weight, which represents the amount necessary to prevent desorbtion of the protein from the polymer matrix and to provide appropriate handling of the composition, yet not so much that the progenitor cells are prevented from infiltrating the matrix, thereby providing the protein the opportunity to assist the osteogenic activity of the progenitor cells.
2 0 In further compositions, proteins of the invention may be combined with other agents beneficial to the treatment of the bone and/or cartilage defect, wound, or tissue in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-a and TGR~3), and insulin-like growth factor (IGF).
2 5 The therapeutic compositions are also presently valuable for veterinary applications. Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins of the present invention.
The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering 3 0 various factors which modify the action of the proteins, e.g., amount of tissue weight desired to be formed, the site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition. For example, the addition of other known growth factors, such as IGF I (insulin like growth factor I}, to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue/bone growth and/or repair, for example, X-rays, histomorphometric determinations and tetracycline labeling.
Polynucleotides of the present invention can also be used for gene therapy.
Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynucleotides of the invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA).
Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells.
Treated cells can then be introduced in vivo for therapeutic purposes.
Patent and literature references cited herein are incorporated by reference as if fully set forth.
SEQUENCE LISTING
<110> Valenzuela, Dario Yuan, Olive Hoffman, Heidi Hall, Jeff Rapiejko, Peter AlphaGene, Inc.
<120> SECRETED PROTEINS AND POLYNUCLEOTIDES ENCODING THEM
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<160> 107 <170> PatentIn Ver. 2.0 <210> 1 <211> 2201 <212> DNA
<213> Homo sapiens <400> 1 tccttcgcct cctgcacctt gggagccctg ggctactctt tcacggcccc tgttgccctg 60 tgatctgtag gtccttgggg acgcacagtt aaggtgccag gacatcctgg aagctgggaa 120 atgatatgta ttcatttcct accaccgtag tggaagagat actatcccta tctttacaac 180 tgatagcatt tccaacagta agctgtgaga ttctgcttga aatcacctct caaacaaata 240 aaaaacagac ccgggagaca tgctacgctc attctgctga agaaataggc atcatagctg 300 ggaaacggat tcacaagacc caggctgttc cctacatatg tttcctcctc cgacatcagt 360 tcatcagtca atcaagccat gtgagagtgg aggccttgta ttccctatta ttcttgggca 420 ctctactcca agtaggaaaa ggccaggagg tcctgttaaa ggatgcactc agagcccggg 480 ctccctaaca tatgagagtg ctaaccagca ggtgtagact tttcaggagt gaagaatgag 540 gcaggcattc caaacctgga ccttcatcac cttttgtttc atctcaagac aattctgagg 600 gactgttttg gagcgtgtct ggaaggtgaa ccttgaagaa gagtgtgggc tttgatgtga 660 ctcagttgag atctttcatg gggaggcagg aattcaatgc ccagaatctg ggctggtgtc 720 tttgaggtca gtaggttgcg tctttgtatc caagtccatt gttactaggt tggaggctgg 780 agattctaaa tggcttccag accatctctc tgattctctt tgggagatgg ggtctgaaag 840 acaatatcag tagttttggg aaattctaga aagtgtgctt ggaaacgtgg gaagagctct 900 tgcctagtgc ctaaatgctc catttgcagc tctagccaag tagatacttg gtaggtatag 960 agccgggttt gcgtttatat cagcaaaacc tatatcagag ttgaagaagt agtcaggaaa 1020 aagcgtcttg gtcgcaggcc ggggaacatc ttaaaagcaa acttctagcc tgctgactct 1080 tggcaatgag tgttggatcc tggctaaagt gccttgaatg cagcatgagg ccaatccatg 1140 aatccaactt ctcatggaga aatgttaata ttttttcagt ttgaatcaat cagggtgaaa 1200 ctaccatgct attggtttgc ttacttttta ttatttcatg taaaatctaa gacaaaatac 1260 attaaatgct tattgacata tgtatttatt cttcaccagg ctgataatat ctgcctaatt 1320 ttaaactttc ttccattttg taggtttcaa cttattctat tgtaagatac tgttaaatct 1380 aatagaggca ttgtcacttt tacgtataat tttattttat ttcatatatt tcctattggc 1440 tttttacatt taaattatgg agcacttcat catataaaaa acttcaatta tatttaaaca 1500 gtaagtcttt ggattttttt gccttgtaat ttccatatta cataataatg agataaacat 1560 taatgttttc agggtacttt aaattttaga taattactca ttgtattcat gtgaaatttg 1620 ttttactgc atgtgtgggt tggaggactg ttttcacttc tgattcatct ttactcttat 1680 ~ctcatcagag ctcatacctc ttgtagttgg gggattgcag tttataattc caataaatgg 1740 'ggcaaattca ataataacat aatacaaatg agtttgaatg caggacaggt cttcaaagca 1800 tacacaacat gggcctacat atgtacaaca ataataattt ataagttact gtttggatgg 1860 aaagtaaaag tacagaaaat ttgttaaagg aaattaaaat ggagatcatg tctcaataat 1920 ctctgagcag acaaaattag ttaggtctca taagtgatct caacctcgct tgatttgcaa 1980 atacaaacaa aacttacatt atttcttgta gctgcatatt gaaaaaagag aaatgaagct 2040 caaccagtca gaagtagcca acaaccttat ataaatagaa actgtccaac aaggtaaaca 2100 gacaaacaaa aaacaataaa aaaagttgtg ctaccaccaa aaaaaaaaaa aaaaaaaaaa 2160 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 2201 <210> 2 <211> 120 <212> PRT
<213> Homo sapiens <400> 2 Met Tyr Ser Phe Pro Thr Thr Val Val Glu Glu Ile Leu Ser Leu Ser Leu Gln Leu Ile Ala Phe Pro Thr Val Ser Cys Glu Ile Leu Leu Glu Ile Thr Ser Gln Thr Asn Lys Lys Gln Thr Arg Glu Thr Cys Tyr Ala His Ser Ala Glu Glu Ile Gly Ile Ile Ala Gly Lys Arg Ile His Lys Thr Gln Ala Val Pro Tyr Ile Cys Phe Leu Leu Arg His Gln Phe Ile Ser Gln Ser Ser His Val Arg Val Glu Ala Leu Tyr Ser Leu Leu Phe Leu Gly Thr Leu Leu Gln Val Gly Lys Gly Gln Glu Val Leu Leu Lys Asp Ala Leu Arg Ala Arg Ala Pro <210> 3 <211> 2498 <212> DNA
<213> Homo sapiens <400> 3 ggtcgtttgg atagtgatga acagaaaatt cagaatgata tcattgatat tttactgact 60 tttacacaag gagttaatga aaaactcaca atctcagaag agactctggc caataatact 120 tggtctttaa tgttaaaaga agttctttct tcaatcttga aggttcctga aggatttttt 180 tctggactca tactcctttc agagctgctg cctcttccat tgcccatgca aacaactcag 240 gttattgagc cacatgatat atcagtggca ctcaacaccc gaaaattgtg gagcatgcac 300 cttcatgttc aagcaaagtt gctccaagaa atagttcgct ctttctctgg cacaacctgc 360 cagcccattc aacatatgtt acggcgtatt tgtgttcaat tgtgtgacct tgcctcacca 420 actgcacttc tgattatgag aactgtgttg gatttgattg tagaagactt gcaaagcact 480 tcagaagata aagaaaaaca gtatactagc caaaccacca ggttgcttgc tcttcttgat 540 gctctggctt cacacaaagc ttgtaaatta gctattttgc atctaattaa tggaactatt 600 aaaggtgatg aaagatatgc agagatattc caggatcttt tagctttggt gcggtctcct 660 ggagacagtg ttattcgcca acagtgtgtt gaatatgtca catccatttt gcagtctctc 720 tgtgatcagg acattgcact tatcttacca agctcttctg aaggttctat ttctgaactg 780 gagcagctct ccaattctct accaaataaa gaattgatga cctcaatctg tgactgtctg 840 ttggctacgc tagctaactc tgagagcagt tacaactgtt tactgacatg tgtcagaaca 900 atgatgtttc ttgcagagca tgattatgga ttatttcatt taaaaagttc tttaaggaaa 960 aacagtagtg ctctgcatag tttactgaaa cgagtggtca gcacatttag taaggacaca 1020 ggagagcttg catcttcatt tttagaattt atgagacaaa ttcttaactc tgacacaatt 1080 ggatgctgtg gagatgataa tggtctcatg gaagtagagg gagctcatac atcacggacg 1140 atgagtatta atgctgcaga gttaaaacag cttctacaaa gcaaagaaga aagtccagaa 1200 aatttgttcc ttgaactaga gaagcttgtt ttggaacatt caaaagatga tgacaatctg 1260 gattctttgt tggacagtgt agttggactt aagcagatgc tggagtcatc aggtgaccct 1320 ttacctctca gtgaccagga tgtagaacca gtactttcag ctccagaatc tcttcagaat 1380 ctgtttaaca ataggactgc ctatgtgctt gctgatgtca tggatgatca gttgaaatct 1440 atgtggttca ctccatttca ggctgaagag atagatacag atctggattt ggtaaaggtt 1500 gacttaattg aactctctga aaaatgctgt agtgactttg atttgcactc agaattagag 1560 cgctcatttt tgtcagaacc atcatctcca ggaagaacca agactactaa aggattcaaa 1620 cttgggaagc acaagcatga gacctttata acgtcaagtg gaaaatctga atacattgaa 1680 cctgccaaaa gagctcatgt tgtgccacca ccaagaggaa ggggcagggg aggatttgga 1740 cagggtatac gacctcatga tatttttcgt cagagaaaac agaacacaag tagaccacca 1800 tctatgcatg tggatgactt tgttgctgct gaaagtaaag aagtggttcc tcaagatgga 1860 atacctccac caaaacggcc actcaaagca tcacagaaga tttcttcccg tggtgggttt 1920 tcaggcaata gaggaggacg gggtgctttc cacagtcaga ataggttttt cacaccacct 1980 gcttcaaaag gaaactacag tcgtcgggaa ggaacaagag gctccagttg gagtgctcag 2040 aatactcctc gaggaaatta caatgaaagt cgtggaggcc agagcaattt taacagaggc 2100 cctcttccac cattacgacc ccttagttct acaggttacc gcccaagtcc tcgggaccgt 2160 gcttctagag gtcgtggggg acttggacct tcctgggcta gtgcaaatag cggcagtgga 2220 ggctcaagag gaaagtttgt tagtggaggc agtggtagag gtcgtcatgt acgctccttt 2280 acacgataaa aatccttttg ggaacatctt aactgtatat gaacatttca cgaggacaat 2340 aaaaataaga cattgaagga ccaatttaga cttagcagtt atctggagac atctgagaga 2400 atatttttat ctgaagaaag cagaatttgt ttgataccta acaagatttc aataaaaatc 2460 caaactttgt atgtaaaaaa aaaaaaaaaa aaaaaaaa 2498 <210> 4 <211> 719 <212> PRT
<213> Homo sapiens <400> 4 Met Leu Lys Glu Val Leu Ser Ser Ile Leu Lys Val Pro Glu Gly Phe Phe Ser Gly Leu Ile Leu Leu Ser Glu Leu Leu Pro Leu Pro Leu Pro Met Gln Thr Thr Gln Val Ile Glu Pro His Asp Ile Ser Val Ala Leu Asn Thr Arg Lys Leu Trp Ser Met His Leu His Val Gln Ala Lys Leu Leu Gln Glu Ile Val Arg Ser Phe Ser Gly Thr Thr Cys Gln Pro Ile Gln His Met Leu Arg Arg Ile Cys Val Gln Leu Cys Asp Leu Ala Ser Pro Thr Ala Leu Leu Ile Met Arg Thr Val Leu Asp Leu Ile Val Glu Asp Leu Gln Ser Thr Ser Glu Asp Lys Glu Lys Gln Tyr Thr Ser Gln Thr Thr Arg Leu Leu Ala Leu Leu Asp Ala Leu Ala Ser His Lys Ala Cys Lys Leu Ala Ile Leu His Leu Ile Asn Gly Thr Ile Lys Gly Asp Glu Arg Tyr Ala Glu Ile Phe Gln Asp Leu Leu Ala Leu Val Arg Ser Pro Gly Asp Ser Val Ile Arg Gln Gln Cys Val Glu Tyr Val Thr Ser Ile Leu Gln Ser Leu Cys Asp Gln Asp Ile Ala Leu Ile Leu Pro Ser Ser Ser Glu Gly Ser Ile Ser Glu Leu Glu Gln Leu Ser Asn Ser Leu Pro Asn Lys Glu Leu Met Thr Ser Ile Cys Asp Cys Leu Leu Ala Thr Leu Ala Asn Ser Glu Ser Ser Tyr Asn Cys Leu Leu Thr Cys Val Arg Thr Met Met Phe Leu Ala Glu His Asp Tyr Gly Leu Phe His Leu Lys Ser Ser Leu Arg Lys Asn Ser Ser Ala Leu His Ser Leu Leu Lys Arg Val Val Ser Thr Phe Ser Lys Asp Thr Gly Glu Leu Ala Ser Ser Phe Leu Glu Phe Met Arg Gln Ile Leu Asn Ser Asp Thr Ile Gly Cys Cys Gly Asp Asp Asn Gly Leu Met Glu Val Glu Gly Ala His Thr Ser Arg Thr Met Ser Ile Asn Ala Ala Glu Leu Lys Gln Leu Leu Gln Ser Lys Glu Glu Ser Pro Glu Asn Leu Phe Leu Glu Leu Glu Lys Leu Val Leu Glu His Ser Lys Asp Asp Asp Asn Leu Asp Ser Leu Leu Asp Ser Val Val Gly Leu Lys Gln Met Leu Glu Ser Ser Gly Asp Pro Leu Pro Leu Ser Asp Gln Asp Val Glu Pro Val Leu Ser Ala Pro Glu Ser Leu Gln Asn Leu Phe Asn Asn Arg Thr Ala Tyr Val Leu Ala Asp Val Met Asp Asp Gln Leu Lys Ser Met Trp Phe Thr Pro Phe Gln Ala Glu Glu Ile Asp Thr Asp Leu Asp Leu Val Lys Val Asp Leu Ile Glu Leu Ser Glu Lys Cys Cys Ser Asp Phe Asp Leu His Ser Glu Leu Glu Arg Ser Phe Leu Ser Glu Pro Ser Ser Pro Gly Arg Thr Lys Thr Thr Lys Gly Phe Lys Leu Gly Lys His Lys His Glu Thr Phe Ile Thr Ser Ser Gly Lys Ser Glu Tyr Ile Glu Pro Ala Lys Arg Ala His Val Val Pro Pro Pro Arg Gly Arg Gly Arg Gly Gly Phe Gly Gln Gly Ile Arg Pro His Asp Ile Phe Arg Gln Arg Lys Gln Asn Thr Ser Arg Pro Pro Ser Met His Val Asp Asp Phe Val Ala Ala Glu Ser Lys Glu Val Val Pro Gln Asp Gly Ile Pro Pro Pro Lys Arg Pro Leu Lys Ala Ser Gln Lys Ile Ser Ser Arg Gly Gly Phe Ser Gly Asn Arg Gly Gly Arg Gly Ala Phe His Ser Gln Asn Arg Phe Phe Thr Pro Pro Ala Ser Lys Gly Asn Tyr Ser Arg Arg Glu Gly Thr Arg Gly Ser Ser Trp Ser Ala Gln Asn Thr Pro Arg Gly Asn Tyr Asn Glu Ser Arg Gly Gly Gln Ser Asn Phe Asn Arg Gly Pro Leu Pro Pro Leu Arg Pro Leu Ser Ser Thr Gly Tyr Arg Pro Ser Pro Arg Asp Arg Ala Ser Arg Gly Arg Gly Gly Leu Gly Pro Ser Trp Ala Ser Ala Asn Ser Gly Ser Gly Gly Ser Arg Gly Lys Phe Val Ser Gly Gly Ser Gly Arg Gly Arg His Val Arg Ser Phe Thr Arg <210> 5 <211> 2054 <212> DNA
<213> Homo sapiens <400> 5 tgcagggcca gggtggggtg tccagcacca gccaagctgg tgctccagcg cacctcccca 60 gagctccccg cactgacggg gctgcaggag caggtgcagt gggcgcccac actggccctg 120 cagtgatgca gggcgggagg gagataagaa gaccccgcag tcaagtggag catggccctc 180 cctggctccc tgtccctggg ctcagcacga ccacacagga cacccagcca gggaattctg 240 aagaccagag agcagcccac gggcatcacg agcgctctgc tcctctcctg ggcccctgct 300 cttcccgaga gctgccccca aatcagacat acctctgtgg ctctcctctg gttcacgttt 360 acagagcata aggctgtctt ggatcccaac aggcacccag ccctgcatgg ggggagcctg 420 ggcctaatag gcaccccctg tacctcaggc tgtggcggga gcagagtccc cccctccggc 480 ccctcttcct ttaccccttc tcctccagca gtggcaaagg ggtaggctct agagccagca 540 caggtcactg cctgacctgg actaagaacc ccacggcccc actgtccaca cactgcctcc 600 ccaccgccca cctcggctgc taggcccctc gcctggactg gactggggag ggaaagcgcc 660 ttttcctgca gctcttcaga gccacagacc tcagggtgga gtgagcccat ggtgggcagt 720 gggcaaggcg gtgggtggtg ggcaaggtgg gacctcctgc agcctggaaa gaggagggag 780 gccaaggcca ttccctaact ccctcctgcc cctggtctga ggaggaggga ctctggagta 840 gcagaggggc tgggaaagag ggggcagggg ctgctgggac actgagcagg agggaggcct 900 gagcacactg ctttggaaat tattctaaac acaaaaaagg gaaagaaaat gttatttctc 960 cctaagtcag gagcatgcag agctagccca cctcatgtcc agctgtccac tttccatcct 1020 ggagaaagaa cagtgtgcct caaactcctg ccctccccag gcctctgggg cccgctggaa 1080 agggctctga ccccctggcc cggccgggct ctctagtggt gatccggctc attctcctgc 1140 aagttggaag cacaattttc cccccaagtg gaggaaaagg aaagggcccc agcctactga 1200 agaggtgttt attttttaac taacagcctc ccaccccatt aagactcacc aggagaggtc 1260 tgagggccat tcagaaccca ctcctgagtg ggtgggtggg tgggactcag tccagagacc 1320 taacattcag aatatagcat tggttgccta ttttgagatg gatttaatct cccacagtat 1380 tcatgagacc atctgatgga atcagatccc tgagccacct tgcaggacgt tttccccaac 1440 ctcttacacc ctggatgtca ctttggaaac caagcccttg gaagcaagtg gggtggcatg 1500 ggagagaagg gaggaggtgg gcacaggtgg tgagcttatg tgtgggcact ctactgcctc 1560 acagaagcca gccaagtgcc aaggtcagct tggctggtct gaggccacct tcttagccaa 1620 aaacctaggg ttcattttca ggactttgat aatgaacaac aaaatgggga cttctttggg 1680 cagatgctag gtcagttgtt ttcacctaat atcctctttt agctgcatgt atatttattt 1740 ataattataa ccctggtgga ctgcagcctt catctttatt gggaatgagt ttgttataaa 1800 tcagaaatgg gtccatgatg accactgttt tccaaaccca gtctgttccc tgctccctcg 1860 ctggcaagcc ccaccacaca ggagtgaggc caggggctag gagttctaag aacagaggct 1920 ggggtgaggg tggcacccag gcagctgcat ctggtctgtt ttaatttaac tgtatttaat 1980 ttgctttcaa aattaaaagt caaatacagt ttttaacagt ectaaaaaaa aaaaaaaaaa 2040 aaaaaaaaaa aaaa 2054 <210> 6 <211> 117 <212> PRT
<213> Homo Sapiens <400> 6 Met Ala Leu Pro Gly Ser Leu Ser Leu Gly Ser Ala Arg Pro His Arg Thr Pro Ser Gln Gly Ile Leu Lys Thr Arg Glu Gln Pro Thr Gly Ile Thr Ser Ala Leu Leu Leu Ser Trp Ala Pro Ala Leu Pro Glu Ser Cys Pro Gln Ile Arg His Thr Ser Val Ala Leu Leu Trp Phe Thr Phe Thr Glu His Lys Ala Val Leu Asp Pro Asn Arg His Pro Ala Leu His Gly Gly Ser Leu Gly Leu Ile Gly Thr Pro Cys Thr Ser Gly Cys Gly Gly Ser Arg Val Pro Pro Ser Gly Pro Ser Ser Phe Thr Pro Ser Pro Pro Ala Val Ala Lys Gly <210> 7 <211> 724 <212> DNA
<213> Homo Sapiens <400> 7 gtggacctgt gctgtctcag tttgctctgg ggtctgggca gtcctgtggt ttgggcagag 60 gcctcagagg gccctaggga cagactgacc caggtctgag cctcttggga gcgtgcggat 120 ggccggcctc agacaggcct ggttgtgggt ttgtcttcca aggggcacac gcgcactctg 180 gtgcttcctg gcattcagaa gagaatgggg aatccagaca tcaggccttc cttctccctg 240 ggaaggatgg caggtgcttg gagccaggcc tgtcttgaga gccagggctc tgggtcttcc 300 tcctccagtg ccctgttcca cgccttcagt gcacaaagca ctcccctcct gggatctctt 360 cagggatccc cgggatgcaa actggccagg gattagaatt ccacatttga gcaaacagac 420 tgagagtgga gaagcaccca gctggacatc ctctaggtgt tcctggcaga ggcccttgct 480 acttgtctgt gcccaaaggc cctagagggt cctagatgtg ggacaaggtc tcagcagggc 540 tccagtccca ggcctggaaa cagctggggg tgggggaagc tggctgggtg ggtgtggtta 600 tcttttccca gcttgtggct ccgaggtgac agaaccaatc tcaggaggct ttgtttggtt 660 aataaaatct actgaatggt ttaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 720 aaaa 724 <210> B
<211> 128 <212> PRT
<213> Homo Sapiens <400> 8 Met Ala Gly Leu Arg Gln Ala Trp Leu Trp Val Cys Leu Pro Arg Gly Thr Arg Ala Leu Trp Cys Phe Leu Ala Phe Arg Arg Glu Trp Gly Ile Gln Thr Ser Gly Leu Pro Ser Pro Trp Glu Gly Trp Gln Val Leu Gly Ala Arg Pro Val Leu Arg Ala Arg Ala Leu Gly Leu Pro Pro Pro Val Pro Cys Ser Thr Pro Ser Val His Lys Ala Leu Pro Ser Trp Asp Leu Phe Arg Asp Pro Arg Asp Ala Asn Trp Pro Gly Ile Arg Ile Pro His Leu Ser Lys Gln Thr Glu Ser Gly Glu Ala Pro Ser Trp Thr Ser Ser Arg Cys Ser Trp Gln Arg Pro Leu Leu Leu Val Cys Ala Gln Arg Pro <210> 9 <211> 2685 <212> DNA
<213> Homo sapiens <400> 9 acaccagctg ccacttcttt tgcctcatga agaactcttg ggccagccaa actgggaacc 60 taggtgtctg ggtcttgtga caaccaaagc actttgacac taccccctgc cgagagaaga 120 ggagtggatg agcctgcggg tttgcctcaa gaaacttcat gagggtctct tactaactcc 180 attacactct ctctcctgga gcctcatctc catgtcaagc aggagggtaa agaagggaac 240 taagagcagg tctttcaagc cacaccccca cctgcggatg gatgggtttc tctgtaggcc 300 atgcaggcct ttgtcgcagc aaaccttccc agcagccctt gagccaagta aaaccagcac 360 aaccagccac cagtggttgg tgaggcagtg cccacaaggc tcatgttgta tgcctttgat 420 aaggccatct tggctttgag tagcagtgtt cctcgtcacc catttccccc tcaggattac 480 aacacctgct atcaaatcat ctaagctgaa aacatgagat gcgcttggaa aggcctagtc 540 agaagccatt tcctcttatc atttccctct cctatgcacc agtaaggccc gtccagagcc 600 ccagcaggga gtgggccctg agtccacact gtccctgagt gatccaggag gctgcccaca 660 tccccacatg tgcactgtgg ttccagtgta gctgctgtga gcccactgcc actgcctcag 720 aagggagcca ctgtgaacct ctcgagtggc tccaaagagc agtggctttt tgagaatggc 780 ccatacttct ggcccggctg gatgaaggga atgccgaccc tttggcctct ccccctcctt 840 ccatctcttc tctctcttgc cctatctctc tttctacttc agaaaaaaaa aaaaaaaaaa 900 agcctgtcat tcacttttta acactttatc ccaaataaga tccctgtgta attctgaagc 960 tggtgatcca cttggaattg tagatagttt caggaagctc ctgcagggct gtccaccgtt 1020 ggtgtgtgcc tcagtatttg gacttccgaa actgaaagtg aasgtgtctt tataggagag 1080 aaacgcatgc tgctctttgg ctctttctgt ccaacttttc tagaaatgac tcaaagtcca 1140 ttaagatttg tgaatattgt ataaattagc tatggaaagt agcaggtcag atggaaaatt 1200 cttttccaca gccctgctct ccgcctccct ccatcttagg agcgcctgcc tcaattcctc 1260 gtcaactgct ttgctccact ccatcccaca ggtgtgagtg ggggaagttt ttcattagga 1320 atacagtctg cgtgacatgg agaatggatg gagggagctt tgctactctg ctcttggcat 1380 gactccagga tttttttctg gaatccaacc tctgtcctct taggagaagg aacctgtcct 1940 tggttcagat ggctgggcat gaggaggaaa atttccatta gtgtagaaaa gtgctggaca 1500 gaatccggtt tggaaaatta caaatccagt tggtcasaat aggccatttc ctatgtgtga 1560 cctattcgtg gtatgccaac tggactgctt cctaaacagg acgaggaaag tgaggaatat 1620 ttttatatga aagccttagc ctgtctggca cccatgaaaa aaactattta tgcactccta 1680 ctttcaccgt ctttttgcat tctctatttg tagcacaaca gagttgaatg ccacaaaaca 1740 ccccgtttat agtgagctgt tttcagtgac caatatcaga aggaggcttg cttctggact 1800 agcctcacta attgccagca gccaccattt tccatggaat ggccttggga cagatgtcac 1860 ctctgttatg gggctctaat aggaaagaga atgttttttc ccttcctatg atcaatactg 1920 caaattattg ctgctcacag cttttatagg attctcccaa ctgaaagttg cagcattttt 1980 ctgtccctgt gcatcagtac taacaaaaga cagcctcacc aagtctgtat atttgaacag 2040 aggcaagtta attcatcccc ccgtgtcaga gccacaggca tgttgagggg gttgatacgt 2100 agcactggac cagggcgcaa agcccagata gttccagcca tgagaggaga gcacaagaat 2160 gctctgcact ctgcactcag caccatcttg ggtctgcttt gcccagatga gggaccacta 2220 acaaccttct cagcacatgt gaatgtggac tgattttaaa atgcattcat tctgctagga 2280 ttgggctgga agctggaaca gtgagagtac tttttctgct cctagtcatc tccctttctc 2340 agcgtgacat cctcctgcag caagcctagt atcactagca gtagttcctg cgactcttag 2400 caacacaacc cgaatatttg ctccctgcat ctgggtcctc caccaggatg ggcctgcgca 2460 tctgcattgc tgtacagaca ascaggcctt ttaatttaca tcctccttta attctcatta 2520 aaatcgcagg gtttttgttt gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2580 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2640 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 2685 <210> 10 <211> 103 <212> PRT
<213> Homo Sapiens <400> 10 Met Ser Leu Arg Val Cys Leu Lys Lys Leu His Glu Gly Leu Leu Leu Thr Pro Leu His Ser Leu Ser Trp Ser Leu Ile Ser Met Ser Ser Arg Arg Val Lys Lys Gly Thr Lys Ser Arg Ser Phe Lys Pro His Pro His Leu Arg Met Asp Gly Phe Leu Cys Arg Pro Cys Arg Pro Leu Ser Gln g Gln Thr Phe Pro Ala Ala Leu Glu Pro Ser Lys Thr Ser Thr Thr Ser His Gln Trp Leu Val Arg Gln Cys Pro Gln Gly Ser Cys Cys Met Pro Leu Ile Arg Pro Ser Trp Leu <210> 11 <211> 1760 <212> DNA
<213> Homo sapiens <400> 11 ggcggggcct cgcacacccc aagaaccatc tttcacccca gcaagggggt gcgacgccac 60 aggtgccatc cccctgttgt cgttttgact ccccccgggg gccacctcca ccccggctgg 120 gtctgctagg tgctctcatg gctgaggatg gggtgagagg gtctccacca gtgccctctg 180 ggccccccat ggaggaagat ggactcaggt ggactccaaa gtctcctctg gaccctgact 240 cgggcctcct ttcatgtact ctgcccaacg gttttggggg acaatctggg ccagaagggg 300 agcgcagctt ggcaccccct gatgccagca tcctcatcag caatgtgtgc agcatcgggg 360 accatgtggc ccaggagctt tttcagggct cagatttggg catggcagaa gaggcagaga 420 ggcctgggga gaaagccggc cagcacagcc ccctgcgaga ggagcatgtg acctgcgtac 480 agagcatctt ggacgaattc cttcaaacgt atggcagcct catacccctc agcactgatg 540 aggtagtaga gaagctggag gacattttcc agcaggagtt ttccacccct tccaggaagg 600 gcctggtgtt gcagctgatc cagtcttacc agcggatgcc aggcaatgcc atggtgaggg 660 gcttccgagt ggcttataag cggcacgtgc tgaccatgga tgacttgggg accttgtatg 720 gacagaactg gctcaatgac caggtgatga acatgtatgg agacctggtc atggacacag 780 tccctgaaaa ggtgcatttc ttcaatagtt tcttctatga taaactccgt accsagggtt 840 atgatggggt gaaaaggtgg accaaaaacg tggacatctt caataaggag ctactgctaa 900 tccccatcca cctggaggtg cattggtccc tcatctctgt tgatgtgagg cgacgcacca 960 tcacctattt tgactcgcag cgtaccctaa accgccgctg ccctaagcat attgccaagt 1020 atctacaggc agaggcggta aagaaagacc gactggattt ccaccagggc tggaaaggtt 1080 acttcaaaat gaatgtggcc aggcagaata atgacagtga ctgtggtgct tttgtgttgc 1140 agtactgcaa gcatctggcc ctgtctcagc cattcagctt cacccagcag gacatgccca 1200 aacttcgtcg gcagatctac aaggagctgt gtcactgcaa actcactgtg tgagcctcgt 1260 accccagacc ccaagcccat aaatgggaag ggagacatgg gagtcccttc ccaagaaact 1320 ccagttcctt tcctctcttg cctcttccca ctcacttccc tttggttttt catatttaaa 1380 tgtttcaatt tctgtatttt tttttctttg agagaatact tgttgatttc tgatgtgcag 1440 ggggtggcta cagaaaagcc cctttcttcc tctgtttgca ggggagtgtg gccctgtggc 1500 ctgggtggag cagtcatcct cccccttccc cgtgcaggga gcaggaaatc agtgctgggg 1560 gtggtgggcg gacaatagga tcactgcctg ccagatcttc aaacttttat atatatatat 1620 atatatatat atatatatat atatatatat atatatatat ataaaaatgc cacggtcctg 1680 ctctggtcaa taaaggatcc tttgttgata aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1740 aaaaaaaaaa aaaaaaaaaa 1760 <210> 12 <211> 371 <212> PRT
<213> Homo Sapiens <400> 12 Met Ala Glu Asp Gly Val Arg Gly Ser Pro Pro Val Pro Ser Gly Pro Pro Met Glu Glu Asp Gly Leu Arg Trp Thr Pro Lys Ser Pro Leu Asp Pro Asp Ser Gly Leu Leu Ser Cys Thr Leu Pro Asn Gly Phe Gly Gly Gln Ser Gly Pro Glu Gly Glu Arg Ser Leu Ala Pro Pro Asp Ala Ser Ile Leu Ile 5er Asn Val Cys Ser Ile Gly Asp His Val Ala Gln Glu Leu Phe Gln Gly Ser Asp Leu Gly Met Ala Glu Glu Ala Glu Arg Pro Gly Glu Lys Ala Gly Gln His Ser Pro Leu Arg Glu Glu His Val Thr Cys Val Gln Ser Ile Leu Asp Glu Phe Leu Gln Thr Tyr Gly Ser Leu Ile Pro Leu Ser Thr Asp Glu Val Val Glu Lys Leu Glu Asp Ile Phe Gln Gln Glu Phe Ser Thr Pro Ser Arg Lys Gly Leu Val Leu Gln Leu Ile Gln Ser Tyr Gln Arg Met Pro Gly Asn Ala Met Val Arg Gly Phe Arg Val Ala Tyr Lys Arg His Val Leu Thr Met Asp Asp Leu Gly Thr Leu Tyr Gly Gln Asn Trp Leu Asn Asp Gln Val Met Asn Met Tyr Gly Asp Leu Val Met Asp Thr Val Pro Glu Lys Val His Phe Phe Asn Ser Phe Phe Tyr Asp Lys Leu Arg Thr Lys Gly Tyr Asp Gly Val Lys Arg Trp Thr Lys Asn Val Asp Ile Phe Asn Lys Glu Leu Leu Leu Ile Pro Ile His Leu Glu Val His Trp Ser Leu Ile Ser Val Asp Val Arg Arg Arg Thr Ile Thr Tyr Phe Asp Ser Gln Arg Thr Leu Asn Arg Arg Cys Pro Lys His Ile Ala Lys Tyr Leu Gln Ala Glu Ala Val Lys Lys Asp Arg Leu Asp Phe His Gln Gly Trp Lys Gly Tyr Phe Lys Met Asn Val Ala Arg Gln Asn Asn Asp Ser Asp Cys Gly Ala Phe Val Leu Gln Tyr Cys Lys His Leu Ala Leu Ser Gln Pro Phe Ser Phe Thr Gln Gln Asp Met Pro Lys Leu Arg Arg Gln Ile Tyr Lys Glu Leu Cys His Cys Lys 1~
Leu Thr Val <210> 13 <211> 1299 <212> DNA
<213> Homo Sapiens <400> 13 agtgctctta aagttccgta cagataaagg aagagatccc agttctgata catatgagga 60 agattctgag ttgttgctcc agatacgaaa tgatgtgctt gactcactgg gtattagtcc 120 tgacctgctt cctgaggact ttgtcaggta ctgcttctcc gagatggccc cagtgtgtgc 180 ggtggttgga gggattttgg cacaggaaat tgtgaaggcc ctgtctcagc gggaccctcc 240 tcacaacaac ttcttcttct tcgatggcat gaaggggaat gggattgtgg agtgccttgg 300 ccccaagtga actcaagatt tggcagcccc agagatgcca actgcagcat gcccacctgt 360 attccctgtc cccttccttc atgaaggcat ctccaggcaa ggaaaactga agtcattggc 420 ccgatacaaa acatttcctg caacgaagga ggtggtgccg acgtgctgct tcccatcacc 480 agcagctgct cgacaagggg cgcagggtgg ctgtctttgt tccagcactg ttcaggctgc 540 ctgtcatccc gggcctgcca gctcccctga gtgatgagca cttccaagca cccctctgcc 600 ctttctctgt ccttatgctg tcccggctcg ccagccctct ggggcattgt gggagatgcc 660 tgccaggaat gagcaagctc tgttgctcgg gagcctcttg tcaccttctt ggacttattc 720 cccacctgat accttataga gaaaagtgtg aattcaggtg gagagtaggc ccaggcccca 780 tgaggcacca gtggaagcac agctccaagt tcagacaggt gcccttagag aggaaaacca 840 tgacaggcaa atgcatttcc tctggagttt gagaccctga caaacaacag gtggcatctg 900 gtgtgctgtt cttgagtttt cgtttaggat tagttgagtt ccagctgggt tttgggagaa 960 aggagatgct accaagtctt ggatgttagg gcgagaccct gcaagttgag tattagagag 1020 cttgtctttc aaggcaggtt cctggggctC cagggctagg agggaggagc ctgccctttt 1080 aacagaaccc cagtcacatg cggctcaagt cactcagagg ctgttgcatt tcagggctat 1140 gttggtcctt tgtttacctc ctaaaccaca gctgtttgtg tttcacatat gttgtgaatt 1200 ttccttggtt ctttttaaag gaatgataat aaagttactt gctttaggaa aaaaaaaaaa 1260 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1299 <210> 14 <211> 85 <212> PRT
<213> Homo Sapiens <400> 14 Met Leu Ser Arg Leu Ala Ser Pro Leu Gly His Cys Gly Arg Cys Leu Pro Gly Met Ser Lys Leu Cys Cys Ser Gly Ala Ser Cys His Leu Leu Gly Leu Ile Pro His Leu Ile Pro Tyr Arg Glu Lys Cys Glu Phe Arg Trp Arg Val Gly Pro Gly Pro Met Arg His Gln Trp Lys His Ser Ser Lys Phe Arg Gln Val Pro Leu Glu Arg Lys Thr Met Thr Gly Lys Cys Ile Ser Ser Gly Val <210> 15 <211> 2996 <212> DNA
<213> Homo Sapiens <400> 15 atttccagct cgcacccggg ctccgatcgc tcgccccgct cctctcgctc tgctcctggc 60 cggggctgcg ggttcggtcc gggcgccggt gcgctcctgc cggtcctcgt gcccgggact 120 ccgggtcccc gcgggctgct gcgcacgatg aagctggccc tgctcctgcc ctgggcgtgt 180 tgctgcctct gcgggtcggc gctggccact ggctttctct atcccttctc ggccgcagct 240 ctgcagcagc acggctaccc cgagcccggc gccggctccc ctggcagcgg ctacgcgagc 300 cgccggcact ggtgccatca cacagtgaca cggacggtgt cctgccaggt gcagaatggc 360 tcggagacgg tggtccagcg cgtgtaccag agctgccggt ggccggggcc ctgcgccaac 420 ctcgtaagtt acaggactct gatcagaccc acctacagag tgtcctaccg cacggtgacg 480 gtgctggagt ggagatgctg ccctggcttc accgggagca actgtgatga ggaatgcatg 540 aactgcaccc ggctcagtga catgagtgag cgactgacca cactggaggc caaggtcctc 600 ctgctagaag cagcagaacg gccctccagc ccggacaacg acctgccagc ccccgagagc 660 actccgccga cctggaatga ggacttcctc cccgacgcca tccctcttgc tcaccctgtg 720 ccacgacaga gaaggcccac gggcccagcc gggcccccgg ggcagacagg accaccaggg 780 cctgcaggcc cccccgggtc tasaggtgac cgaggccaga caggagagaa gggtccagcg 840 gggccgcctg ggctcctggg gcctccaggg ccccgtgggc ttcctggaga gatggggcgc 900 cccggccccc caggaccacc cggcccagca ggcaacccag gcccctcacc aaacagcccc 960 cagggcgccc tctactccct gcagccgcct acagacaaag acaatggaga ctcaaggctg 1020 gcctctgcca tcgtggacac agtgctggca ggtgtcccag gaccccgggg tccccctggt 1080 ccaccaggtc cccctgggcc tcgaggtccc ccaggacccc caggaacacc tggatcccag 1140 ggcctggctg gagagcgagg cacagtgggg ccgtctggtg aacctggcgt gaagggggaa 1200 gaaggagaga sagccgccac tgcagagggc gagggggtgc agcagctgag agaggccctg 1260 aagatcctgg cagsgcgagt cctcatcctg gagcacatga ttgggatcca cgatcccctg 1320 gcctccccag agggaggttc tggccaggat gctgccctga gagccaacct caagatgaag 1380 aggggtggcg cccaacccga tggggtcctt gctgccctgc ttgggcccga ccctggacag 1440 aagagcgtgg accaggccag cagcaggaag tgagagccca ctgctccagg acaccctgtc 1500 ctggctagag acccagcccc agaggcctga gccgccgctg tttcctaaag atgcccccag 1560 gggaactggg ctccaggcgt ggatgattgt gaggacatgg ggggctttgg ggacagataa 1620 tgtctccagg ggcagggtct ggaggggcca acaccctcat cagagccctc ctctggcctg 1680 tcccctcccc tacccccact cccggctgga gacggggtct gggtgggctg ggtgctggga 1740 atgagaataa tcctaatacc catcatttat tgagtccctg ctgtaactgg ccctgtccag 1800 ggaactttcg ttacgttgtc tcattattta acccttagga ggtaagctta ttatccccac 1860 ttcacaaggg gaccgaggct cagacggtag aaataaccct ctcttggcca ccagatcacg 1920 ggtggcaggg gcaggatttg aacccaggac cctcagttcc tgaagccatg ttctcttgac 1980 cctgccagct tcccctcttc gagagaaaac tcagacaggg agggcgcagg gccagaacgg 2040 ctccttaagg caggcagggc tgcggggagg ctgggccagc cagcctgagg gggtaggcag 2100 ggtcctgcag ggcctggggc ttcccttcct catccccctt ccccactggc tcggggagca 2160 gcctggactg cagctctcag aggccaggga gaccctgaat aaatcactgc cagccatacg 2220 gacttgagga ccttgagaga gaagcattgg gggtgcaagg gtcccccaaa ccagataggc 2280 atccctggcc actgcctccc agtcttgctg agcccacccg ctctctctgg gtccatccca 2340 tccctgagcc aggggaggca gcatttcatg ggcatgtcta tcagaggtgg gacttgcagc 2400 ctctgcccca cgagtttgtc tctcagtgga ctctataggt ttgctacttt tgcatgacac 2460 agcaagccca gtgtcccctt tgcaagctgc agagagggaa acagagtccc aggcctgctg 2520 ggaagagatg ctcctgcctc ccaccttcca gagttggggg cctggcaggc tccatggcag 2580 gcaccaggtc cctagcagcc cagaacagct ctgactggag ccctcaaggc ctctggggcc 2640 agggtctccg tgatcagctc agccctggtg ttcctctctt gctgggctgg gacctgggac 2700 acagccacgg cagcaaactc agagaattga aggtgctggc gccaccctgg ggcactctgt 2760 cttcacagca ggagtgactg tctccagtgc tcttggtact cctgtttggc tgtggcctgg 2820 tccctctggg ccctgggatc ttcttctggc ccttgaggca ggtctggaga ggcagtctct 2880 gtcttcatgg aggggtggtc agaggcgggc gggaccacca gcctgtagcg ttattattat 2940 atgtgacaat aaaggtgctc tccccacaaa aaaaaaaaaa aaaaasaaaa aaaaaa 2996 <210> 16 <211> 441 <212> PRT
<213> Homo Sapiens <400> 16 Met Lys Leu Ala Leu Leu Leu Pro Trp Ala Cys Cys Cys Leu Cys Gly Ser Ala Leu Ala Thr Gly Phe Leu Tyr Pro Phe Ser Ala Ala Ala Leu Gln Gln His Gly Tyr Pro Glu Pro Gly Ala Gly Ser Pro Gly Ser Gly Tyr Ala Ser Arg Arg His Trp Cys His His Thr Val Thr Arg Thr Val Ser Cys Gln Val Gln Asn Gly Ser Glu Thr Val Val Gln Arg Val Tyr Gln Ser Cys Arg Trp Pro Gly Pro Cys Ala Asn Leu Val Ser Tyr Arg Thr Leu Ile Arg Pro Thr Tyr Arg Val Ser Tyr Arg Thr Val Thr Val Leu Glu Trp Arg Cys Cys Pro Gly Phe Thr Gly Ser Asn Cys Asp Glu Glu Cys Met Asn Cys Thr Arg Leu Ser Asp Met Ser Glu Arg Leu Thr Thr Leu Glu Ala Lys Val Leu Leu Leu Glu Ala Ala Glu Arg Pro Ser Ser Pro Asp Asn Asp Leu Pro Ala Pro Glu Ser Thr Pro Pro Thr Trp Asn Glu Asp Phe Leu Pro Asp Ala Ile Pro Leu Ala His Pro Val Pro Arg Gln Arg Arg Pro Thr Gly Pro Ala Gly Pro Pro Gly Gln Thr Gly Pro Pro Gly Pro Ala Gly Pro Pro Gly Ser Lys Gly Asp Arg Gly Gln Thr Gly Glu Lys Gly Pro Ala Gly Pro Pro Gly Leu Leu Gly Pro Pro Gly Pro Arg Gly Leu Pro Gly Glu Met Gly Arg Pro Gly Pro Pro Gly Pro Pro Gly Pro Ala Gly Asn Pro Gly Pro Ser Pro Asn Ser Pro Gln Gly Ala Leu Tyr Ser Leu Gln Pro Pro Thr Asp Lys Asp Asn Gly Asp Ser Arg Leu Ala Ser Ala Ile Val Asp Thr Val Leu Ala Gly Val Pro Gly Pro Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Arg Gly Pro Pro Gly Pro Pro Gly Thr Pro Gly Ser Gln Gly Leu Ala Gly Glu Arg Gly Thr Val Gly Pro Ser Gly Glu Pro Gly Val Lys Gly Glu Glu Gly Glu Lys Ala Ala Thr Ala Glu Gly Glu Gly Val Gln Gln Leu Arg Glu Ala Leu Lys Ile Leu Ala Glu Arg Val Leu Ile Leu Glu His Met Ile Gly Ile His Asp Pro Leu Ala Ser Pro Glu Gly Gly Ser Gly Gln Asp Ala Ala Leu Arg Ala Asn Leu Lys Met Lys Arg Gly Gly Ala Gln Pro Asp Gly Val Leu Ala Ala Leu Leu Gly Pro Asp Pro Gly Gln Lys Ser Val Asp Gln Ala Ser Ser Arg Lys <210> 17 <211> 850 <212> DNA
<213> Homo sapiens <400> 17 cgagggcgtt cctgtcgggg ctgcagcggc gggagggagc ccagtggagg cgccctcccg 60 aagcgccact gcccatgctg accacccagc cctccggctg ctgatgtcat gagtaacacc 120 actgtgccca atgcccccca ggccaacagc gactccatgg tgggctatgt gttggggccc 180 ttcttcctca tcaccctggt cggggtggtg gtggctgtgg taatgtatgt acagaagaaa 240 aagcgggtgg accggctgcg ccatcacctg ctccccatgt acagctatga cccagctgag 300 gaactgcatg aggctgagca ggagctgctc tctgacatgg gagaccccaa ggtggtacat 360 ggctggcaga gtggctacca gcacaagcgg atgccactgc tggatgtcaa gacgtgacct 420 gacccccttg ccccaccctt cagagcctgg ggtcctggac tgcctggggc cctgccatct 480 gcttcccctg ctgtcacctg gctccccctg ctgggtgctg ggtctccatt tctccctcca 540 cccaccctca gcagcatctg cttcccatgc cctcaccatc acctcactgc ccccaggcct 600 tctgcccttt gtgggtgttg agctcaccgc ccacccacag gcactcatgg gaagaggctt 660 tccttctggg atggcggcgg ctggtagaca cctttgcttt ctctagccct cctgggctgg 720 gcttgggcac aaatccccag gcaggctttg gagttgtttc catggtgatg gggccagatg 780 tatagtattc agtatatatt ttgtaaataa aatgttttgt ggctaaaaaa aaaaaaaaaa 840 saaaaaaaaa 850 <210> 1B
<211> 102 <212> PRT
<213> Homo sapiens <400> 18 Met Ser Asn Thr Thr Val Pro Asn Ala Pro Gln Ala Asn Ser Asp Ser Met Val Gly Tyr Val Leu Gly Pro Phe Phe Leu Ile Thr Leu Val Gly Val Val Val Ala Val Val Met Tyr Val Gln Lys Lys Lys Arg Val Asp Arg Leu Arg His His Leu Leu Pro Met Tyr Ser Tyr Asp Pro Ala Glu Glu Leu His Glu Ala Glu Gln Glu Leu Leu Ser Asp Met Gly Asp Pro Lys Val Val His Gly Trp Gln Ser Gly Tyr Gln His Lys Arg Met Pro Leu Leu Asp Val Lys Thr <210> 19 <211> 1108 <212> DNA
<213> Homo sapiens <400> 19 ataaactccc aggccccgcc cacgccccgc cggggcctta tcctggaccc gggatcccgc 60 gcgcctggag acagggtcca gatctgcctc gagcccctcg aaaccaggac tccagcacct 120 ctggtcccgc cctcacccgg acccctggcc ctcacgtctc ctccagggat ggcgctggcg 180 gctttgatga tcgccctcgg cagcctcggc ctccacacct ggcaggccca ggctgttccc 240 accatcctgc ccctgggcct ggctccagac acctttgacg atacctatgt gggttgtgca 300 gaggagatgg aggagaaggc agcccccctg ctaaaggagg aaatggccca ccatgccctg 360 ctgcgggaat cctgggaggc agcccaggag acctgggagg acaagcgtcg agggcttacc 420 ttgccccctg gcttcaaagc ccagaatgga atagccatta tggtctacac caactcatcg 480 aacaccttgt actgggagtt gaatcaggcc gtgcggacgg gcggaggctc ccgggagctc 540 tacatgaggc actttccctt caaggccctg catttctacc tgatccgggc cctgcagctg 600 ctgcgaggca gtgggggctg cagcagggga cctggggagg tggtgttccg aggtgtgggc 660 agccttcgct ttgaacccaa gaggctgggg gactctgtcc gcttgggcca gtttgcctcc 720 agctccctgg ataaggcagt ggcccacaga tttggggaga agaggcgggg ctgtgtgtct 780 gcgccaggag ccctgggaac gggtgacctt catatgacga agaggcacct ccagcagcct B40 tgagaagcaa gaacatggtt ccggacccag ccctagcagc cttctcccca accaggatgt 900 tggcctgggg aggccacagc agggctgagg gaactctgct atgtgatggg gacttcctgg 960 gacaagcaag gaaagtactg aggcagccac ttgattgaac ggtgttgcaa tgtggagaca 1020 tggagtttta ttgaggtagc tacgtgatta aatggtattg cagtgtggaa aaaaaaaaaa 1080 aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1108 <210> 20 <211> 224 <212> PRT
<213> Homo sapiens <400> 20 Met Ala Leu Ala Ala Leu Met Ile Ala Leu Gly Ser Leu Gly Leu His Thr Trp Gln Ala Gln Ala Val Pro Thr Ile Leu Pro Leu Gly Leu Ala Pro Asp Thr Phe Asp Asp Thr Tyr Val Gly Cys Ala Glu Glu Met Glu Glu Lys Ala Ala Pro Leu Leu Lys Glu Glu Met Ala His His Ala Leu Leu Arg Glu Ser Trp Glu Ala Ala Gln Glu Thr Trp Glu Asp Lys Arg Arg Gly Leu Thr Leu Pro Pro Gly Phe Lys Ala Gln Asn Gly Ile Ala Ile Met Val Tyr Thr Asn Ser Ser Asn Thr Leu Tyr Trp Glu Leu Asn Gln Ala Val Arg Thr Gly Gly Gly Ser Arg Glu Leu Tyr Met Arg His Phe Pro Phe Lys Ala Leu His Phe Tyr Leu Ile Arg Ala Leu Gln Leu Leu Arg Gly Ser Gly Gly Cys Ser Arg Gly Pro Gly Glu Val Val Phe Arg Gly Val Gly Ser Leu Arg Phe Glu Pro Lys Arg Leu Gly Asp Ser Val Arg Leu Gly Gln Phe Ala Ser Ser Ser Leu Asp Lys Ala Val Ala His Arg Phe Gly Glu Lys Arg Arg Gly Cys Val Ser Ala Pro Gly Ala Leu Gly Thr Gly Asp Leu His Met Thr Lys Arg His Leu Gln Gln Pro <210> 21 <211> 1589 <212> DNA
<213> Homo sapiens <400> 21 tctgaacctg tcttgtcctg ggtcctccag ttgttggaag ccactctttt ccccaaccat 60 gctgaaatgc cacctttacc acacactgat gtcttacata gacttagatc tatttctgga 120 acttctcttc tcttcgctta cttgggtgtc tcatctggca ccagccatac aattttaact 180 attgtcaatt tctaatgtct tattatgtgg tgggatgagt cccttcactc ttcttttaca 240 aaatttccta gttattctct cacatctatt cttccacata aactttaaat tgtgcccagt 300 cctccacccc ctgtcccatt cccaccccca aattctgggc tctgtcattc cctgtgccat 360 catcttcccc ccattgtaat tactgtccac tcagggctgt gaaatagact atgttctata 420 aagagggaca aaaagggcat cctgatcttg agagaagcct gctgttcctc ccatcatttc 480 acctgccccc taagcccagg agttgtcatg agaggtcacc aggcccccac tcaatctcag 540 cttgggaacc aaagtcaccc accttggttg tgttggggtg gacccgccat ctgtccctgg 600 tccagacgag aaagaggagt ctctcctagg cctggagctg ggaaagaatg tgtggcccag 660 ttgtctgcac ttctaattct catcatggag aaacctttat tcctatctcc ctttcctgaa 720 ctggtttttt gttgtttttg tttcattttg ttttgggggg atagtttctt gctctttaat 780 ttggagtctc cagtaccttt gggatgcagg cagttcttgc ctgggccttc tcggaaccct 840 cactccccta gcccactctt gcgctacctg caggaggctg ccaacctggt gcattctgac 900 aagcctccca cccaaatctc tctcctgcca ttgtgtccaa aatcccacca ttagaggctc 960 ttgtagggaa gagcgtttct tgaaggcttt taggccttcc agagccagga gggaagtcag 1020 acaatagcag gaagtcccca ggccttttca aagttccaaa ccaagctctc ctgattttaa 1080 tgtagagatc ataccaaccc aggtggggga ggagggtccc cagccccagg cagcagccat 1140 caccccctcc actgaaaaca atattggagg ctgctttggg actgcccttc tcagccccct 1200 aagtctgttt tgtaatgcct gtggtgctct ccctcctgga cctttcctct cgggggtcac 1260 cacactttgc taactcttgt gtgcacatat tttataatag agtagcgagg gaatggtgcc 1320 gcctccagct tccgtaagct gcccgggctc tggggggctc tgggacaatc ggggctggga 1380 agtgactgtg ctcttattgt acactcttta tttctgtgta tctttggctt gtgctctttg 1440 taattaatgg gatttgtctg ccttttcaac actatactga gcaataacaa taaatgcaca 1500 cgtggaaatg cagacacggt acacatcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1560 aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1589 <210> 22 <211> 148 <212> PRT
<213> Homo sapiens <400> 22 Met Arg Gly His Gln Ala Pro Thr Gln Ser Gln Leu Gly Asn Gln Ser His Pro Pro Trp Leu Cys Trp Gly Gly Pro Ala Ile Cys Pro Trp Ser Arg Arg Glu Arg Gly Val Ser Pro Arg Pro Gly Ala Gly Lys Glu Cys Val Ala Gln Leu Ser Ala Leu Leu Ile Leu Ile Met Glu Lys Pro Leu Phe Leu Ser Pro Phe Pro Glu Leu Val Phe Cys Cys Phe Cys Phe Ile Leu Phe Trp Gly Asp Ser Phe Leu Leu Phe Asn Leu Glu Ser Pro Val Pro Leu Gly Cys Arg Gln Phe Leu Pro Gly Pro Ser Arg Asn Pro His Ser Pro Ser Pro Leu Leu Arg Tyr Leu Gln Glu Ala Ala Asn Leu Val His Ser Asp Lys Pro Pro Thr Gln Ile Ser Leu Leu Pro Leu Cys Pro Lys Ser His His <210> 23 <211> 2538 <212> DNA
<213> Homo Sapiens <400> 23 aaaggttgta taccctgaaa taccatctga taaaacctgc agaaaggata attttagttc 60 ataaatgtga ccctcattgt tggcgcatca gtgagatggg agagaacagg ctgagtcaaa 120 ggagatgatc ctcccagctg cccccaccca actgttactt ctctgtagat caagaagtga 180 tgtggcacag gctctgggtt cagattctag cttctccact cacttgttgc atggctacat 240 caagttactt actgtctcta cgctttcatg ttatcttcaa aattgggata atatgattcc 300 atcagtggct atcgtttttt taatatggcc cagagacctc ctgaaattag acatgggtgg 360 caatttattt tgttttggga ttcagaaagg aaacatttgt aaaactgtgc tcaaggatca 420 aaaatcctgc agttattttg actgttacaa cctccttatt aatgctacca aggcatttca 480 gagagttgct tcctgaagtg actccattca tctgagctct gtggtgttcc gtcataatat 540 gtggtgagct ttaatcttcc ctttcagctc aggaagctgt gagtcattta tctacttgtg 600 caaagaggac agagacatcc tatctcttat gttcatcagt ttgttcagat ctatagtggt 660 tgtattggag aaacctggct gttatccaaa agggtaggtt ggaagaggct taccacacac 720 attgaatata tttcttaaag ctgctatgga aataaagtga tgtcaccttc tacccctaat 780 ttgcatgtgg ctggaatctc tgaggcatgg gtttgccctt cccaccctcc tgtgcgttgg 840 tgtctcagac ttgtaatctt gcttggtgaa gaagtcattc tttgtttttt tgggtagatg 900 gaaatgggtg gcccaaagtg tacctctaaa ctcatatctg cttgctccca ctgttaggga 960 gatgtctaga cacggagaaa agggcttggt aattaattga ctttgggaaa ttccacttaa 1020 aagtagagat acaatttttt ttattttata aaatatttca aacaaagagg aaattggaag 1080 agtaatataa cacacacatg tatatgtaaa agttactgac tatatatgcc aagggccatt 1140 ttgagtttct aagagggtga atatagattg tgatatttac atatttgttg gacttttttc 1200 tagagcatct ttcctttggg atacattttg ggaaatattg gtttataatt tattttcttg 1260 gtgggaaaga catggataag tatctatacc ttgagataaa taactaaaac tgcataatta 1320 aagaaataag ttgtcaagtg aatttcacaa gcacaaggga gagttaaagt gttgtagtgg 1380 gtcatataag ctttgacata tttttcctca taaagctgat aactcttcag tattgagttt 1440 ctaaaaaagg aagtatttcc tgtggtaaat tttcacttgt gtatctgtga ataccattat 1500 tgtgtgtgaa acttaaaaac tggtagagaa cactaccttt ctcaataaat cagtacccac 1560 gatgggtcta gtgtggaaga caggagggtg tgggaagtgt tgttgtaaca gaatttaaaa 1620 gtgccaaggg agaagaaatt cacaaggtgt ttatatccag gaaagtgtat ttaataatgt 1680 tttttacatt ctctaagaaa aaaagattga aaatatcagg agagtctcaa tgaaaagaac 1?40 atacaaaaag aacataccag gattctagga ctgatacatt ttctgtcaac gctattgcta 1800 ttacaagtaa agggattaag cacttgtgaa tgttgatacc atgtataata actctaattg 1860 gatattgttc aacgtttatt tccatattac ccaatattta gtgcattgta actaatagaa 1920 ggccctcata gccaacctta cttgatcttc ttgataacct tgagaggtgg atattattat 1980 ccccatttta tagatgtgta aaataagcct cagagaagaa tagaagtttc tgttgaaaaa 2040 tatatatgaa gaattttata ccaaatgaca gatatttgtc aaacatttca gaaaacattt 2100 ggagaccggc agagtttttt aaataattga aataattgga attggtacct aagcagcaaa 2160 ggaaatttaa ggagaaagaa tattttgaag taaattataa attaaacaat gtgaaataca 2220 gttttcatag gttgtcataa atgctttcat gtagtttgtg catgctttgc aactcagctg 2280 caagtgctta cagaaactaa ttttttattt ttaacaattt tttgcaagtt tttgaaaatg 2340 ttttgattgt caggttcata gacttctaac tcaaaactaa tgtaacaaaa tattagaaaa 2400 agtggaaata ttagaaaggg gatcttagaa tttataaaaa taaatatctg aagagtacct 2460 atttgaaaaa atgtagtctt gttttatcat atattagtta cagtaaaaat tatcaaaaaa 2520 aaaaaaaaaa aaaaaaaa 2538 <210> 24 <211> 123 <212> PRT
<213> Homo sapiens <400> 24 Met Ile Leu Pro Ala Ala Pro Thr Gln Leu Leu Leu Leu Cys Arg Ser Arg Ser Asp Val Ala Gln Ala Leu Gly Ser Asp Ser Ser Phe Ser Thr His Leu Leu His Gly Tyr Ile Lys Leu Leu Thr Val Ser Thr Leu Ser Cys Tyr Leu Gln Asn Trp Asp Asn Met Ile Pro Ser Val Ala Ile Val Phe Leu Ile Trp Pro Arg Asp Leu Leu Lys Leu Asp Met Gly Gly Asn Leu Phe Cys Phe Gly Ile Gln Lys Gly Asn Ile Cys Lys Thr Val Leu Lys Asp Gln Lys Ser Cys Ser Tyr Phe Asp Cys Tyr Asn Leu Leu Ile 1g Asn Ala Thr Lys Ala Phe Gln Arg Val Ala Ser <210> 25 <211> 4466 <212> DNA
<213> Homo Sapiens <400> 25 gttgcggaga acctacaagt ctccgctccg gcatgcgcgg cgcgcccaaa tcaggaagac 60 ttctgcctct aatagggctg tgcgagagag gcagatgctc tgccgccagc tggcctctgc 120 gggcacgggg ccttgcccag tgcatccagc ttccaacggg actagtccag cgccagccct 180 gcctgcccga gcacggaatc tttaagaatc cgccagcact tggtagcgtc tgcagccacc 240 caggtagcat acgctctttg ctgtgtagaa gaaatgccca tacgacagct ttgcccctgt 300 ttgaagacct cccttcttgc ctctccagac gtgttccccg aggagatctt ccttccgtcc 360 ttcctggcgc cctggttgcc caccttgccg tgcttcctct tacgtgctag ctttgtacct 420 atcgctcact gcatgctcgc ctccctcttg ctggcatccc ggcctgtttc aatgactacc 480 gctctgctac ttaggcacag ggactccgcc gcacgctgac ggaccacgag ggctgacccc 540 ttccagcctg acttggttca tggaggctcc tactctgccc tctccaagct cccctggcgg 600 ctccccacct ggttgcccag ttcctattga tgagctctgg acagaaagat gcccgtttgg 660 ccaggctggt ggcttgatgg gtgtacctgg agagggggtc tggcttcctg cccaagatgc 720 ctcccagccc tgccagggcc cggtgcagcg ggcagggcct catctgtgct gtagtggtcg 780 agtggtcgct gcaaggagcg tagttctgcc atgtctgggg gccaggttcc actctgcaca 840 tgaatatgca gtctgggagg ccctactgct catactggga aggaccaatg ttgcacctct 900 gttaatgcct gacttcagct gctggtgttc tgatggagcc agaggcttgg ggaatctgga 960 acttgcctgc taaataaggt catggtggac tctcagccat tgggcaggtc tatcaggctg 1020 caggttccta cacacccacg cctgagggcc atagcaggct aagggtggat accagcgact 1080 ccctttgctg cccaggatct ccatgggcag tgccacagcg gctgatgctc agtcactcct 1140 gcttctaccc cctgtcactg atggcgagcc ttgcccagct tgagacctgt tcccatctcc 1200 attcaggtgc catgtggcct tcactgcagc cctgcagcca cccacgcacc atctgtgggt 1260 ctccaaaggc accttgtagc atgtactccc cgtgcctggg caatcagatg ggctgccttt 1320 gtccaaggga aaacagactc ccttcgggaa acatccttaa gcacttaagg ccgggggggg 1380 gtgtctgcct ctggcaaccc agccagggtc ttggtggcat ttgtaaaagc aaagagctgt 1440 ggactgccgt ggtcctagtg tggtgacaat gcagcactgg catgcatgtc cttctgaagg 1500 acctcatcct tcctcacagg cggatgacca agaaatcatt ttgtggctgg gtttggccac 1560 gccctttgga ctgtgctgtt ccgccatatt tcaatgccaa atgaaccaca ttgacatgac 1620 ctggaccata gggcttccta tcctgggctc agctgcccct gtctgaaggg tcctggcttg 1680 attgcagaag gacaacctcc gcacccacct aaagacatgt atatgtcttg ggatcccaga 1740 gattgggtcc ttgggcctgg cttcttaaga gttttgatga tgctgggaaa agtgactgcg 1800 attctgaaga accgctgcct tgcaaggtca aggacattca gtggttgctg gggtccgcag 1860 actactgcca cccactcacc atcaactctg ttagcccaat tgccctgctg aacaactgcc 1920 tgaatacagg ctttaggttc ccctggactc cagccaaggc tgttcaggtg ggaccatggt 1980 gctctttaag cgtgatcgga gggaagacac acagcagggc caccattcca tgaatgggag 2040 gtgtacagat cactttctct ttgtgctcag ttctcttctg tctccagcag ctatattggt 2100 aagactagta cctgccaggg agaggtgccc ccaagtgaag gggtacagtg gcacctggga 2160 aaaggcacct ggaaggtttc catgtggccc agcccagcat ggaagcaggg tgggaactct 2220 gctgtgtcgc cagccctcac tctactcaag tggctttttg agagccctgc catgtctgtg 2280 tcaggcctgt gctgcttcac accctacagc tgcctgggaa aggccggcca cgctccctgt 2340 ccacacactc cctgtccaca cactccctgt ccacaactgc agccgggccc tctgcctatg 2400 ggcacccaat ccaagcagct gctccacctt tgtttggcat ggtgatttgt gttttttctc 2460 ttggtgctta tgtgtgtggg cttgggacga gtgctggtat gcacttagga ccttcttgat 2520 agctccctgc actttggaac acggagcaga tgagagaggg tcaggggctt gccctccacc 2580 ttggacttgg aagaagccca cattggagag gtgaggaccc catggtggct ctagtggaag 2640 atacgttagt ctccagctaa ggaggatgag gcgcagcccc agagggagac ctcagtgata 2700 ggggatcagg ctacgaaagt gggggaaggg agatgctttg tacatatttt ggggttataa 2760 tttctctaaa ttttaggaga acgggtattg attgataaaa gggacaggca gtagtgttca 2820 acagtgcatg tgaaggaaag ttctgttttc catggttttg acattctttg gactgtattg 2880 tgactgctgt ctggtccaca tggtaccctt ttggtaagta ggcttcagtg cataccaggg 2940 tatcactgga gatgggagtt agtgaagggg tgactccctg gcctagtata gtgtgaccct 3000 gggacaactt aatgtcctaa agcattttgg tgacttctag ggaatagcaa agacctattt 3060 cattgtcccc aggtaagtat gtgatgagca atgaggagga gtggaaaaca aaacccagaa 3120 agtgcggcag gaccagcctg acgcacacgc tcctgttgtc atggcagaca gccgccttgg 3180 gtgggcacca ccctggcagt tccagcctgt aggggagtga agggacatgg ctgagctggg 3240 catgtgctga ggttgactta gggaacaagc cctgggattg gacaaaaggg cccatgctgc 3300 agccactgac tgggggcaga gctctgggtg gaagagggaa gagatcctaa tggaggcgcc 3360 tccatctgca accacagttg taaggctcat ggcacctctg cttggaaagc actggtttag 3420 ggacttagag aggtaggcac aaggtgggtc tcctgggtag ggaagcaaga gcagactgtt 3480 gggccaacag gagaagctcc ccagagtagg ggagaaggtt ggggtgtagg gccttccacg 3540 tggaacagac agcccctgtg tctctgtctc ttggggacct gagtttgggt ggggtggcag 3600 ttggcacagc gcagatgcgg tagagatggg aggaaaccca gctcctcact tccgtgtgcc 3660 tcatgccttt gcatacacaa gcaccaaacc tactaggtct tctcattacc catgtaaacc 3720 acatgttaga taaatttttg caagtagagg aaagaaggaa ataaaacatc acattttggt 3780 gtctctcagg ctttcccccc caactatggt ttctttgctt tttgttttaa catagttttg 3840 ttgctgtctt ctgtaatgat acagttttgt gcagctgttt tcacttagca tatcgtgggc 3900 atctcccctt atgattacta aatattttat tttggagtgg ctgtgtactc tcccattgac 3960 tagatggacc attgtgccag ttgccaatca ctaatgctgt tactaacttt tcagttataa 4020 attgatgaat atctttgtgc acaggctgtt tcccaatgtc aagttattag ggtagactcc 4080 aggaggtggg attcttcaac taaagaatat gaaaaccttt gaggctttta ctacatattg 4140 acaaaatggt ttccggaaat atttgtatcc ccttacactg ccaccagcaa ggataaacat 4200 gtccatcttg cccgtattgg~gaattatcat ctggctaaat atttgctaat ttgataatga 4260 aaaaatagca tcgtgtttca gttggcattt cactgacttc tagcacggtt gaacatcttt 4320 catgtggagc gattgtattt cctcctttgt ggattgtcag tgtcctttgc tctatcttct 4380 ggggtcagat aaatttgtat gagctcggta tatattaaag atattaacct ggtgtgtgtc 4440 ataaaaaaaa aaaaaaaaaa aaaaaa 4466 <210> 26 <211> 125 <212> PRT
<213> Homo sapiens <400> 26 Met Arg Gly Ala Pro Lys Ser Gly Arg Leu Leu Pro Leu Ile Gly Leu Cys Glu Arg Gly Arg Cys Ser Ala Ala Ser Trp Pro Leu Arg Ala Arg Gly Leu Ala Gln Cys Ile Gln Leu Pro Thr Gly Leu Val Gln Arg Gln Pro Cys Leu Pro Glu His Gly Ile Phe Lys Asn Pro Pro Ala Leu Gly Ser Val Cys Ser His Pro Gly Ser Ile Arg Ser Leu Leu Cys Arg Arg Asn Ala His Thr Thr Ala Leu Pro Leu Phe Glu Asp Leu Pro Ser Cys Leu Ser Arg Arg Val Pro Arg Gly Asp Leu Pro Ser Val Leu Pro Gly Ala Leu Val Ala His Leu Ala Val Leu Pro Leu Thr Cys <210> 27 <211> 2667 WO 99/55721 PC'T/US99/08504 <212> DNA
<213> Homo Sapiens <400> 27 gtcccctggg acccatgggc cttctgggtg tgtgtagggg acagcgcctg gattaagcca 60 gggaagtaag gacttggatt gttaagaaac agccctctgg ctgctgtggg gaacccagga 120 aggcagcttg gagccttctc cagggccctg gctggcggca cagggggctg ctcacatgtc 180 caggacccgt gaaggaccca ggaggtggtg gacagggccg gtagcccgag gtgcactggg 240 atgggggctc tgcatgtgtc tgaaggtggc agccgtcagg cacagcttct cgccccctcc 300 tcaccccaca ggaagagcag cgaggaggcc atgcgggagc gacagcaggt ggtgtccctg 360 gccgccatgc gggagcccag cctgctgcgg ttctacgtgt cccgcgagtg gctcaacaag 420 ttcaacacct tcgcagagcc aggccccatc accaaccaga ccttcctctg ctcccacgga 480 ggtgaggcgc cccctgtggt gggagagcag ggtgggcagc tgggccgagc cacagcttcg 540 ctccctgtac cttcttccca ggcatcccgc cccacaaata ccactacatc gacgacctgg 600 tggtcatcct gccccagaac gtctgggagc acctgtacaa cagattcggg ggtggccccg 660 ccgtgaacca cctgtacgtg tgctccatct gccaggtgga gatcgaggca ctggccaagc 720 gcaggaggat cgagatcgac accttcatca agttgaacaa ggccttccag gccgaggagt 780 cgccgggcgt catctactgc atcagcatgc agtggttccg ggagtgggag gcgttcgtca 840 aggggaagga caacgagccc cccgggccca ttgacaacag caggattgca caggtcaaag 900 gaagcggcca tgtccagctg aagcagggag ctgactacgg gcagatttcg gaggagacct 960 ggacctacct gaacagcctg tatggaggtg gccccgagat tgccatccgc cagagtgtgg 1020 cgcagccgct gggcccagag aacctgcacg gggagcagaa gatcgaagcc gagacgcggg 1080 ccgtgtgatc tgctgggcta gtctgtaagt cgccccggct ggtccctcca tggcactctg 1140 ggtcctctcc tcactctcca gagaccctca catgtccttt tgaacatcca aagagcaggt 1200 ccctgaaagc accttcctgg aggatgtggg agggccctgg acatggcccg gccccactgc 1260 tgagtgcccg tgtccccaca gccccatgtg ccccaccccg cggaaggcgt gtttgtgccc 1320 agaagagagg ccgggctgct gcagaacccc gccgtgtaaa gaggcagaaa agttggtttg 1380 gtttgcagta acgctgcaac tagaaaatat atgcacttca ggcttgttga aacgaccaag 1440 actctgtgac gttaatttgg gtctttgtcc tggcagtgcc tctgccagtc actgtcatcg 1500 ttgtgtcccc cacaactgtc ctcttgctag ctcggcccag ctttgtccct ggagcccgat 1560 gctacccctg tcagacagag gctgcggcct gggccagagt cagggagtag ctgctgcttc 1620 acggcgtctc cactgtgcga ttggcccgga gccccgaaga ctcggaggga gctgctcagg 1680 gccggtgagc gcagccagaa gccctggcca gtgaggagct cacaggtcct ccctggtggt 1740 cccgccgcac ctctgcatct cctgggcgtc accaggaagg ctctgaagtc ccgggctgct 1800 ctcagcactt ctcctgcaga ctgaagactc tggactcatt gctgattgga acaccaggag 1860 gaggttggat ttctgccagt gggggatgtt tctggaggca gctggtcccc cacaccgcgt 1920 cctgctgagc ctgccccctg gattggctgt aatttgcctc gaagttcagc agttcatctt 1980 catgggaaat ttgctgagcc cccaccaggg aaccggatga tgaaacaggg atacctcaca 2040 gcttggccat ttgaggcaaa ggcagcttcc cgagctgatg ctaaagaaga cagactttcc 2100 cttcctccca gcagcagcag tgcagagccc gcctggaggg atgtgggggc tgtgcagggt 2160 gcagcgctca ggtggatcct gggaagcagc ctctggatgc tgagtggagg gagccactga 2220 gcacagcaag gcaccaaagc ccctggagaa accgccaggg cgaggtgcga ccatcatcag 2280 gatcaaagca gacggggcgt gggtggggaa ggggctctgg gaccagaccc cccacactac 2340 tgcgtctttg tttctatcag tctttgtaga agcaggtggt ggtggaaatt ccagcaggtg 2400 ggtcccgcag aggccctgag gcctcacttt tcggatcttc tgtcccagat cctgctccct 2460 ccctgctgag cctggggttc ccctggcatt ggccccagcc ttctgaaagc cggcgctgca 2520 gccagaggcc gcacgctgca ctgtcgcgac gcagagaggc ttctgtgcag gctgggatcg 2580 ggccccatgt ctgtgctgtc tagtttgtgt tcaaaatgtc agaataaaca cagaataaat 2640 gttaaaaaaa aaaaaaaaaa aaasaaa 2667 <210> 28 <211> 232 <212> PRT
<213> Homo Sapiens <400> 2B
Met Ser Arg Thr Arg Glu Gly Pro Arg Arg Trp Trp Thr Gly Pro Val Ala Arg Gly Ala Leu Gly Trp Gly Leu Cys Met Cys Leu Lys Val Ala Ala Val Arg His Ser Phe Ser Pro Pro Pro His Pro Thr Gly Arg Ala Ala Arg Arg Pro Cys Gly Ser Asp Ser Arg Trp Cys Pro Trp Pro Pro Cys Gly Ser Pro Ala Cys Cys Gly Ser Thr Cys Pro AIa Ser Gly Ser Thr Ser Ser Thr Pro Ser Gln Ser Gln Ala Pro Ser Pro Thr Arg Pro Ser Ser Ala Pro Thr Glu Val Arg Arg Pro Leu Trp Trp Glu Ser Arg Val Gly Ser Trp Ala Glu Pro Gln Leu Arg Ser Leu Tyr Leu Leu Pro Arg His Pro Ala Pro Gln Ile Pro Leu His Arg Arg Pro Gly Gly His Pro Ala Pro Glu Arg Leu Gly Ala Pro Val Gln Gln Ile Arg Gly Trp Pro Arg Arg Glu Pro Pro Val Arg Val Leu His Leu Pro Gly Gly Asp Arg Gly Thr Gly Gln Ala Gln Glu Asp Arg Asp Arg His Leu His Gln Val Glu Gln Gly Leu Pro Gly Arg Gly Val Ala Gly Arg His Leu Leu His Gln His Ala Val Val Pro Gly Val Gly Gly Val Arg Gln Gly Glu Gly Gln Arg Ala Pro Arg Ala His <210> 29 <211> 2699 <212> DNA
<213> Homo sapiens <400> 29 agaaattgcc gtggatattg taaaacatgc ctttattact aaatccatga cattactgca 60 gatgtctaca gtgaatatag agccagtctt gcttttgacc ttgttagcag ccgacagaaa 120 aatgcataca ctgattacag tgactctgta gcacggagga tgggctttat tcctctccca 180 ctagctgttt tactcatcag agttgtaaca agctcaatta aagtgcaagg aatcctgtct 240 tatgcctgtg tcatactctt ctattttggg ttgatatccc tgaaagtact taatagcatc 300 gtgctgttgg ggaaatcgtg ccagtatgtg aaggaagcca aaatggaaga gaagctgtcg 360 aatcctcccg caacctgcac tccaggcaag ccgtccagta aatcacagaa caaatgtaaa 420 ccctctcaag gcctttccac agaagaaaac ctgtctgcct ccatcaccaa acaacctatt 480 catcaaaagg aaaatatcat accattactt gtgacaagca attctgatca gtttttgaca 540 actccagatg gtgacgagaa ggacataacg caggacaatt ctgaattaaa acacagatcc 600 tcaaagaaag atttgttaga gatagacagg ttcacaattt gtggaaaccg aattgactga 660 atctgtggct tcatgcgctg aagaagctgg gtcctggggc aacaagtgct gtgttgccag 720 gacaaataga tgctaaacat ggcacttaaa tatttattta aaaacttaaa ttattattgg 780 caagcaaatc ttagtatctt tcttccagta atatggcctg gctgagggtc agaccacagg 840 acaggagcga cctccggcct tgactgtctg ggaagcttga tggattataa aacttcctcc 900 tgcctggcca agcagcagca tcatttccag gacccaacaa aggcaacatc aaaatctgtt 960 ttgctttgtc agtctgggct tccagaatgt tgaatttgcc tcaaggcctc ttcagtataa 1020 ggaaatacct ggaaaactgt gaaactttta ccacgacgta atctttccag tctcatacta 1080 ttttcacaaa cagttttcaa acgttacttc atctgccaaa gcattaaaaa aattaaacat 1140 aagtcaagat aaatgttctt accaccagaa taacccttaa agatgtatct taattaatca 1200 gaataaaagg ctaccttaaa taagacatga tgaatagtag cattttgtag ggttaaaaaa 1260 aaatgctaaa ctagtttatt tattaaaaaa ataattaatg aaggctatgc attactggga 1320 aaaatccttc ataatttttc agtttactct ttaaagcaaa atgtgagctg tatgtcattt 1380 aattggtgga taaaacaaat ttccttacaa aagggcactt tttacaccaa ggaagcagag 1440 cagtgttaac tttaaggtat acttaactga ttttgcttta aaactaatta cttcataaat 1500 tattacagct aaaaggattc gatgttgaac aggctgaaaa attgtcaatg tacaaaattc 1560 aaaactgtca actttaactg taaagtaaat gctccaagtg tgttagacag catcatcttg 1620 cttgggctta ccaaatgcat tagtctttgt gtttgggtcg acagcgagtg tgcctgtgct 1680 ggggcagggt gtgtgttctg tgggagggtg tctgtgggga tgtgactatc agggtgggcc 1740 tgtgctgggg atggggcagg cctgggtctg gagaggattt tgtgtgaaag taaatggggt 1800 gtttgaggcg tatgggtggc tgttggtgtg gggaggcatc tgtgtatggc tgttgggaac 1860 agcaaccaaa aggtgctttt tggttttatt tgagatgaag attgtgtttc cgcttaatta 1920 ctagtttgtg gtctatatca tagaagttat ttcccacccc attttatctt gacaaccgtg 1980 tttgcatttc tgtaaaactt ctacaacttc tggtgtcaga actgtccaga agatggtact 2040 gttaactgtt atttcctttg atgttttgat tttgaagttt agctctcatg caaatgtttc 2100 aggcgtacat acataggcag aaagcaattt ttaggtgatt tgtctgtttc ttggatgaaa 2160 tataaagcaa gctttaatgt tctgacttgt tcatttgaaa tacaaaaaag taagtgaatt 2220 ttaatgtttt gcattaacta aagaaatctg aagattaatg ttgaggaaat tgtatggaca 2280 tgcctttgtg aaaccaggaa gtattttaag ttaaaaatga aaaaggtttt aattgctttg 2340 tgtgtgtttt aatggagccc cattttagaa ttattttttc catctccctt taccaacsaa 2400 aggaacaatg ccaccgtgaa tggaatagtt tggggaaagc tttgccaaac acaaccctga 2460 tttcagagca ggaacatggt ttggatagat cttcagttcc gcttgaatta ttctgttact 2520 gcgctgtcat tttcagaaga tttccattcc tttgcagatg ctgttgggag ttcgggatta 2580 tgttcatttc ttctgtttta atggcattca gtactaattt tataagtgca tcttgtgtga 2640 atctcaataa attcagtttt gtaatcttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2699 <210> 30 <211> 166 <212> PRT
<213> Homo sapiens <400> 30 Met Gly Phe Ile Pro Leu Pro Leu Ala Val Leu Leu Ile Arg Val Val Thr Ser Ser Ile Lys Val Gln Gly Ile Leu Ser Tyr Ala Cys Val Ile Leu Phe Tyr Phe Gly Leu Ile Ser Leu Lys Val Leu Asn Ser Ile Val Leu Leu Gly Lys Ser Cys Gln Tyr Val Lys Glu Ala Lys Met Glu Glu Lys Leu Ser Asn Pro Pro Ala Thr Cys Thr Pro Gly Lys Pro Ser Ser Lys Ser Gln Asn Lys Cys Lys Pro Ser Gln Gly Leu Ser Thr Glu Glu Asn Leu Ser Ala Ser Ile Thr Lys Gln Pro Ile His Gln Lys Glu Asn Ile Ile Pro Leu Leu Val Thr Ser Asn Ser Asp Gln Phe Leu Thr Thr Pro Asp Gly Asp Glu Lys Asp Ile Thr Gln Asp Asn Ser Glu Leu Lys His Arg Ser Ser Lys Lys Asp Leu Leu Glu Ile Asp Arg Phe Thr Ile Cys Gly Asn Arg Ile Asp <210> 31 <211> 1300 <212> DNA
<213> Homo sapiens <400> 31 tctccccccg ggctccgccc accccacgcc gggaacccac gcgggccact acaagcccgc 60 cctttcctac gtctggtcca gtcggtcttc ctccggcccg ggccctggcc cagctagccg 120 gccatggaag tgaagaaaat gtttggaagc tctgtgaata catcaaaaac catgaccagt 180 atcctttaga agaatgttat gctgtcttca tatctaatga gaggaagatg atacctatct 240 ggaaacaaca ggcgagacct ggagatggac ctgtgatctg ggattaccat gttgttttgc 300 ttcatgtttc aagtggagga cagagcttca tttatgatct cgatactgtc ttgccatttc 360 cctgcctctt tgacacttat gtagaagatg ccattaagtc tgatgatgac attcacccac 420 agtttaggag gaaatttaga gtgatctgtg cagattcata tttgaagaac tttgcttctg 480 accgatctca catgaaagac tccagtggga attggagaga gcctccgccg ccatatccct 540 gcattgagac tggagattcc aaaatgaacc tgaacgattt catcagtatg gatcccaagg 600 taggatgggg cgccgtctac acactatccg aatttacaca tcggtttggc agtaaaaact 660 gctgaacttg gcctcaagat gtggaactgt ggagaaattc taggacatga acaagctatc 720 ctttcatcga ggacagcaaa cattatggta cagttggctt ggaattatgt ctttctcttt 780 taatttgatt gagtggaaat ctgagtgagt acaaatataa atgaacaaca taaaaacttt 840 tgttttgaca tgtcaaattg aaacttgata aagtgcgtac ttgctaagat attcctgtgg 900 ctcatgcgtt acaacacgag gacttaagcc agtaatcgtt tttgttcaga tagaggtgtg 960 gaggtagagc cagcccctca tgtctgttct ggatgttttg tgtctctcca gctacactgt 1020 aagttccttg agggcagggc catggcccat tgctctgtga atctcaaatg cccataaaag 1080 gtgcccataa aatgttttct tgaacatttg aatgtgctgt tgtctggaaa ggggtaatat 1140 tgtgagctga atcagcaata agtattagtc tttttggact atggtattgt taasaagact 1200 gcagccctct cagacttgag cgttaattgg cttatttatt tatggcttta aataaaatcg 1260 atttaacgtt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1300 <210> 32 <211> 145 <212> PRT
<213> Homo sapiens <400> 32 Met Ile Pro Ile Trp Lys Gln Gln Ala Arg Pro Gly Asp Gly Pro Val Ile Trp Asp Tyr His Val Val Leu Leu His Val Ser Ser Gly Gly Gln Ser Phe Ile Tyr Asp Leu Asp Thr Val Leu Pro Phe Pro Cys Leu Phe Asp Thr Tyr Val Glu Asp Ala Ile Lys Ser Asp Asp Asp Ile His Pro Gln Phe Arg Arg Lys Phe Arg Val Ile Cys Ala Asp Ser Tyr Leu Lys Asn Phe Ala Ser Asp Arg Ser His Met Lys Asp Ser Ser Gly Asn Trp Arg Glu Pro Pro Pro Pro Tyr Pro Cys Ile Glu Thr Gly Asp Ser Lys Met Asn Leu Asn Asp Phe Ile Ser Met Asp Pro Lys Val Gly Trp Gly Ala Val Tyr Thr Leu Ser Glu Phe Thr His Arg Phe Gly Ser Lys Asn Cys <210> 33 <211> 1256 <212> DNA
<213> Homo Sapiens <400> 33 ctcgcttcta actggactgc acgttggtga cagcgtccca agctggtgac agacccactc 60 tgtaactttc agctagattc agccaccaga tcccagaaac atgacccttg ctgcctacaa 120 agagsagatg aaggagctcc cgctggtgtc cttgttctgc tcctgcttcc tggccgatcc 180 cctgaataag tcgtcctaca aatatgaagc agacacggtg gacctgaatt ggtgcgtcat 240 ttccgacatg gaagtcatcg agctgascaa atgcacctcg ggccaatcct ttgaagtcat 300 cctgaagcca ccctcctttg atggggttcc cgagttcaac gcctccctgc caaggcggcg 360 agacccatcc ctggaagaga tccagasgaa actagaagcg gctgaggagc gaaggaagta 420 ccaggasgcg gagctcctga aacacctagc agagaaacgg gaacatgaga gagaggtgat 480 ccaaaaggcc attgaggaaa acaacaactt catcaagatg gctaaggaaa aactggccca 540 gaagatggaa tccaacaagg agaacaggga ggcccacctc gccgccatgt tggaacggct 600 gcaagagaag gacaagcacg ccgaggaggt gcggaaaaac aaggagctga aggaagaggc 660 ctccaggtaa agcctagagg ccaaagaact ttccaggtca gccggacagc tccagcagct 720 ccacgttcca ggcagcctcg cccgccggct gcgctcccag cactggggtt tggggggagg 780 ggggtggcca aggggcgttt cctctgcttt tggtgtttgt acatgttaag aattgaccag 840 tgaagccatc ctatttgttt ccggggaaca atgaccgggt gggagagggg agaggagaga 900 gtttgggaaa gggagatgga gaagaactca aggacattgc aaccctgccc ggcgcagatc 960 tgattttcac atctctacct ggacattgag cctccaggca ccatgttgag gagagatgaa 1020 aaccagggcg gtagaacttc agggtgaagg acagagtcct gggtggggca gcggctgcag 1080 ggcgcaccag agaacccagc cagagggggt gtgagtacca gtggtgttgc ttccaccctg 1140 cagcaggtgg gatgaggtct gtgtgtgtgt gtgaaccatc attttttgat catcatgacc 1200 aatgaaacat tgaaaaaaaa aaaaaasaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 1256 <210> 34 <211> 189 <212> PRT
<213> Homo Sapiens <400> 34 Met Thr Leu Ala Ala Tyr Lys Glu Lys Met Lys Glu Leu Pro Leu Val Ser Leu Phe Cys Ser Cys Phe Leu Ala Asp Pro Leu Asn Lys Ser Ser Tyr Lys Tyr Glu Ala Asp Thr Val Asp Leu Asn Trp Cys Val Ile Ser Asp Met Glu Val Ile Glu Leu Asn Lys Cys Thr Ser Gly Gln Ser Phe Glu Val Ile Leu Lys Pro Pro Ser Phe Asp Gly Val Pro Glu Phe Asn Ala Ser Leu Pro Arg Arg Arg Asp Pro Ser Leu Glu Glu Ile Gln Lys Lys Leu Glu Ala Ala Glu Glu Arg Arg Lys Tyr Gln Glu Ala Glu Leu Leu Lys His Leu Ala Glu Lys Arg Glu His Glu Arg Glu Val Ile Gln Lys Ala Ile Glu Glu Asn Asn Asn Phe Ile Lys Met Ala Lys Glu Lys Leu Ala Gln Lys Met Glu Ser Asn Lys Glu Asn Arg Glu Ala His Leu Ala Ala Met Leu Glu Arg Leu Gln Glu Lys Asp Lys His Ala Glu Glu Val Arg Lys Asn Lys Glu Leu Lys Glu Glu Ala Ser Arg <210> 35 <211> 1783 <212> DNA
<213> Homo sapiens <400> 35 aaggataatg gcctccagct cagatggaat atctctatca tatagacctg ttgttacagg 60 gcaggatcgg atgatggaca ctgaagtcct cagcttgcta agttcagttg ctctccctag 120 cctccttttg gcttcagagt cttttgattc catctatcct ggtatttttt gtgtgctgat 180 gtttagttct ggattggttt cagctgtgct aataggsagg gcgttgtctt ttcaagcaat 240 cttaaaaggt ggtcaatcaa aaggccagag tctgastccc ttctgtggct taaataattt 300 gaggatcaag tccagtgtct tgttaatccc tgttctactg tgccagacac tatcttgaat 360 gcttttatat gttcaggttc aaaatcgctc tttcatacca ggggatgata gtaacgtgta 420 acttgcaata gattccttca tcttagtaat aagatgatca gtctagttag gacaaaatag 480 agattgaata aattaacttt tccaagttta cagagtaaaa atgagcagat ctctgcctgg 540 ttttgtgsaa aagagttagc actggtaaat agaatatttc tactcctaca ccattctttc 600 agtatatcat cactgaagac aggaagatag gcacacagat tcttcctcgt agtaattcat 660 agtgcactag gtgaaagaga tgaagtatgt attaaaagta caatgtgatg gcatttatta 720 ttcagataat cccaggattc tagaagaaaa taaagaagag tgacagttca gttagggtgt 780 gaacttccag aggagcactg cttaagctga acttgagagc attgtgcaaa agcacagtag 840 tctgttaaga actagaaata acctagcttg tgccacttcg ggagtattaa gacataagcc 900 tagaaaggta ggcaaaggtt agatcttaga ctgtcttgta tttttctcat tcctgttgat 960 tacctacctc aaaattgaat atgtttttcc tcctgcctaa cacaaaacta cccaagggca 1020 gaaatttaaa ttcttccttg gtgtatgtgc aaagaaggtt gaatatattc atgcctacct 1080 tattttggac taggaataca gtagtatact ttccgaagac ttgcctgaat agtatataag 1140 gtggaggcaa ctgactagtt aggtcagtat ttttagaaac tcttaatagc tcatactctt 1200 gataccaaaa gcagccctga ttgttaaagc acacacctgc acaagaagca gtgatggttg 1260 catttacatt tcctgggtgc acaaaaaaaa attctcaaaa agcaaggact tacgcttttt 1320 gcaaagcctt tgagaagtta ctggatcata ggaagcttat aacaagaatg gaagattctt 1380 WO 99/55721 PC'C/US99/08504 aaataactca ctttctttgg tatccagtaa cagtagatgt tcaaaatatg tagctgatta 1440 ataccagcat tgtgaacgct gtacaacctt gtggttatta ctaagcaagt tactactagc 1500 ttctgaaaag tagcttcata attaatgtta tttatacact gccttccatg acttttactt 1560 tgccctaagc taatctccaa aatctgaaat gctactccaa tatcagaaaa aaagggggag 1620 gtggaattat atttcctgtg attttaagag tacagagaat catgcacatc tctgattagt 1680 tcatatatgt ctagtgtgta ataaaagtca agatgaactc tcaaaaaaaa aaaaaaaaaa 1740 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1783 <210> 36 <211> 116 <212> PRT
<213> Homo Sapiens <400> 36 Met Ala Ser Ser Ser Asp Gly Ile Ser Leu Ser Tyr Arg Pro Val Val Thr Gly Gln Asp Arg Met Met Asp Thr Glu Val Leu Ser Leu Leu Ser Ser Val Ala Leu Pro Ser Leu Leu Leu Ala Ser Glu Ser Phe Asp Ser Ile Tyr Pro Gly Ile Phe Cys Val Leu Met Phe Ser Ser Gly Leu Val Ser Ala Val Leu Ile Gly Arg Ala Leu Ser Phe Gln Ala Ile Leu Lys Gly Gly Gln Ser Lys Gly Gln Ser Leu Asn Pro Phe Cys Gly Leu Asn Asn Leu Arg Ile Lys Ser Ser Val Leu Leu Ile Pro Val Leu Leu Cys Gln Thr Leu Ser <210> 37 <211> 1725 <212> DNA
<213> Homo Sapiens <400> 37 ggttggtaat aggaaatgga ggggctgctg aggtcctgtg aatgtttctg tcattgtact 60 ttcttccaga agcctgcaga gaatggaagc atcttcttta ttgtcctttc ctggcatgtc 120 catccttatt gtcactacgt tgcaactgga gtttgatttg gatctggttt taaaattctt 180 ctgtgcaata gatgggtttg aggatttagc ggccctgatg tcttggtcat agcctggtaa 240 gaatgtccat gctgaggagc cagatgttgt atttctaact gcctgagtca cacagaatag 300 ggtaagagcc tgaccccatt ctgtaaatca gaaagcaagg atggagaccc tttcctgctg 360 ctattattgg ctctctttga ggaagttgga ggttaaggaa ggaacttgtt tgtttccgta 420 tacgactcct tcttctctct agttcagtct tcagccagtc cagcgctctc ttccacactt 480 cagagcccct tcagagaaag cattagcagg aatgagacaa ggcagagctg cagtgccccc 540 tgaggcttcc acacatcttt ctgaatatta tttttcaagt aacaagggca gggacagcgg 600 aaacagctgc ccaccccccc catcccagca gctcagctaa gccctgatga gaatgaagcc 660 acaggagttg tctgaggtga acccagccgc tcagccacac atggaagcca ttgcctttgc 720 acatagttct tgggttcttt ttcctaaaaa ggtaaggagc tgaggtgtgt ggttttttaa 780 tattaagaat atataatgga aaacacacga ctgacgctca ggcatcttcc cctactcccc 840 aacagatccc cagaagacag cgtggaaggc agtgtagaca gtaaatcggg cttcagttct 900 atagccaaga agagatcagc tgctgaaacc accagtgggt accccaggcc acctgccttt 960 gaacttgggg atttgccatg tctgatcttg tcacatactt gcttttttac aagatgaact 1020 ctttgtattt atgatttggg gggcaatgaa aggtgcaatg caggaactgc tgctgccgag 1080 ctcgctggtc acatgggggt gccaggcggg attctggaaa accagtgcac ttaaactgat 1140 cctgaagaga gctgtcccag cactctggcc accaggaggg ccagattccc cagaaactac 1200 cttttgccca aagaacatgc tcagtatttg gggcatttcc tcccacaaac cctgactgct 1260 tctgttacct cagggccttg gtacctggat actgccacag aattggggcg ggtgggggag 1320 gggcctattt ttaaataaaa taactgttca aagttggggg ttttttaaaa aattaagaaa 1380 aaggaaagct attctgtatt gcaccttttc acaatttaat acattttctt acattttcct 1440 gtgattttcg aaactaaacc attgtgtgtc ctgtagtgtc ctggttgagc tgccgctcag 1500 cagcttcctc ggggggattt ggaacacctg tgtctgtcgc cgcactgcct gtgggagggg 1560 cccagagggc tgctgggact ggcgtctgta cacacttgtt tggccttttc tgtagttgat 1620 gctgtaaact ctatggcttt ttaaaaacga tttcatgttt ttatttagta ttggaaatcc 1680 aatacacttt tttaatccaa tcaaaaaaaa aaaaaaaaaa aaaaa 1725 <210> 38 <211> 74 <212> PRT
<213> Homo Sapiens <400> 38 Met Ile Trp Gly Ala Met Lys Gly Ala Met Gln Glu Leu Leu Leu Pro Ser Ser Leu Val Thr Trp Gly Cys Gln Ala Gly Phe Trp Lys Thr Ser Ala Leu Lys Leu Ile Leu Lys Arg Ala Val Pro Ala Leu Trp Pro Pro Gly Gly Pro Asp Ser Pro Glu Thr Thr Phe Cys Pro Lys Asn Met Leu Ser Ile Trp Gly Ile Ser Ser His Lys Pro <210> 39 <211> 1953 <212> DNA
<213> Homo sapiens <400> 39 gcccttcagg ctctgtctct gtggagactg ggctttggga gggagaaaga gggacctagc 60 gcgggccgcg caggcgcacg gtgggcagct gcaatggcgc tgtcgtgtac ccttaacagg 120 tatctgctcc tcatggcgca ggagcatctg gagttccgcc tgccggaaat aaagtctttg 180 cttttgcttt ttggaggtca gtttgccagc agtcaagaaa cttatggaaa gtcaccattt 240 tggattctta gcattccctc tgaagatatt gcaagaaatt tgatgaaacg gacagtgtgt 300 gccaagtcta tatttgaact atggggtcat ggacaatctc ctgaggagct gtacagttct 360 cttaaaaact accctgtgga gaagatggtt ccatttctac attcggactc tacatataaa 420 ataaagattc acacttttaa taagacattg acacaagaag agaaaatcaa gcgaatagat 480 gcacttgaat ttctgccatt tgaaggaaaa gtgaatttaa agaaaccgca acatgtattt 540 tctgttttgg aggattatgg tttagaccca aactgcatcc ctgagaatcc acataatatt 600 tattttggta gatggattgc agatggacag agagagctta ttgagtcata cagtgtcaaa 660 aagagacact ttattggaaa tacaagtatg gatgctggtt tgtcattcat tatggctaac 720 catggaaaag tgaaagaaaa tgatattgtc tttgatccat ttgttggaac aggtggcctg 780 ctgatagcat gtgctcattt tggtgcatat gtgtatggga cagacataga ctacaacaca 840 gttcatggct tgggaaaggc tactaggaaa aaccagaagt ggagaggacc agatgaaaac 900 attagggcca atcttcgtca atatggttta gagaagtatt accttgatgt cctggtttca 960 gatgcatcta aaccttcctg gaggaagggc acatattttg atgcaatcat tactgatcct 1020 ccatatggta tcagagaatc tacaagaaga acaggttcac agaaggagat accaaagggg 1080 atagaaaaat gggaaaaatg tccagaaagc catgttcctg tttccttgag ttatcatctg 1140 agtgatatgt ttcttgacct gttaaacttc gcagctgaga ccctcgtttt aggtggaaga 1240 ctagtctatt ggttaccggt gtatacgcca gaatacactg aagagatggt gccttggcac 1260 ccttgcctgg aactcgttag caactgcgag cagaagcttt ccagtcacac atcaaggcgc 1320 ttgatcacaa tggaaaaggt gaagaaattt gagaatcggg accagtattc acatctgcta 1380 agtgatcatt ttctgccata ccaaggtcat aattccttcc gtgagaaata ttttagtggg 1440 gtaacaaaaa gaattgccaa ggaagaaaaa tccacccagg aatgaaaatt aagattttga 1500 caatgaagaa agaataagaa tttgatttaa aaagacatct ggatgtgaac tttcatgtat 1560 gatccagaaa ataggtacgg ttttaaaata ttttatatag aaaagctaca aagtaaattg 1620 agcaatgctt ttaaagttat ctttgtttta tagacttttt tgttgtatgt attacagtct 1680 ttataatctt atttaatgta tatttgtact ttcaagtact gatggagata gactcaaaac 1740 agttattttt ttacaattaa tctacaaagg gaattaatat tgttgacttt taaaacatct 1800 gctggatata ttatatgcaa ttaatagtag ttaagaattt attcatttgg tagatatgtt 1860 tatttggttt ttggttgtca tcgatttaca ttgccactaa taaaccatat tgagaatttc 1920 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1953 <210> 40 <211> 463 <212> PRT
<213> Homo Sapiens <400> 40 Met Ala Leu Ser Cys Thr Leu Asn Arg Tyr Leu Leu Leu Met Ala Gln Glu His Leu Glu Phe Arg Leu Pro Glu Ile Lys Ser Leu Leu Leu Leu Phe Gly Gly Gln Phe Ala Ser Ser Gln Glu Thr Tyr Gly Lys Ser Pro Phe Trp Ile Leu Ser Ile Pro Ser Glu Asp Ile Ala Arg Asn Leu Met Lys Arg Thr Val Cys Ala Lys Ser Ile Phe Glu Leu Trp Gly His Gly 65 70 75 8~
Gln Ser Pro Glu Glu Leu Tyr Ser Ser Leu Lys Asn Tyr Pro Val Glu Lys Met Val Pro Phe Leu His Ser Asp Ser Thr Tyr Lys Ile Lys Ile His Thr Phe Asn Lys Thr Leu Thr Gln Glu Glu Lys Ile Lys Arg Ile Asp Ala Leu Glu Phe Leu Pro Phe Glu Gly Lys Val Asn Leu Lys Lys Pro Gln His Val Phe Ser Val Leu Glu Asp Tyr Gly Leu Asp Pro Asn Cys Ile Pro Glu Asn Pro His Asn Ile Tyr Phe Gly Arg Trp Ile Ala Asp Gly Gln Arg Glu Leu Ile Glu Ser Tyr Ser Val Lys Lys Arg His Phe Ile Gly Asn Thr Ser Met Asp Ala Gly Leu Ser Phe Ile Met Ala Asn His GIy Lys Val Lys Glu Asn Asp Ile Val Phe Asp Pro Phe Val Gly Thr Gly Gly Leu Leu Ile Ala Cys Ala His Phe Gly Ala Tyr Val Tyr Gly Thr Asp Ile Asp Tyr Asn Thr Val His Gly Leu Gly Lys Ala Thr Arg Lys Asn Gln Lys Trp Arg Gly Pro Asp Glu Asn Ile Arg Ala Asn Leu Arg Gln Tyr Gly Leu Glu Lys Tyr Tyr Leu Asp Val Leu Val Ser Asp Ala Ser Lys Pro Ser Trp Arg Lys Gly Thr Tyr Phe Asp Ala Ile Ile Thr Asp Pro Pro Tyr Gly Ile Arg Glu Ser Thr Arg Arg Thr Gly Ser Gln Lys Glu Ile Pro Lys Gly Ile Glu Lys Trp Glu Lys Cys Pro Glu Ser His Val Pro Val Ser Leu Ser Tyr His Leu Ser Asp Met Phe Leu Asp Leu Leu Asn Phe Ala Ala Glu Thr Leu Val Leu Gly Gly Arg Leu Val Tyr Trp Leu Pro Val Tyr Thr Pro Glu Tyr Thr Glu Glu Met Val Pro Trp His Pro Cys Leu Glu Leu Val Ser Asn Cys Glu Gln Lys Leu Ser Ser His Thr Ser Arg Arg Leu Ile Thr Met Glu Lys Val Lys Lys Phe Glu Asn Arg Asp Gln Tyr Ser His Leu Leu Ser Asp His Phe Leu Pro Tyr Gln Gly His Asn Ser Phe Arg Glu Lys Tyr Phe Ser Gly Val Thr Lys Arg Ile Ala Lys Glu Glu Lys Ser Thr Gln Glu <210> 41 <211> 1605 <212> DNA
<213> Homo Sapiens <400> 41 agggagattc ctcgaaacta gtgtgtgttt attaaaagga gaaaggataa caatagaatg 60 ttctaaaacc agaagtccaa gtgcgtgtct acttatggga ccaataaata aagaacagac 120 atttgatttg aggtgaggta aaagcctgaa acatggaatg gcattctgtt ttgatggatt 180 ttcatttctt cgcacttctg agacggcaaa gccaaccact tagaagcctt ccacatcttt 240 gtcacctgcc tggctcctgc tctctgatgt acctctgggt agtgagatgg aaatggtgcc 300 tgcagaagtt ggggagaagg atacttttgc acagcctcca tgatgtcttt attgcaaata 360 tggatgacaa gggtctctgt tacaggggcc tcagagcacc ttcgtttctc ctctagacca 420 gggacaggtg tagagataag gactggcaac cagagcctca gcatccaaag atggactgaa 480 gtgggatggc tgacaggcac ataacttacg ggaaagggaa tttcatacat acgatttttg 540 ttttgtgggt aggagggctt atcatcaaca ctgattttat aatctgacaa taaatgtctt 600 tcattaaaga gtttacctaa atgatgttcg attatatgta taatttataa aatatttatg 660 tatagtttgt ttattcaggt atatgtataa tttattgaac acctactatg tcccagcata 720 tctacaaaac tgggtacata catactgtct aactgctaat ccacatttcc agtcttacaa 780 aggacataat gattagttaa gccctaattt agatttgagg aaactgaagc tgagagaggg 840 ttaagtaaat tacccaaagt acagctaata agacccagaa tctcagtctc actccttggg 900 atcctgtgta tttccctgag tcttctaaca tatgaaaatt catatctaaa tcaacaagtg 960 actgtaatct ggtactataa atactaaata aacacttctt cataacactg taccaattca 1020 gcttttaaat tttattactt tgctttcctg tcctttgcca actcttaacc tagttaatcc 1080 tagttctgtt gacattggac caggctcagt aaataaacga atggatttcc agcctttttt 1140 tcccatctgt tcctgctttt agtcctctga atctgcttct tttcttactg ctgctttatt 1200 ttacagtgat tttgtcaaac atagaataca ggactaaaaa tgcaaagaaa ttgggtctgt 2260 gtttaatttt gatgtttcaa attttgagct tccaagtctt tgtggccacc caatgaagtt 1320 tgagtctgcc tgttcagatg tgaaaggtaa gggctgcagc aggtttaagg gtggcccttc 1380 accaccctgt tgtcacctgc acaggcactc ccccatttgc agatgaagaa atgttcagag 1440 aagaaaaatg atggaccaaa cgtctgtttg cacaattgaa actctaccag tggactattc 1500 tattttcaca gctacctagt ttctgccgat gattttttta aatgtgaaat aaacagtgat 1560 actttaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 1605 <210> 42 <211> 87 <212> PRT
<213> Homo sapiens <400> 42 Met Glu Trp His Ser Val Leu Met Asp Phe His Phe Phe Ala Leu Leu Arg Arg Gln Ser Gln Pro Leu Arg Ser Leu Pro His Leu Cys His Leu Pro Gly Ser Cys Ser Leu Met Tyr Leu Trp Val Val Arg Trp Lys Trp Cys Leu Gln Lys Leu Gly Arg Arg Ile Leu Leu His Ser Leu His Asp Val Phe Ile Ala Asn Met Asp Asp Lys Gly Leu Cys Tyr Arg Gly Leu Arg Ala Pro Ser Phe Leu Leu <210> 43 <211> 1936 <212> DNA
<213> Homo sapiens <400> 43 agaaactccc atctccctca ccagccggaa agtacgagtc ggctcagcct ggagggaccc 60 aaccagagcc tggcctggga gccaggatgg ccatccacaa agccttggtg atgtgcctgg 120 gactgcctct cttcctgttc ccaggggcct gggcccaggg ccatgtccca cccggctgca 180 gccaaggcct caaccccctg tactacaacc tgtgtgaccg ctctggggcg tggggcatcg 240 tcctggaggc cgtggctggg gcgggcattg tcaccacgtt tgtgctcacc atcatcctgg 300 tggccagcct cccctttgtg caggacacca agaaacggag cctgctgggg acccaggtat 360 tcttccttct ggggaccctg ggcctcttct gcctcgtgtt tgcctgtgtg gtgaagcccg 420 acttctccac ctgtgcctct cggcgcttcc tctttggggt tctgttcgcc atctgcttct 480 cttgtctggc ggctcacgtc tttgccctca acttcctggc ccggaagaac cacgggcccc 540 ggggctgggt gatcttcact gtggctctgc tgctgaccct ggtagaggtc atcatcaata 600 cagagtggct gatcatcacc ctggttcggg gcagtggcga gggcggccct cagggcaaca 660 gcagcgcagg ctgggccgtg gcctccccct gtgccatcgc caacatggac tttgtcatgg 720 cactcatcta cgtcatgctg ctgctgctgg gtgccttcct gggggcctgg cccgccctgt 780 gtggccgcta caagcgctgg cgtaagcatg gggtctttgt gctcctcacc acagccacct 840 ccgttgccat atgggtggtg tggatcgtca tgtatactta cggcaacaag cagcacaaca 900 gtcccacctg ggatgacccc acgctggcca tcgccctcgc cgccaatgcc tgggccttcg 960 tcctcttcta cgtcatcccc gaggtctccc aggtgaccaa gtccagccca gagcaaagct 1020 accaggggga catgtacccc acccggggcg tgggctatga gaccatcctg aaagagcaga 1080 agggtcagag catgttcgtg gagaacaagg ccttttccat ggatgagccg gttgcagcta 1140 agaggccggt gtcaccatac agcgggtaca atgggcagct gctgaccagt gtgtaccagc 1200 ccactgagat ggccctgatg cacaaagttc cgtccgaagg agcttacgac atcatcctcc 1260 cacgggccac cgccaacagc caggtgatgg gcagtgccaa ctcgaccctg cgggctgaag 1320 acatgtactc ggcccagagc caccaggcgg ccacaccgcc gaaagacggc aagaactctc 1380 aggtctttag aaacccctac gtgtgggact gagtcagcgg tggcgaggag aggcggtcgg 1440 atttggggag ggccctgagg acctggcccc gggcaaggga ctctccaggc tcctcctccc 1500 cctggcaggc ccagcaacat gtgccccaga tgtggaaggg cctccctctc tgccagtgtt 1560 tgggtgggtg tcatgggtgt ccccacccac tcctcagtgt ttgtggagtc gaggagccaa 1620 ccccagcctc ctgccaggat cacctcggcg gtcacactcc agccasatag tgttctcggg 1680 gtggtggctg ggcagcgcct atgtttctct ggagattcct gcaacctcaa gagacttccc 1740 aggcgctcag gcctggatct tgctcctctg tgaggaacaa gggtgcctaa taaatacatt 1800 tctgctttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1860 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1920 aaaaaaaaaa aaaaaa 1936 <210> 44 <211> 441 <212> PRT
<213> Homo sapiens <400> 44 Met Ala Ile His Lys Ala Leu Val Met Cys Leu Gly Leu Pro Leu Phe Leu Phe Pro Gly Ala Trp Ala Gln Gly His Val Pro Pro Gly Cys Ser Gln Gly Leu Asn Pro Leu Tyr Tyr Asn Leu Cys Asp Arg Ser Gly Ala Trp Gly Ile Val Leu Glu Ala Val Ala Gly Ala Gly Ile Val Thr Thr Phe Val Leu Thr Ile Ile Leu Val Ala Ser Leu Pro Phe Val Gln Asp Thr Lys Lys Arg Ser Leu Leu Gly Thr Gln Val Phe Phe Leu Leu Gly Thr Leu Gly Leu Phe Cys Leu Val Phe Ala Cys Val Val Lys Pro Asp Phe Ser Thr Cys Ala Ser Arg Arg Phe Leu Phe Gly Val Leu Phe Ala WO 99/55721 PC'T/US99/08504 Ile Cys Phe Ser Cys Leu Ala Ala His Val Phe Ala Leu Asn Phe Leu Ala Arg Lys Asn His Gly Pro Arg Gly Trp Val Ile Phe Thr Val Ala Leu Leu Leu Thr Leu Val Glu Val Ile Ile Asn Thr Glu Trp Leu Ile Ile Thr Leu Val Arg Gly Ser Gly Glu Gly Gly Pro Gln Gly Asn Ser Ser Ala Gly Trp Ala Val Ala Ser Pro Cys Ala Ile Ala Asn Met Asp Phe Val Met Ala Leu Ile Tyr Val Met Leu Leu Leu Leu Gly Ala Phe Leu Gly Ala Trp Pro Ala Leu Cys Gly Arg Tyr Lys Arg Trp Arg Lys His Gly Val Phe Val Leu Leu Thr Thr Ala Thr Ser Val Ala Ile Trp Val Val Trp Ile Val Met Tyr Thr Tyr Gly Asn Lys Gln His Asn Ser Pro Thr Trp Asp Asp Pro Thr Leu Ala Ile Ala Leu Ala Ala Asn Ala Trp Ala Phe Val Leu Phe Tyr Val Ile Pro Glu Val Ser Gln Val Thr Lys Ser Ser Pro Glu Gln Ser Tyr Gln Gly Asp Met Tyr Pro Thr Arg Gly Val Gly Tyr Glu Thr Ile Leu Lys Glu Gln Lys Gly Gln Ser Met Phe Val Glu Asn Lys Ala Phe Ser Met Asp Glu Pro Val Ala Ala Lys Arg Pro Val Ser Pro Tyr Ser Gly Tyr Asn Gly Gln Leu Leu Thr Ser Val Tyr Gln Pro Thr Glu Met Ala Leu Met His Lys Val Pro Ser Glu Gly Ala Tyr Asp Ile Ile Leu Pro Arg Ala Thr Ala Asn Ser GIn Val Met Gly Ser Ala Asn Ser Thr Leu Arg Ala Glu Asp Met Tyr Ser Ala Gln Ser His Gln Ala Ala Thr Pro Pro Lys Asp Gly Lys Asn Ser Gln Val Phe Arg Asn Pro Tyr Val Trp Asp <210> 45 <211> 1773 <212> DNA
<213> Homo Sapiens <400> 45 cgcgccgcgc cttcccctgc aaggatgcgg ccctctgcgc ctacgcggtc acctacacag 60 cgatgtacgt gactctcgtg ttccgcgtga agggctcccg cctggtcaaa ccctcgctct 120 gcctggcctt gctgtgcccg gccttcctgg tgggcgtggt ccgcgtggcc gagtaccgaa 180 accactggtc ggacgtgctg gctggcttcc tgacaggggc ggccatcgcc acctttttgg 240 tcacctgcgt tgtgcataac tttcagagcc ggccaccctc tggccgaagg ctctctccct 300 gggaggacct gggccaagcc cccaccatgg atagccccct cgaaaagaac ccgaggtctg 360 caggccgcat tcgacaccgg cacggctcac cccatccaag tcgcagaact gcgcccgccg 420 tggccacctg atccccagct gtgtctcctc cagggcccca gccatgtgtt cgtcgccccg 480 tgtgccccgt cctcgattga ggtctgagcc gacgcccttg cccctgcccc tacccctgcc 540 agcgcccacc cccagccagg gcccctcgcc ttcctcccct ggacctgggg ggccaggcgg 600 gggtggtgga cgtggccgga agctgctgct gcccacgccc ctgctgcggg acctgtacac 660 cctgagtgga ctctatccct cccccttcca ccgggacaac ttcagccctt acctgtttgc 720 cagccgtgac cacctgctgt gaggcccgac cacccaccca gaatctgccc agtccccact 780 tcttccctgc cacgcgtgtg tgtgcgtgtg ccacgtgagt gccaaagtcc cctgcccccc 840 aagccagcca gacccagaca ttagtaagat ggctagaagg acatttagga gacatctgcc 900 tctctggccc tctgagatat cccgatgggc acaaatggaa ggtgcgcact tgcccctact 960 attgcccttt taagggccaa agcttgaccc cattggccat tgcctggcta atgagaaccc 1020 ctggttctca gaattttaac caaaaggagt tggctccaac caatgggagc cttcccctca 1080 cttcttagaa tcctcctgca agagggcaac tccagccagt gttcagcgac tgaacagcca 1140 ataggagccc ttggtttcca gaatttctag agtgggtggg catgattcca gtcaatgggg 1200 gaccgcccgt gtctaagcat gtgcaaagga gaggagggag atgaggtcat tgtttgtcat 1260 tgagtcttct ctcagaatca gcgagcccag ctgtagggtg gggggcaggc tcccccatgg 1320 cagggtcctt ggggtacccc ttttcctctc agcccctccc tgtgtgcggc ctctccacct 1380 ctcacccact ctctcctaat cccctactta agtagggctt gccccacttc agaggttttg 1440 gggttcaggg tgctgtgtct ccccttgcct gtgcccaggt catcccaaac ccttctgtta 1500 tttattaggg ctgtgggaag ggtttttctt ctttttcttg gaacctgccc ctgttcttca 1560 cactgccccc catgcctcag cctcatacag atgtgccatc atggggggca tgggtggagc 1620 agaggggctc cctcaccccg ggcaggcaas ggcagtgggt agaggaggca ctgcccccct 1680 ttcctgcccc ctcctcatct ttaataaaga cctggcttct catctttaat aaagacctgt 1740 ttgtaacaga aaaaaaaaaa aaaaaaaaaa aaa 1773 <210> 46 <211> 122 <212> PRT
<213> Homo Sapiens <400> 46 Met Tyr Val Thr Leu Val Phe Arg Val Lys Gly Ser Arg Leu Val Lys Pro Ser Leu Cys Leu Ala Leu Leu Cys Pro Ala Phe Leu Val Gly Val Val Arg Val Ala Glu Tyr Arg Asn His Trp Ser Asp Val Leu Ala Gly Phe Leu Thr Gly Ala Ala Ile Ala Thr Phe Leu Val Thr Cys Val Val His Asn Phe Gln Ser Arg Pro Pro Ser Gly Arg Arg Leu Ser Pro Trp Glu Asp Leu Gly Gln Ala Pro Thr Met Asp Ser Pro Leu Glu Lys Asn Pro Arg Ser Ala Gly Arg Ile Arg His Arg His Gly Ser Pro His Pro Ser Arg Arg Thr Ala Pro Ala Val Ala Thr <210> 47 <211> 1974 <212> DNA
<213> Homo sapiens <400> 47 tctgcatcct tcccgacctt cccagcaata tgcatcttgc acgtctggtc ggctcctgct 60 ccctccttct gctactgggg gccctgtctg gatgggcggc cagcgatgac cccattgaga 120 aggtcattga agggatcaac cgagggctga gcaatgcaga gagagaggtg ggcaaggccc 180 tggatggcat caacagtgga atcacgcatg ccggaaggga agtggagasg gttttcaacg 240 gacttagcaa catggggagc cacaccggca aggagttgga caaaggcgtc caggggctca 300 accacggcat ggacaaggtt gcccatgaga tcaaccatgg tattggacaa gcaggaaagg 360 aagcagagaa gcttggccat ggggtcaaca acgctgctgg acaggttggg aaggaggcag 420 acaaactgat ccatcatggg gtccatcacg gggccaacca ggcgggaagt gaggcaggga 480 agtttggcca gggagtcgac aatgctgcag ggcaggctgg aaatgaggct gggaggtttg 540 gccagggagt ccaccatgct gcagggcagg ccggaaatga ggctgggagg tttggccagg 600 gagtccacca tgctgcaggg caggccggaa atgaggctgg gagatttggc cagggggccc 660 accatggtct cagtgagggc tggaaggaga cagagaagtt tggccagggg atccaccatg 720 ctgccggtca ggttgggaag gaggcagaga agtttggcca gggggcccac catgctgcgg 780 ggcaggccgg aaatgaggca gggagatttg gccagggggt ccaccatggt ctcagtgagg 840 gctggaagga gacagagaag tttggccagg gggtccacca tactgctggt caggttggga 900 aggaggcaga gaagtttggc cagggggccc accatgctgc ggggcaggcc ggaaatgagg 960 cagggagatt tggccagggg gcccaccatg ctgcggggca ggccggaaat gaggctggga 1020 ggtttggcca gggggtccac catggtctca gtgagggctg gaaggagaca gagaagtttg 1080 gccagggggt ccaccatgct gccagtcagt ttgggaagga aacagagaag ctcggccatg 1140 gggtccacca tggggttaat gaggcctgga aggaagcaga gaagtttggc cagggtgtcc 1200 accatgctgc ctcgcaggtg gggaaggagg aagacagagt ggtccaaggc ctccatcatg 1260 gcgttagtca ggctggaagg gagggggggc agtttggcca cgacattcac cacacagcag 1320 ggcaggctgg gaaagaggga gacatagcag ttcatggtgt ccaacctggg gtccacgagg 1380 ccgggaagga ggcagggcag tttggccagg gagttcacca tacccttgaa caggccggga 1440 aggaagcaga caaagcggtc caagggttcc acactggggt ccaccaggct gggaaggaag 1500 cagagaaact tggccaaggg gtcaaccatg ctgctgacca ggctggaaag gaagtggaga 1560 agcttggcca aggtgcccac catgctgctg gccaggccgg gaaggagctg cagaatgctc 1620 ataatggggt caaccaagcc agcaaggagg ccaaccagct gctgaatggc aaccatcaaa 1680 gcggatcttc cagccatcaa ggaggggcca caaccacgcc gttagcctct ggggcctcag 1740 tcaacacgcc tttcatcaac cttcccgccc tgtggaggag cgtcgccaac atcatgccct 1800 aaactggcat ccggccttgc tgggagaata atgtcgccgt tgtcacatca gctgacatga 1860 cctggagggg ttgggggtgg gggacaggtt tctgaaatcc ctgaaggggg ttgtactggg 1920 atttgtgaat aaacttgata cactatgctg tcaaaaaaaa aaaaaaaaaa aaaa 1974 <210> 48 <211> 590 <212> PRT
<213> Homo sapiens <400> 4B
Met His Leu Ala Arg Leu Val Gly Ser Cys Ser Leu Leu Leu Leu Leu Gly Ala Leu Ser Gly Trp Ala Ala Ser Asp Asp Pro Ile Glu Lys Val Ile Glu Gly Ile Asn Arg Gly Leu Ser Asn Ala Glu Arg Glu Val Gly Lys Ala Leu Asp Gly Ile Asn Ser Gly Ile Thr His Ala Gly Arg Glu Val Glu Lys Val Phe Asn Gly Leu Ser Asn Met Gly Ser His Thr Gly Lys Glu Leu Asp Lys Gly Val Gln Gly Leu Asn His Gly Met Asp Lys Val Ala His Glu Ile Asn His Gly Ile Gly GIn Ala Gly Lys Glu Ala Glu Lys Leu Gly His Gly Val Asn Asn Ala Ala Gly Gln Val Gly Lys Glu Ala Asp Lys Leu Ile His His Gly Val His His Gly Ala Asn Gln Ala Gly Ser Glu Ala Gly Lys Phe Gly Gln Gly Val Asp Asn Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Ala His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln Gly Ile His His Ala Ala Gly Gln Val Gly Lys Glu Ala Glu Lys Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln Gly Val His His Thr Ala Gly Gln Val Gly Lys Glu Ala Glu Lys Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln WO 99/55721 1'CTIUS99/0$504 Gly Val His His Ala Ala Ser Gln Phe Gly Lys Glu Thr Glu Lys Leu Gly His Gly Val His His Gly Val Asn Glu Ala Trp Lys Glu Ala Glu Lys Phe Gly Gln Gly Val His His Ala Ala Ser Gln Val Gly Lys Glu Glu Asp Arg Val Val Gln Gly Leu His His Gly Val Ser Gln Ala Gly Arg Glu Gly Gly Gln Phe Gly His Asp Ile His His Thr Ala Gly Gln Ala Gly Lys Glu Gly Asp Ile Ala Val His Gly Val Gln Pro Gly Val His Glu Ala Gly Lys Glu Ala Gly Gln Phe Gly Gln Gly Val His His Thr Leu Glu Gln Ala Gly Lys Glu Ala Asp Lys Ala Val Gln Gly Phe His Thr Gly Val His Gln Ala Gly Lys Glu Ala Glu Lys Leu Gly Gln Gly Val Asn His Ala Ala Asp Gln Ala Gly Lys Glu Val Glu Lys Leu Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Lys Glu Leu Gln Asn Ala His Asn Gly Val Asn Gln Ala Ser Lys Glu Ala Asn Gln Leu Leu Asn Gly Asn His Gln Ser Gly Ser Ser Ser His Gln Gly Gly Ala Thr Thr Thr Pro Leu Ala Ser Gly Ala Ser Val Asn Thr Pro Phe Ile Asn Leu Pro Ala Leu Trp Arg Ser Val Ala Asn Ile Met Pro <210> 49 <211> 923 <212> DNA
<213> Homo sapiens <400> 49 gagagctgga tccttgaaaa tctactctat cagctgctgt ggttgccacc attctcagga 60 ccctcgccat gaaagccctt atgctgctca ccctgtctgt tctgctctgc tgggtctcag 120 ctgacattcg ctgtcactcc tgctacaagg tccctgtgct gggctgtgtg gaccggcagt 180 cctgccgcct ggagccagga cagcaatgcc tgacaacaca tgcatacctt ggtaagatgt 240 gggttttctc caatctgcgc tgtggcacac cagaagagcc ctgtcaggag gccttcaacc 300 aaaccaaccg taagctgggt ctgacatata acaccacctg ctgcaacaag gacaactgca 360 acagcgcagg accccggccc actccagccc tgggccttgt cttccttacc tccttggctg 420 gccttggcct ctggctgctg cactgagact cattccattg gctgcccctc ctcccacctg 480 ccttggcctg agcctctctc cctgtgtctc tgtatcccct ggctttacag aatcgtctct 540 ccctagctcc catttcttta attaaacact gttccgagtg gtctcctcat ccgtccttcc 600 cacctcacac ccttcactct cctttttctg ggtcccttcc cacttccttc caggacctcc 660 attggctcct agaagggctc cccactttgc ttcctatact ctgctgtccc ctacttgagg 720 agggattggg atctggggcc tgaaatgggg cttctgtgtt gtccccagtg aaggctccca 780 caaggacctg atgacctcac tgtacagagc tgactcccca aatccaggct cccatatgta 840 ccccatcccc catactcacc tctttccatt ttgagtaata aatgtctgag tctgaaaaaa 900 aaaaaaaaaa aaaaaaaaaa aaa 923 <210> 50 <211> 125 <212> PRT
<213> Homo Sapiens <400> 50 Met Lys Ala Leu Met Leu Leu Thr Leu Ser Val Leu Leu Cys Trp Val Ser Ala Asp Ile Arg Cys His Ser Cys Tyr Lys Val Pro Val Leu Gly Cys Val Asp Arg Gln Ser Cys Arg Leu Glu Pro Gly Gln Gln Cys Leu Thr Thr His Ala Tyr Leu Gly Lys Met Trp Val Phe Ser Asn Leu Arg Cys Gly Thr Pro Glu Glu Pro Cys Gln Glu Ala Phe Asn Gln Thr Asn Arg Lys Leu Gly Leu Thr Tyr Asn Thr Thr Cys Cys Asn Lys Asp Asn Cys Asn Ser Ala Gly Pro Arg Pro Thr Pro Ala Leu Gly Leu Val Phe Leu Thr Ser Leu Ala Gly Leu Gly Leu Trp Leu Leu His <210> 51 <211> 1493 <212> D13A
<213> Homo Sapiens <400> 51 ggagaagccc aggcagttga ggacaggaga gagaaggctg cagacccaga gggagggagg 60 acagggagtc ggaaggagga ggacagagga gggcacagag acgcagagca agggcggcaa 120 ggaggagacc ctggtgggag gaagacactc tggagagaga gggggctggg cagagatgaa 180 gttccagggg cccctggcct gcctcctgct ggccctctgc ctgggcagtg gggaggctgg 240 ccccctgcag agcggagagg aaagcactgg gacaaatatt ggggaggccc ttggacatgg 300 cctgggagac gccctgagcg aaggggtggg aaaggccatt ggcaaagagg ccggaggggc 360 agctggctct aaagtcagtg aggcccttgg ccaagggacc agagaagcag ttggcactgg 420 agtcaggcag gttccaggct ttggcgtagc agatgctttg ggcaacaggg tcggggaagc 480 agcccatgct ctgggaaaca ctgggcacga gattggcaga caggcagaag atgtcattcg 540 acacggagca gatgctgtcc gcggctcctg gcagggggtg cctggccaca atggtgcttg 600 ggaaacttct ggaggccatg gcatctttgg ctctcaaggt ggccttggag gccagggcca 660 gggcaatcct ggaggtctgg ggactccgtg ggtccacgga taccccggaa actcagcagg 720 cagctttgga atgaatcctc agggagctcc ctggggtcaa ggaggcaatg gagggccacc 780 aaactttggg accaacactc agggagctgt ggcccagcct ggctatggtt cagtgagagc 840 cagcaaccag aatgaagggt gcacgaatcc cccaccatct ggctcaggtg gaggctccag 900 caactctggg ggaggcagcg gctcacagtc gggcagcagt ggcagtggca gcaatggtga 960 caacaacaat ggcagcagca gtggtggcag cagcagtggc agcagcagtg gcggcagcag 1020 tggcggcagc agtggtggca gcagtggcaa cagtggtggc agcagaggtg acagcggcag 1080 tgagtcctcc tggggatcca gcaccggctc ctcctccggc aaccacggtg gagcggcgga 1140 ggaaatggac ataaacccgg gaactctgag acgtctcctg ggatgtttaa ctttgacact 1200 ttctggaaga attttaaatc caagctgggt ttcatcaact gggatgccat aaacaaggac 1260 cagagaagct ctcgcatccc gtgacctcca gacaaggagc caccagattg gatgggagcc 1320 cccacactcc ctccttaaaa caccaccctc tcatcactaa tctcagccct tgcccttgaa 1380 ataaacctta gctgccccac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1440 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1493 <210> 52 <211> 358 <212> PRT
<213> Homo sapiens <400> 52 Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu Gly Ser Gly Glu Ala Gly Pro Leu Gln Ser Gly Glu Glu Ser Thr Gly Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp Ala Leu Ser Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly Gly Ala Ala Gly Ser Lys Val Ser Glu Ala Leu Gly Gln Gly Thr Arg Glu Ala Val Gly Thr Gly Val Arg Gln Val Pro Gly Phe Gly Val Ala Asp Ala Leu Gly Asn Arg Val Gly Glu Ala Ala His Ala Leu GIy Asn Thr Gly His Glu Ile Gly Arg Gln Ala Glu Asp Val Ile Arg His Gly Ala Asp Ala Val Arg Gly Ser Trp Gln Gly Val Pro Gly His Asn Gly Ala Trp Glu Thr Ser Gly Gly His Gly Ile Phe Gly Ser Gln Gly Gly Leu Gly Gly Gln Gly Gln Gly Asn Pro Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr Pro Gly Asn Ser Ala Gly Ser Phe Gly Met Asn Pro Gln Gly Ala Pro Trp Gly Gln Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr Gln Gly Ala Val Ala Gln Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn Gln Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gln Ser Gly Ser Ser Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ala Ala Glu Glu Met Asp Ile Asn Pro Gly Thr Leu Arg Arg Leu Leu Gly Cys Leu Thr Leu Thr Leu Ser Gly Arg Ile Leu Asn Pro Ser Trp Val Ser Ser Thr Gly Met Pro <210> 53 <211> 1897 <212> DNA
<213> Homo sapiens <400> 53 acagaggagg gcacagagac gcagagcaag ggcggcaagg aggagaccct ggtgggagga 60 agacactctg gagagagagg gggctgggca gagatgaagt tccaggggcc cctggcctgc 120 ctcctgctgg ccctctgcct gggcagtggg gaggctggcc ccctgcagag cggagaggaa 180 agcactggga caaatattgg ggaggccctt ggacatggcc tgggagacgc cctgagcgaa 240 ggggtgggaa aggccattgg caaagaggcc ggaggggcag ctggctctaa agtcagtgag 300 gcccttggcc aagggaccag agaagcagtt ggcactggag tcaggcaggt tccaggcttt 360 ggcgtagcag atgctttggg caacagggtc ggggaagcag cccatgctct gggaaacact 420 gggcacgaga ttggcagaca ggcagaagat gtcattcgac acggagcaga tgctgtccgc 480 ggctcctggc agggggtgcc tggccacaat ggtgcttggg aaacttctgg aggccatggc 540 atctttggct ctcaaggtgg ccttggaggc cagggccagg gcaatcctgg aggtctgggg 600 actccgtggg tccacggata ccccggaaac tcagcaggca gctttggaat gaatcctcag 660 ggagctccct ggggtcaagg aggcaatgga gggccaccaa actttgggac caacactcag 720 ggagctgtgg cccagcctgg ctatggttca gtgagagcca gcaaccagaa tgaagggtgc 780 acgaatcccc caccatctgg ctcaggtgga ggctccagca actctggggg aggcagcggc 840 tcacagtcgg gcagcagtgg cagtggcagc aatggtgaca acaacaatgg cagcagcagt 900 ggtggcagca gcagtggcag cagcagtggc ggcagcagtg gcggcagcag tggtggcagc 960 agtggcaaca gtggtggcag cagaggtgac agcggcagtg agtcctcctg gggatccagc 1020 accggctcct cctccggcaa ccacggtggg agcggcggag gaaatggaca taaacccggg 1080 gggcaagggt cgagctgggg cagtggagga ggtgacgctg ttggtggagt caatactgtg 1140 aactctgaga cgtctcctgg gatgtttaac tttgacactt tctggaagaa ttttaaatcc 1200 aagctgggtt tcatcaactg ggatgccata aacaagaacc aggtcccgcc ccccagcacc 1260 cgagccctcc tctacttcag ccgactctgg gaggatttca aacagaacac tcctttcctc 1320 aactggaaag caattattga gggtgcggac gcgtcatcac tgcagaaacg tgcaggcaga 1380 gccgatcaga actacaatta caaccagcat gcgtatccca ctgcctatgg tgggaagtac 1440 tcagtcaaga cccctgcaaa ggggggagtc tcaccttctt cctcggcttc ccgggtgcaa 1500 cctggcctgc taggcaattt cttgcaacca 1560 tgcagtgggt ccaccgaggc gaagttttgg cccgaaaagc tcccctt ggcccccagcctg 1620 actggtcgtc tgccagccct agggagctcc ggcccggctg ctggggaccc agcttgtctc 1680 ccacacctct tccttgtttc gtttcctagg ttcccactgc accagcc tcgtcacatacac 1740 actgtggtgc cagcatcttt ttcagtggcc ctgtacctcc cactgtgaca gttctccagg 1800 tccctttggt aaggaggagc gacctgaagt ttcctacttt aaacatgaat cttgtttccc 1860 tgagtttctc taaaaaaaaa tgtggaaata aaaaaaaaaa aaaaaaa 1897 aaaaaaaaaa aaaaaaaaaa <210> 54 <211> 479 <212> PRT
<2I3> Homo sapiens <400> 54 Met Lys Phe Pro Ala CysLeu LeuLeu LeuCys Leu Gln Gly Leu Ala Gly Ser Gly Gly Leu GlnSer GlyGlu SerThr Gly Glu Ala Pro Glu Thr Asn Ile Ala Gly HisGly LeuGly AlaLeu Ser Gly Glu Leu Asp Glu Gly Val Ala Gly LysGlu AlaGly AlaAla Gly Gly Lys Ile Gly Ser Lys Val Ala Gly GlnGly ThrArg AlaVal Gly Ser Glu Leu Glu Thr Gly Val Val Gly PheGly ValAla AlaLeu Gly Arg Gln Pro Asp Asn Arg Val Ala His AlaLeu GlyAsn GlyHis Glu Gly Glu Ala Thr Ile Gly Arg Glu Val IleArg HisGly AspAla Val Gln Ala Asp Ala Arg Gly Ser Gly Pro GlyHis AsnGly TrpGlu Thr Trp Gln Val Ala Ser Gly Gly Ile Gly SerGln GlyGly GlyGly Gln His Gly Phe Leu Gly Gln Gly Gly Leu GlyThr ProTrp HisGly Tyr Asn Pro Gly Val Pro Gly Asn Gly Phe GlyMet AsnPro GlyAla Pro Ser Ala Ser Gln Trp Gly Gln Asn Gly ProPro AsnPhe ThrAsn Thr Gly Gly Gly Gly Gln Gly Ala Gln Gly TyrGly SerVal AlaSer Asn Val Ala Pro Arg Gln Asn Glu Thr Pro ProPro SerGly GlyGly Gly Gly Cys Asn Ser Ser Ser Asn Gly Ser GlySer GlnSer SerSer Gly Ser Gly Gly Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ser Gly Gly Gly Asn Gly His Lys Pro Gly Gly Gln Gly Ser Ser Trp Gly Ser Gly Gly Gly Asp Ala Val Gly Gly Val Asn Thr Val Asn Ser Glu Thr Ser Pro Gly Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys Ser Lys Leu Gly Phe Ile Asn Trp Asp Ala Ile Asn Lys Asn Gln Val Pro Pro Pro Ser Thr Arg Ala Leu Leu Tyr Phe Ser Arg Leu Trp Glu Asp Phe Lys Gln Asn Thr Pro Phe Leu Asn Trp Lys Ala Ile Ile Glu Gly Ala Asp Ala Ser Ser Leu Gln Lys Arg Ala Gly Arg Ala Asp Gln Asn Tyr Asn Tyr Asn Gln His Ala Tyr Pro Thr Ala Tyr Gly Gly Lys Tyr Ser Val Lys Thr Pro Ala Lys Gly Gly Val Ser Pro Ser Ser Ser Ala Ser Arg Val Gln Pro Gly Leu Leu Gln Trp Val Lys Phe Trp <210> 55 <211> 1532 <212> DNA
<213> Homo sapiens <400> 55 gaagagcccc tgcggccggg cgcgaaaatg gcggcggcgg cgacggccgg gcgctcctga 60 agcagcagtt atggagcttc cctcagggcc ggggccggag cggctctttg actcgcaccg 120 gcttccgggt gactgcttcc tactgctcgt gctgctgctc tacgcgccag tcgggttctg 180 cctcctcgtc ctgcgcctgt ttctcgggat ccacgtcttc ctggtcagct gcgcgctgcc 240 agacagcgtc cttcgcagat tcgtagtgcg gaccatgtgt gcggtgctag ggctcgtggc 300 ccggcaggag gactccggac tccgggatca cagtgtcagg gtcctcattt ccaaccatgt 360 gacacctttc gaccacaaca tagtcaattt gcttaccacc tgtagcaccc ctctactcaa 420 tagtcccccc agctttgtgt gctggtctcg gggcttcatg gagatgaatg ggcgggggga 480 gttggtggag tcactcaaga gattctgtgc ttccacgagg cttcccccca ctcctctgct 540 gctattccct gaggaagagg ccaccaatgg ccgggagggg ctcctgcgct tcagttcctg 600 gccattttct atccaagatg tggtacaacc tcttaccctg caagttcaga gacccctggt 660 ctctgtgacg gtgtcagatg cctcctgggt ctcagaactg ctgtggtcac ttttcgtccc 720 tttcacggtg tatcaagtaa ggtggcttcg tcctgttcat cgccaactag gggaagcgaa 780 tgaggagttt gcactccgtg tacaacagct ggtggccaag gaattgggcc agacagggac 840 acggctcact ccagctgaca aagcagagca catgaagcga caaagacacc ccagattgcg 900 cccccagtca gcccagtctt ctttccctcc ctcccctggt ccttctcctg atgtgcaact 960 ggcaactctg gctcagagag tcaaggaagt tttgccccat gtgccattgg gtgtcatcca 1020 gagagacctg gccaagactg gctgtgtaga cttgactatc actaatctgc ttgagggggc 1080 cgtagctttc atgcctgaag acatcaccaa gggaactcag tccctaccca cagcctctgc 1140 ctccaagttt cccagctctg gcccggtgac ccctcagcca acagccctaa catttgccaa 1200 gtcttcctgg gcccggcagg agagcctgca ggagcgcaag caagcactat atgaatacgc 1260 aagaaggaga ttcacagaga gacgagccca ggaggctgac tgagctcaaa ggaacaggat 1320 ggcacccaga gccgcaggac ggagactggg ggcagccctc acccaactca caacaggctg 1380 gatgggtggg tggtaaaaag ggaaggatga ggctccccca atgtcacatt aaattcatgg 1440 ttttcattca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1532 <210> 56 <211> 410 <212> PRT
<213> Homo sapiens <400> 56 Met Glu Leu Pro Ser Gly Pro Gly Pro Glu Arg Leu Phe Asp Ser His Arg Leu Pro Gly Asp Cys Phe Leu Leu Leu Val Leu Leu Leu Tyr Ala Pro Val Gly Phe Cys Leu Leu Val Leu Arg Leu Phe Leu Gly Ile His Val Phe Leu Val Ser Cys Ala Leu Pro Asp Ser Val Leu Arg Arg Phe Val Val Arg Thr Met Cys Ala Val Leu Gly Leu Val Ala Arg Gln Glu Asp Ser Gly Leu Arg Asp His Ser Val Arg Val Leu Ile Ser Asn His Val Thr Pro Phe Asp His Asn Ile Val Asn Leu Leu Thr Thr Cys Ser Thr Pro Leu Leu Asn Ser Pro Pro Ser Phe Val Cys Trp Ser Arg Gly Phe Met Glu Met Asn Gly Arg Gly Glu Leu Val Glu Ser Leu Lys Arg Phe Cys Ala Ser Thr Arg Leu Pro Pro Thr Pro Leu Leu Leu Phe Pro Glu Glu Glu Ala Thr Asn Gly Arg Glu Gly Leu Leu Arg Phe Ser Ser Trp Pro Phe Ser Ile Gln Asp Val Val Gln Pro Leu Thr Leu Gln Val Gln Arg Pro Leu Val Ser Val Thr Val Ser Asp Ala Ser Trp Val Ser Glu Leu Leu Trp Ser Leu Phe Val Pro Phe Thr Val Tyr Gln Val Arg Trp Leu Arg Pro Val His Arg Gln Leu Gly Glu Ala Asn Glu Glu Phe Ala Leu Arg Val Gln Gln Leu Val Ala Lys Glu Leu Gly Gln Thr Gly Thr Arg Leu Thr Pro Ala Asp Lys Ala Glu His Met Lys Arg Gln Arg His Pro Arg Leu Arg Pro Gln Ser Ala Gln Ser Ser Phe Pro Pro Ser Pro Gly Pro Ser Pro Asp Val Gln Leu Ala Thr Leu Ala Gln Arg Val Lys Glu Val Leu Pro His Val Pro Leu Gly Val Ile Gln Arg Asp Leu Ala Lys Thr Gly Cys Val Asp Leu Thr Ile Thr Asn Leu Leu Glu Gly Ala Val Ala Phe Met Pro Glu Asp Ile Thr Lys Gly Thr Gln Ser Leu Pro Thr Ala Ser Ala Ser Lys Phe Pro Ser Ser Gly Pro Val Thr Pro Gln Pro Thr Ala Leu Thr Phe Ala Lys Ser Ser Trp Ala Arg Gln Glu Ser Leu Gln Glu Arg Lys Gln Ala Leu Tyr Glu Tyr Ala Arg Arg Arg Phe Thr Glu Arg Arg Ala Gln Glu Ala Asp <210> 57 <211> 2093 <212> DNA
<213> Homo sapiens <400> 57 cgcgtttcag cgaagtcgca cgtgaaggat agcagtggcc tgagaaagac ccagtcatgg 60 cagcctccag catcagttca ccatggggaa agcatgtgtt caaagccatt ctgatggtcc 120 tagtggccct tatcctcctc cactcagcat tggcccagtc ccgtcgagac tttgcaccac 180 caggccaaca gaagagagaa gccccagttg atgtcttgac ccagataggt cgatctgtgc 240 gagggacact ggatgcctgg attgggccag agaccatgca cctggtgtca gagtcttcgt 300 cccaagtgtt gtgggccatc tcatcagcca tttctgtggc cttctttgct ctgtctggga 360 tcgccgcaca gctgctgaat gccttgggac tagctggtga ttacctcgcc cagggcctga 420 agctcagccc tggccaggtc cagaccttcc tgctgtgggg agcaggggcc ctggtcgtct 480 actggctgct gtctctgctc ctcggcttgg tcttggcctt gctggggcgg atcctgtggg 540 gcctgaagct tgtcatcttc ctggccggct tcgtggccct gatgaggtcg gtgcccgacc 600 cttccacccg ggccctgcta ctcctggcct tgctgatcct ctacgccctg ctgagccggc 660 tcactggctc ccgagcctct ggggcccaac tcgaggccaa ggtgcgaggg ctggaacgcc 720 aggtggagga gctgcgctgg cgccagaggc gagcggccaa gggggcccgc agtgtggagg 780 aggagtgagc cggatgcccc acacaccgcc agtgtcatac caaagagctg agctgcttcg 840 gggccatgca gccctcctgc cagccccctg cccttttctt gccctgtctc tgaaccttca 900 gaacattgat ccttgccgca gccccactag ccaagagaaa cagagaaaga ccattccccc 960 tgcctgtcct tgcggccctg tcttctgagg ttctctgtct ggggttggct ctcttaaccc 1020 tttctctgct cccagcctgc ctcaccaggg aaggttggag gggcctccct ctggcttctg 1080 catctgcgcc agcaaacatc actgccgttg gtctctcatg acttaactgg cttccctctg 1140 ctgctgcctt ggcttcctcc taatgctcgt gctctcctgt ccttctgaag ttgctccttg 1200 gccaaatctc cagctccctt cttgttttcc tcatcctcct accctgtact cccaccaaac 1260 catggtcctt taaggcacgc tcctgtcctc ctcattgccc agcagtaggg aggggcaggg 1320 gtaaggggac ctgaggataa agggtgggga aacagggtcc cctgaggcct gtgggggctg 1380 caggggagga ggatgtacct tgtgtctctt tcaagtgcct taatccgagc cagcagggcc 1440 ttctgcttgc ctgctgccat actgtatgta ggaaagtgtt ctgtggctgc tttgtgtcaa 1500 gaaaagagca gtcactctca gaatcttgat tccccatcag ccaaagcaaa agatggctgc 1560 tgctttgtag gcatgtgcct gcaagtggga ccttgctggg cattatatgc cctgtggggg 1620 tttcagagac cctgaaagag gagggaggac ccgcctcctt gtctgcacaa ctgcatgcac 1680 ttctctcccc atcgctccac aacctgaaac cgagaaggag ttgctgacca gtgcccaccc 1740 cggcagcccg ggaggaacac aggcagctcc tttcccttca cgtggtctgc agagagcagg 1800 gtgagctgcc agctgcccct ctccaccagg gtaccctgtc ttggtggtta ggggccactt 1860 ttcctttgag gctctagtgg aggtggatgt ccttctctgc caggcttggc acatgatgtg 1920 aagaataaat gcccaattct tactgttcag gtttgatgtg gaatcacagc tgcagtgata 1980 tatatttttt atcagtgctt ggttggtttt aaataaagtg cacgctattt tattatcttg 2040 ttctgaataa aatgtattta ctccaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 2093 <210> 58 <211> 243 <212> PRT
<213> Homo Sapiens <400> 58 Met Ala Ala Ser Ser Ile Ser Ser Pro Trp Gly Lys His Val Phe Lys Ala Ile Leu Met Val Leu Val Ala Leu Ile Leu Leu His Ser Ala Leu Ala Gln Ser Arg Arg Asp Phe Ala Pro Pro Gly Gln Gln Lys Arg Glu Ala Pro Val Asp Val Leu Thr Gln Ile Gly Arg Ser Val Arg Gly Thr Leu Asp Ala Trp Ile Gly Pro Glu Thr Met His Leu Val Ser Glu Ser Ser Ser Gln Val Leu Trp Ala Ile Ser Ser Ala Ile Ser Val Ala Phe Phe Ala Leu Ser Gly Ile Ala Ala Gln Leu Leu Asn Ala Leu Gly Leu Ala Gly Asp Tyr Leu Ala Gln Gly Leu Lys Leu Ser Pro Gly Gln Val Gln Thr Phe Leu Leu Trp Gly Ala Gly Ala Leu Val Val Tyr Trp Leu Leu Ser Leu Leu Leu Gly Leu Val Leu Ala Leu Leu Gly Arg Ile Leu Trp Gly Leu Lys Leu Val Ile Phe Leu Ala Gly Phe Val Ala Leu Met Arg Ser Val Pro Asp Pro Ser Thr Arg Ala Leu Leu Leu Leu Ala Leu Leu Ile Leu Tyr Ala Leu Leu Ser Arg Leu Thr Gly Ser Arg Ala Ser Gly Ala Gln Leu Glu Ala Lys Val Arg Gly Leu Glu Arg Gln Val Glu Glu Leu Arg Trp Arg Gln Arg Arg Ala Ala Lys Gly Ala Arg Ser Val Glu Glu Glu <210> 59 <211> 1372 <212> DNA
<213> Homo sapiens <400> 59 atcggcgtcc gcagcgggcg gctgctgagc tgccttgagg tgcagtgttg gggatccaga 60 gccatgtcgg acctgctact actgggcctg attgggggcc tgactctctt actgctgctg 120 acgctgctgg cctttgccgg gtactcaggg ctactggctg gggtggaagt gagtgctggg 180 tcacccccca tccgcaacgt cactgtggcc tacaagttcc acatggggct ctatggtgag 240 actgggcggc ttttcactga gagctgcagc atctctccca agctccgctc catcgctgtc 300 tactatgaca acccccacat ggtgccccct gataagtgcc gatgtgccgt gggcagcatc 360 ctgagtgaag gtgaggaatc gccctcccct gagctcatcg acctctacca gasatttggc 420 ttcaaggtgt tctccttccc ggcacccagc catgtggtga cagccacctt cccctacacc 480 accattctgt ccatctggct ggctacccgc cgtgtccatc ctgccttgga cacctacatc 540 aaggagcgga agctgtgtgc ctatcctcgg ctggagatct accaggaaga ccagatccat 600 ttcatgtgcc cactggcacg gcagggagac ttctatgtgc ctgagatgaa ggagacagag 660 tggaaatggc gggggcttgt ggaggccatt gacacccagg tggatggcac aggagctgac 720 acaatgagtg acacgagttc tgtaagcttg gaagtgagcc ctggcagccg ggagacttca 780 gctgccacac tgtcacctgg ggcgagcagc cgtggctggg atgacggtga cacccgcagc 840 gagcacagct acagcgagtc aggtgccagc ggctcctctt ttgaggagct ggacttggag 900 ggcgaggggc ccttagggga gtcacggctg gaccctggga ctgagcccct ggggactacc 960 sagtggctct gggagcccac tgcccctgag aagggcaagg agtaacccat ggcctgcacc 1020 ctcctgcagt gcagttgctg aggaactgag cagactctcc agcagactct ccagccctct 1080 tcctccttcc tctgggggag gaggggttcc tgagggacct gacttcccct gctccaggcc 1140 tcttgctaag ccttctcctc actgcccttt aggctcccag ggccagagga gccagggact 1200 attttctgca ccagccccca gggctgccgc ccctgttgtg tctttttttc agactcacag 1260 tggagcttcc aggacccaga ataaagccaa tgatttactt gtttcacctg gaaaaaaaaa 1320 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1372 <210> 60 <211> 313 <212> PRT
<213> Homo sapiens <400> 60 Met Ser Asp Leu Leu Leu Leu Gly Leu Ile Gly Gly Leu Thr Leu Leu Leu Leu Leu Thr Leu Leu Ala Phe Ala Gly Tyr Ser Gly Leu Leu Ala Gly Val Glu Val Ser Ala Gly Ser Pro Pro Ile Arg Asn Val Thr Val Ala Tyr Lys Phe His Met Gly Leu Tyr Gly Glu Thr Gly Arg Leu Phe Thr Glu Ser Cys Ser Ile Ser Pro Lys Leu Arg Ser Ile Ala Val Tyr Tyr Asp Asn Pro His Met Val Pro Pro Asp Lys Cys Arg Cys Ala Val Gly Ser Ile Leu Ser Glu Gly Glu Glu Ser Pro Ser Pro Glu Leu Ile Asp Leu Tyr Gln Lys Phe Gly Phe Lys Val Phe Ser Phe Pro Ala Pro Ser His Val Val Thr Ala Thr Phe Pro Tyr Thr Thr Ile Leu Ser Ile Trp Leu Ala Thr Arg Arg Val His Pro Ala Leu Asp Thr Tyr Ile Lys Glu Arg Lys Leu Cys Ala Tyr Pro Arg Leu Glu Ile Tyr Gln Glu Asp 165 1?0 175 Gln Ile His Phe Met Cys Pro Leu Ala Arg Gln Gly Asp Phe Tyr Val Pro Glu Met Lys Glu Thr Glu Trp Lys Trp Arg Gly Leu Val Glu Ala Ile Asp Thr Gln Val Asp Gly Thr Gly Ala Asp Thr Met Ser Asp Thr Ser Ser Val Ser Leu Glu Val Ser Pro Gly Ser Arg Glu Thr Ser Ala Ala Thr Leu Ser Pro Gly Ala Ser Ser Arg Gly Trp Asp Asp Gly Asp Thr Arg Ser Glu His Ser Tyr Ser Glu Ser Gly Ala Ser Gly Ser Ser Phe Glu Glu Leu Asp Leu Glu Gly Glu Gly Pro Leu Gly Glu Ser Arg Leu Asp Pro Gly Thr Glu Pro Leu Gly Thr Thr Lys Trp Leu Trp Glu Pro Thr Ala Pro Glu Lys Gly Lys Glu <210> 61 <211> 1529 <212> DNA
<213> Homo sapiens <400> 61 gggctgcctg gtccaggaag ggggtgcggc tctgtcagga aacctggact ctcaaggccc 60 accagcctct ccgtgagtgt tagaaatcac agatacagta tatacttaat tacactaaat 120 tattgctggg attccttata agcactaatt atacctgatt ataggttaaa atatttattt 180 tgtcaaaata ttttcttggg aatgtgttta accctttctg cgttcattgt tgctgagatg 240 tgaaaactaa ccattccctc ctgcctacct ttttggccac tgggcggcag agaatggcgc 300 tatgtgcagt tgggcccctg gcaccatggg cctttggcct gcctgctgca gagtagccct 360 gcctgggcag tctccaggca ctgagcaggc catctgtggc caggctgaga gaatgactgg 420 ctcgcttacc agcgtgcatg ggacaaggag ctttggagcc tcaaggggtt gttgctggcc 480 tgggctagag ggaaaggtga ccatccgtct gtcctcctgt ctttctatta gcgcctccat 540 gtgagtgatg gtgccttggt tcactagcct tcccccacca ccccaccatg ccacctggtg 600 gtcttggggc ctgtgctgtc actccagccc ctggggagga gaggacccag cccggagagt 660 tggggcaagg gctccacatg gcccaagggc aacagatgct cgcagggcag ctgctgccga 720 tgctcacgct cctgcccccc tccttcccgc tgccacaccc caccctgggc ccccgcagac 780 acgcatctct aactcagttg ggcccagcct tctggatggc ttggggtagg ccatgggccc 840 acctggggcc aggccagccc ctggggcagc tctggaagag cagtgtggag gagcacttgc 900 ttgcagcctg gcttcagcct ctggcactgc tggagtggtc cctgggagct tctgcactgt 960 cggctttggg gacgtctcac ccacttgggt tacagtaggc cttccccacc cagagagaag 1020 tgtttccacc ccagagacat tgtctgtcag cccctgaagt gctcgcctcc cccagtgccc 1080 gtcaccagcc cttcctatct gtggggtcca agtcaggctt cccctgcggc caccagccat 1140 agggagcagc catcagcccc cgagtcagaa ctgcttctgt ctgtccatac ctccaggctc 1200 tcccggagag ggggacggat atttatttcc taaagtttgc acttaattgt gaggattctc 1260 aggattgttg ggggctactg aaaagaggaa tgtgttgaat gtcgcgtttg ctgtccactc 1320 gtcctagaag tttagtgttt ttgtcactgt catgtgtttc tgtgggcaga gctggttctg 1380 gagggtgggt cagtgcaccc gaggctcaga gcatccatcc accccactgg ccctccttcc 1440 agataccctc tctctaattg ggttcttgca tgtaaaatac tccacaataa ataaataatt 1500 gaacaaaaaa aaaaaaaaaa aaaaaaaaa 1529 <210> 62 <211> 136 <212> PRT
<213> Homo sapiens <400> 62 Met Pro Pro Gly Gly Leu Gly Ala Cys Ala Val Thr Pro Ala Pro Gly Glu Glu Arg Thr Gln Pro Gly Glu Leu Gly Gln Gly Leu His Met Ala Gln Gly Gln Gln Met Leu Ala Gly Gln Leu Leu Pro Met Leu Thr Leu Leu Pro Pro Ser Phe Pro Leu Pro His Pro Thr Leu Gly Pro Arg Arg His Ala Ser Leu Thr Gln Leu Gly Pro Ala Phe Trp Met Ala Trp Gly Arg Pro Trp Ala His Leu Gly Pro Gly Gln Pro Leu Gly Gln Leu Trp Lys Ser Ser Val Glu Glu His Leu Leu Ala Ala Trp Leu Gln Pro Leu Ala Leu Leu Glu Trp Ser Leu Gly Ala Ser Ala Leu Ser Ala Leu Gly Thr Ser His Pro Leu Gly Leu Gln <210> 63 <211> 2242 <212> DNA
<213> Homo Sapiens <400> 63 gagctgaggt ggcagtggtt ccaccaacat ggagctctcg cagatgtcgg agctcatggg 60 gctgtcggtg ttgcttgggc tgctggccct gatggcgacg gcggcggtag cgcgggggtg 120 gctgcgcgcg ggggaggaga ggagcggccg gcccgcctgc caaaaagcaa atggatttcc 180 acctgacaaa tcttcgggat ccaagaagca gaaacaatat cagcggattc ggaaggagaa 240 gcctcaacaa cacaacttca cccaccgcct cctggctgca gctctgaaga gccacagcgg 300 gaacatatct tgcatggact ttagcagcaa tggcaaatac ctggctacct gtgcagatga 360 tcgcaccatc cgcatctgga gcaccaagga cttcctgcag cgagagcacc gcagcatgag 420 agccaacgtg gagctggacc acgccaccct ggtgcgcttc agccctgact gcagagcctt 480 catcgtctgg ctggccaacg gggacaccct ccgtgtcttc aagatgacca agcgggagga 540 tgggggctac accttcacag ccaccccaga ggacttccct aaaaagcaca aggcgcctgt 600 catcgacatt ggcattgcta acacagggaa gtttatcatg actgcctcca gtgacaccac 660 tgtcctcatc tggagcctga agggtcaagt gctgtctacc atcaacacca accagatgaa 720 caacacacac gctgctgtat ctccctgtgg cagatttgta gcctcgtgtg gcttcacccc 780 agatgtgaag gtttgggaag tctgctttgg aaagaagggg gagttccagg aggtggtgcg 840 agccttcgaa ctaaagggcc actccgcggc tgtgcactcg tttgctttct ccaacgactc 900 acggaggatg gcttctgtct ccaaggatgg tacatggaaa ctgtgggaca cagatgtgga 960 atacaagaag aagcaggacc cctacttgct gaagacaggc cgctttgaag aggcggcggg 1020 tgccgcgccg tgccgcctgg ccctctcccc caacgcccag gtcttggcct tggccagtgg 1080 cagtagtatt catctctaca atacccggcg gggcgagaag gaggagtgct ttgagcgggt 1140 ccatggcgag tgtatcgcca acttgtcctt tgacatcact ggccgctttc tggcctcctg 1200 tggggaccgg gcggtgcggc tgtttcacaa cactcctggc caccgagcca tggtggagga 1260 gatgcagggc cacctgaagc gggcctccaa cgagagcacc cgccagaggc tgcagcagca 1320 gctgacccag gcccaagaga ccctgaagag cctgggtgcc ctgaagaagt gactctggga 1380 gggcccggcg cagaggattg aggaggaggg atctggcctc ctcatggcac tgctgccatc 1440 tttcctccca ggtggaagcc tttcagaagg agtctcctgg ttttcttact ggtggccctg 1500 cttcttccca ttgaaactac tcttgtctac ttaggtctct ctcttcttgc tggctgtgac 1560 tcctccctga ctagtggcca aggtgctttt cttcctccca ggcccagtgg gtggaatctg 1620 tccccacctg gcactgagga gaatggtaga gaggagagga gagagagaga gaatgtgatt 1680 tttggccttg tggcagcaca tcctcacacc caaagaagtt tgtaaatgtt ccagaacaac 1740 ctagagaaca cctgagtact aagcagcagt tttgcaagga tgggagactg ggatagcttc 1800 ccatcacaga actgtgttcc atcaaaaaga cactaaggga tttccttctg ggcctcagtt 1860 ctatttgtaa gatggagaat aatcctctct gtgaactcct tgcaaagatg atatgaggct 1920 aagagaatat caagtcccca ggtctggaag aaaagtagaa aagagtagta ctattgtcca 1980 atgtcatgaa agtggtaaaa gtgggaacca gtgtgctttg aaaccaaatt agaaacacat 2040 tccttgggaa ggcaaagttt tctgggactt gatcatacat tttatatggt tgggacttct 2100 ctcttcggga gatgatatct tgtttaagga gacctctttt cagttcatca agttcatcag 2160 atatttgagt gcccactctg tgcccaaata aatatgagct ggggattaaa tacgaaaaaa 2220 aaaaaaaaaa aaaaaaaaaa as 2242 <210> 64 <211> 447 <212> PRT
<213> Homo sapiens <400> 64 Met Glu Leu Ser Gln Met Ser Glu Leu Met Gly Leu Ser Val Leu Leu Gly Leu Leu Ala Leu Met Ala Thr Ala Ala Val Ala Arg Gly Trp Leu Arg Ala Gly Glu Glu Arg Ser Gly Arg Pro Ala Cys Gln Lys Ala Asn Gly Phe Pro Pro Asp Lys Ser Ser Gly Ser Lys Lys Gln Lys Gln Tyr Gln Arg Ile Arg Lys Glu Lys Pro Gln Gln His Asn Phe Thr His Arg Leu Leu Ala AIa Ala Leu Lys Ser His Ser Gly Asn Ile Ser Cys Met Asp Phe Ser Ser Asn Gly Lys Tyr Leu Ala Thr Cys Ala Asp Asp Arg Thr Ile Arg Ile Trp Ser Thr Lys Asp Phe Leu Gln Arg Glu His Arg Ser Met Arg Ala Asn Val Glu Leu Asp His Ala Thr Leu Val Arg Phe Ser Pro Asp Cys Arg Ala Phe Ile Val Trp Leu Ala Asn Gly Asp Thr 145 ' 150 155 160 Leu Arg Val Phe Lys Met Thr Lys Arg Glu Asp Gly Gly Tyr Thr Phe Thr Ala Thr Pro Glu Asp Phe Pro Lys Lys His Lys Ala Pro Val Ile Asp Ile Gly Ile Ala Asn Thr Gly Lys Phe Ile Met Thr Ala Ser S'er Asp Thr Thr Val Leu Ile Trp Ser Leu Lys Gly Gln Val Leu Ser Thr Ile Asn Thr Asn Gln Met Asn Asn Thr His Ala Ala Val Ser Pro Cys Gly Arg Phe Val Ala Ser Cys Gly Phe Thr Pro Asp Val Lys Val Trp Glu Val Cys Phe Gly Lys Lys Gly Glu Phe Gln Glu Val Val Arg Ala Phe Glu Leu Lys Gly His Ser Ala Ala Val His Ser Phe Ala Phe Ser Asn Asp Ser Arg Arg Met Ala Ser Val Ser Lys Asp Gly Thr Trp Lys Leu Trp Asp Thr Asp Val Glu Tyr Lys Lys Lys Gln Asp Pro Tyr Leu Leu Lys Thr Gly Arg Phe Glu Glu Ala Ala Gly Ala Ala Pro Cys Arg Leu Ala Leu Ser Pro Asn Ala Gln Val Leu Ala Leu Ala Ser Gly Ser Ser Ile His Leu Tyr Asn Thr Arg Arg Gly Glu Lys Glu Glu Cys Phe Glu Arg Val His Gly Glu Cys Ile Ala Asn Leu Ser Phe Asp Ile Thr Gly Arg Phe Leu Ala Ser Cys Gly Asp Arg Ala Val Arg Leu Phe His Asn Thr Pro Gly His Arg Ala Met Val Glu Glu Met Gln Gly His Leu Lys Arg Ala Ser Asn Glu Ser Thr Arg Gln Arg Leu Gln Gln Gln Leu Thr Gln Ala Gln Glu Thr Leu Lys Ser Leu Gly Ala Leu Lys Lys <210> 65 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 65 aagtgatctc aacctcgctt g 21 <210> 66 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 66 gtcagaacca tcatctccag g 21 <210> 67 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 67 cagtccagtc caggcgag 18 <210> 68 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> ss aggaagcacc agagtgcg le <210> 69 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 69 ccatctgacc tgctactttc c 21 <210> 70 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 70 gctgatgagg atgctggc 18 <210> 71 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 71 ctcaggaagc aggtcaggac 20 <210> 72 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 72 ctctgatgag ggtgttggc 19 <210> 73 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 73 cacaggcact catgggaag i9 <210> 74 WO 99/55721 PC'T/US99/08504 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 74 ctggagacag ggtccagatc 20 <210> 75 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 75 tggaagaata gatgtgagag 20 <210> 76 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 76 tcagagagtt gcttcctgaa g 21 <210> 77 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 77 gctcctactc tgccctctcc 20 <210> 7B
<211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 78 gaaggtctgg ttggtgatgg 20 <210> 79 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 79 cagttctgac accagaagtt g 21 <210> 80 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 80 tttcatcgag gacagcaaac 20 <210> 81 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 81 aggacagagt cctgggtgg 19 <210> 82 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 82 cagagatgtg catgattccc 20 <210> 83 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 83 agcgtggaag gcagtgtag 19 <210> 84 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 84 ccaaggcacc atctcttcag 20 <210> 85 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 85 aatcagtgtt gatgataagc c 21 <210> 86 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 86 tggactttgt catggcactc 20 <210> 87 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 87 ttctgcgact tggatggg 18 <210> 88 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 88 ggaaggaggc agagaagttt g 21 <210> 89 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 89 gctcaccctg tctgttctgc 20 <210> 90 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 90 ccagggtctc ctccttgc 18 <210> 91 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 91 ggaacttcat ctctgcccag 20 <210> 92 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 92 ccagctttgt gtgctggtc 19 <210> 93 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 93 gccaacagaa gagagaagcc 20 <210> 94 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 94 tcctggaagc tccactgtg 19 <210> 95 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 95 aggtaggcag gagggaatg 19 <210> 96 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 96 tcctctctgt gaactccttg c 21 <210> 97 <211> 85 <212> PRT
<213> Homo Sapiens <400> 97 Met Tyr Ser Phe Pro Thr Thr Val Val Glu Glu Ile Leu Ser Leu Ser Leu Gln Leu Ile Ala Phe Pro Thr Val Ser Cys Glu Ile Leu Leu Glu Ile Thr Ser Gln Thr Asn Lys Lys Gln Thr Arg Glu Thr Cys Tyr Ala His Ser Ala Glu Glu Ile Gly Ile Ile Ala Gly Lys Arg Ile His Arg 5p 55 60 Pro Arg Leu Phe Pro Thr Tyr Val Ser Ser Ser Asp Ile Ser Ser Ser Val Asn Gln Ala Met <210> 9B
<211> 161 <212> PRT
<213> Homo Sapiens <400> 98 Met Trp Pro Gly Arg Ile Met Thr Val Thr Val Val Leu Leu Cys Cys Ser Thr Ala Ser Ile Trp Pro Cys Leu Ser His Ser Ala Ser Pro Ser Arg Thr Cys Pro Asn Phe Val Gly Arg Ser Thr Arg Ser Cys Val Thr Ala Asn Ser Leu Cys Glu Pro Arg Thr Pro Asp Pro Lys Pro Ile Asn Gly Lys Gly Asp Met Gly Val Pro Ser Gln Glu Thr Pro Val Pro Phe Leu Ser Cys Leu Phe Pro Leu Thr Ser Leu Trp Phe Phe Ile Phe Lys Cys Phe Asn Phe Cys Ile Phe Phe Ser Leu Arg Glu Tyr Leu Leu Ile Ser Asp Val Gln Gly Val Ala Thr Glu Lys Pro Leu Ser Ser Ser Val Cys Arg Gly Val Trp Pro Cys Gly Leu Gly Gly Ala Val Ile Leu Pro Leu Pro Arg Ala Gly Ser Arg Lys Ser Val Leu Gly Val Val Gly Gly Gln <210> 99 <211> 159 <212> PRT
<213> Homo Sapiens <400> 99 Met Tyr Arg Arg Lys Ser Gly Trp Thr Gly Cys Ala Ile Thr Cys Ser Pro Cys Thr Ala Met Thr Gln Leu Arg Asn Cys Met Arg Leu Ser Arg Ser Cys Ser Leu Thr Trp Glu Thr Pro Arg Trp Tyr Met Ala Gly Arg Val Ala Thr Ser Thr Ser Gly Cys His Cys Trp Met Ser Arg Arg Asp Leu Thr Pro Leu Pro His Pro Ser Glu Pro Gly Val Leu Asp Cys Leu Gly Pro Cys His Leu Leu Pro Leu Leu Ser Pro Gly Ser Pro Cys Trp Val Leu Gly Leu His Phe Ser Leu His Pro Pro Ser Ala Ala Ser Ala Ser His Ala Leu Thr Ile Thr Ser Leu Pro Pro Gly Leu Leu Pro Phe Val Gly Val Glu Leu Thr Ala His Pro Gln Ala Leu Met Gly Arg Gly Phe Pro Ser Gly Met Ala Ala Ala Gly Arg His Leu Cys Phe Leu <210> 100 <211> 54 <212> PRT
<213> Homo Sapiens <400> 100 Met Ser Pro Phe Thr Leu Leu Leu Gln Asn Phe Leu Val Ile Leu Ser His Leu Phe Phe His Ile Asn Phe Lys Leu Cys Pro Val Leu His Pro Leu Ser His Ser His Pro Gln Ile Leu Gly Ser Val Ile Pro Cys Ala Ile Ile Phe Pro Pro Leu <210> 101 <211> 212 <212> PRT
<213> Homo sapiens <400> 101 Met Val Leu Phe Lys Arg Asp Arg Arg Glu Asp Thr Gln Gln Gly His His Ser Met Asn Gly Arg Cys Thr Asp His Phe Leu Phe Val Leu Ser Ser Leu Leu Ser Pro Ala Ala Ile Leu Val Arg Leu Val Pro Ala Arg Glu Arg Cys Pro Gln Val Lys Gly Tyr Ser Gly Thr Trp Glu Lys Ala Pro Gly Arg Phe Pro Cys Gly Pro Ala Gln His Gly Ser Arg Val Gly Thr Leu Leu Cys Arg Gln Pro Ser Leu Tyr Ser Ser Gly Phe Leu Arg Ala Leu Pro Cys Leu Cys Gln Ala Cys Ala Ala Ser His Pro Thr Ala Ala Trp Glu Arg Pro Ala Thr Leu Pro Val His Thr Leu Pro Val His Thr Leu Pro Val His Asn Cys Ser Arg Ala Leu Cys Leu Trp Ala Pro Asn Pro Ser Ser Cys Ser Thr Phe Val Trp His Gly Asp Leu Cys Phe Phe Ser Trp Cys Leu Cys Val Trp Ala Trp Asp Glu Cys Trp Tyr Ala Leu Arg Thr Phe Leu Ile Ala Pro Cys Thr Leu Glu His Gly Ala Asp Glu Arg Gly Ser Gly Ala Cys Pro Pro Pro Trp Thr Trp Lys Lys Pro Thr Leu Glu Arg <210> 102 <211> 73 <212> PRT
<213> Homo Sapiens <400> 202 Met Glu Asn Thr Arg Leu Thr Leu Arg His Leu Pro Leu Leu Pro Asn Arg Ser Pro Glu Asp Ser Val Glu Gly Ser Val Asp Ser Lys Ser Gly Phe Ser Ser Ile Ala Lys Lys Arg Ser Ala Ala Glu Thr Thr Ser Gly Tyr Pro Arg Pro Pro Ala Phe Glu Leu Gly Asp Leu Pro Cys Leu Ile Leu Ser His Thr Cys Phe Phe Thr Arg <210> 103 <211> 302 <212> PRT
<213> Homo Sapiens <400> 103 Met Ala Ile His Lys Ala Leu Val Met Cys Leu Gly Leu Pro Leu Phe Leu Phe Pro Gly Ala Trp Ala Gln Gly His Val Pro Pro Gly Cys Ser Gln Gly Leu Asn Pro Leu Tyr Tyr Asn Leu Cys Asp Arg Ser Gly Ala Trp Gly Ile Val Leu Glu Ala Val Ala Gly Ala Gly Ile Val Thr Thr Phe Val Leu Thr Ile Ile Leu Val Ala Ser Leu Pro Phe Val Gln Asp Thr Lys Lys Arg Ser Leu Leu Gly Thr Gln Val Phe Phe Leu Leu Gly Thr Leu Gly Leu Phe Cys Leu Val Phe Ala Cys Val Val Lys Pro Asp Phe Ser Thr Cys Ala Ser Arg Arg Phe Leu Phe Gly Val Leu Phe Ala Ile Cys Phe Ser Cys Leu Ala Ala His Val Phe Ala Leu Asn Phe Leu Ala Arg Lys Asn His Gly Pro Arg Gly Trp Val Ile Phe Thr Val Ala Leu Leu Leu Thr Leu Val Glu Val Ile Ile Asn Thr Glu Trp Leu Ile Ile Thr Leu Val Arg Gly Ser Gly Glu Gly Gly Pro Gln Gly Asn Ser Ser Ala Ala Gly Pro Trp Pro Pro Pro Val Pro Ser Pro Thr Trp Thr Leu Ser Trp His Ser Ser Thr Ser Cys Cys Cys Cys Trp Val Pro Ser Trp Gly Pro Gly Pro Pro Cys Val Ala Ala Thr Ser Ala Gly Val Ser Met Gly Ser Leu Cys Ser Ser Pro Gln Pro Pro Pro Leu Pro Tyr Gly Trp Cys Gly Ser Ser Cys Ile Leu Thr Ala Thr Ser Ser Thr Thr Val Pro Pro Gly Met Thr Pro Arg Trp Pro Ser Pro Ser Pro Pro Met Pro Gly Pro Ser Ser Ser Ser Thr Ser Ser Pro Arg Ser Pro Arg <210> 104 <211> 114 <212> PRT
<213> Homo sapiens <400> 104 Met Ala Gly Ser Leu Gly Tyr Pro Phe Ser Ser Gln Pro Leu Pro Val Cys Gly Leu Ser Thr Ser His Pro Leu Phe Leu Ile Pro Tyr Leu Ser Arg Ala Cys Pro Thr Ser Glu Val Leu Gly Phe Arg Val Leu Cys Leu Pro Leu Pro Val Pro Arg Ser Ser Gln Thr Leu Leu Leu Phe Ile Arg Ala Val Gly Arg Val Phe Leu Leu Phe Leu Gly Thr Cys Pro Cys Ser Ser His Cys Pro Pro Cys Leu Ser Leu Ile Gln Met Cys His His Gly Gly His Gly Trp Ser Arg Gly Ala Pro Ser Pro Arg Ala Gly Lys Gly Ser Gly <210> 105 <211> 18 <212> PRT
<213> Homo sapiens <400> 105 His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val <210> 106 <211> 369 <212> PRT
<213> Homo Sapiens <400> 106 Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu Gly Ser Gly Glu Ala Gly Pro Leu Gln Ser Gly Glu Glu Ser Thr Gly Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp Ala Leu Ser Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly Gly Ala Ala Gly Ser Lys Val Ser Glu Ala Leu Gly Gln Gly Thr Arg Glu Ala Val Gly 65 70 ?5 80 Thr Gly Val Arg Gln Val Pro Gly Phe Gly Val Ala Asp Ala Leu Gly Asn Arg Val Gly Glu Ala Ala His Ala Leu Gly Asn Thr Gly His Glu Ile Gly Arg Gln Ala Glu Asp Val Ile Arg His Gly Ala Asp Ala Val Arg Gly Ser Trp Gln Gly Val Pro Gly His Asn Gly Ala Trp Glu Thr Ser Gly Gly His Gly Ile Phe Gly Ser Gln Gly Gly Leu Gly Gly Gln Gly Gln Gly Asn Pro Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr Pro Gly Asn Ser Ala Gly Ser Phe Gly Met Asn Pro Gln Gly Ala Pro Trp Gly Gln Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr Gln Gly Ala Val Ala Gln Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn Gln Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gln Ser Gly Ser Ser Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ser Gly Gly Gly Asn Gly His Lys Pro Gly Asn Ser Glu Thr Ser Pro Gly Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys Ser Lys Leu Gly Phe Ile Asn Trp Asp Ala Ile Asn Lys Asp Gln Arg Ser Ser Arg Ile Pro <210> 107 <211> 74 <212> PRT
<213> Homo Sapiens <400> 107 Met Gly Pro Pro Gly Ala Arg Pro Ala Pro Gly Ala Ala Leu Glu Glu Gln Cys Gly Gly Ala Leu Ala Cys Ser Leu Ala Ser Ala Ser Gly Thr Ala Gly Val Val Pro Gly Ser Phe Cys Thr Val Gly Phe Gly Asp Val Ser Pro Thr Trp Val Thr Val Gly Leu Pro His Pro Glu Arg Ser Val Ser Thr Pro Glu Thr Leu Ser Val Ser Pro
<213> Homo sapiens <400> 17 cgagggcgtt cctgtcgggg ctgcagcggc gggagggagc ccagtggagg cgccctcccg 60 aagcgccact gcccatgctg accacccagc cctccggctg ctgatgtcat gagtaacacc 120 actgtgccca atgcccccca ggccaacagc gactccatgg tgggctatgt gttggggccc 180 ttcttcctca tcaccctggt cggggtggtg gtggctgtgg taatgtatgt acagaagaaa 240 aagcgggtgg accggctgcg ccatcacctg ctccccatgt acagctatga cccagctgag 300 gaactgcatg aggctgagca ggagctgctc tctgacatgg gagaccccaa ggtggtacat 360 ggctggcaga gtggctacca gcacaagcgg atgccactgc tggatgtcaa gacgtgacct 420 gacccccttg ccccaccctt cagagcctgg ggtcctggac tgcctggggc cctgccatct 480 gcttcccctg ctgtcacctg gctccccctg ctgggtgctg ggtctccatt tctccctcca 540 cccaccctca gcagcatctg cttcccatgc cctcaccatc acctcactgc ccccaggcct 600 tctgcccttt gtgggtgttg agctcaccgc ccacccacag gcactcatgg gaagaggctt 660 tccttctggg atggcggcgg ctggtagaca cctttgcttt ctctagccct cctgggctgg 720 gcttgggcac aaatccccag gcaggctttg gagttgtttc catggtgatg gggccagatg 780 tatagtattc agtatatatt ttgtaaataa aatgttttgt ggctaaaaaa aaaaaaaaaa 840 saaaaaaaaa 850 <210> 1B
<211> 102 <212> PRT
<213> Homo sapiens <400> 18 Met Ser Asn Thr Thr Val Pro Asn Ala Pro Gln Ala Asn Ser Asp Ser Met Val Gly Tyr Val Leu Gly Pro Phe Phe Leu Ile Thr Leu Val Gly Val Val Val Ala Val Val Met Tyr Val Gln Lys Lys Lys Arg Val Asp Arg Leu Arg His His Leu Leu Pro Met Tyr Ser Tyr Asp Pro Ala Glu Glu Leu His Glu Ala Glu Gln Glu Leu Leu Ser Asp Met Gly Asp Pro Lys Val Val His Gly Trp Gln Ser Gly Tyr Gln His Lys Arg Met Pro Leu Leu Asp Val Lys Thr <210> 19 <211> 1108 <212> DNA
<213> Homo sapiens <400> 19 ataaactccc aggccccgcc cacgccccgc cggggcctta tcctggaccc gggatcccgc 60 gcgcctggag acagggtcca gatctgcctc gagcccctcg aaaccaggac tccagcacct 120 ctggtcccgc cctcacccgg acccctggcc ctcacgtctc ctccagggat ggcgctggcg 180 gctttgatga tcgccctcgg cagcctcggc ctccacacct ggcaggccca ggctgttccc 240 accatcctgc ccctgggcct ggctccagac acctttgacg atacctatgt gggttgtgca 300 gaggagatgg aggagaaggc agcccccctg ctaaaggagg aaatggccca ccatgccctg 360 ctgcgggaat cctgggaggc agcccaggag acctgggagg acaagcgtcg agggcttacc 420 ttgccccctg gcttcaaagc ccagaatgga atagccatta tggtctacac caactcatcg 480 aacaccttgt actgggagtt gaatcaggcc gtgcggacgg gcggaggctc ccgggagctc 540 tacatgaggc actttccctt caaggccctg catttctacc tgatccgggc cctgcagctg 600 ctgcgaggca gtgggggctg cagcagggga cctggggagg tggtgttccg aggtgtgggc 660 agccttcgct ttgaacccaa gaggctgggg gactctgtcc gcttgggcca gtttgcctcc 720 agctccctgg ataaggcagt ggcccacaga tttggggaga agaggcgggg ctgtgtgtct 780 gcgccaggag ccctgggaac gggtgacctt catatgacga agaggcacct ccagcagcct B40 tgagaagcaa gaacatggtt ccggacccag ccctagcagc cttctcccca accaggatgt 900 tggcctgggg aggccacagc agggctgagg gaactctgct atgtgatggg gacttcctgg 960 gacaagcaag gaaagtactg aggcagccac ttgattgaac ggtgttgcaa tgtggagaca 1020 tggagtttta ttgaggtagc tacgtgatta aatggtattg cagtgtggaa aaaaaaaaaa 1080 aaaaaaaaaa aaaaaaaaaa aaaaaaaa 1108 <210> 20 <211> 224 <212> PRT
<213> Homo sapiens <400> 20 Met Ala Leu Ala Ala Leu Met Ile Ala Leu Gly Ser Leu Gly Leu His Thr Trp Gln Ala Gln Ala Val Pro Thr Ile Leu Pro Leu Gly Leu Ala Pro Asp Thr Phe Asp Asp Thr Tyr Val Gly Cys Ala Glu Glu Met Glu Glu Lys Ala Ala Pro Leu Leu Lys Glu Glu Met Ala His His Ala Leu Leu Arg Glu Ser Trp Glu Ala Ala Gln Glu Thr Trp Glu Asp Lys Arg Arg Gly Leu Thr Leu Pro Pro Gly Phe Lys Ala Gln Asn Gly Ile Ala Ile Met Val Tyr Thr Asn Ser Ser Asn Thr Leu Tyr Trp Glu Leu Asn Gln Ala Val Arg Thr Gly Gly Gly Ser Arg Glu Leu Tyr Met Arg His Phe Pro Phe Lys Ala Leu His Phe Tyr Leu Ile Arg Ala Leu Gln Leu Leu Arg Gly Ser Gly Gly Cys Ser Arg Gly Pro Gly Glu Val Val Phe Arg Gly Val Gly Ser Leu Arg Phe Glu Pro Lys Arg Leu Gly Asp Ser Val Arg Leu Gly Gln Phe Ala Ser Ser Ser Leu Asp Lys Ala Val Ala His Arg Phe Gly Glu Lys Arg Arg Gly Cys Val Ser Ala Pro Gly Ala Leu Gly Thr Gly Asp Leu His Met Thr Lys Arg His Leu Gln Gln Pro <210> 21 <211> 1589 <212> DNA
<213> Homo sapiens <400> 21 tctgaacctg tcttgtcctg ggtcctccag ttgttggaag ccactctttt ccccaaccat 60 gctgaaatgc cacctttacc acacactgat gtcttacata gacttagatc tatttctgga 120 acttctcttc tcttcgctta cttgggtgtc tcatctggca ccagccatac aattttaact 180 attgtcaatt tctaatgtct tattatgtgg tgggatgagt cccttcactc ttcttttaca 240 aaatttccta gttattctct cacatctatt cttccacata aactttaaat tgtgcccagt 300 cctccacccc ctgtcccatt cccaccccca aattctgggc tctgtcattc cctgtgccat 360 catcttcccc ccattgtaat tactgtccac tcagggctgt gaaatagact atgttctata 420 aagagggaca aaaagggcat cctgatcttg agagaagcct gctgttcctc ccatcatttc 480 acctgccccc taagcccagg agttgtcatg agaggtcacc aggcccccac tcaatctcag 540 cttgggaacc aaagtcaccc accttggttg tgttggggtg gacccgccat ctgtccctgg 600 tccagacgag aaagaggagt ctctcctagg cctggagctg ggaaagaatg tgtggcccag 660 ttgtctgcac ttctaattct catcatggag aaacctttat tcctatctcc ctttcctgaa 720 ctggtttttt gttgtttttg tttcattttg ttttgggggg atagtttctt gctctttaat 780 ttggagtctc cagtaccttt gggatgcagg cagttcttgc ctgggccttc tcggaaccct 840 cactccccta gcccactctt gcgctacctg caggaggctg ccaacctggt gcattctgac 900 aagcctccca cccaaatctc tctcctgcca ttgtgtccaa aatcccacca ttagaggctc 960 ttgtagggaa gagcgtttct tgaaggcttt taggccttcc agagccagga gggaagtcag 1020 acaatagcag gaagtcccca ggccttttca aagttccaaa ccaagctctc ctgattttaa 1080 tgtagagatc ataccaaccc aggtggggga ggagggtccc cagccccagg cagcagccat 1140 caccccctcc actgaaaaca atattggagg ctgctttggg actgcccttc tcagccccct 1200 aagtctgttt tgtaatgcct gtggtgctct ccctcctgga cctttcctct cgggggtcac 1260 cacactttgc taactcttgt gtgcacatat tttataatag agtagcgagg gaatggtgcc 1320 gcctccagct tccgtaagct gcccgggctc tggggggctc tgggacaatc ggggctggga 1380 agtgactgtg ctcttattgt acactcttta tttctgtgta tctttggctt gtgctctttg 1440 taattaatgg gatttgtctg ccttttcaac actatactga gcaataacaa taaatgcaca 1500 cgtggaaatg cagacacggt acacatcaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1560 aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 1589 <210> 22 <211> 148 <212> PRT
<213> Homo sapiens <400> 22 Met Arg Gly His Gln Ala Pro Thr Gln Ser Gln Leu Gly Asn Gln Ser His Pro Pro Trp Leu Cys Trp Gly Gly Pro Ala Ile Cys Pro Trp Ser Arg Arg Glu Arg Gly Val Ser Pro Arg Pro Gly Ala Gly Lys Glu Cys Val Ala Gln Leu Ser Ala Leu Leu Ile Leu Ile Met Glu Lys Pro Leu Phe Leu Ser Pro Phe Pro Glu Leu Val Phe Cys Cys Phe Cys Phe Ile Leu Phe Trp Gly Asp Ser Phe Leu Leu Phe Asn Leu Glu Ser Pro Val Pro Leu Gly Cys Arg Gln Phe Leu Pro Gly Pro Ser Arg Asn Pro His Ser Pro Ser Pro Leu Leu Arg Tyr Leu Gln Glu Ala Ala Asn Leu Val His Ser Asp Lys Pro Pro Thr Gln Ile Ser Leu Leu Pro Leu Cys Pro Lys Ser His His <210> 23 <211> 2538 <212> DNA
<213> Homo Sapiens <400> 23 aaaggttgta taccctgaaa taccatctga taaaacctgc agaaaggata attttagttc 60 ataaatgtga ccctcattgt tggcgcatca gtgagatggg agagaacagg ctgagtcaaa 120 ggagatgatc ctcccagctg cccccaccca actgttactt ctctgtagat caagaagtga 180 tgtggcacag gctctgggtt cagattctag cttctccact cacttgttgc atggctacat 240 caagttactt actgtctcta cgctttcatg ttatcttcaa aattgggata atatgattcc 300 atcagtggct atcgtttttt taatatggcc cagagacctc ctgaaattag acatgggtgg 360 caatttattt tgttttggga ttcagaaagg aaacatttgt aaaactgtgc tcaaggatca 420 aaaatcctgc agttattttg actgttacaa cctccttatt aatgctacca aggcatttca 480 gagagttgct tcctgaagtg actccattca tctgagctct gtggtgttcc gtcataatat 540 gtggtgagct ttaatcttcc ctttcagctc aggaagctgt gagtcattta tctacttgtg 600 caaagaggac agagacatcc tatctcttat gttcatcagt ttgttcagat ctatagtggt 660 tgtattggag aaacctggct gttatccaaa agggtaggtt ggaagaggct taccacacac 720 attgaatata tttcttaaag ctgctatgga aataaagtga tgtcaccttc tacccctaat 780 ttgcatgtgg ctggaatctc tgaggcatgg gtttgccctt cccaccctcc tgtgcgttgg 840 tgtctcagac ttgtaatctt gcttggtgaa gaagtcattc tttgtttttt tgggtagatg 900 gaaatgggtg gcccaaagtg tacctctaaa ctcatatctg cttgctccca ctgttaggga 960 gatgtctaga cacggagaaa agggcttggt aattaattga ctttgggaaa ttccacttaa 1020 aagtagagat acaatttttt ttattttata aaatatttca aacaaagagg aaattggaag 1080 agtaatataa cacacacatg tatatgtaaa agttactgac tatatatgcc aagggccatt 1140 ttgagtttct aagagggtga atatagattg tgatatttac atatttgttg gacttttttc 1200 tagagcatct ttcctttggg atacattttg ggaaatattg gtttataatt tattttcttg 1260 gtgggaaaga catggataag tatctatacc ttgagataaa taactaaaac tgcataatta 1320 aagaaataag ttgtcaagtg aatttcacaa gcacaaggga gagttaaagt gttgtagtgg 1380 gtcatataag ctttgacata tttttcctca taaagctgat aactcttcag tattgagttt 1440 ctaaaaaagg aagtatttcc tgtggtaaat tttcacttgt gtatctgtga ataccattat 1500 tgtgtgtgaa acttaaaaac tggtagagaa cactaccttt ctcaataaat cagtacccac 1560 gatgggtcta gtgtggaaga caggagggtg tgggaagtgt tgttgtaaca gaatttaaaa 1620 gtgccaaggg agaagaaatt cacaaggtgt ttatatccag gaaagtgtat ttaataatgt 1680 tttttacatt ctctaagaaa aaaagattga aaatatcagg agagtctcaa tgaaaagaac 1?40 atacaaaaag aacataccag gattctagga ctgatacatt ttctgtcaac gctattgcta 1800 ttacaagtaa agggattaag cacttgtgaa tgttgatacc atgtataata actctaattg 1860 gatattgttc aacgtttatt tccatattac ccaatattta gtgcattgta actaatagaa 1920 ggccctcata gccaacctta cttgatcttc ttgataacct tgagaggtgg atattattat 1980 ccccatttta tagatgtgta aaataagcct cagagaagaa tagaagtttc tgttgaaaaa 2040 tatatatgaa gaattttata ccaaatgaca gatatttgtc aaacatttca gaaaacattt 2100 ggagaccggc agagtttttt aaataattga aataattgga attggtacct aagcagcaaa 2160 ggaaatttaa ggagaaagaa tattttgaag taaattataa attaaacaat gtgaaataca 2220 gttttcatag gttgtcataa atgctttcat gtagtttgtg catgctttgc aactcagctg 2280 caagtgctta cagaaactaa ttttttattt ttaacaattt tttgcaagtt tttgaaaatg 2340 ttttgattgt caggttcata gacttctaac tcaaaactaa tgtaacaaaa tattagaaaa 2400 agtggaaata ttagaaaggg gatcttagaa tttataaaaa taaatatctg aagagtacct 2460 atttgaaaaa atgtagtctt gttttatcat atattagtta cagtaaaaat tatcaaaaaa 2520 aaaaaaaaaa aaaaaaaa 2538 <210> 24 <211> 123 <212> PRT
<213> Homo sapiens <400> 24 Met Ile Leu Pro Ala Ala Pro Thr Gln Leu Leu Leu Leu Cys Arg Ser Arg Ser Asp Val Ala Gln Ala Leu Gly Ser Asp Ser Ser Phe Ser Thr His Leu Leu His Gly Tyr Ile Lys Leu Leu Thr Val Ser Thr Leu Ser Cys Tyr Leu Gln Asn Trp Asp Asn Met Ile Pro Ser Val Ala Ile Val Phe Leu Ile Trp Pro Arg Asp Leu Leu Lys Leu Asp Met Gly Gly Asn Leu Phe Cys Phe Gly Ile Gln Lys Gly Asn Ile Cys Lys Thr Val Leu Lys Asp Gln Lys Ser Cys Ser Tyr Phe Asp Cys Tyr Asn Leu Leu Ile 1g Asn Ala Thr Lys Ala Phe Gln Arg Val Ala Ser <210> 25 <211> 4466 <212> DNA
<213> Homo Sapiens <400> 25 gttgcggaga acctacaagt ctccgctccg gcatgcgcgg cgcgcccaaa tcaggaagac 60 ttctgcctct aatagggctg tgcgagagag gcagatgctc tgccgccagc tggcctctgc 120 gggcacgggg ccttgcccag tgcatccagc ttccaacggg actagtccag cgccagccct 180 gcctgcccga gcacggaatc tttaagaatc cgccagcact tggtagcgtc tgcagccacc 240 caggtagcat acgctctttg ctgtgtagaa gaaatgccca tacgacagct ttgcccctgt 300 ttgaagacct cccttcttgc ctctccagac gtgttccccg aggagatctt ccttccgtcc 360 ttcctggcgc cctggttgcc caccttgccg tgcttcctct tacgtgctag ctttgtacct 420 atcgctcact gcatgctcgc ctccctcttg ctggcatccc ggcctgtttc aatgactacc 480 gctctgctac ttaggcacag ggactccgcc gcacgctgac ggaccacgag ggctgacccc 540 ttccagcctg acttggttca tggaggctcc tactctgccc tctccaagct cccctggcgg 600 ctccccacct ggttgcccag ttcctattga tgagctctgg acagaaagat gcccgtttgg 660 ccaggctggt ggcttgatgg gtgtacctgg agagggggtc tggcttcctg cccaagatgc 720 ctcccagccc tgccagggcc cggtgcagcg ggcagggcct catctgtgct gtagtggtcg 780 agtggtcgct gcaaggagcg tagttctgcc atgtctgggg gccaggttcc actctgcaca 840 tgaatatgca gtctgggagg ccctactgct catactggga aggaccaatg ttgcacctct 900 gttaatgcct gacttcagct gctggtgttc tgatggagcc agaggcttgg ggaatctgga 960 acttgcctgc taaataaggt catggtggac tctcagccat tgggcaggtc tatcaggctg 1020 caggttccta cacacccacg cctgagggcc atagcaggct aagggtggat accagcgact 1080 ccctttgctg cccaggatct ccatgggcag tgccacagcg gctgatgctc agtcactcct 1140 gcttctaccc cctgtcactg atggcgagcc ttgcccagct tgagacctgt tcccatctcc 1200 attcaggtgc catgtggcct tcactgcagc cctgcagcca cccacgcacc atctgtgggt 1260 ctccaaaggc accttgtagc atgtactccc cgtgcctggg caatcagatg ggctgccttt 1320 gtccaaggga aaacagactc ccttcgggaa acatccttaa gcacttaagg ccgggggggg 1380 gtgtctgcct ctggcaaccc agccagggtc ttggtggcat ttgtaaaagc aaagagctgt 1440 ggactgccgt ggtcctagtg tggtgacaat gcagcactgg catgcatgtc cttctgaagg 1500 acctcatcct tcctcacagg cggatgacca agaaatcatt ttgtggctgg gtttggccac 1560 gccctttgga ctgtgctgtt ccgccatatt tcaatgccaa atgaaccaca ttgacatgac 1620 ctggaccata gggcttccta tcctgggctc agctgcccct gtctgaaggg tcctggcttg 1680 attgcagaag gacaacctcc gcacccacct aaagacatgt atatgtcttg ggatcccaga 1740 gattgggtcc ttgggcctgg cttcttaaga gttttgatga tgctgggaaa agtgactgcg 1800 attctgaaga accgctgcct tgcaaggtca aggacattca gtggttgctg gggtccgcag 1860 actactgcca cccactcacc atcaactctg ttagcccaat tgccctgctg aacaactgcc 1920 tgaatacagg ctttaggttc ccctggactc cagccaaggc tgttcaggtg ggaccatggt 1980 gctctttaag cgtgatcgga gggaagacac acagcagggc caccattcca tgaatgggag 2040 gtgtacagat cactttctct ttgtgctcag ttctcttctg tctccagcag ctatattggt 2100 aagactagta cctgccaggg agaggtgccc ccaagtgaag gggtacagtg gcacctggga 2160 aaaggcacct ggaaggtttc catgtggccc agcccagcat ggaagcaggg tgggaactct 2220 gctgtgtcgc cagccctcac tctactcaag tggctttttg agagccctgc catgtctgtg 2280 tcaggcctgt gctgcttcac accctacagc tgcctgggaa aggccggcca cgctccctgt 2340 ccacacactc cctgtccaca cactccctgt ccacaactgc agccgggccc tctgcctatg 2400 ggcacccaat ccaagcagct gctccacctt tgtttggcat ggtgatttgt gttttttctc 2460 ttggtgctta tgtgtgtggg cttgggacga gtgctggtat gcacttagga ccttcttgat 2520 agctccctgc actttggaac acggagcaga tgagagaggg tcaggggctt gccctccacc 2580 ttggacttgg aagaagccca cattggagag gtgaggaccc catggtggct ctagtggaag 2640 atacgttagt ctccagctaa ggaggatgag gcgcagcccc agagggagac ctcagtgata 2700 ggggatcagg ctacgaaagt gggggaaggg agatgctttg tacatatttt ggggttataa 2760 tttctctaaa ttttaggaga acgggtattg attgataaaa gggacaggca gtagtgttca 2820 acagtgcatg tgaaggaaag ttctgttttc catggttttg acattctttg gactgtattg 2880 tgactgctgt ctggtccaca tggtaccctt ttggtaagta ggcttcagtg cataccaggg 2940 tatcactgga gatgggagtt agtgaagggg tgactccctg gcctagtata gtgtgaccct 3000 gggacaactt aatgtcctaa agcattttgg tgacttctag ggaatagcaa agacctattt 3060 cattgtcccc aggtaagtat gtgatgagca atgaggagga gtggaaaaca aaacccagaa 3120 agtgcggcag gaccagcctg acgcacacgc tcctgttgtc atggcagaca gccgccttgg 3180 gtgggcacca ccctggcagt tccagcctgt aggggagtga agggacatgg ctgagctggg 3240 catgtgctga ggttgactta gggaacaagc cctgggattg gacaaaaggg cccatgctgc 3300 agccactgac tgggggcaga gctctgggtg gaagagggaa gagatcctaa tggaggcgcc 3360 tccatctgca accacagttg taaggctcat ggcacctctg cttggaaagc actggtttag 3420 ggacttagag aggtaggcac aaggtgggtc tcctgggtag ggaagcaaga gcagactgtt 3480 gggccaacag gagaagctcc ccagagtagg ggagaaggtt ggggtgtagg gccttccacg 3540 tggaacagac agcccctgtg tctctgtctc ttggggacct gagtttgggt ggggtggcag 3600 ttggcacagc gcagatgcgg tagagatggg aggaaaccca gctcctcact tccgtgtgcc 3660 tcatgccttt gcatacacaa gcaccaaacc tactaggtct tctcattacc catgtaaacc 3720 acatgttaga taaatttttg caagtagagg aaagaaggaa ataaaacatc acattttggt 3780 gtctctcagg ctttcccccc caactatggt ttctttgctt tttgttttaa catagttttg 3840 ttgctgtctt ctgtaatgat acagttttgt gcagctgttt tcacttagca tatcgtgggc 3900 atctcccctt atgattacta aatattttat tttggagtgg ctgtgtactc tcccattgac 3960 tagatggacc attgtgccag ttgccaatca ctaatgctgt tactaacttt tcagttataa 4020 attgatgaat atctttgtgc acaggctgtt tcccaatgtc aagttattag ggtagactcc 4080 aggaggtggg attcttcaac taaagaatat gaaaaccttt gaggctttta ctacatattg 4140 acaaaatggt ttccggaaat atttgtatcc ccttacactg ccaccagcaa ggataaacat 4200 gtccatcttg cccgtattgg~gaattatcat ctggctaaat atttgctaat ttgataatga 4260 aaaaatagca tcgtgtttca gttggcattt cactgacttc tagcacggtt gaacatcttt 4320 catgtggagc gattgtattt cctcctttgt ggattgtcag tgtcctttgc tctatcttct 4380 ggggtcagat aaatttgtat gagctcggta tatattaaag atattaacct ggtgtgtgtc 4440 ataaaaaaaa aaaaaaaaaa aaaaaa 4466 <210> 26 <211> 125 <212> PRT
<213> Homo sapiens <400> 26 Met Arg Gly Ala Pro Lys Ser Gly Arg Leu Leu Pro Leu Ile Gly Leu Cys Glu Arg Gly Arg Cys Ser Ala Ala Ser Trp Pro Leu Arg Ala Arg Gly Leu Ala Gln Cys Ile Gln Leu Pro Thr Gly Leu Val Gln Arg Gln Pro Cys Leu Pro Glu His Gly Ile Phe Lys Asn Pro Pro Ala Leu Gly Ser Val Cys Ser His Pro Gly Ser Ile Arg Ser Leu Leu Cys Arg Arg Asn Ala His Thr Thr Ala Leu Pro Leu Phe Glu Asp Leu Pro Ser Cys Leu Ser Arg Arg Val Pro Arg Gly Asp Leu Pro Ser Val Leu Pro Gly Ala Leu Val Ala His Leu Ala Val Leu Pro Leu Thr Cys <210> 27 <211> 2667 WO 99/55721 PC'T/US99/08504 <212> DNA
<213> Homo Sapiens <400> 27 gtcccctggg acccatgggc cttctgggtg tgtgtagggg acagcgcctg gattaagcca 60 gggaagtaag gacttggatt gttaagaaac agccctctgg ctgctgtggg gaacccagga 120 aggcagcttg gagccttctc cagggccctg gctggcggca cagggggctg ctcacatgtc 180 caggacccgt gaaggaccca ggaggtggtg gacagggccg gtagcccgag gtgcactggg 240 atgggggctc tgcatgtgtc tgaaggtggc agccgtcagg cacagcttct cgccccctcc 300 tcaccccaca ggaagagcag cgaggaggcc atgcgggagc gacagcaggt ggtgtccctg 360 gccgccatgc gggagcccag cctgctgcgg ttctacgtgt cccgcgagtg gctcaacaag 420 ttcaacacct tcgcagagcc aggccccatc accaaccaga ccttcctctg ctcccacgga 480 ggtgaggcgc cccctgtggt gggagagcag ggtgggcagc tgggccgagc cacagcttcg 540 ctccctgtac cttcttccca ggcatcccgc cccacaaata ccactacatc gacgacctgg 600 tggtcatcct gccccagaac gtctgggagc acctgtacaa cagattcggg ggtggccccg 660 ccgtgaacca cctgtacgtg tgctccatct gccaggtgga gatcgaggca ctggccaagc 720 gcaggaggat cgagatcgac accttcatca agttgaacaa ggccttccag gccgaggagt 780 cgccgggcgt catctactgc atcagcatgc agtggttccg ggagtgggag gcgttcgtca 840 aggggaagga caacgagccc cccgggccca ttgacaacag caggattgca caggtcaaag 900 gaagcggcca tgtccagctg aagcagggag ctgactacgg gcagatttcg gaggagacct 960 ggacctacct gaacagcctg tatggaggtg gccccgagat tgccatccgc cagagtgtgg 1020 cgcagccgct gggcccagag aacctgcacg gggagcagaa gatcgaagcc gagacgcggg 1080 ccgtgtgatc tgctgggcta gtctgtaagt cgccccggct ggtccctcca tggcactctg 1140 ggtcctctcc tcactctcca gagaccctca catgtccttt tgaacatcca aagagcaggt 1200 ccctgaaagc accttcctgg aggatgtggg agggccctgg acatggcccg gccccactgc 1260 tgagtgcccg tgtccccaca gccccatgtg ccccaccccg cggaaggcgt gtttgtgccc 1320 agaagagagg ccgggctgct gcagaacccc gccgtgtaaa gaggcagaaa agttggtttg 1380 gtttgcagta acgctgcaac tagaaaatat atgcacttca ggcttgttga aacgaccaag 1440 actctgtgac gttaatttgg gtctttgtcc tggcagtgcc tctgccagtc actgtcatcg 1500 ttgtgtcccc cacaactgtc ctcttgctag ctcggcccag ctttgtccct ggagcccgat 1560 gctacccctg tcagacagag gctgcggcct gggccagagt cagggagtag ctgctgcttc 1620 acggcgtctc cactgtgcga ttggcccgga gccccgaaga ctcggaggga gctgctcagg 1680 gccggtgagc gcagccagaa gccctggcca gtgaggagct cacaggtcct ccctggtggt 1740 cccgccgcac ctctgcatct cctgggcgtc accaggaagg ctctgaagtc ccgggctgct 1800 ctcagcactt ctcctgcaga ctgaagactc tggactcatt gctgattgga acaccaggag 1860 gaggttggat ttctgccagt gggggatgtt tctggaggca gctggtcccc cacaccgcgt 1920 cctgctgagc ctgccccctg gattggctgt aatttgcctc gaagttcagc agttcatctt 1980 catgggaaat ttgctgagcc cccaccaggg aaccggatga tgaaacaggg atacctcaca 2040 gcttggccat ttgaggcaaa ggcagcttcc cgagctgatg ctaaagaaga cagactttcc 2100 cttcctccca gcagcagcag tgcagagccc gcctggaggg atgtgggggc tgtgcagggt 2160 gcagcgctca ggtggatcct gggaagcagc ctctggatgc tgagtggagg gagccactga 2220 gcacagcaag gcaccaaagc ccctggagaa accgccaggg cgaggtgcga ccatcatcag 2280 gatcaaagca gacggggcgt gggtggggaa ggggctctgg gaccagaccc cccacactac 2340 tgcgtctttg tttctatcag tctttgtaga agcaggtggt ggtggaaatt ccagcaggtg 2400 ggtcccgcag aggccctgag gcctcacttt tcggatcttc tgtcccagat cctgctccct 2460 ccctgctgag cctggggttc ccctggcatt ggccccagcc ttctgaaagc cggcgctgca 2520 gccagaggcc gcacgctgca ctgtcgcgac gcagagaggc ttctgtgcag gctgggatcg 2580 ggccccatgt ctgtgctgtc tagtttgtgt tcaaaatgtc agaataaaca cagaataaat 2640 gttaaaaaaa aaaaaaaaaa aaasaaa 2667 <210> 28 <211> 232 <212> PRT
<213> Homo Sapiens <400> 2B
Met Ser Arg Thr Arg Glu Gly Pro Arg Arg Trp Trp Thr Gly Pro Val Ala Arg Gly Ala Leu Gly Trp Gly Leu Cys Met Cys Leu Lys Val Ala Ala Val Arg His Ser Phe Ser Pro Pro Pro His Pro Thr Gly Arg Ala Ala Arg Arg Pro Cys Gly Ser Asp Ser Arg Trp Cys Pro Trp Pro Pro Cys Gly Ser Pro Ala Cys Cys Gly Ser Thr Cys Pro AIa Ser Gly Ser Thr Ser Ser Thr Pro Ser Gln Ser Gln Ala Pro Ser Pro Thr Arg Pro Ser Ser Ala Pro Thr Glu Val Arg Arg Pro Leu Trp Trp Glu Ser Arg Val Gly Ser Trp Ala Glu Pro Gln Leu Arg Ser Leu Tyr Leu Leu Pro Arg His Pro Ala Pro Gln Ile Pro Leu His Arg Arg Pro Gly Gly His Pro Ala Pro Glu Arg Leu Gly Ala Pro Val Gln Gln Ile Arg Gly Trp Pro Arg Arg Glu Pro Pro Val Arg Val Leu His Leu Pro Gly Gly Asp Arg Gly Thr Gly Gln Ala Gln Glu Asp Arg Asp Arg His Leu His Gln Val Glu Gln Gly Leu Pro Gly Arg Gly Val Ala Gly Arg His Leu Leu His Gln His Ala Val Val Pro Gly Val Gly Gly Val Arg Gln Gly Glu Gly Gln Arg Ala Pro Arg Ala His <210> 29 <211> 2699 <212> DNA
<213> Homo sapiens <400> 29 agaaattgcc gtggatattg taaaacatgc ctttattact aaatccatga cattactgca 60 gatgtctaca gtgaatatag agccagtctt gcttttgacc ttgttagcag ccgacagaaa 120 aatgcataca ctgattacag tgactctgta gcacggagga tgggctttat tcctctccca 180 ctagctgttt tactcatcag agttgtaaca agctcaatta aagtgcaagg aatcctgtct 240 tatgcctgtg tcatactctt ctattttggg ttgatatccc tgaaagtact taatagcatc 300 gtgctgttgg ggaaatcgtg ccagtatgtg aaggaagcca aaatggaaga gaagctgtcg 360 aatcctcccg caacctgcac tccaggcaag ccgtccagta aatcacagaa caaatgtaaa 420 ccctctcaag gcctttccac agaagaaaac ctgtctgcct ccatcaccaa acaacctatt 480 catcaaaagg aaaatatcat accattactt gtgacaagca attctgatca gtttttgaca 540 actccagatg gtgacgagaa ggacataacg caggacaatt ctgaattaaa acacagatcc 600 tcaaagaaag atttgttaga gatagacagg ttcacaattt gtggaaaccg aattgactga 660 atctgtggct tcatgcgctg aagaagctgg gtcctggggc aacaagtgct gtgttgccag 720 gacaaataga tgctaaacat ggcacttaaa tatttattta aaaacttaaa ttattattgg 780 caagcaaatc ttagtatctt tcttccagta atatggcctg gctgagggtc agaccacagg 840 acaggagcga cctccggcct tgactgtctg ggaagcttga tggattataa aacttcctcc 900 tgcctggcca agcagcagca tcatttccag gacccaacaa aggcaacatc aaaatctgtt 960 ttgctttgtc agtctgggct tccagaatgt tgaatttgcc tcaaggcctc ttcagtataa 1020 ggaaatacct ggaaaactgt gaaactttta ccacgacgta atctttccag tctcatacta 1080 ttttcacaaa cagttttcaa acgttacttc atctgccaaa gcattaaaaa aattaaacat 1140 aagtcaagat aaatgttctt accaccagaa taacccttaa agatgtatct taattaatca 1200 gaataaaagg ctaccttaaa taagacatga tgaatagtag cattttgtag ggttaaaaaa 1260 aaatgctaaa ctagtttatt tattaaaaaa ataattaatg aaggctatgc attactggga 1320 aaaatccttc ataatttttc agtttactct ttaaagcaaa atgtgagctg tatgtcattt 1380 aattggtgga taaaacaaat ttccttacaa aagggcactt tttacaccaa ggaagcagag 1440 cagtgttaac tttaaggtat acttaactga ttttgcttta aaactaatta cttcataaat 1500 tattacagct aaaaggattc gatgttgaac aggctgaaaa attgtcaatg tacaaaattc 1560 aaaactgtca actttaactg taaagtaaat gctccaagtg tgttagacag catcatcttg 1620 cttgggctta ccaaatgcat tagtctttgt gtttgggtcg acagcgagtg tgcctgtgct 1680 ggggcagggt gtgtgttctg tgggagggtg tctgtgggga tgtgactatc agggtgggcc 1740 tgtgctgggg atggggcagg cctgggtctg gagaggattt tgtgtgaaag taaatggggt 1800 gtttgaggcg tatgggtggc tgttggtgtg gggaggcatc tgtgtatggc tgttgggaac 1860 agcaaccaaa aggtgctttt tggttttatt tgagatgaag attgtgtttc cgcttaatta 1920 ctagtttgtg gtctatatca tagaagttat ttcccacccc attttatctt gacaaccgtg 1980 tttgcatttc tgtaaaactt ctacaacttc tggtgtcaga actgtccaga agatggtact 2040 gttaactgtt atttcctttg atgttttgat tttgaagttt agctctcatg caaatgtttc 2100 aggcgtacat acataggcag aaagcaattt ttaggtgatt tgtctgtttc ttggatgaaa 2160 tataaagcaa gctttaatgt tctgacttgt tcatttgaaa tacaaaaaag taagtgaatt 2220 ttaatgtttt gcattaacta aagaaatctg aagattaatg ttgaggaaat tgtatggaca 2280 tgcctttgtg aaaccaggaa gtattttaag ttaaaaatga aaaaggtttt aattgctttg 2340 tgtgtgtttt aatggagccc cattttagaa ttattttttc catctccctt taccaacsaa 2400 aggaacaatg ccaccgtgaa tggaatagtt tggggaaagc tttgccaaac acaaccctga 2460 tttcagagca ggaacatggt ttggatagat cttcagttcc gcttgaatta ttctgttact 2520 gcgctgtcat tttcagaaga tttccattcc tttgcagatg ctgttgggag ttcgggatta 2580 tgttcatttc ttctgtttta atggcattca gtactaattt tataagtgca tcttgtgtga 2640 atctcaataa attcagtttt gtaatcttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa 2699 <210> 30 <211> 166 <212> PRT
<213> Homo sapiens <400> 30 Met Gly Phe Ile Pro Leu Pro Leu Ala Val Leu Leu Ile Arg Val Val Thr Ser Ser Ile Lys Val Gln Gly Ile Leu Ser Tyr Ala Cys Val Ile Leu Phe Tyr Phe Gly Leu Ile Ser Leu Lys Val Leu Asn Ser Ile Val Leu Leu Gly Lys Ser Cys Gln Tyr Val Lys Glu Ala Lys Met Glu Glu Lys Leu Ser Asn Pro Pro Ala Thr Cys Thr Pro Gly Lys Pro Ser Ser Lys Ser Gln Asn Lys Cys Lys Pro Ser Gln Gly Leu Ser Thr Glu Glu Asn Leu Ser Ala Ser Ile Thr Lys Gln Pro Ile His Gln Lys Glu Asn Ile Ile Pro Leu Leu Val Thr Ser Asn Ser Asp Gln Phe Leu Thr Thr Pro Asp Gly Asp Glu Lys Asp Ile Thr Gln Asp Asn Ser Glu Leu Lys His Arg Ser Ser Lys Lys Asp Leu Leu Glu Ile Asp Arg Phe Thr Ile Cys Gly Asn Arg Ile Asp <210> 31 <211> 1300 <212> DNA
<213> Homo sapiens <400> 31 tctccccccg ggctccgccc accccacgcc gggaacccac gcgggccact acaagcccgc 60 cctttcctac gtctggtcca gtcggtcttc ctccggcccg ggccctggcc cagctagccg 120 gccatggaag tgaagaaaat gtttggaagc tctgtgaata catcaaaaac catgaccagt 180 atcctttaga agaatgttat gctgtcttca tatctaatga gaggaagatg atacctatct 240 ggaaacaaca ggcgagacct ggagatggac ctgtgatctg ggattaccat gttgttttgc 300 ttcatgtttc aagtggagga cagagcttca tttatgatct cgatactgtc ttgccatttc 360 cctgcctctt tgacacttat gtagaagatg ccattaagtc tgatgatgac attcacccac 420 agtttaggag gaaatttaga gtgatctgtg cagattcata tttgaagaac tttgcttctg 480 accgatctca catgaaagac tccagtggga attggagaga gcctccgccg ccatatccct 540 gcattgagac tggagattcc aaaatgaacc tgaacgattt catcagtatg gatcccaagg 600 taggatgggg cgccgtctac acactatccg aatttacaca tcggtttggc agtaaaaact 660 gctgaacttg gcctcaagat gtggaactgt ggagaaattc taggacatga acaagctatc 720 ctttcatcga ggacagcaaa cattatggta cagttggctt ggaattatgt ctttctcttt 780 taatttgatt gagtggaaat ctgagtgagt acaaatataa atgaacaaca taaaaacttt 840 tgttttgaca tgtcaaattg aaacttgata aagtgcgtac ttgctaagat attcctgtgg 900 ctcatgcgtt acaacacgag gacttaagcc agtaatcgtt tttgttcaga tagaggtgtg 960 gaggtagagc cagcccctca tgtctgttct ggatgttttg tgtctctcca gctacactgt 1020 aagttccttg agggcagggc catggcccat tgctctgtga atctcaaatg cccataaaag 1080 gtgcccataa aatgttttct tgaacatttg aatgtgctgt tgtctggaaa ggggtaatat 1140 tgtgagctga atcagcaata agtattagtc tttttggact atggtattgt taasaagact 1200 gcagccctct cagacttgag cgttaattgg cttatttatt tatggcttta aataaaatcg 1260 atttaacgtt aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1300 <210> 32 <211> 145 <212> PRT
<213> Homo sapiens <400> 32 Met Ile Pro Ile Trp Lys Gln Gln Ala Arg Pro Gly Asp Gly Pro Val Ile Trp Asp Tyr His Val Val Leu Leu His Val Ser Ser Gly Gly Gln Ser Phe Ile Tyr Asp Leu Asp Thr Val Leu Pro Phe Pro Cys Leu Phe Asp Thr Tyr Val Glu Asp Ala Ile Lys Ser Asp Asp Asp Ile His Pro Gln Phe Arg Arg Lys Phe Arg Val Ile Cys Ala Asp Ser Tyr Leu Lys Asn Phe Ala Ser Asp Arg Ser His Met Lys Asp Ser Ser Gly Asn Trp Arg Glu Pro Pro Pro Pro Tyr Pro Cys Ile Glu Thr Gly Asp Ser Lys Met Asn Leu Asn Asp Phe Ile Ser Met Asp Pro Lys Val Gly Trp Gly Ala Val Tyr Thr Leu Ser Glu Phe Thr His Arg Phe Gly Ser Lys Asn Cys <210> 33 <211> 1256 <212> DNA
<213> Homo Sapiens <400> 33 ctcgcttcta actggactgc acgttggtga cagcgtccca agctggtgac agacccactc 60 tgtaactttc agctagattc agccaccaga tcccagaaac atgacccttg ctgcctacaa 120 agagsagatg aaggagctcc cgctggtgtc cttgttctgc tcctgcttcc tggccgatcc 180 cctgaataag tcgtcctaca aatatgaagc agacacggtg gacctgaatt ggtgcgtcat 240 ttccgacatg gaagtcatcg agctgascaa atgcacctcg ggccaatcct ttgaagtcat 300 cctgaagcca ccctcctttg atggggttcc cgagttcaac gcctccctgc caaggcggcg 360 agacccatcc ctggaagaga tccagasgaa actagaagcg gctgaggagc gaaggaagta 420 ccaggasgcg gagctcctga aacacctagc agagaaacgg gaacatgaga gagaggtgat 480 ccaaaaggcc attgaggaaa acaacaactt catcaagatg gctaaggaaa aactggccca 540 gaagatggaa tccaacaagg agaacaggga ggcccacctc gccgccatgt tggaacggct 600 gcaagagaag gacaagcacg ccgaggaggt gcggaaaaac aaggagctga aggaagaggc 660 ctccaggtaa agcctagagg ccaaagaact ttccaggtca gccggacagc tccagcagct 720 ccacgttcca ggcagcctcg cccgccggct gcgctcccag cactggggtt tggggggagg 780 ggggtggcca aggggcgttt cctctgcttt tggtgtttgt acatgttaag aattgaccag 840 tgaagccatc ctatttgttt ccggggaaca atgaccgggt gggagagggg agaggagaga 900 gtttgggaaa gggagatgga gaagaactca aggacattgc aaccctgccc ggcgcagatc 960 tgattttcac atctctacct ggacattgag cctccaggca ccatgttgag gagagatgaa 1020 aaccagggcg gtagaacttc agggtgaagg acagagtcct gggtggggca gcggctgcag 1080 ggcgcaccag agaacccagc cagagggggt gtgagtacca gtggtgttgc ttccaccctg 1140 cagcaggtgg gatgaggtct gtgtgtgtgt gtgaaccatc attttttgat catcatgacc 1200 aatgaaacat tgaaaaaaaa aaaaaasaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 1256 <210> 34 <211> 189 <212> PRT
<213> Homo Sapiens <400> 34 Met Thr Leu Ala Ala Tyr Lys Glu Lys Met Lys Glu Leu Pro Leu Val Ser Leu Phe Cys Ser Cys Phe Leu Ala Asp Pro Leu Asn Lys Ser Ser Tyr Lys Tyr Glu Ala Asp Thr Val Asp Leu Asn Trp Cys Val Ile Ser Asp Met Glu Val Ile Glu Leu Asn Lys Cys Thr Ser Gly Gln Ser Phe Glu Val Ile Leu Lys Pro Pro Ser Phe Asp Gly Val Pro Glu Phe Asn Ala Ser Leu Pro Arg Arg Arg Asp Pro Ser Leu Glu Glu Ile Gln Lys Lys Leu Glu Ala Ala Glu Glu Arg Arg Lys Tyr Gln Glu Ala Glu Leu Leu Lys His Leu Ala Glu Lys Arg Glu His Glu Arg Glu Val Ile Gln Lys Ala Ile Glu Glu Asn Asn Asn Phe Ile Lys Met Ala Lys Glu Lys Leu Ala Gln Lys Met Glu Ser Asn Lys Glu Asn Arg Glu Ala His Leu Ala Ala Met Leu Glu Arg Leu Gln Glu Lys Asp Lys His Ala Glu Glu Val Arg Lys Asn Lys Glu Leu Lys Glu Glu Ala Ser Arg <210> 35 <211> 1783 <212> DNA
<213> Homo sapiens <400> 35 aaggataatg gcctccagct cagatggaat atctctatca tatagacctg ttgttacagg 60 gcaggatcgg atgatggaca ctgaagtcct cagcttgcta agttcagttg ctctccctag 120 cctccttttg gcttcagagt cttttgattc catctatcct ggtatttttt gtgtgctgat 180 gtttagttct ggattggttt cagctgtgct aataggsagg gcgttgtctt ttcaagcaat 240 cttaaaaggt ggtcaatcaa aaggccagag tctgastccc ttctgtggct taaataattt 300 gaggatcaag tccagtgtct tgttaatccc tgttctactg tgccagacac tatcttgaat 360 gcttttatat gttcaggttc aaaatcgctc tttcatacca ggggatgata gtaacgtgta 420 acttgcaata gattccttca tcttagtaat aagatgatca gtctagttag gacaaaatag 480 agattgaata aattaacttt tccaagttta cagagtaaaa atgagcagat ctctgcctgg 540 ttttgtgsaa aagagttagc actggtaaat agaatatttc tactcctaca ccattctttc 600 agtatatcat cactgaagac aggaagatag gcacacagat tcttcctcgt agtaattcat 660 agtgcactag gtgaaagaga tgaagtatgt attaaaagta caatgtgatg gcatttatta 720 ttcagataat cccaggattc tagaagaaaa taaagaagag tgacagttca gttagggtgt 780 gaacttccag aggagcactg cttaagctga acttgagagc attgtgcaaa agcacagtag 840 tctgttaaga actagaaata acctagcttg tgccacttcg ggagtattaa gacataagcc 900 tagaaaggta ggcaaaggtt agatcttaga ctgtcttgta tttttctcat tcctgttgat 960 tacctacctc aaaattgaat atgtttttcc tcctgcctaa cacaaaacta cccaagggca 1020 gaaatttaaa ttcttccttg gtgtatgtgc aaagaaggtt gaatatattc atgcctacct 1080 tattttggac taggaataca gtagtatact ttccgaagac ttgcctgaat agtatataag 1140 gtggaggcaa ctgactagtt aggtcagtat ttttagaaac tcttaatagc tcatactctt 1200 gataccaaaa gcagccctga ttgttaaagc acacacctgc acaagaagca gtgatggttg 1260 catttacatt tcctgggtgc acaaaaaaaa attctcaaaa agcaaggact tacgcttttt 1320 gcaaagcctt tgagaagtta ctggatcata ggaagcttat aacaagaatg gaagattctt 1380 WO 99/55721 PC'C/US99/08504 aaataactca ctttctttgg tatccagtaa cagtagatgt tcaaaatatg tagctgatta 1440 ataccagcat tgtgaacgct gtacaacctt gtggttatta ctaagcaagt tactactagc 1500 ttctgaaaag tagcttcata attaatgtta tttatacact gccttccatg acttttactt 1560 tgccctaagc taatctccaa aatctgaaat gctactccaa tatcagaaaa aaagggggag 1620 gtggaattat atttcctgtg attttaagag tacagagaat catgcacatc tctgattagt 1680 tcatatatgt ctagtgtgta ataaaagtca agatgaactc tcaaaaaaaa aaaaaaaaaa 1740 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1783 <210> 36 <211> 116 <212> PRT
<213> Homo Sapiens <400> 36 Met Ala Ser Ser Ser Asp Gly Ile Ser Leu Ser Tyr Arg Pro Val Val Thr Gly Gln Asp Arg Met Met Asp Thr Glu Val Leu Ser Leu Leu Ser Ser Val Ala Leu Pro Ser Leu Leu Leu Ala Ser Glu Ser Phe Asp Ser Ile Tyr Pro Gly Ile Phe Cys Val Leu Met Phe Ser Ser Gly Leu Val Ser Ala Val Leu Ile Gly Arg Ala Leu Ser Phe Gln Ala Ile Leu Lys Gly Gly Gln Ser Lys Gly Gln Ser Leu Asn Pro Phe Cys Gly Leu Asn Asn Leu Arg Ile Lys Ser Ser Val Leu Leu Ile Pro Val Leu Leu Cys Gln Thr Leu Ser <210> 37 <211> 1725 <212> DNA
<213> Homo Sapiens <400> 37 ggttggtaat aggaaatgga ggggctgctg aggtcctgtg aatgtttctg tcattgtact 60 ttcttccaga agcctgcaga gaatggaagc atcttcttta ttgtcctttc ctggcatgtc 120 catccttatt gtcactacgt tgcaactgga gtttgatttg gatctggttt taaaattctt 180 ctgtgcaata gatgggtttg aggatttagc ggccctgatg tcttggtcat agcctggtaa 240 gaatgtccat gctgaggagc cagatgttgt atttctaact gcctgagtca cacagaatag 300 ggtaagagcc tgaccccatt ctgtaaatca gaaagcaagg atggagaccc tttcctgctg 360 ctattattgg ctctctttga ggaagttgga ggttaaggaa ggaacttgtt tgtttccgta 420 tacgactcct tcttctctct agttcagtct tcagccagtc cagcgctctc ttccacactt 480 cagagcccct tcagagaaag cattagcagg aatgagacaa ggcagagctg cagtgccccc 540 tgaggcttcc acacatcttt ctgaatatta tttttcaagt aacaagggca gggacagcgg 600 aaacagctgc ccaccccccc catcccagca gctcagctaa gccctgatga gaatgaagcc 660 acaggagttg tctgaggtga acccagccgc tcagccacac atggaagcca ttgcctttgc 720 acatagttct tgggttcttt ttcctaaaaa ggtaaggagc tgaggtgtgt ggttttttaa 780 tattaagaat atataatgga aaacacacga ctgacgctca ggcatcttcc cctactcccc 840 aacagatccc cagaagacag cgtggaaggc agtgtagaca gtaaatcggg cttcagttct 900 atagccaaga agagatcagc tgctgaaacc accagtgggt accccaggcc acctgccttt 960 gaacttgggg atttgccatg tctgatcttg tcacatactt gcttttttac aagatgaact 1020 ctttgtattt atgatttggg gggcaatgaa aggtgcaatg caggaactgc tgctgccgag 1080 ctcgctggtc acatgggggt gccaggcggg attctggaaa accagtgcac ttaaactgat 1140 cctgaagaga gctgtcccag cactctggcc accaggaggg ccagattccc cagaaactac 1200 cttttgccca aagaacatgc tcagtatttg gggcatttcc tcccacaaac cctgactgct 1260 tctgttacct cagggccttg gtacctggat actgccacag aattggggcg ggtgggggag 1320 gggcctattt ttaaataaaa taactgttca aagttggggg ttttttaaaa aattaagaaa 1380 aaggaaagct attctgtatt gcaccttttc acaatttaat acattttctt acattttcct 1440 gtgattttcg aaactaaacc attgtgtgtc ctgtagtgtc ctggttgagc tgccgctcag 1500 cagcttcctc ggggggattt ggaacacctg tgtctgtcgc cgcactgcct gtgggagggg 1560 cccagagggc tgctgggact ggcgtctgta cacacttgtt tggccttttc tgtagttgat 1620 gctgtaaact ctatggcttt ttaaaaacga tttcatgttt ttatttagta ttggaaatcc 1680 aatacacttt tttaatccaa tcaaaaaaaa aaaaaaaaaa aaaaa 1725 <210> 38 <211> 74 <212> PRT
<213> Homo Sapiens <400> 38 Met Ile Trp Gly Ala Met Lys Gly Ala Met Gln Glu Leu Leu Leu Pro Ser Ser Leu Val Thr Trp Gly Cys Gln Ala Gly Phe Trp Lys Thr Ser Ala Leu Lys Leu Ile Leu Lys Arg Ala Val Pro Ala Leu Trp Pro Pro Gly Gly Pro Asp Ser Pro Glu Thr Thr Phe Cys Pro Lys Asn Met Leu Ser Ile Trp Gly Ile Ser Ser His Lys Pro <210> 39 <211> 1953 <212> DNA
<213> Homo sapiens <400> 39 gcccttcagg ctctgtctct gtggagactg ggctttggga gggagaaaga gggacctagc 60 gcgggccgcg caggcgcacg gtgggcagct gcaatggcgc tgtcgtgtac ccttaacagg 120 tatctgctcc tcatggcgca ggagcatctg gagttccgcc tgccggaaat aaagtctttg 180 cttttgcttt ttggaggtca gtttgccagc agtcaagaaa cttatggaaa gtcaccattt 240 tggattctta gcattccctc tgaagatatt gcaagaaatt tgatgaaacg gacagtgtgt 300 gccaagtcta tatttgaact atggggtcat ggacaatctc ctgaggagct gtacagttct 360 cttaaaaact accctgtgga gaagatggtt ccatttctac attcggactc tacatataaa 420 ataaagattc acacttttaa taagacattg acacaagaag agaaaatcaa gcgaatagat 480 gcacttgaat ttctgccatt tgaaggaaaa gtgaatttaa agaaaccgca acatgtattt 540 tctgttttgg aggattatgg tttagaccca aactgcatcc ctgagaatcc acataatatt 600 tattttggta gatggattgc agatggacag agagagctta ttgagtcata cagtgtcaaa 660 aagagacact ttattggaaa tacaagtatg gatgctggtt tgtcattcat tatggctaac 720 catggaaaag tgaaagaaaa tgatattgtc tttgatccat ttgttggaac aggtggcctg 780 ctgatagcat gtgctcattt tggtgcatat gtgtatggga cagacataga ctacaacaca 840 gttcatggct tgggaaaggc tactaggaaa aaccagaagt ggagaggacc agatgaaaac 900 attagggcca atcttcgtca atatggttta gagaagtatt accttgatgt cctggtttca 960 gatgcatcta aaccttcctg gaggaagggc acatattttg atgcaatcat tactgatcct 1020 ccatatggta tcagagaatc tacaagaaga acaggttcac agaaggagat accaaagggg 1080 atagaaaaat gggaaaaatg tccagaaagc catgttcctg tttccttgag ttatcatctg 1140 agtgatatgt ttcttgacct gttaaacttc gcagctgaga ccctcgtttt aggtggaaga 1240 ctagtctatt ggttaccggt gtatacgcca gaatacactg aagagatggt gccttggcac 1260 ccttgcctgg aactcgttag caactgcgag cagaagcttt ccagtcacac atcaaggcgc 1320 ttgatcacaa tggaaaaggt gaagaaattt gagaatcggg accagtattc acatctgcta 1380 agtgatcatt ttctgccata ccaaggtcat aattccttcc gtgagaaata ttttagtggg 1440 gtaacaaaaa gaattgccaa ggaagaaaaa tccacccagg aatgaaaatt aagattttga 1500 caatgaagaa agaataagaa tttgatttaa aaagacatct ggatgtgaac tttcatgtat 1560 gatccagaaa ataggtacgg ttttaaaata ttttatatag aaaagctaca aagtaaattg 1620 agcaatgctt ttaaagttat ctttgtttta tagacttttt tgttgtatgt attacagtct 1680 ttataatctt atttaatgta tatttgtact ttcaagtact gatggagata gactcaaaac 1740 agttattttt ttacaattaa tctacaaagg gaattaatat tgttgacttt taaaacatct 1800 gctggatata ttatatgcaa ttaatagtag ttaagaattt attcatttgg tagatatgtt 1860 tatttggttt ttggttgtca tcgatttaca ttgccactaa taaaccatat tgagaatttc 1920 taaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1953 <210> 40 <211> 463 <212> PRT
<213> Homo Sapiens <400> 40 Met Ala Leu Ser Cys Thr Leu Asn Arg Tyr Leu Leu Leu Met Ala Gln Glu His Leu Glu Phe Arg Leu Pro Glu Ile Lys Ser Leu Leu Leu Leu Phe Gly Gly Gln Phe Ala Ser Ser Gln Glu Thr Tyr Gly Lys Ser Pro Phe Trp Ile Leu Ser Ile Pro Ser Glu Asp Ile Ala Arg Asn Leu Met Lys Arg Thr Val Cys Ala Lys Ser Ile Phe Glu Leu Trp Gly His Gly 65 70 75 8~
Gln Ser Pro Glu Glu Leu Tyr Ser Ser Leu Lys Asn Tyr Pro Val Glu Lys Met Val Pro Phe Leu His Ser Asp Ser Thr Tyr Lys Ile Lys Ile His Thr Phe Asn Lys Thr Leu Thr Gln Glu Glu Lys Ile Lys Arg Ile Asp Ala Leu Glu Phe Leu Pro Phe Glu Gly Lys Val Asn Leu Lys Lys Pro Gln His Val Phe Ser Val Leu Glu Asp Tyr Gly Leu Asp Pro Asn Cys Ile Pro Glu Asn Pro His Asn Ile Tyr Phe Gly Arg Trp Ile Ala Asp Gly Gln Arg Glu Leu Ile Glu Ser Tyr Ser Val Lys Lys Arg His Phe Ile Gly Asn Thr Ser Met Asp Ala Gly Leu Ser Phe Ile Met Ala Asn His GIy Lys Val Lys Glu Asn Asp Ile Val Phe Asp Pro Phe Val Gly Thr Gly Gly Leu Leu Ile Ala Cys Ala His Phe Gly Ala Tyr Val Tyr Gly Thr Asp Ile Asp Tyr Asn Thr Val His Gly Leu Gly Lys Ala Thr Arg Lys Asn Gln Lys Trp Arg Gly Pro Asp Glu Asn Ile Arg Ala Asn Leu Arg Gln Tyr Gly Leu Glu Lys Tyr Tyr Leu Asp Val Leu Val Ser Asp Ala Ser Lys Pro Ser Trp Arg Lys Gly Thr Tyr Phe Asp Ala Ile Ile Thr Asp Pro Pro Tyr Gly Ile Arg Glu Ser Thr Arg Arg Thr Gly Ser Gln Lys Glu Ile Pro Lys Gly Ile Glu Lys Trp Glu Lys Cys Pro Glu Ser His Val Pro Val Ser Leu Ser Tyr His Leu Ser Asp Met Phe Leu Asp Leu Leu Asn Phe Ala Ala Glu Thr Leu Val Leu Gly Gly Arg Leu Val Tyr Trp Leu Pro Val Tyr Thr Pro Glu Tyr Thr Glu Glu Met Val Pro Trp His Pro Cys Leu Glu Leu Val Ser Asn Cys Glu Gln Lys Leu Ser Ser His Thr Ser Arg Arg Leu Ile Thr Met Glu Lys Val Lys Lys Phe Glu Asn Arg Asp Gln Tyr Ser His Leu Leu Ser Asp His Phe Leu Pro Tyr Gln Gly His Asn Ser Phe Arg Glu Lys Tyr Phe Ser Gly Val Thr Lys Arg Ile Ala Lys Glu Glu Lys Ser Thr Gln Glu <210> 41 <211> 1605 <212> DNA
<213> Homo Sapiens <400> 41 agggagattc ctcgaaacta gtgtgtgttt attaaaagga gaaaggataa caatagaatg 60 ttctaaaacc agaagtccaa gtgcgtgtct acttatggga ccaataaata aagaacagac 120 atttgatttg aggtgaggta aaagcctgaa acatggaatg gcattctgtt ttgatggatt 180 ttcatttctt cgcacttctg agacggcaaa gccaaccact tagaagcctt ccacatcttt 240 gtcacctgcc tggctcctgc tctctgatgt acctctgggt agtgagatgg aaatggtgcc 300 tgcagaagtt ggggagaagg atacttttgc acagcctcca tgatgtcttt attgcaaata 360 tggatgacaa gggtctctgt tacaggggcc tcagagcacc ttcgtttctc ctctagacca 420 gggacaggtg tagagataag gactggcaac cagagcctca gcatccaaag atggactgaa 480 gtgggatggc tgacaggcac ataacttacg ggaaagggaa tttcatacat acgatttttg 540 ttttgtgggt aggagggctt atcatcaaca ctgattttat aatctgacaa taaatgtctt 600 tcattaaaga gtttacctaa atgatgttcg attatatgta taatttataa aatatttatg 660 tatagtttgt ttattcaggt atatgtataa tttattgaac acctactatg tcccagcata 720 tctacaaaac tgggtacata catactgtct aactgctaat ccacatttcc agtcttacaa 780 aggacataat gattagttaa gccctaattt agatttgagg aaactgaagc tgagagaggg 840 ttaagtaaat tacccaaagt acagctaata agacccagaa tctcagtctc actccttggg 900 atcctgtgta tttccctgag tcttctaaca tatgaaaatt catatctaaa tcaacaagtg 960 actgtaatct ggtactataa atactaaata aacacttctt cataacactg taccaattca 1020 gcttttaaat tttattactt tgctttcctg tcctttgcca actcttaacc tagttaatcc 1080 tagttctgtt gacattggac caggctcagt aaataaacga atggatttcc agcctttttt 1140 tcccatctgt tcctgctttt agtcctctga atctgcttct tttcttactg ctgctttatt 1200 ttacagtgat tttgtcaaac atagaataca ggactaaaaa tgcaaagaaa ttgggtctgt 2260 gtttaatttt gatgtttcaa attttgagct tccaagtctt tgtggccacc caatgaagtt 1320 tgagtctgcc tgttcagatg tgaaaggtaa gggctgcagc aggtttaagg gtggcccttc 1380 accaccctgt tgtcacctgc acaggcactc ccccatttgc agatgaagaa atgttcagag 1440 aagaaaaatg atggaccaaa cgtctgtttg cacaattgaa actctaccag tggactattc 1500 tattttcaca gctacctagt ttctgccgat gattttttta aatgtgaaat aaacagtgat 1560 actttaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 1605 <210> 42 <211> 87 <212> PRT
<213> Homo sapiens <400> 42 Met Glu Trp His Ser Val Leu Met Asp Phe His Phe Phe Ala Leu Leu Arg Arg Gln Ser Gln Pro Leu Arg Ser Leu Pro His Leu Cys His Leu Pro Gly Ser Cys Ser Leu Met Tyr Leu Trp Val Val Arg Trp Lys Trp Cys Leu Gln Lys Leu Gly Arg Arg Ile Leu Leu His Ser Leu His Asp Val Phe Ile Ala Asn Met Asp Asp Lys Gly Leu Cys Tyr Arg Gly Leu Arg Ala Pro Ser Phe Leu Leu <210> 43 <211> 1936 <212> DNA
<213> Homo sapiens <400> 43 agaaactccc atctccctca ccagccggaa agtacgagtc ggctcagcct ggagggaccc 60 aaccagagcc tggcctggga gccaggatgg ccatccacaa agccttggtg atgtgcctgg 120 gactgcctct cttcctgttc ccaggggcct gggcccaggg ccatgtccca cccggctgca 180 gccaaggcct caaccccctg tactacaacc tgtgtgaccg ctctggggcg tggggcatcg 240 tcctggaggc cgtggctggg gcgggcattg tcaccacgtt tgtgctcacc atcatcctgg 300 tggccagcct cccctttgtg caggacacca agaaacggag cctgctgggg acccaggtat 360 tcttccttct ggggaccctg ggcctcttct gcctcgtgtt tgcctgtgtg gtgaagcccg 420 acttctccac ctgtgcctct cggcgcttcc tctttggggt tctgttcgcc atctgcttct 480 cttgtctggc ggctcacgtc tttgccctca acttcctggc ccggaagaac cacgggcccc 540 ggggctgggt gatcttcact gtggctctgc tgctgaccct ggtagaggtc atcatcaata 600 cagagtggct gatcatcacc ctggttcggg gcagtggcga gggcggccct cagggcaaca 660 gcagcgcagg ctgggccgtg gcctccccct gtgccatcgc caacatggac tttgtcatgg 720 cactcatcta cgtcatgctg ctgctgctgg gtgccttcct gggggcctgg cccgccctgt 780 gtggccgcta caagcgctgg cgtaagcatg gggtctttgt gctcctcacc acagccacct 840 ccgttgccat atgggtggtg tggatcgtca tgtatactta cggcaacaag cagcacaaca 900 gtcccacctg ggatgacccc acgctggcca tcgccctcgc cgccaatgcc tgggccttcg 960 tcctcttcta cgtcatcccc gaggtctccc aggtgaccaa gtccagccca gagcaaagct 1020 accaggggga catgtacccc acccggggcg tgggctatga gaccatcctg aaagagcaga 1080 agggtcagag catgttcgtg gagaacaagg ccttttccat ggatgagccg gttgcagcta 1140 agaggccggt gtcaccatac agcgggtaca atgggcagct gctgaccagt gtgtaccagc 1200 ccactgagat ggccctgatg cacaaagttc cgtccgaagg agcttacgac atcatcctcc 1260 cacgggccac cgccaacagc caggtgatgg gcagtgccaa ctcgaccctg cgggctgaag 1320 acatgtactc ggcccagagc caccaggcgg ccacaccgcc gaaagacggc aagaactctc 1380 aggtctttag aaacccctac gtgtgggact gagtcagcgg tggcgaggag aggcggtcgg 1440 atttggggag ggccctgagg acctggcccc gggcaaggga ctctccaggc tcctcctccc 1500 cctggcaggc ccagcaacat gtgccccaga tgtggaaggg cctccctctc tgccagtgtt 1560 tgggtgggtg tcatgggtgt ccccacccac tcctcagtgt ttgtggagtc gaggagccaa 1620 ccccagcctc ctgccaggat cacctcggcg gtcacactcc agccasatag tgttctcggg 1680 gtggtggctg ggcagcgcct atgtttctct ggagattcct gcaacctcaa gagacttccc 1740 aggcgctcag gcctggatct tgctcctctg tgaggaacaa gggtgcctaa taaatacatt 1800 tctgctttaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1860 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1920 aaaaaaaaaa aaaaaa 1936 <210> 44 <211> 441 <212> PRT
<213> Homo sapiens <400> 44 Met Ala Ile His Lys Ala Leu Val Met Cys Leu Gly Leu Pro Leu Phe Leu Phe Pro Gly Ala Trp Ala Gln Gly His Val Pro Pro Gly Cys Ser Gln Gly Leu Asn Pro Leu Tyr Tyr Asn Leu Cys Asp Arg Ser Gly Ala Trp Gly Ile Val Leu Glu Ala Val Ala Gly Ala Gly Ile Val Thr Thr Phe Val Leu Thr Ile Ile Leu Val Ala Ser Leu Pro Phe Val Gln Asp Thr Lys Lys Arg Ser Leu Leu Gly Thr Gln Val Phe Phe Leu Leu Gly Thr Leu Gly Leu Phe Cys Leu Val Phe Ala Cys Val Val Lys Pro Asp Phe Ser Thr Cys Ala Ser Arg Arg Phe Leu Phe Gly Val Leu Phe Ala WO 99/55721 PC'T/US99/08504 Ile Cys Phe Ser Cys Leu Ala Ala His Val Phe Ala Leu Asn Phe Leu Ala Arg Lys Asn His Gly Pro Arg Gly Trp Val Ile Phe Thr Val Ala Leu Leu Leu Thr Leu Val Glu Val Ile Ile Asn Thr Glu Trp Leu Ile Ile Thr Leu Val Arg Gly Ser Gly Glu Gly Gly Pro Gln Gly Asn Ser Ser Ala Gly Trp Ala Val Ala Ser Pro Cys Ala Ile Ala Asn Met Asp Phe Val Met Ala Leu Ile Tyr Val Met Leu Leu Leu Leu Gly Ala Phe Leu Gly Ala Trp Pro Ala Leu Cys Gly Arg Tyr Lys Arg Trp Arg Lys His Gly Val Phe Val Leu Leu Thr Thr Ala Thr Ser Val Ala Ile Trp Val Val Trp Ile Val Met Tyr Thr Tyr Gly Asn Lys Gln His Asn Ser Pro Thr Trp Asp Asp Pro Thr Leu Ala Ile Ala Leu Ala Ala Asn Ala Trp Ala Phe Val Leu Phe Tyr Val Ile Pro Glu Val Ser Gln Val Thr Lys Ser Ser Pro Glu Gln Ser Tyr Gln Gly Asp Met Tyr Pro Thr Arg Gly Val Gly Tyr Glu Thr Ile Leu Lys Glu Gln Lys Gly Gln Ser Met Phe Val Glu Asn Lys Ala Phe Ser Met Asp Glu Pro Val Ala Ala Lys Arg Pro Val Ser Pro Tyr Ser Gly Tyr Asn Gly Gln Leu Leu Thr Ser Val Tyr Gln Pro Thr Glu Met Ala Leu Met His Lys Val Pro Ser Glu Gly Ala Tyr Asp Ile Ile Leu Pro Arg Ala Thr Ala Asn Ser GIn Val Met Gly Ser Ala Asn Ser Thr Leu Arg Ala Glu Asp Met Tyr Ser Ala Gln Ser His Gln Ala Ala Thr Pro Pro Lys Asp Gly Lys Asn Ser Gln Val Phe Arg Asn Pro Tyr Val Trp Asp <210> 45 <211> 1773 <212> DNA
<213> Homo Sapiens <400> 45 cgcgccgcgc cttcccctgc aaggatgcgg ccctctgcgc ctacgcggtc acctacacag 60 cgatgtacgt gactctcgtg ttccgcgtga agggctcccg cctggtcaaa ccctcgctct 120 gcctggcctt gctgtgcccg gccttcctgg tgggcgtggt ccgcgtggcc gagtaccgaa 180 accactggtc ggacgtgctg gctggcttcc tgacaggggc ggccatcgcc acctttttgg 240 tcacctgcgt tgtgcataac tttcagagcc ggccaccctc tggccgaagg ctctctccct 300 gggaggacct gggccaagcc cccaccatgg atagccccct cgaaaagaac ccgaggtctg 360 caggccgcat tcgacaccgg cacggctcac cccatccaag tcgcagaact gcgcccgccg 420 tggccacctg atccccagct gtgtctcctc cagggcccca gccatgtgtt cgtcgccccg 480 tgtgccccgt cctcgattga ggtctgagcc gacgcccttg cccctgcccc tacccctgcc 540 agcgcccacc cccagccagg gcccctcgcc ttcctcccct ggacctgggg ggccaggcgg 600 gggtggtgga cgtggccgga agctgctgct gcccacgccc ctgctgcggg acctgtacac 660 cctgagtgga ctctatccct cccccttcca ccgggacaac ttcagccctt acctgtttgc 720 cagccgtgac cacctgctgt gaggcccgac cacccaccca gaatctgccc agtccccact 780 tcttccctgc cacgcgtgtg tgtgcgtgtg ccacgtgagt gccaaagtcc cctgcccccc 840 aagccagcca gacccagaca ttagtaagat ggctagaagg acatttagga gacatctgcc 900 tctctggccc tctgagatat cccgatgggc acaaatggaa ggtgcgcact tgcccctact 960 attgcccttt taagggccaa agcttgaccc cattggccat tgcctggcta atgagaaccc 1020 ctggttctca gaattttaac caaaaggagt tggctccaac caatgggagc cttcccctca 1080 cttcttagaa tcctcctgca agagggcaac tccagccagt gttcagcgac tgaacagcca 1140 ataggagccc ttggtttcca gaatttctag agtgggtggg catgattcca gtcaatgggg 1200 gaccgcccgt gtctaagcat gtgcaaagga gaggagggag atgaggtcat tgtttgtcat 1260 tgagtcttct ctcagaatca gcgagcccag ctgtagggtg gggggcaggc tcccccatgg 1320 cagggtcctt ggggtacccc ttttcctctc agcccctccc tgtgtgcggc ctctccacct 1380 ctcacccact ctctcctaat cccctactta agtagggctt gccccacttc agaggttttg 1440 gggttcaggg tgctgtgtct ccccttgcct gtgcccaggt catcccaaac ccttctgtta 1500 tttattaggg ctgtgggaag ggtttttctt ctttttcttg gaacctgccc ctgttcttca 1560 cactgccccc catgcctcag cctcatacag atgtgccatc atggggggca tgggtggagc 1620 agaggggctc cctcaccccg ggcaggcaas ggcagtgggt agaggaggca ctgcccccct 1680 ttcctgcccc ctcctcatct ttaataaaga cctggcttct catctttaat aaagacctgt 1740 ttgtaacaga aaaaaaaaaa aaaaaaaaaa aaa 1773 <210> 46 <211> 122 <212> PRT
<213> Homo Sapiens <400> 46 Met Tyr Val Thr Leu Val Phe Arg Val Lys Gly Ser Arg Leu Val Lys Pro Ser Leu Cys Leu Ala Leu Leu Cys Pro Ala Phe Leu Val Gly Val Val Arg Val Ala Glu Tyr Arg Asn His Trp Ser Asp Val Leu Ala Gly Phe Leu Thr Gly Ala Ala Ile Ala Thr Phe Leu Val Thr Cys Val Val His Asn Phe Gln Ser Arg Pro Pro Ser Gly Arg Arg Leu Ser Pro Trp Glu Asp Leu Gly Gln Ala Pro Thr Met Asp Ser Pro Leu Glu Lys Asn Pro Arg Ser Ala Gly Arg Ile Arg His Arg His Gly Ser Pro His Pro Ser Arg Arg Thr Ala Pro Ala Val Ala Thr <210> 47 <211> 1974 <212> DNA
<213> Homo sapiens <400> 47 tctgcatcct tcccgacctt cccagcaata tgcatcttgc acgtctggtc ggctcctgct 60 ccctccttct gctactgggg gccctgtctg gatgggcggc cagcgatgac cccattgaga 120 aggtcattga agggatcaac cgagggctga gcaatgcaga gagagaggtg ggcaaggccc 180 tggatggcat caacagtgga atcacgcatg ccggaaggga agtggagasg gttttcaacg 240 gacttagcaa catggggagc cacaccggca aggagttgga caaaggcgtc caggggctca 300 accacggcat ggacaaggtt gcccatgaga tcaaccatgg tattggacaa gcaggaaagg 360 aagcagagaa gcttggccat ggggtcaaca acgctgctgg acaggttggg aaggaggcag 420 acaaactgat ccatcatggg gtccatcacg gggccaacca ggcgggaagt gaggcaggga 480 agtttggcca gggagtcgac aatgctgcag ggcaggctgg aaatgaggct gggaggtttg 540 gccagggagt ccaccatgct gcagggcagg ccggaaatga ggctgggagg tttggccagg 600 gagtccacca tgctgcaggg caggccggaa atgaggctgg gagatttggc cagggggccc 660 accatggtct cagtgagggc tggaaggaga cagagaagtt tggccagggg atccaccatg 720 ctgccggtca ggttgggaag gaggcagaga agtttggcca gggggcccac catgctgcgg 780 ggcaggccgg aaatgaggca gggagatttg gccagggggt ccaccatggt ctcagtgagg 840 gctggaagga gacagagaag tttggccagg gggtccacca tactgctggt caggttggga 900 aggaggcaga gaagtttggc cagggggccc accatgctgc ggggcaggcc ggaaatgagg 960 cagggagatt tggccagggg gcccaccatg ctgcggggca ggccggaaat gaggctggga 1020 ggtttggcca gggggtccac catggtctca gtgagggctg gaaggagaca gagaagtttg 1080 gccagggggt ccaccatgct gccagtcagt ttgggaagga aacagagaag ctcggccatg 1140 gggtccacca tggggttaat gaggcctgga aggaagcaga gaagtttggc cagggtgtcc 1200 accatgctgc ctcgcaggtg gggaaggagg aagacagagt ggtccaaggc ctccatcatg 1260 gcgttagtca ggctggaagg gagggggggc agtttggcca cgacattcac cacacagcag 1320 ggcaggctgg gaaagaggga gacatagcag ttcatggtgt ccaacctggg gtccacgagg 1380 ccgggaagga ggcagggcag tttggccagg gagttcacca tacccttgaa caggccggga 1440 aggaagcaga caaagcggtc caagggttcc acactggggt ccaccaggct gggaaggaag 1500 cagagaaact tggccaaggg gtcaaccatg ctgctgacca ggctggaaag gaagtggaga 1560 agcttggcca aggtgcccac catgctgctg gccaggccgg gaaggagctg cagaatgctc 1620 ataatggggt caaccaagcc agcaaggagg ccaaccagct gctgaatggc aaccatcaaa 1680 gcggatcttc cagccatcaa ggaggggcca caaccacgcc gttagcctct ggggcctcag 1740 tcaacacgcc tttcatcaac cttcccgccc tgtggaggag cgtcgccaac atcatgccct 1800 aaactggcat ccggccttgc tgggagaata atgtcgccgt tgtcacatca gctgacatga 1860 cctggagggg ttgggggtgg gggacaggtt tctgaaatcc ctgaaggggg ttgtactggg 1920 atttgtgaat aaacttgata cactatgctg tcaaaaaaaa aaaaaaaaaa aaaa 1974 <210> 48 <211> 590 <212> PRT
<213> Homo sapiens <400> 4B
Met His Leu Ala Arg Leu Val Gly Ser Cys Ser Leu Leu Leu Leu Leu Gly Ala Leu Ser Gly Trp Ala Ala Ser Asp Asp Pro Ile Glu Lys Val Ile Glu Gly Ile Asn Arg Gly Leu Ser Asn Ala Glu Arg Glu Val Gly Lys Ala Leu Asp Gly Ile Asn Ser Gly Ile Thr His Ala Gly Arg Glu Val Glu Lys Val Phe Asn Gly Leu Ser Asn Met Gly Ser His Thr Gly Lys Glu Leu Asp Lys Gly Val Gln Gly Leu Asn His Gly Met Asp Lys Val Ala His Glu Ile Asn His Gly Ile Gly GIn Ala Gly Lys Glu Ala Glu Lys Leu Gly His Gly Val Asn Asn Ala Ala Gly Gln Val Gly Lys Glu Ala Asp Lys Leu Ile His His Gly Val His His Gly Ala Asn Gln Ala Gly Ser Glu Ala Gly Lys Phe Gly Gln Gly Val Asp Asn Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Ala His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln Gly Ile His His Ala Ala Gly Gln Val Gly Lys Glu Ala Glu Lys Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln Gly Val His His Thr Ala Gly Gln Val Gly Lys Glu Ala Glu Lys Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val His His Gly Leu Ser Glu Gly Trp Lys Glu Thr Glu Lys Phe Gly Gln WO 99/55721 1'CTIUS99/0$504 Gly Val His His Ala Ala Ser Gln Phe Gly Lys Glu Thr Glu Lys Leu Gly His Gly Val His His Gly Val Asn Glu Ala Trp Lys Glu Ala Glu Lys Phe Gly Gln Gly Val His His Ala Ala Ser Gln Val Gly Lys Glu Glu Asp Arg Val Val Gln Gly Leu His His Gly Val Ser Gln Ala Gly Arg Glu Gly Gly Gln Phe Gly His Asp Ile His His Thr Ala Gly Gln Ala Gly Lys Glu Gly Asp Ile Ala Val His Gly Val Gln Pro Gly Val His Glu Ala Gly Lys Glu Ala Gly Gln Phe Gly Gln Gly Val His His Thr Leu Glu Gln Ala Gly Lys Glu Ala Asp Lys Ala Val Gln Gly Phe His Thr Gly Val His Gln Ala Gly Lys Glu Ala Glu Lys Leu Gly Gln Gly Val Asn His Ala Ala Asp Gln Ala Gly Lys Glu Val Glu Lys Leu Gly Gln Gly Ala His His Ala Ala Gly Gln Ala Gly Lys Glu Leu Gln Asn Ala His Asn Gly Val Asn Gln Ala Ser Lys Glu Ala Asn Gln Leu Leu Asn Gly Asn His Gln Ser Gly Ser Ser Ser His Gln Gly Gly Ala Thr Thr Thr Pro Leu Ala Ser Gly Ala Ser Val Asn Thr Pro Phe Ile Asn Leu Pro Ala Leu Trp Arg Ser Val Ala Asn Ile Met Pro <210> 49 <211> 923 <212> DNA
<213> Homo sapiens <400> 49 gagagctgga tccttgaaaa tctactctat cagctgctgt ggttgccacc attctcagga 60 ccctcgccat gaaagccctt atgctgctca ccctgtctgt tctgctctgc tgggtctcag 120 ctgacattcg ctgtcactcc tgctacaagg tccctgtgct gggctgtgtg gaccggcagt 180 cctgccgcct ggagccagga cagcaatgcc tgacaacaca tgcatacctt ggtaagatgt 240 gggttttctc caatctgcgc tgtggcacac cagaagagcc ctgtcaggag gccttcaacc 300 aaaccaaccg taagctgggt ctgacatata acaccacctg ctgcaacaag gacaactgca 360 acagcgcagg accccggccc actccagccc tgggccttgt cttccttacc tccttggctg 420 gccttggcct ctggctgctg cactgagact cattccattg gctgcccctc ctcccacctg 480 ccttggcctg agcctctctc cctgtgtctc tgtatcccct ggctttacag aatcgtctct 540 ccctagctcc catttcttta attaaacact gttccgagtg gtctcctcat ccgtccttcc 600 cacctcacac ccttcactct cctttttctg ggtcccttcc cacttccttc caggacctcc 660 attggctcct agaagggctc cccactttgc ttcctatact ctgctgtccc ctacttgagg 720 agggattggg atctggggcc tgaaatgggg cttctgtgtt gtccccagtg aaggctccca 780 caaggacctg atgacctcac tgtacagagc tgactcccca aatccaggct cccatatgta 840 ccccatcccc catactcacc tctttccatt ttgagtaata aatgtctgag tctgaaaaaa 900 aaaaaaaaaa aaaaaaaaaa aaa 923 <210> 50 <211> 125 <212> PRT
<213> Homo Sapiens <400> 50 Met Lys Ala Leu Met Leu Leu Thr Leu Ser Val Leu Leu Cys Trp Val Ser Ala Asp Ile Arg Cys His Ser Cys Tyr Lys Val Pro Val Leu Gly Cys Val Asp Arg Gln Ser Cys Arg Leu Glu Pro Gly Gln Gln Cys Leu Thr Thr His Ala Tyr Leu Gly Lys Met Trp Val Phe Ser Asn Leu Arg Cys Gly Thr Pro Glu Glu Pro Cys Gln Glu Ala Phe Asn Gln Thr Asn Arg Lys Leu Gly Leu Thr Tyr Asn Thr Thr Cys Cys Asn Lys Asp Asn Cys Asn Ser Ala Gly Pro Arg Pro Thr Pro Ala Leu Gly Leu Val Phe Leu Thr Ser Leu Ala Gly Leu Gly Leu Trp Leu Leu His <210> 51 <211> 1493 <212> D13A
<213> Homo Sapiens <400> 51 ggagaagccc aggcagttga ggacaggaga gagaaggctg cagacccaga gggagggagg 60 acagggagtc ggaaggagga ggacagagga gggcacagag acgcagagca agggcggcaa 120 ggaggagacc ctggtgggag gaagacactc tggagagaga gggggctggg cagagatgaa 180 gttccagggg cccctggcct gcctcctgct ggccctctgc ctgggcagtg gggaggctgg 240 ccccctgcag agcggagagg aaagcactgg gacaaatatt ggggaggccc ttggacatgg 300 cctgggagac gccctgagcg aaggggtggg aaaggccatt ggcaaagagg ccggaggggc 360 agctggctct aaagtcagtg aggcccttgg ccaagggacc agagaagcag ttggcactgg 420 agtcaggcag gttccaggct ttggcgtagc agatgctttg ggcaacaggg tcggggaagc 480 agcccatgct ctgggaaaca ctgggcacga gattggcaga caggcagaag atgtcattcg 540 acacggagca gatgctgtcc gcggctcctg gcagggggtg cctggccaca atggtgcttg 600 ggaaacttct ggaggccatg gcatctttgg ctctcaaggt ggccttggag gccagggcca 660 gggcaatcct ggaggtctgg ggactccgtg ggtccacgga taccccggaa actcagcagg 720 cagctttgga atgaatcctc agggagctcc ctggggtcaa ggaggcaatg gagggccacc 780 aaactttggg accaacactc agggagctgt ggcccagcct ggctatggtt cagtgagagc 840 cagcaaccag aatgaagggt gcacgaatcc cccaccatct ggctcaggtg gaggctccag 900 caactctggg ggaggcagcg gctcacagtc gggcagcagt ggcagtggca gcaatggtga 960 caacaacaat ggcagcagca gtggtggcag cagcagtggc agcagcagtg gcggcagcag 1020 tggcggcagc agtggtggca gcagtggcaa cagtggtggc agcagaggtg acagcggcag 1080 tgagtcctcc tggggatcca gcaccggctc ctcctccggc aaccacggtg gagcggcgga 1140 ggaaatggac ataaacccgg gaactctgag acgtctcctg ggatgtttaa ctttgacact 1200 ttctggaaga attttaaatc caagctgggt ttcatcaact gggatgccat aaacaaggac 1260 cagagaagct ctcgcatccc gtgacctcca gacaaggagc caccagattg gatgggagcc 1320 cccacactcc ctccttaaaa caccaccctc tcatcactaa tctcagccct tgcccttgaa 1380 ataaacctta gctgccccac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1440 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 1493 <210> 52 <211> 358 <212> PRT
<213> Homo sapiens <400> 52 Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu Gly Ser Gly Glu Ala Gly Pro Leu Gln Ser Gly Glu Glu Ser Thr Gly Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp Ala Leu Ser Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly Gly Ala Ala Gly Ser Lys Val Ser Glu Ala Leu Gly Gln Gly Thr Arg Glu Ala Val Gly Thr Gly Val Arg Gln Val Pro Gly Phe Gly Val Ala Asp Ala Leu Gly Asn Arg Val Gly Glu Ala Ala His Ala Leu GIy Asn Thr Gly His Glu Ile Gly Arg Gln Ala Glu Asp Val Ile Arg His Gly Ala Asp Ala Val Arg Gly Ser Trp Gln Gly Val Pro Gly His Asn Gly Ala Trp Glu Thr Ser Gly Gly His Gly Ile Phe Gly Ser Gln Gly Gly Leu Gly Gly Gln Gly Gln Gly Asn Pro Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr Pro Gly Asn Ser Ala Gly Ser Phe Gly Met Asn Pro Gln Gly Ala Pro Trp Gly Gln Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr Gln Gly Ala Val Ala Gln Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn Gln Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gln Ser Gly Ser Ser Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ala Ala Glu Glu Met Asp Ile Asn Pro Gly Thr Leu Arg Arg Leu Leu Gly Cys Leu Thr Leu Thr Leu Ser Gly Arg Ile Leu Asn Pro Ser Trp Val Ser Ser Thr Gly Met Pro <210> 53 <211> 1897 <212> DNA
<213> Homo sapiens <400> 53 acagaggagg gcacagagac gcagagcaag ggcggcaagg aggagaccct ggtgggagga 60 agacactctg gagagagagg gggctgggca gagatgaagt tccaggggcc cctggcctgc 120 ctcctgctgg ccctctgcct gggcagtggg gaggctggcc ccctgcagag cggagaggaa 180 agcactggga caaatattgg ggaggccctt ggacatggcc tgggagacgc cctgagcgaa 240 ggggtgggaa aggccattgg caaagaggcc ggaggggcag ctggctctaa agtcagtgag 300 gcccttggcc aagggaccag agaagcagtt ggcactggag tcaggcaggt tccaggcttt 360 ggcgtagcag atgctttggg caacagggtc ggggaagcag cccatgctct gggaaacact 420 gggcacgaga ttggcagaca ggcagaagat gtcattcgac acggagcaga tgctgtccgc 480 ggctcctggc agggggtgcc tggccacaat ggtgcttggg aaacttctgg aggccatggc 540 atctttggct ctcaaggtgg ccttggaggc cagggccagg gcaatcctgg aggtctgggg 600 actccgtggg tccacggata ccccggaaac tcagcaggca gctttggaat gaatcctcag 660 ggagctccct ggggtcaagg aggcaatgga gggccaccaa actttgggac caacactcag 720 ggagctgtgg cccagcctgg ctatggttca gtgagagcca gcaaccagaa tgaagggtgc 780 acgaatcccc caccatctgg ctcaggtgga ggctccagca actctggggg aggcagcggc 840 tcacagtcgg gcagcagtgg cagtggcagc aatggtgaca acaacaatgg cagcagcagt 900 ggtggcagca gcagtggcag cagcagtggc ggcagcagtg gcggcagcag tggtggcagc 960 agtggcaaca gtggtggcag cagaggtgac agcggcagtg agtcctcctg gggatccagc 1020 accggctcct cctccggcaa ccacggtggg agcggcggag gaaatggaca taaacccggg 1080 gggcaagggt cgagctgggg cagtggagga ggtgacgctg ttggtggagt caatactgtg 1140 aactctgaga cgtctcctgg gatgtttaac tttgacactt tctggaagaa ttttaaatcc 1200 aagctgggtt tcatcaactg ggatgccata aacaagaacc aggtcccgcc ccccagcacc 1260 cgagccctcc tctacttcag ccgactctgg gaggatttca aacagaacac tcctttcctc 1320 aactggaaag caattattga gggtgcggac gcgtcatcac tgcagaaacg tgcaggcaga 1380 gccgatcaga actacaatta caaccagcat gcgtatccca ctgcctatgg tgggaagtac 1440 tcagtcaaga cccctgcaaa ggggggagtc tcaccttctt cctcggcttc ccgggtgcaa 1500 cctggcctgc taggcaattt cttgcaacca 1560 tgcagtgggt ccaccgaggc gaagttttgg cccgaaaagc tcccctt ggcccccagcctg 1620 actggtcgtc tgccagccct agggagctcc ggcccggctg ctggggaccc agcttgtctc 1680 ccacacctct tccttgtttc gtttcctagg ttcccactgc accagcc tcgtcacatacac 1740 actgtggtgc cagcatcttt ttcagtggcc ctgtacctcc cactgtgaca gttctccagg 1800 tccctttggt aaggaggagc gacctgaagt ttcctacttt aaacatgaat cttgtttccc 1860 tgagtttctc taaaaaaaaa tgtggaaata aaaaaaaaaa aaaaaaa 1897 aaaaaaaaaa aaaaaaaaaa <210> 54 <211> 479 <212> PRT
<2I3> Homo sapiens <400> 54 Met Lys Phe Pro Ala CysLeu LeuLeu LeuCys Leu Gln Gly Leu Ala Gly Ser Gly Gly Leu GlnSer GlyGlu SerThr Gly Glu Ala Pro Glu Thr Asn Ile Ala Gly HisGly LeuGly AlaLeu Ser Gly Glu Leu Asp Glu Gly Val Ala Gly LysGlu AlaGly AlaAla Gly Gly Lys Ile Gly Ser Lys Val Ala Gly GlnGly ThrArg AlaVal Gly Ser Glu Leu Glu Thr Gly Val Val Gly PheGly ValAla AlaLeu Gly Arg Gln Pro Asp Asn Arg Val Ala His AlaLeu GlyAsn GlyHis Glu Gly Glu Ala Thr Ile Gly Arg Glu Val IleArg HisGly AspAla Val Gln Ala Asp Ala Arg Gly Ser Gly Pro GlyHis AsnGly TrpGlu Thr Trp Gln Val Ala Ser Gly Gly Ile Gly SerGln GlyGly GlyGly Gln His Gly Phe Leu Gly Gln Gly Gly Leu GlyThr ProTrp HisGly Tyr Asn Pro Gly Val Pro Gly Asn Gly Phe GlyMet AsnPro GlyAla Pro Ser Ala Ser Gln Trp Gly Gln Asn Gly ProPro AsnPhe ThrAsn Thr Gly Gly Gly Gly Gln Gly Ala Gln Gly TyrGly SerVal AlaSer Asn Val Ala Pro Arg Gln Asn Glu Thr Pro ProPro SerGly GlyGly Gly Gly Cys Asn Ser Ser Ser Asn Gly Ser GlySer GlnSer SerSer Gly Ser Gly Gly Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ser Gly Gly Gly Asn Gly His Lys Pro Gly Gly Gln Gly Ser Ser Trp Gly Ser Gly Gly Gly Asp Ala Val Gly Gly Val Asn Thr Val Asn Ser Glu Thr Ser Pro Gly Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys Ser Lys Leu Gly Phe Ile Asn Trp Asp Ala Ile Asn Lys Asn Gln Val Pro Pro Pro Ser Thr Arg Ala Leu Leu Tyr Phe Ser Arg Leu Trp Glu Asp Phe Lys Gln Asn Thr Pro Phe Leu Asn Trp Lys Ala Ile Ile Glu Gly Ala Asp Ala Ser Ser Leu Gln Lys Arg Ala Gly Arg Ala Asp Gln Asn Tyr Asn Tyr Asn Gln His Ala Tyr Pro Thr Ala Tyr Gly Gly Lys Tyr Ser Val Lys Thr Pro Ala Lys Gly Gly Val Ser Pro Ser Ser Ser Ala Ser Arg Val Gln Pro Gly Leu Leu Gln Trp Val Lys Phe Trp <210> 55 <211> 1532 <212> DNA
<213> Homo sapiens <400> 55 gaagagcccc tgcggccggg cgcgaaaatg gcggcggcgg cgacggccgg gcgctcctga 60 agcagcagtt atggagcttc cctcagggcc ggggccggag cggctctttg actcgcaccg 120 gcttccgggt gactgcttcc tactgctcgt gctgctgctc tacgcgccag tcgggttctg 180 cctcctcgtc ctgcgcctgt ttctcgggat ccacgtcttc ctggtcagct gcgcgctgcc 240 agacagcgtc cttcgcagat tcgtagtgcg gaccatgtgt gcggtgctag ggctcgtggc 300 ccggcaggag gactccggac tccgggatca cagtgtcagg gtcctcattt ccaaccatgt 360 gacacctttc gaccacaaca tagtcaattt gcttaccacc tgtagcaccc ctctactcaa 420 tagtcccccc agctttgtgt gctggtctcg gggcttcatg gagatgaatg ggcgggggga 480 gttggtggag tcactcaaga gattctgtgc ttccacgagg cttcccccca ctcctctgct 540 gctattccct gaggaagagg ccaccaatgg ccgggagggg ctcctgcgct tcagttcctg 600 gccattttct atccaagatg tggtacaacc tcttaccctg caagttcaga gacccctggt 660 ctctgtgacg gtgtcagatg cctcctgggt ctcagaactg ctgtggtcac ttttcgtccc 720 tttcacggtg tatcaagtaa ggtggcttcg tcctgttcat cgccaactag gggaagcgaa 780 tgaggagttt gcactccgtg tacaacagct ggtggccaag gaattgggcc agacagggac 840 acggctcact ccagctgaca aagcagagca catgaagcga caaagacacc ccagattgcg 900 cccccagtca gcccagtctt ctttccctcc ctcccctggt ccttctcctg atgtgcaact 960 ggcaactctg gctcagagag tcaaggaagt tttgccccat gtgccattgg gtgtcatcca 1020 gagagacctg gccaagactg gctgtgtaga cttgactatc actaatctgc ttgagggggc 1080 cgtagctttc atgcctgaag acatcaccaa gggaactcag tccctaccca cagcctctgc 1140 ctccaagttt cccagctctg gcccggtgac ccctcagcca acagccctaa catttgccaa 1200 gtcttcctgg gcccggcagg agagcctgca ggagcgcaag caagcactat atgaatacgc 1260 aagaaggaga ttcacagaga gacgagccca ggaggctgac tgagctcaaa ggaacaggat 1320 ggcacccaga gccgcaggac ggagactggg ggcagccctc acccaactca caacaggctg 1380 gatgggtggg tggtaaaaag ggaaggatga ggctccccca atgtcacatt aaattcatgg 1440 ttttcattca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1500 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1532 <210> 56 <211> 410 <212> PRT
<213> Homo sapiens <400> 56 Met Glu Leu Pro Ser Gly Pro Gly Pro Glu Arg Leu Phe Asp Ser His Arg Leu Pro Gly Asp Cys Phe Leu Leu Leu Val Leu Leu Leu Tyr Ala Pro Val Gly Phe Cys Leu Leu Val Leu Arg Leu Phe Leu Gly Ile His Val Phe Leu Val Ser Cys Ala Leu Pro Asp Ser Val Leu Arg Arg Phe Val Val Arg Thr Met Cys Ala Val Leu Gly Leu Val Ala Arg Gln Glu Asp Ser Gly Leu Arg Asp His Ser Val Arg Val Leu Ile Ser Asn His Val Thr Pro Phe Asp His Asn Ile Val Asn Leu Leu Thr Thr Cys Ser Thr Pro Leu Leu Asn Ser Pro Pro Ser Phe Val Cys Trp Ser Arg Gly Phe Met Glu Met Asn Gly Arg Gly Glu Leu Val Glu Ser Leu Lys Arg Phe Cys Ala Ser Thr Arg Leu Pro Pro Thr Pro Leu Leu Leu Phe Pro Glu Glu Glu Ala Thr Asn Gly Arg Glu Gly Leu Leu Arg Phe Ser Ser Trp Pro Phe Ser Ile Gln Asp Val Val Gln Pro Leu Thr Leu Gln Val Gln Arg Pro Leu Val Ser Val Thr Val Ser Asp Ala Ser Trp Val Ser Glu Leu Leu Trp Ser Leu Phe Val Pro Phe Thr Val Tyr Gln Val Arg Trp Leu Arg Pro Val His Arg Gln Leu Gly Glu Ala Asn Glu Glu Phe Ala Leu Arg Val Gln Gln Leu Val Ala Lys Glu Leu Gly Gln Thr Gly Thr Arg Leu Thr Pro Ala Asp Lys Ala Glu His Met Lys Arg Gln Arg His Pro Arg Leu Arg Pro Gln Ser Ala Gln Ser Ser Phe Pro Pro Ser Pro Gly Pro Ser Pro Asp Val Gln Leu Ala Thr Leu Ala Gln Arg Val Lys Glu Val Leu Pro His Val Pro Leu Gly Val Ile Gln Arg Asp Leu Ala Lys Thr Gly Cys Val Asp Leu Thr Ile Thr Asn Leu Leu Glu Gly Ala Val Ala Phe Met Pro Glu Asp Ile Thr Lys Gly Thr Gln Ser Leu Pro Thr Ala Ser Ala Ser Lys Phe Pro Ser Ser Gly Pro Val Thr Pro Gln Pro Thr Ala Leu Thr Phe Ala Lys Ser Ser Trp Ala Arg Gln Glu Ser Leu Gln Glu Arg Lys Gln Ala Leu Tyr Glu Tyr Ala Arg Arg Arg Phe Thr Glu Arg Arg Ala Gln Glu Ala Asp <210> 57 <211> 2093 <212> DNA
<213> Homo sapiens <400> 57 cgcgtttcag cgaagtcgca cgtgaaggat agcagtggcc tgagaaagac ccagtcatgg 60 cagcctccag catcagttca ccatggggaa agcatgtgtt caaagccatt ctgatggtcc 120 tagtggccct tatcctcctc cactcagcat tggcccagtc ccgtcgagac tttgcaccac 180 caggccaaca gaagagagaa gccccagttg atgtcttgac ccagataggt cgatctgtgc 240 gagggacact ggatgcctgg attgggccag agaccatgca cctggtgtca gagtcttcgt 300 cccaagtgtt gtgggccatc tcatcagcca tttctgtggc cttctttgct ctgtctggga 360 tcgccgcaca gctgctgaat gccttgggac tagctggtga ttacctcgcc cagggcctga 420 agctcagccc tggccaggtc cagaccttcc tgctgtgggg agcaggggcc ctggtcgtct 480 actggctgct gtctctgctc ctcggcttgg tcttggcctt gctggggcgg atcctgtggg 540 gcctgaagct tgtcatcttc ctggccggct tcgtggccct gatgaggtcg gtgcccgacc 600 cttccacccg ggccctgcta ctcctggcct tgctgatcct ctacgccctg ctgagccggc 660 tcactggctc ccgagcctct ggggcccaac tcgaggccaa ggtgcgaggg ctggaacgcc 720 aggtggagga gctgcgctgg cgccagaggc gagcggccaa gggggcccgc agtgtggagg 780 aggagtgagc cggatgcccc acacaccgcc agtgtcatac caaagagctg agctgcttcg 840 gggccatgca gccctcctgc cagccccctg cccttttctt gccctgtctc tgaaccttca 900 gaacattgat ccttgccgca gccccactag ccaagagaaa cagagaaaga ccattccccc 960 tgcctgtcct tgcggccctg tcttctgagg ttctctgtct ggggttggct ctcttaaccc 1020 tttctctgct cccagcctgc ctcaccaggg aaggttggag gggcctccct ctggcttctg 1080 catctgcgcc agcaaacatc actgccgttg gtctctcatg acttaactgg cttccctctg 1140 ctgctgcctt ggcttcctcc taatgctcgt gctctcctgt ccttctgaag ttgctccttg 1200 gccaaatctc cagctccctt cttgttttcc tcatcctcct accctgtact cccaccaaac 1260 catggtcctt taaggcacgc tcctgtcctc ctcattgccc agcagtaggg aggggcaggg 1320 gtaaggggac ctgaggataa agggtgggga aacagggtcc cctgaggcct gtgggggctg 1380 caggggagga ggatgtacct tgtgtctctt tcaagtgcct taatccgagc cagcagggcc 1440 ttctgcttgc ctgctgccat actgtatgta ggaaagtgtt ctgtggctgc tttgtgtcaa 1500 gaaaagagca gtcactctca gaatcttgat tccccatcag ccaaagcaaa agatggctgc 1560 tgctttgtag gcatgtgcct gcaagtggga ccttgctggg cattatatgc cctgtggggg 1620 tttcagagac cctgaaagag gagggaggac ccgcctcctt gtctgcacaa ctgcatgcac 1680 ttctctcccc atcgctccac aacctgaaac cgagaaggag ttgctgacca gtgcccaccc 1740 cggcagcccg ggaggaacac aggcagctcc tttcccttca cgtggtctgc agagagcagg 1800 gtgagctgcc agctgcccct ctccaccagg gtaccctgtc ttggtggtta ggggccactt 1860 ttcctttgag gctctagtgg aggtggatgt ccttctctgc caggcttggc acatgatgtg 1920 aagaataaat gcccaattct tactgttcag gtttgatgtg gaatcacagc tgcagtgata 1980 tatatttttt atcagtgctt ggttggtttt aaataaagtg cacgctattt tattatcttg 2040 ttctgaataa aatgtattta ctccaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 2093 <210> 58 <211> 243 <212> PRT
<213> Homo Sapiens <400> 58 Met Ala Ala Ser Ser Ile Ser Ser Pro Trp Gly Lys His Val Phe Lys Ala Ile Leu Met Val Leu Val Ala Leu Ile Leu Leu His Ser Ala Leu Ala Gln Ser Arg Arg Asp Phe Ala Pro Pro Gly Gln Gln Lys Arg Glu Ala Pro Val Asp Val Leu Thr Gln Ile Gly Arg Ser Val Arg Gly Thr Leu Asp Ala Trp Ile Gly Pro Glu Thr Met His Leu Val Ser Glu Ser Ser Ser Gln Val Leu Trp Ala Ile Ser Ser Ala Ile Ser Val Ala Phe Phe Ala Leu Ser Gly Ile Ala Ala Gln Leu Leu Asn Ala Leu Gly Leu Ala Gly Asp Tyr Leu Ala Gln Gly Leu Lys Leu Ser Pro Gly Gln Val Gln Thr Phe Leu Leu Trp Gly Ala Gly Ala Leu Val Val Tyr Trp Leu Leu Ser Leu Leu Leu Gly Leu Val Leu Ala Leu Leu Gly Arg Ile Leu Trp Gly Leu Lys Leu Val Ile Phe Leu Ala Gly Phe Val Ala Leu Met Arg Ser Val Pro Asp Pro Ser Thr Arg Ala Leu Leu Leu Leu Ala Leu Leu Ile Leu Tyr Ala Leu Leu Ser Arg Leu Thr Gly Ser Arg Ala Ser Gly Ala Gln Leu Glu Ala Lys Val Arg Gly Leu Glu Arg Gln Val Glu Glu Leu Arg Trp Arg Gln Arg Arg Ala Ala Lys Gly Ala Arg Ser Val Glu Glu Glu <210> 59 <211> 1372 <212> DNA
<213> Homo sapiens <400> 59 atcggcgtcc gcagcgggcg gctgctgagc tgccttgagg tgcagtgttg gggatccaga 60 gccatgtcgg acctgctact actgggcctg attgggggcc tgactctctt actgctgctg 120 acgctgctgg cctttgccgg gtactcaggg ctactggctg gggtggaagt gagtgctggg 180 tcacccccca tccgcaacgt cactgtggcc tacaagttcc acatggggct ctatggtgag 240 actgggcggc ttttcactga gagctgcagc atctctccca agctccgctc catcgctgtc 300 tactatgaca acccccacat ggtgccccct gataagtgcc gatgtgccgt gggcagcatc 360 ctgagtgaag gtgaggaatc gccctcccct gagctcatcg acctctacca gasatttggc 420 ttcaaggtgt tctccttccc ggcacccagc catgtggtga cagccacctt cccctacacc 480 accattctgt ccatctggct ggctacccgc cgtgtccatc ctgccttgga cacctacatc 540 aaggagcgga agctgtgtgc ctatcctcgg ctggagatct accaggaaga ccagatccat 600 ttcatgtgcc cactggcacg gcagggagac ttctatgtgc ctgagatgaa ggagacagag 660 tggaaatggc gggggcttgt ggaggccatt gacacccagg tggatggcac aggagctgac 720 acaatgagtg acacgagttc tgtaagcttg gaagtgagcc ctggcagccg ggagacttca 780 gctgccacac tgtcacctgg ggcgagcagc cgtggctggg atgacggtga cacccgcagc 840 gagcacagct acagcgagtc aggtgccagc ggctcctctt ttgaggagct ggacttggag 900 ggcgaggggc ccttagggga gtcacggctg gaccctggga ctgagcccct ggggactacc 960 sagtggctct gggagcccac tgcccctgag aagggcaagg agtaacccat ggcctgcacc 1020 ctcctgcagt gcagttgctg aggaactgag cagactctcc agcagactct ccagccctct 1080 tcctccttcc tctgggggag gaggggttcc tgagggacct gacttcccct gctccaggcc 1140 tcttgctaag ccttctcctc actgcccttt aggctcccag ggccagagga gccagggact 1200 attttctgca ccagccccca gggctgccgc ccctgttgtg tctttttttc agactcacag 1260 tggagcttcc aggacccaga ataaagccaa tgatttactt gtttcacctg gaaaaaaaaa 1320 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa as 1372 <210> 60 <211> 313 <212> PRT
<213> Homo sapiens <400> 60 Met Ser Asp Leu Leu Leu Leu Gly Leu Ile Gly Gly Leu Thr Leu Leu Leu Leu Leu Thr Leu Leu Ala Phe Ala Gly Tyr Ser Gly Leu Leu Ala Gly Val Glu Val Ser Ala Gly Ser Pro Pro Ile Arg Asn Val Thr Val Ala Tyr Lys Phe His Met Gly Leu Tyr Gly Glu Thr Gly Arg Leu Phe Thr Glu Ser Cys Ser Ile Ser Pro Lys Leu Arg Ser Ile Ala Val Tyr Tyr Asp Asn Pro His Met Val Pro Pro Asp Lys Cys Arg Cys Ala Val Gly Ser Ile Leu Ser Glu Gly Glu Glu Ser Pro Ser Pro Glu Leu Ile Asp Leu Tyr Gln Lys Phe Gly Phe Lys Val Phe Ser Phe Pro Ala Pro Ser His Val Val Thr Ala Thr Phe Pro Tyr Thr Thr Ile Leu Ser Ile Trp Leu Ala Thr Arg Arg Val His Pro Ala Leu Asp Thr Tyr Ile Lys Glu Arg Lys Leu Cys Ala Tyr Pro Arg Leu Glu Ile Tyr Gln Glu Asp 165 1?0 175 Gln Ile His Phe Met Cys Pro Leu Ala Arg Gln Gly Asp Phe Tyr Val Pro Glu Met Lys Glu Thr Glu Trp Lys Trp Arg Gly Leu Val Glu Ala Ile Asp Thr Gln Val Asp Gly Thr Gly Ala Asp Thr Met Ser Asp Thr Ser Ser Val Ser Leu Glu Val Ser Pro Gly Ser Arg Glu Thr Ser Ala Ala Thr Leu Ser Pro Gly Ala Ser Ser Arg Gly Trp Asp Asp Gly Asp Thr Arg Ser Glu His Ser Tyr Ser Glu Ser Gly Ala Ser Gly Ser Ser Phe Glu Glu Leu Asp Leu Glu Gly Glu Gly Pro Leu Gly Glu Ser Arg Leu Asp Pro Gly Thr Glu Pro Leu Gly Thr Thr Lys Trp Leu Trp Glu Pro Thr Ala Pro Glu Lys Gly Lys Glu <210> 61 <211> 1529 <212> DNA
<213> Homo sapiens <400> 61 gggctgcctg gtccaggaag ggggtgcggc tctgtcagga aacctggact ctcaaggccc 60 accagcctct ccgtgagtgt tagaaatcac agatacagta tatacttaat tacactaaat 120 tattgctggg attccttata agcactaatt atacctgatt ataggttaaa atatttattt 180 tgtcaaaata ttttcttggg aatgtgttta accctttctg cgttcattgt tgctgagatg 240 tgaaaactaa ccattccctc ctgcctacct ttttggccac tgggcggcag agaatggcgc 300 tatgtgcagt tgggcccctg gcaccatggg cctttggcct gcctgctgca gagtagccct 360 gcctgggcag tctccaggca ctgagcaggc catctgtggc caggctgaga gaatgactgg 420 ctcgcttacc agcgtgcatg ggacaaggag ctttggagcc tcaaggggtt gttgctggcc 480 tgggctagag ggaaaggtga ccatccgtct gtcctcctgt ctttctatta gcgcctccat 540 gtgagtgatg gtgccttggt tcactagcct tcccccacca ccccaccatg ccacctggtg 600 gtcttggggc ctgtgctgtc actccagccc ctggggagga gaggacccag cccggagagt 660 tggggcaagg gctccacatg gcccaagggc aacagatgct cgcagggcag ctgctgccga 720 tgctcacgct cctgcccccc tccttcccgc tgccacaccc caccctgggc ccccgcagac 780 acgcatctct aactcagttg ggcccagcct tctggatggc ttggggtagg ccatgggccc 840 acctggggcc aggccagccc ctggggcagc tctggaagag cagtgtggag gagcacttgc 900 ttgcagcctg gcttcagcct ctggcactgc tggagtggtc cctgggagct tctgcactgt 960 cggctttggg gacgtctcac ccacttgggt tacagtaggc cttccccacc cagagagaag 1020 tgtttccacc ccagagacat tgtctgtcag cccctgaagt gctcgcctcc cccagtgccc 1080 gtcaccagcc cttcctatct gtggggtcca agtcaggctt cccctgcggc caccagccat 1140 agggagcagc catcagcccc cgagtcagaa ctgcttctgt ctgtccatac ctccaggctc 1200 tcccggagag ggggacggat atttatttcc taaagtttgc acttaattgt gaggattctc 1260 aggattgttg ggggctactg aaaagaggaa tgtgttgaat gtcgcgtttg ctgtccactc 1320 gtcctagaag tttagtgttt ttgtcactgt catgtgtttc tgtgggcaga gctggttctg 1380 gagggtgggt cagtgcaccc gaggctcaga gcatccatcc accccactgg ccctccttcc 1440 agataccctc tctctaattg ggttcttgca tgtaaaatac tccacaataa ataaataatt 1500 gaacaaaaaa aaaaaaaaaa aaaaaaaaa 1529 <210> 62 <211> 136 <212> PRT
<213> Homo sapiens <400> 62 Met Pro Pro Gly Gly Leu Gly Ala Cys Ala Val Thr Pro Ala Pro Gly Glu Glu Arg Thr Gln Pro Gly Glu Leu Gly Gln Gly Leu His Met Ala Gln Gly Gln Gln Met Leu Ala Gly Gln Leu Leu Pro Met Leu Thr Leu Leu Pro Pro Ser Phe Pro Leu Pro His Pro Thr Leu Gly Pro Arg Arg His Ala Ser Leu Thr Gln Leu Gly Pro Ala Phe Trp Met Ala Trp Gly Arg Pro Trp Ala His Leu Gly Pro Gly Gln Pro Leu Gly Gln Leu Trp Lys Ser Ser Val Glu Glu His Leu Leu Ala Ala Trp Leu Gln Pro Leu Ala Leu Leu Glu Trp Ser Leu Gly Ala Ser Ala Leu Ser Ala Leu Gly Thr Ser His Pro Leu Gly Leu Gln <210> 63 <211> 2242 <212> DNA
<213> Homo Sapiens <400> 63 gagctgaggt ggcagtggtt ccaccaacat ggagctctcg cagatgtcgg agctcatggg 60 gctgtcggtg ttgcttgggc tgctggccct gatggcgacg gcggcggtag cgcgggggtg 120 gctgcgcgcg ggggaggaga ggagcggccg gcccgcctgc caaaaagcaa atggatttcc 180 acctgacaaa tcttcgggat ccaagaagca gaaacaatat cagcggattc ggaaggagaa 240 gcctcaacaa cacaacttca cccaccgcct cctggctgca gctctgaaga gccacagcgg 300 gaacatatct tgcatggact ttagcagcaa tggcaaatac ctggctacct gtgcagatga 360 tcgcaccatc cgcatctgga gcaccaagga cttcctgcag cgagagcacc gcagcatgag 420 agccaacgtg gagctggacc acgccaccct ggtgcgcttc agccctgact gcagagcctt 480 catcgtctgg ctggccaacg gggacaccct ccgtgtcttc aagatgacca agcgggagga 540 tgggggctac accttcacag ccaccccaga ggacttccct aaaaagcaca aggcgcctgt 600 catcgacatt ggcattgcta acacagggaa gtttatcatg actgcctcca gtgacaccac 660 tgtcctcatc tggagcctga agggtcaagt gctgtctacc atcaacacca accagatgaa 720 caacacacac gctgctgtat ctccctgtgg cagatttgta gcctcgtgtg gcttcacccc 780 agatgtgaag gtttgggaag tctgctttgg aaagaagggg gagttccagg aggtggtgcg 840 agccttcgaa ctaaagggcc actccgcggc tgtgcactcg tttgctttct ccaacgactc 900 acggaggatg gcttctgtct ccaaggatgg tacatggaaa ctgtgggaca cagatgtgga 960 atacaagaag aagcaggacc cctacttgct gaagacaggc cgctttgaag aggcggcggg 1020 tgccgcgccg tgccgcctgg ccctctcccc caacgcccag gtcttggcct tggccagtgg 1080 cagtagtatt catctctaca atacccggcg gggcgagaag gaggagtgct ttgagcgggt 1140 ccatggcgag tgtatcgcca acttgtcctt tgacatcact ggccgctttc tggcctcctg 1200 tggggaccgg gcggtgcggc tgtttcacaa cactcctggc caccgagcca tggtggagga 1260 gatgcagggc cacctgaagc gggcctccaa cgagagcacc cgccagaggc tgcagcagca 1320 gctgacccag gcccaagaga ccctgaagag cctgggtgcc ctgaagaagt gactctggga 1380 gggcccggcg cagaggattg aggaggaggg atctggcctc ctcatggcac tgctgccatc 1440 tttcctccca ggtggaagcc tttcagaagg agtctcctgg ttttcttact ggtggccctg 1500 cttcttccca ttgaaactac tcttgtctac ttaggtctct ctcttcttgc tggctgtgac 1560 tcctccctga ctagtggcca aggtgctttt cttcctccca ggcccagtgg gtggaatctg 1620 tccccacctg gcactgagga gaatggtaga gaggagagga gagagagaga gaatgtgatt 1680 tttggccttg tggcagcaca tcctcacacc caaagaagtt tgtaaatgtt ccagaacaac 1740 ctagagaaca cctgagtact aagcagcagt tttgcaagga tgggagactg ggatagcttc 1800 ccatcacaga actgtgttcc atcaaaaaga cactaaggga tttccttctg ggcctcagtt 1860 ctatttgtaa gatggagaat aatcctctct gtgaactcct tgcaaagatg atatgaggct 1920 aagagaatat caagtcccca ggtctggaag aaaagtagaa aagagtagta ctattgtcca 1980 atgtcatgaa agtggtaaaa gtgggaacca gtgtgctttg aaaccaaatt agaaacacat 2040 tccttgggaa ggcaaagttt tctgggactt gatcatacat tttatatggt tgggacttct 2100 ctcttcggga gatgatatct tgtttaagga gacctctttt cagttcatca agttcatcag 2160 atatttgagt gcccactctg tgcccaaata aatatgagct ggggattaaa tacgaaaaaa 2220 aaaaaaaaaa aaaaaaaaaa as 2242 <210> 64 <211> 447 <212> PRT
<213> Homo sapiens <400> 64 Met Glu Leu Ser Gln Met Ser Glu Leu Met Gly Leu Ser Val Leu Leu Gly Leu Leu Ala Leu Met Ala Thr Ala Ala Val Ala Arg Gly Trp Leu Arg Ala Gly Glu Glu Arg Ser Gly Arg Pro Ala Cys Gln Lys Ala Asn Gly Phe Pro Pro Asp Lys Ser Ser Gly Ser Lys Lys Gln Lys Gln Tyr Gln Arg Ile Arg Lys Glu Lys Pro Gln Gln His Asn Phe Thr His Arg Leu Leu Ala AIa Ala Leu Lys Ser His Ser Gly Asn Ile Ser Cys Met Asp Phe Ser Ser Asn Gly Lys Tyr Leu Ala Thr Cys Ala Asp Asp Arg Thr Ile Arg Ile Trp Ser Thr Lys Asp Phe Leu Gln Arg Glu His Arg Ser Met Arg Ala Asn Val Glu Leu Asp His Ala Thr Leu Val Arg Phe Ser Pro Asp Cys Arg Ala Phe Ile Val Trp Leu Ala Asn Gly Asp Thr 145 ' 150 155 160 Leu Arg Val Phe Lys Met Thr Lys Arg Glu Asp Gly Gly Tyr Thr Phe Thr Ala Thr Pro Glu Asp Phe Pro Lys Lys His Lys Ala Pro Val Ile Asp Ile Gly Ile Ala Asn Thr Gly Lys Phe Ile Met Thr Ala Ser S'er Asp Thr Thr Val Leu Ile Trp Ser Leu Lys Gly Gln Val Leu Ser Thr Ile Asn Thr Asn Gln Met Asn Asn Thr His Ala Ala Val Ser Pro Cys Gly Arg Phe Val Ala Ser Cys Gly Phe Thr Pro Asp Val Lys Val Trp Glu Val Cys Phe Gly Lys Lys Gly Glu Phe Gln Glu Val Val Arg Ala Phe Glu Leu Lys Gly His Ser Ala Ala Val His Ser Phe Ala Phe Ser Asn Asp Ser Arg Arg Met Ala Ser Val Ser Lys Asp Gly Thr Trp Lys Leu Trp Asp Thr Asp Val Glu Tyr Lys Lys Lys Gln Asp Pro Tyr Leu Leu Lys Thr Gly Arg Phe Glu Glu Ala Ala Gly Ala Ala Pro Cys Arg Leu Ala Leu Ser Pro Asn Ala Gln Val Leu Ala Leu Ala Ser Gly Ser Ser Ile His Leu Tyr Asn Thr Arg Arg Gly Glu Lys Glu Glu Cys Phe Glu Arg Val His Gly Glu Cys Ile Ala Asn Leu Ser Phe Asp Ile Thr Gly Arg Phe Leu Ala Ser Cys Gly Asp Arg Ala Val Arg Leu Phe His Asn Thr Pro Gly His Arg Ala Met Val Glu Glu Met Gln Gly His Leu Lys Arg Ala Ser Asn Glu Ser Thr Arg Gln Arg Leu Gln Gln Gln Leu Thr Gln Ala Gln Glu Thr Leu Lys Ser Leu Gly Ala Leu Lys Lys <210> 65 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 65 aagtgatctc aacctcgctt g 21 <210> 66 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 66 gtcagaacca tcatctccag g 21 <210> 67 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 67 cagtccagtc caggcgag 18 <210> 68 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> ss aggaagcacc agagtgcg le <210> 69 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 69 ccatctgacc tgctactttc c 21 <210> 70 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 70 gctgatgagg atgctggc 18 <210> 71 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 71 ctcaggaagc aggtcaggac 20 <210> 72 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 72 ctctgatgag ggtgttggc 19 <210> 73 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 73 cacaggcact catgggaag i9 <210> 74 WO 99/55721 PC'T/US99/08504 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 74 ctggagacag ggtccagatc 20 <210> 75 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 75 tggaagaata gatgtgagag 20 <210> 76 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 76 tcagagagtt gcttcctgaa g 21 <210> 77 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 77 gctcctactc tgccctctcc 20 <210> 7B
<211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 78 gaaggtctgg ttggtgatgg 20 <210> 79 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 79 cagttctgac accagaagtt g 21 <210> 80 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 80 tttcatcgag gacagcaaac 20 <210> 81 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 81 aggacagagt cctgggtgg 19 <210> 82 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 82 cagagatgtg catgattccc 20 <210> 83 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 83 agcgtggaag gcagtgtag 19 <210> 84 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 84 ccaaggcacc atctcttcag 20 <210> 85 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 85 aatcagtgtt gatgataagc c 21 <210> 86 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 86 tggactttgt catggcactc 20 <210> 87 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 87 ttctgcgact tggatggg 18 <210> 88 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 88 ggaaggaggc agagaagttt g 21 <210> 89 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 89 gctcaccctg tctgttctgc 20 <210> 90 <211> 18 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 90 ccagggtctc ctccttgc 18 <210> 91 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 91 ggaacttcat ctctgcccag 20 <210> 92 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 92 ccagctttgt gtgctggtc 19 <210> 93 <211> 20 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 93 gccaacagaa gagagaagcc 20 <210> 94 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 94 tcctggaagc tccactgtg 19 <210> 95 <211> 19 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 95 aggtaggcag gagggaatg 19 <210> 96 <211> 21 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide <400> 96 tcctctctgt gaactccttg c 21 <210> 97 <211> 85 <212> PRT
<213> Homo Sapiens <400> 97 Met Tyr Ser Phe Pro Thr Thr Val Val Glu Glu Ile Leu Ser Leu Ser Leu Gln Leu Ile Ala Phe Pro Thr Val Ser Cys Glu Ile Leu Leu Glu Ile Thr Ser Gln Thr Asn Lys Lys Gln Thr Arg Glu Thr Cys Tyr Ala His Ser Ala Glu Glu Ile Gly Ile Ile Ala Gly Lys Arg Ile His Arg 5p 55 60 Pro Arg Leu Phe Pro Thr Tyr Val Ser Ser Ser Asp Ile Ser Ser Ser Val Asn Gln Ala Met <210> 9B
<211> 161 <212> PRT
<213> Homo Sapiens <400> 98 Met Trp Pro Gly Arg Ile Met Thr Val Thr Val Val Leu Leu Cys Cys Ser Thr Ala Ser Ile Trp Pro Cys Leu Ser His Ser Ala Ser Pro Ser Arg Thr Cys Pro Asn Phe Val Gly Arg Ser Thr Arg Ser Cys Val Thr Ala Asn Ser Leu Cys Glu Pro Arg Thr Pro Asp Pro Lys Pro Ile Asn Gly Lys Gly Asp Met Gly Val Pro Ser Gln Glu Thr Pro Val Pro Phe Leu Ser Cys Leu Phe Pro Leu Thr Ser Leu Trp Phe Phe Ile Phe Lys Cys Phe Asn Phe Cys Ile Phe Phe Ser Leu Arg Glu Tyr Leu Leu Ile Ser Asp Val Gln Gly Val Ala Thr Glu Lys Pro Leu Ser Ser Ser Val Cys Arg Gly Val Trp Pro Cys Gly Leu Gly Gly Ala Val Ile Leu Pro Leu Pro Arg Ala Gly Ser Arg Lys Ser Val Leu Gly Val Val Gly Gly Gln <210> 99 <211> 159 <212> PRT
<213> Homo Sapiens <400> 99 Met Tyr Arg Arg Lys Ser Gly Trp Thr Gly Cys Ala Ile Thr Cys Ser Pro Cys Thr Ala Met Thr Gln Leu Arg Asn Cys Met Arg Leu Ser Arg Ser Cys Ser Leu Thr Trp Glu Thr Pro Arg Trp Tyr Met Ala Gly Arg Val Ala Thr Ser Thr Ser Gly Cys His Cys Trp Met Ser Arg Arg Asp Leu Thr Pro Leu Pro His Pro Ser Glu Pro Gly Val Leu Asp Cys Leu Gly Pro Cys His Leu Leu Pro Leu Leu Ser Pro Gly Ser Pro Cys Trp Val Leu Gly Leu His Phe Ser Leu His Pro Pro Ser Ala Ala Ser Ala Ser His Ala Leu Thr Ile Thr Ser Leu Pro Pro Gly Leu Leu Pro Phe Val Gly Val Glu Leu Thr Ala His Pro Gln Ala Leu Met Gly Arg Gly Phe Pro Ser Gly Met Ala Ala Ala Gly Arg His Leu Cys Phe Leu <210> 100 <211> 54 <212> PRT
<213> Homo Sapiens <400> 100 Met Ser Pro Phe Thr Leu Leu Leu Gln Asn Phe Leu Val Ile Leu Ser His Leu Phe Phe His Ile Asn Phe Lys Leu Cys Pro Val Leu His Pro Leu Ser His Ser His Pro Gln Ile Leu Gly Ser Val Ile Pro Cys Ala Ile Ile Phe Pro Pro Leu <210> 101 <211> 212 <212> PRT
<213> Homo sapiens <400> 101 Met Val Leu Phe Lys Arg Asp Arg Arg Glu Asp Thr Gln Gln Gly His His Ser Met Asn Gly Arg Cys Thr Asp His Phe Leu Phe Val Leu Ser Ser Leu Leu Ser Pro Ala Ala Ile Leu Val Arg Leu Val Pro Ala Arg Glu Arg Cys Pro Gln Val Lys Gly Tyr Ser Gly Thr Trp Glu Lys Ala Pro Gly Arg Phe Pro Cys Gly Pro Ala Gln His Gly Ser Arg Val Gly Thr Leu Leu Cys Arg Gln Pro Ser Leu Tyr Ser Ser Gly Phe Leu Arg Ala Leu Pro Cys Leu Cys Gln Ala Cys Ala Ala Ser His Pro Thr Ala Ala Trp Glu Arg Pro Ala Thr Leu Pro Val His Thr Leu Pro Val His Thr Leu Pro Val His Asn Cys Ser Arg Ala Leu Cys Leu Trp Ala Pro Asn Pro Ser Ser Cys Ser Thr Phe Val Trp His Gly Asp Leu Cys Phe Phe Ser Trp Cys Leu Cys Val Trp Ala Trp Asp Glu Cys Trp Tyr Ala Leu Arg Thr Phe Leu Ile Ala Pro Cys Thr Leu Glu His Gly Ala Asp Glu Arg Gly Ser Gly Ala Cys Pro Pro Pro Trp Thr Trp Lys Lys Pro Thr Leu Glu Arg <210> 102 <211> 73 <212> PRT
<213> Homo Sapiens <400> 202 Met Glu Asn Thr Arg Leu Thr Leu Arg His Leu Pro Leu Leu Pro Asn Arg Ser Pro Glu Asp Ser Val Glu Gly Ser Val Asp Ser Lys Ser Gly Phe Ser Ser Ile Ala Lys Lys Arg Ser Ala Ala Glu Thr Thr Ser Gly Tyr Pro Arg Pro Pro Ala Phe Glu Leu Gly Asp Leu Pro Cys Leu Ile Leu Ser His Thr Cys Phe Phe Thr Arg <210> 103 <211> 302 <212> PRT
<213> Homo Sapiens <400> 103 Met Ala Ile His Lys Ala Leu Val Met Cys Leu Gly Leu Pro Leu Phe Leu Phe Pro Gly Ala Trp Ala Gln Gly His Val Pro Pro Gly Cys Ser Gln Gly Leu Asn Pro Leu Tyr Tyr Asn Leu Cys Asp Arg Ser Gly Ala Trp Gly Ile Val Leu Glu Ala Val Ala Gly Ala Gly Ile Val Thr Thr Phe Val Leu Thr Ile Ile Leu Val Ala Ser Leu Pro Phe Val Gln Asp Thr Lys Lys Arg Ser Leu Leu Gly Thr Gln Val Phe Phe Leu Leu Gly Thr Leu Gly Leu Phe Cys Leu Val Phe Ala Cys Val Val Lys Pro Asp Phe Ser Thr Cys Ala Ser Arg Arg Phe Leu Phe Gly Val Leu Phe Ala Ile Cys Phe Ser Cys Leu Ala Ala His Val Phe Ala Leu Asn Phe Leu Ala Arg Lys Asn His Gly Pro Arg Gly Trp Val Ile Phe Thr Val Ala Leu Leu Leu Thr Leu Val Glu Val Ile Ile Asn Thr Glu Trp Leu Ile Ile Thr Leu Val Arg Gly Ser Gly Glu Gly Gly Pro Gln Gly Asn Ser Ser Ala Ala Gly Pro Trp Pro Pro Pro Val Pro Ser Pro Thr Trp Thr Leu Ser Trp His Ser Ser Thr Ser Cys Cys Cys Cys Trp Val Pro Ser Trp Gly Pro Gly Pro Pro Cys Val Ala Ala Thr Ser Ala Gly Val Ser Met Gly Ser Leu Cys Ser Ser Pro Gln Pro Pro Pro Leu Pro Tyr Gly Trp Cys Gly Ser Ser Cys Ile Leu Thr Ala Thr Ser Ser Thr Thr Val Pro Pro Gly Met Thr Pro Arg Trp Pro Ser Pro Ser Pro Pro Met Pro Gly Pro Ser Ser Ser Ser Thr Ser Ser Pro Arg Ser Pro Arg <210> 104 <211> 114 <212> PRT
<213> Homo sapiens <400> 104 Met Ala Gly Ser Leu Gly Tyr Pro Phe Ser Ser Gln Pro Leu Pro Val Cys Gly Leu Ser Thr Ser His Pro Leu Phe Leu Ile Pro Tyr Leu Ser Arg Ala Cys Pro Thr Ser Glu Val Leu Gly Phe Arg Val Leu Cys Leu Pro Leu Pro Val Pro Arg Ser Ser Gln Thr Leu Leu Leu Phe Ile Arg Ala Val Gly Arg Val Phe Leu Leu Phe Leu Gly Thr Cys Pro Cys Ser Ser His Cys Pro Pro Cys Leu Ser Leu Ile Gln Met Cys His His Gly Gly His Gly Trp Ser Arg Gly Ala Pro Ser Pro Arg Ala Gly Lys Gly Ser Gly <210> 105 <211> 18 <212> PRT
<213> Homo sapiens <400> 105 His His Ala Ala Gly Gln Ala Gly Asn Glu Ala Gly Arg Phe Gly Gln Gly Val <210> 106 <211> 369 <212> PRT
<213> Homo Sapiens <400> 106 Met Lys Phe Gln Gly Pro Leu Ala Cys Leu Leu Leu Ala Leu Cys Leu Gly Ser Gly Glu Ala Gly Pro Leu Gln Ser Gly Glu Glu Ser Thr Gly Thr Asn Ile Gly Glu Ala Leu Gly His Gly Leu Gly Asp Ala Leu Ser Glu Gly Val Gly Lys Ala Ile Gly Lys Glu Ala Gly Gly Ala Ala Gly Ser Lys Val Ser Glu Ala Leu Gly Gln Gly Thr Arg Glu Ala Val Gly 65 70 ?5 80 Thr Gly Val Arg Gln Val Pro Gly Phe Gly Val Ala Asp Ala Leu Gly Asn Arg Val Gly Glu Ala Ala His Ala Leu Gly Asn Thr Gly His Glu Ile Gly Arg Gln Ala Glu Asp Val Ile Arg His Gly Ala Asp Ala Val Arg Gly Ser Trp Gln Gly Val Pro Gly His Asn Gly Ala Trp Glu Thr Ser Gly Gly His Gly Ile Phe Gly Ser Gln Gly Gly Leu Gly Gly Gln Gly Gln Gly Asn Pro Gly Gly Leu Gly Thr Pro Trp Val His Gly Tyr Pro Gly Asn Ser Ala Gly Ser Phe Gly Met Asn Pro Gln Gly Ala Pro Trp Gly Gln Gly Gly Asn Gly Gly Pro Pro Asn Phe Gly Thr Asn Thr Gln Gly Ala Val Ala Gln Pro Gly Tyr Gly Ser Val Arg Ala Ser Asn Gln Asn Glu Gly Cys Thr Asn Pro Pro Pro Ser Gly Ser Gly Gly Gly Ser Ser Asn Ser Gly Gly Gly Ser Gly Ser Gln Ser Gly Ser Ser Gly Ser Gly Ser Asn Gly Asp Asn Asn Asn Gly Ser Ser Ser Gly Gly Ser Ser Ser Gly Ser Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Gly Ser Ser Gly Asn Ser Gly Gly Ser Arg Gly Asp Ser Gly Ser Glu Ser Ser Trp Gly Ser Ser Thr Gly Ser Ser Ser Gly Asn His Gly Gly Ser Gly Gly Gly Asn Gly His Lys Pro Gly Asn Ser Glu Thr Ser Pro Gly Met Phe Asn Phe Asp Thr Phe Trp Lys Asn Phe Lys Ser Lys Leu Gly Phe Ile Asn Trp Asp Ala Ile Asn Lys Asp Gln Arg Ser Ser Arg Ile Pro <210> 107 <211> 74 <212> PRT
<213> Homo Sapiens <400> 107 Met Gly Pro Pro Gly Ala Arg Pro Ala Pro Gly Ala Ala Leu Glu Glu Gln Cys Gly Gly Ala Leu Ala Cys Ser Leu Ala Ser Ala Ser Gly Thr Ala Gly Val Val Pro Gly Ser Phe Cys Thr Val Gly Phe Gly Asp Val Ser Pro Thr Trp Val Thr Val Gly Leu Pro His Pro Glu Arg Ser Val Ser Thr Pro Glu Thr Leu Ser Val Ser Pro
Claims (73)
1. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:1;
(b) the nucleotide sequence of SEQ ID NO:1 from nucleotide 126 to nucleotide 485;
(c) the nucleotide sequence of SEQ ID NO:1 from nucleotide 207 to nucleotide 485;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:2;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2, the fragment comprising eight contiguous amino acids of SEQ ID NO:2;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:1.
(a) the nucleotide sequence of SEQ ID NO:1;
(b) the nucleotide sequence of SEQ ID NO:1 from nucleotide 126 to nucleotide 485;
(c) the nucleotide sequence of SEQ ID NO:1 from nucleotide 207 to nucleotide 485;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb2_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:2;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2, the fragment comprising eight contiguous amino acids of SEQ ID NO:2;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:1.
2. The polynucleotide of claim 1 wherein said polynucleotide is operably linked to at least one expression control sequence.
3. A host cell transformed with the polynucleotide of claim 2.
4. The host cell of claim 3, wherein said cell is a mammalian cell.
5. A process for producing a protein encoded by the polynucleotide of claim 2, which process comprises:
(a) growing a culture of a host cell transformed with the polynucleotide of claim 2 in a suitable culture medium; and (b) purifying said protein from the culture.
(a) growing a culture of a host cell transformed with the polynucleotide of claim 2 in a suitable culture medium; and (b) purifying said protein from the culture.
6. A protein produced according to the process of claim 5.
7. An isolated polynucleotide encoding the protein of claim 6.
8. The polynucleotide of claim 7, wherein the polynucleotide comprises the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804.
9. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:2;
(b) a fragment of the amino acid sequence of SEQ ID NO:2, the fragment comprising eight contiguous amino acids of SEQ ID NO:2; and (c) the amino acid sequence encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:2;
(b) a fragment of the amino acid sequence of SEQ ID NO:2, the fragment comprising eight contiguous amino acids of SEQ ID NO:2; and (c) the amino acid sequence encoded by the cDNA insert of clone vb2_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
10. The protein of claim 9, wherein said protein comprises the amino acid sequence of SEQ ID NO:2.
11. A composition comprising the protein of claim 9 and a pharmaceutically acceptable carrier.
12. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:3;
(b) the nucleotide sequence of SEQ ID NO:3 from nucleotide 130 to nucleotide 2286;
(c) the nucleotide sequence of SEQ ID NO:3 from nucleotide 214 to nucleotide 2286;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:4;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight contiguous amino acids of SEQ ID NO:4;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:3.
(a) the nucleotide sequence of SEQ ID NO:3;
(b) the nucleotide sequence of SEQ ID NO:3 from nucleotide 130 to nucleotide 2286;
(c) the nucleotide sequence of SEQ ID NO:3 from nucleotide 214 to nucleotide 2286;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb3_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:4;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight contiguous amino acids of SEQ ID NO:4;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:3.
13. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:4;
(b) a fragment of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight contiguous amino acids of SEQ ID NO:4; and (c) the amino acid sequence encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:4;
(b) a fragment of the amino acid sequence of SEQ ID NO:4, the fragment comprising eight contiguous amino acids of SEQ ID NO:4; and (c) the amino acid sequence encoded by the cDNA insert of clone vb3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
14. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:5;
(b) the nucleotide sequence of SEQ ID NO:5 from nucleotide 172 to nucleotide 522;
(c) the nucleotide sequence of SEQ ID NO:5 from nucleotide 214 to nucleotide 522;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:6;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6, the fragment comprising eight contiguous amino acids of SEQ ID NO:6;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:5.
(a) the nucleotide sequence of SEQ ID NO:5;
(b) the nucleotide sequence of SEQ ID NO:5 from nucleotide 172 to nucleotide 522;
(c) the nucleotide sequence of SEQ ID NO:5 from nucleotide 214 to nucleotide 522;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb4_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:6;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6, the fragment comprising eight contiguous amino acids of SEQ ID NO:6;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:5.
15. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:6;
(b) a fragment of the amino acid sequence of SEQ ID NO:6, the fragment comprising eight contiguous amino acids of SEQ ID NO:6; and (c) the amino acid sequence encoded by the cDNA insert of clone vb4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(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 vb4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
16. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:7;
(b) the nucleotide sequence of SEQ ID NO:7 from nucleotide 119 to nucleotide 502;
(c) the nucleotide sequence of SEQ ID NO:7 from nucleotide 176 to nucleotide 502;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:8;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8, the fragment comprising eight contiguous amino acids of SEQ ID NO:8;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:7.
(a) the nucleotide sequence of SEQ ID NO:7;
(b) the nucleotide sequence of SEQ ID NO:7 from nucleotide 119 to nucleotide 502;
(c) the nucleotide sequence of SEQ ID NO:7 from nucleotide 176 to nucleotide 502;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb5_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:8;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8, the fragment comprising eight contiguous amino acids of SEQ ID NO:8;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:7.
17. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:8;
(b) a fragment of the amino acid sequence of SEQ ID NO:8, the fragment comprising eight contiguous amino acids of SEQ ID NO:8; and (c) the amino acid sequence encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:8;
(b) a fragment of the amino acid sequence of SEQ ID NO:8, the fragment comprising eight contiguous amino acids of SEQ ID NO:8; and (c) the amino acid sequence encoded by the cDNA insert of clone vb5_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
18. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:9;
(b) the nucleotide sequence of SEQ ID NO:9 from nucleotide 128 to nucleotide 436;
(c) the nucleotide sequence of SEQ ID NO:9 from nucleotide 203 to nucleotide 436;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:10;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:10, the fragment comprising eight contiguous amino acids of SEQ ID NO:10;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:9.
(a) the nucleotide sequence of SEQ ID NO:9;
(b) the nucleotide sequence of SEQ ID NO:9 from nucleotide 128 to nucleotide 436;
(c) the nucleotide sequence of SEQ ID NO:9 from nucleotide 203 to nucleotide 436;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb6_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:10;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:10, the fragment comprising eight contiguous amino acids of SEQ ID NO:10;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:9.
19. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID NO:10, the fragment comprising eight contiguous amino acids of SEQ ID NO:10; and (c) the amino acid sequence encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:10;
(b) a fragment of the amino acid sequence of SEQ ID NO:10, the fragment comprising eight contiguous amino acids of SEQ ID NO:10; and (c) the amino acid sequence encoded by the cDNA insert of clone vb6_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
20. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:11;
(b) the nucleotide sequence of SEQ ID NO:11 from nucleotide 138 to nucleotide 1250;
(c) the nucleotide sequence of SEQ ID NO:11 from nucleotide 279 to nucleotide 1250;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb7_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb7_1 deposited under accession number ATCC 98804;
(g} a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb7_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:12;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:12, the fragment comprising eight contiguous amino acids of SEQ ID NO:12;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:11.
(a) the nucleotide sequence of SEQ ID NO:11;
(b) the nucleotide sequence of SEQ ID NO:11 from nucleotide 138 to nucleotide 1250;
(c) the nucleotide sequence of SEQ ID NO:11 from nucleotide 279 to nucleotide 1250;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb7_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb7 1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb7_1 deposited under accession number ATCC 98804;
(g} a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb7_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:12;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:12, the fragment comprising eight contiguous amino acids of SEQ ID NO:12;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:11.
21. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:12;
(b} a fragment of the amino acid sequence of SEQ ID NO:12, the fragment comprising eight contiguous amino acids of SEQ ID NO:12; and (c) the amino acid sequence encoded by the cDNA insert of clone vb7_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:12;
(b} a fragment of the amino acid sequence of SEQ ID NO:12, the fragment comprising eight contiguous amino acids of SEQ ID NO:12; and (c) the amino acid sequence encoded by the cDNA insert of clone vb7_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
22. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:13;
(b) the nucleotide sequence of SEQ ID NO:13 from nucleotide 615 to nucleotide 869;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vb8_1 deposited under accession number ATCC 98804;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:14;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:14, the fragment comprising eight contiguous amino acids of SEQ ID NO:14;
(g) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and (h) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:13.
(a) the nucleotide sequence of SEQ ID NO:13;
(b) the nucleotide sequence of SEQ ID NO:13 from nucleotide 615 to nucleotide 869;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vb8_1 deposited under accession number ATCC 98804;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:14;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:14, the fragment comprising eight contiguous amino acids of SEQ ID NO:14;
(g) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and (h) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:13.
23. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:14;
(b) a fragment of the amino acid sequence of SEQ ID NO:14, the fragment comprising eight contiguous amino acids of SEQ ID NO:14; and (c) the amino acid sequence encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:14;
(b) a fragment of the amino acid sequence of SEQ ID NO:14, the fragment comprising eight contiguous amino acids of SEQ ID NO:14; and (c) the amino acid sequence encoded by the cDNA insert of clone vb8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
24. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:15;
(b) the nucleotide sequence of SEQ ID NO:15 from nucleotide 148 to nucleotide 1470;
(c) the nucleotide sequence of SEQ ID NO:15 from nucleotide 193 to nucleotide 1470;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:16;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:16, the fragment comprising eight contiguous amino acids of SEQ ID NO:16;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:15.
(a) the nucleotide sequence of SEQ ID NO:15;
(b) the nucleotide sequence of SEQ ID NO:15 from nucleotide 148 to nucleotide 1470;
(c) the nucleotide sequence of SEQ ID NO:15 from nucleotide 193 to nucleotide 1470;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vb9_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:16;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:16, the fragment comprising eight contiguous amino acids of SEQ ID NO:16;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:15.
25. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:16;
(b) a fragment of the amino acid sequence of SEQ ID NO:16, the fragment comprising eight contiguous amino acids of SEQ ID NO:16; and (c) the amino acid sequence encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:16;
(b) a fragment of the amino acid sequence of SEQ ID NO:16, the fragment comprising eight contiguous amino acids of SEQ ID NO:16; and (c) the amino acid sequence encoded by the cDNA insert of clone vb9_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
26. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:17;
(b) the nucleotide sequence of SEQ ID NO:17 from nucleotide 109 to nucleotide 414;
(c) the nucleotide sequence of SEQ ID NO:17 from nucleotide 217 to nucleotide 414;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:18;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight contiguous amino acids of SEQ ID NO:18;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:17.
(a) the nucleotide sequence of SEQ ID NO:17;
(b) the nucleotide sequence of SEQ ID NO:17 from nucleotide 109 to nucleotide 414;
(c) the nucleotide sequence of SEQ ID NO:17 from nucleotide 217 to nucleotide 414;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc3_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:18;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight contiguous amino acids of SEQ ID NO:18;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:17.
27. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:18;
(b) a fragment of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight contiguous amino acids of SEQ ID NO:18; and (c) the amino acid sequence encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:18;
(b) a fragment of the amino acid sequence of SEQ ID NO:18, the fragment comprising eight contiguous amino acids of SEQ ID NO:18; and (c) the amino acid sequence encoded by the cDNA insert of clone vc3_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
28. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:19;
(b) the nucleotide sequence of SEQ ID NO:19 from nucleotide 169 to nucleotide 840;
(c) the nucleotide sequence of SEQ ID NO:19 from nucleotide 211 to nucleotide 840;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:20;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:20; the fragment comprising eight contiguous amino acids of SEQ ID NO:20;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:19.
(a) the nucleotide sequence of SEQ ID NO:19;
(b) the nucleotide sequence of SEQ ID NO:19 from nucleotide 169 to nucleotide 840;
(c) the nucleotide sequence of SEQ ID NO:19 from nucleotide 211 to nucleotide 840;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc4_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:20;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:20; the fragment comprising eight contiguous amino acids of SEQ ID NO:20;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:19.
29. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:20;
(b) a fragment of the amino acid sequence of SEQ ID NO:20, the fragment comprising eight contiguous amino acids of SEQ ID NO:20; and (c) the amino acid sequence encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:20;
(b) a fragment of the amino acid sequence of SEQ ID NO:20, the fragment comprising eight contiguous amino acids of SEQ ID NO:20; and (c) the amino acid sequence encoded by the cDNA insert of clone vc4_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
30. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:21;
(b) the nucleotide sequence of SEQ ID NO:21 from nucleotide 508 to nucleotide 951;
(c) the nucleotide sequence of SEQ ID NO:21 from nucleotide 733 to nucleotide 951;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the foil-length protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:22;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22, the fragment comprising eight contiguous amino acids of SEQ ID NO:22;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)(g), and that has a length that is at least 25% of the length of SEQ ID NO:21.
(a) the nucleotide sequence of SEQ ID NO:21;
(b) the nucleotide sequence of SEQ ID NO:21 from nucleotide 508 to nucleotide 951;
(c) the nucleotide sequence of SEQ ID NO:21 from nucleotide 733 to nucleotide 951;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the foil-length protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc5_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:22;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22, the fragment comprising eight contiguous amino acids of SEQ ID NO:22;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)(g), and that has a length that is at least 25% of the length of SEQ ID NO:21.
31. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:22;
(b) a fragment of the amino acid sequence of SEQ ID NO:22, the fragment comprising eight contiguous amino acids of SEQ ID NO:22; and (c) the amino acid sequence encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:22;
(b) a fragment of the amino acid sequence of SEQ ID NO:22, the fragment comprising eight contiguous amino acids of SEQ ID NO:22; and (c) the amino acid sequence encoded by the cDNA insert of clone vc5_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
32. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:23;
(b) the nucleotide sequence of SEQ ID NO:23 from nucleotide 125 to nucleotide 493;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vc7_1 deposited under accession number ATCC 98748;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:24;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24, the fragment comprising eight contiguous amino acids of SEQ ID NO:24;
(g) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and (h) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:23.
(a) the nucleotide sequence of SEQ ID NO:23;
(b) the nucleotide sequence of SEQ ID NO:23 from nucleotide 125 to nucleotide 493;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vc7_1 deposited under accession number ATCC 98748;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:24;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24, the fragment comprising eight contiguous amino acids of SEQ ID NO:24;
(g) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and (h) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:23.
33. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:24;
(b) a fragment of the amino acid sequence of SEQ ID NO:24, the fragment comprising eight contiguous amino acids of SEQ ID NO:24; and (c) the amino acid sequence encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:24;
(b) a fragment of the amino acid sequence of SEQ ID NO:24, the fragment comprising eight contiguous amino acids of SEQ ID NO:24; and (c) the amino acid sequence encoded by the cDNA insert of clone vc7_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
34. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:25;
(b) the nucleotide sequence of SEQ ID NO:25 from nucleotide 33 to nucleotide 407;
(c) the nucleotide sequence of SEQ ID NO:25 from nucleotide 99 to nucleotide 407;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:26;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26, the fragment comprising eight contiguous amino acids of SEQ ID NO:6;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:25.
(a) the nucleotide sequence of SEQ ID NO:25;
(b) the nucleotide sequence of SEQ ID NO:25 from nucleotide 33 to nucleotide 407;
(c) the nucleotide sequence of SEQ ID NO:25 from nucleotide 99 to nucleotide 407;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc9_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:26;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26, the fragment comprising eight contiguous amino acids of SEQ ID NO:6;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:25.
35. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:26;
(b) a fragment of the amino acid sequence of SEQ ID NO:26, the fragment comprising eight contiguous amino acids of SEQ ID NO:26; and (c) the amino acid sequence encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:26;
(b) a fragment of the amino acid sequence of SEQ ID NO:26, the fragment comprising eight contiguous amino acids of SEQ ID NO:26; and (c) the amino acid sequence encoded by the cDNA insert of clone vc9_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
36. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:27;
(b) the nucleotide sequence of SEQ ID NO:27 from nucleotide 176 to nucleotide 871;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vc10_1 deposited under accession number ATCC 98748;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc10_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:28;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28, the fragment comprising eight contiguous amino acids of SEQ ID NO:28;
(g) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and (h) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:27.
(a) the nucleotide sequence of SEQ ID NO:27;
(b) the nucleotide sequence of SEQ ID NO:27 from nucleotide 176 to nucleotide 871;
(c) the nucleotide sequence of the full-length protein coding sequence of clone vc10_1 deposited under accession number ATCC 98748;
(d) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc10_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:28;
(f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28, the fragment comprising eight contiguous amino acids of SEQ ID NO:28;
(g) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d);
and (h) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(d), and that has a length that is at least 25% of the length of SEQ ID NO:27.
37. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:28;
(b) a fragment of the amino acid sequence of SEQ ID NO:28, the fragment comprising eight contiguous amino acids of SEQ ID NO:28; and (c) the amino acid sequence encoded by the cDNA insert of clone vc10_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:28;
(b) a fragment of the amino acid sequence of SEQ ID NO:28, the fragment comprising eight contiguous amino acids of SEQ ID NO:28; and (c) the amino acid sequence encoded by the cDNA insert of clone vc10_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
38. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:29;
(b) the nucleotide sequence of SEQ ID NO:29 from nucleotide 160 to nucleotide 657;
(c) the nucleotide sequence of SEQ ID NO:29 from nucleotide 214 to nucleotide 657;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc11_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc11_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:30;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:30, the fragment comprising eight contiguous amino acids of SEQ ID NO:30;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:29.
(a) the nucleotide sequence of SEQ ID NO:29;
(b) the nucleotide sequence of SEQ ID NO:29 from nucleotide 160 to nucleotide 657;
(c) the nucleotide sequence of SEQ ID NO:29 from nucleotide 214 to nucleotide 657;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc11_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc11_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:30;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:30, the fragment comprising eight contiguous amino acids of SEQ ID NO:30;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:29.
39. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:30;
(b) a fragment of the amino acid sequence of SEQ ID NO:30, the fragment comprising eight contiguous amino acids of SEQ ID NO:30; and (c) the amino acid sequence encoded by the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:30;
(b) a fragment of the amino acid sequence of SEQ ID NO:30, the fragment comprising eight contiguous amino acids of SEQ ID NO:30; and (c) the amino acid sequence encoded by the cDNA insert of clone vc11_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
40. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:31;
(b) the nucleotide sequence of SEQ ID NO:31 from nucleotide 228 to nucleotide 662;
(c) the nucleotide sequence of SEQ ID NO:31 from nucleotide 327 to nucleotide 662;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc14_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc14_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:32;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:32, the fragment comprising eight contiguous amino acids of SEQ ID NO:32;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:31.
(a) the nucleotide sequence of SEQ ID NO:31;
(b) the nucleotide sequence of SEQ ID NO:31 from nucleotide 228 to nucleotide 662;
(c) the nucleotide sequence of SEQ ID NO:31 from nucleotide 327 to nucleotide 662;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc14_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc14_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:32;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:32, the fragment comprising eight contiguous amino acids of SEQ ID NO:32;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:31.
41. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:32;
(b) a fragment of the amino acid sequence of SEQ ID NO:32, the fragment comprising eight contiguous amino acids of SEQ ID NO:32; and (c) the amino acid sequence encoded by the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:32;
(b) a fragment of the amino acid sequence of SEQ ID NO:32, the fragment comprising eight contiguous amino acids of SEQ ID NO:32; and (c) the amino acid sequence encoded by the cDNA insert of clone vc14_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
42. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:33;
(b) the nucleotide sequence of SEQ ID NO:33 from nucleotide 101 to nucleotide 667;
(c) the nucleotide sequence of SEQ ID NO:33 from nucleotide 182 to nucleotide 667;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc16_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc16_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:34;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34, the fragment comprising eight contiguous amino acids of SEQ ID NO:34;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:33.
(a) the nucleotide sequence of SEQ ID NO:33;
(b) the nucleotide sequence of SEQ ID NO:33 from nucleotide 101 to nucleotide 667;
(c) the nucleotide sequence of SEQ ID NO:33 from nucleotide 182 to nucleotide 667;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc16_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc16_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:34;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34, the fragment comprising eight contiguous amino acids of SEQ ID NO:34;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:33.
43. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:34;
(b) a fragment of the amino acid sequence of SEQ ID NO:34, the fragment comprising eight contiguous amino acids of SEQ ID NO:34; and (c) the amino acid sequence encoded by the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:34;
(b) a fragment of the amino acid sequence of SEQ ID NO:34, the fragment comprising eight contiguous amino acids of SEQ ID NO:34; and (c) the amino acid sequence encoded by the cDNA insert of clone vc16_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
44. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:35;
(b) the nucleotide sequence of SEQ ID NO:35 from nucleotide 8 to nucleotide 355;
(c) the nucleotide sequence of SEQ ID NO:35 from nucleotide 134 to nucleotide 355;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc17_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc17_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc17_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc17_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:36;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight contiguous amino acids of SEQ ID NO:36;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:35.
(a) the nucleotide sequence of SEQ ID NO:35;
(b) the nucleotide sequence of SEQ ID NO:35 from nucleotide 8 to nucleotide 355;
(c) the nucleotide sequence of SEQ ID NO:35 from nucleotide 134 to nucleotide 355;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc17_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc17_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc17_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc17_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:36;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight contiguous amino acids of SEQ ID NO:36;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:35.
45. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:36;
(b) a fragment of the amino acid sequence of SEQ ID NO:36, the fragment comprising eight contiguous amino acids of SEQ ID NO:36; and (c) the amino acid sequence encoded by the cDNA insert of clone vc17-1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(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 vc17-1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
46. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:37;
(b) the nucleotide sequence of SEQ ID NO:37 from nucleotide 1031 to nucleotide 1252;
(c) the nucleotide sequence of SEQ ID NO:37 from nucleotide 1100 to nucleotide 1252;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc21_1 deposited under accession number ATCC 98785;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc21_1 deposited under accession number ATCC 98785;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:38;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:38, the fragment comprising eight contiguous amino acids of SEQ ID NO:38;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:37.
(a) the nucleotide sequence of SEQ ID NO:37;
(b) the nucleotide sequence of SEQ ID NO:37 from nucleotide 1031 to nucleotide 1252;
(c) the nucleotide sequence of SEQ ID NO:37 from nucleotide 1100 to nucleotide 1252;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc21_1 deposited under accession number ATCC 98785;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc21_1 deposited under accession number ATCC 98785;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:38;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:38, the fragment comprising eight contiguous amino acids of SEQ ID NO:38;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:37.
47. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:38;
(b) the amino acid sequence of SEQ ID NO:38 from amino acid 29 to amino acid 74;
(c) a fragment of the amino acid sequence of SEQ ID NO:38, the fragment comprising eight contiguous amino acids of SEQ ID NO:38; and (d) the amino acid sequence encoded by the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:38;
(b) the amino acid sequence of SEQ ID NO:38 from amino acid 29 to amino acid 74;
(c) a fragment of the amino acid sequence of SEQ ID NO:38, the fragment comprising eight contiguous amino acids of SEQ ID NO:38; and (d) the amino acid sequence encoded by the cDNA insert of clone vc21_1 deposited under accession number ATCC 98785;
the protein being substantially free from other mammalian proteins.
48. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:39;
(b) the nucleotide sequence of SEQ ID NO:39 from nucleotide 94 to nucleotide 1482;
(c) the nucleotide sequence of SEQ ID NO:39 from nucleotide 214 to nucleotide 1482;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc23_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc23_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:40;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40, the fragment comprising eight contiguous amino acids of SEQ ID NO:40;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:39.
(a) the nucleotide sequence of SEQ ID NO:39;
(b) the nucleotide sequence of SEQ ID NO:39 from nucleotide 94 to nucleotide 1482;
(c) the nucleotide sequence of SEQ ID NO:39 from nucleotide 214 to nucleotide 1482;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc23_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc23_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:40;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40, the fragment comprising eight contiguous amino acids of SEQ ID NO:40;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:39.
49. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:40;
(b) a fragment of the amino acid sequence of SEQ ID NO:40, the fragment comprising eight contiguous amino acids of SEQ ID NO:40; and (c) the amino acid sequence encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:40;
(b) a fragment of the amino acid sequence of SEQ ID NO:40, the fragment comprising eight contiguous amino acids of SEQ ID NO:40; and (c) the amino acid sequence encoded by the cDNA insert of clone vc23_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
50. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:41;
(b) the nucleotide sequence of SEQ ID NO:41 from nucleotide 153 to nucleotide 413;
(c) the nucleotide sequence of SEQ ID NO:41 from nucleotide 264 to nucleotide 413;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc25_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc25_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:42;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42, the fragment comprising eight contiguous amino acids of SEQ ID NO:42;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:41.
(a) the nucleotide sequence of SEQ ID NO:41;
(b) the nucleotide sequence of SEQ ID NO:41 from nucleotide 153 to nucleotide 413;
(c) the nucleotide sequence of SEQ ID NO:41 from nucleotide 264 to nucleotide 413;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc25_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc25_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:42;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:42, the fragment comprising eight contiguous amino acids of SEQ ID NO:42;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:41.
51. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:42;
(b) a fragment of the amino acid sequence of SEQ ID NO:42, the fragment comprising eight contiguous amino acids of SEQ ID NO:42; and (c) the amino acid sequence encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:42;
(b) a fragment of the amino acid sequence of SEQ ID NO:42, the fragment comprising eight contiguous amino acids of SEQ ID NO:42; and (c) the amino acid sequence encoded by the cDNA insert of clone vc25_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
52. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:43;
(b) the nucleotide sequence of SEQ ID NO:43 from nucleotide 87 to nucleotide 1409;
(c) the nucleotide sequence of SEQ ID NO:43 from nucleotide 156 to nucleotide 1409;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:44;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight contiguous amino acids of SEQ ID NO:44;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:43.
(a) the nucleotide sequence of SEQ ID NO:43;
(b) the nucleotide sequence of SEQ ID NO:43 from nucleotide 87 to nucleotide 1409;
(c) the nucleotide sequence of SEQ ID NO:43 from nucleotide 156 to nucleotide 1409;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vc26_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:44;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight contiguous amino acids of SEQ ID NO:44;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:43.
53. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:44;
(b) a fragment of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight contiguous amino acids of SEQ ID NO:44; and (c) the amino acid sequence encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:44;
(b) a fragment of the amino acid sequence of SEQ ID NO:44, the fragment comprising eight contiguous amino acids of SEQ ID NO:44; and (c) the amino acid sequence encoded by the cDNA insert of clone vc26_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
54. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:45;
(b) the nucleotide sequence of SEQ ID NO:45 from nucleotide 63 to nucleotide 428;
(c) the nucleotide sequence of SEQ ID NO:45 from nucleotide 156 to nucleotide 428;
(d) the nucleotide sequence of SEQ ID NO:45 from nucleotide 356 to nucleotide 1773;
(e) the nucleotide sequence of the full-length protein coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
(f) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(g) the nucleotide sequence of a mature protein coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(i) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:46;
(j) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46, the fragment comprising eight contiguous amino acids of SEQ ID NO:46;
(k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(h);
and (l) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(h), and that has a length that is at least 25% of the length of SEQ ID NO:45.
(a) the nucleotide sequence of SEQ ID NO:45;
(b) the nucleotide sequence of SEQ ID NO:45 from nucleotide 63 to nucleotide 428;
(c) the nucleotide sequence of SEQ ID NO:45 from nucleotide 156 to nucleotide 428;
(d) the nucleotide sequence of SEQ ID NO:45 from nucleotide 356 to nucleotide 1773;
(e) the nucleotide sequence of the full-length protein coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
(f) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(g) the nucleotide sequence of a mature protein coding sequence of clone vc30_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
(i) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:46;
(j) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46, the fragment comprising eight contiguous amino acids of SEQ ID NO:46;
(k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(h);
and (l) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(h), and that has a length that is at least 25% of the length of SEQ ID NO:45.
55. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:46;
(b) the amino acid sequence of SEQ ID NO:46 from amino acid 1 to amino acid 97;
(c) a fragment of the amino acid sequence of SEQ ID NO:46, the fragment comprising eight contiguous amino acids of SEQ ID NO:46; and (d) the amino acid sequence encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:46;
(b) the amino acid sequence of SEQ ID NO:46 from amino acid 1 to amino acid 97;
(c) a fragment of the amino acid sequence of SEQ ID NO:46, the fragment comprising eight contiguous amino acids of SEQ ID NO:46; and (d) the amino acid sequence encoded by the cDNA insert of clone vc30_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
56. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:47;
(b) the nucleotide sequence of SEQ ID NO:47 from nucleotide 30 to nucleotide 1799;
(c) the nucleotide sequence of SEQ ID NO:47 from nucleotide 90 to nucleotide 1799;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd1_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd1_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:48;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48, the fragment comprising eight contiguous amino acids of SEQ ID NO:48;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:47.
(a) the nucleotide sequence of SEQ ID NO:47;
(b) the nucleotide sequence of SEQ ID NO:47 from nucleotide 30 to nucleotide 1799;
(c) the nucleotide sequence of SEQ ID NO:47 from nucleotide 90 to nucleotide 1799;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd1_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd1_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:48;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48, the fragment comprising eight contiguous amino acids of SEQ ID NO:48;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:47.
57. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:48;
(b) a fragment of the amino acid sequence of SEQ ID NO:48, the fragment comprising eight contiguous amino acids of SEQ ID NO:48; and (c) the amino acid sequence encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:48;
(b) a fragment of the amino acid sequence of SEQ ID NO:48, the fragment comprising eight contiguous amino acids of SEQ ID NO:48; and (c) the amino acid sequence encoded by the cDNA insert of clone vd1_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
58. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:49;
(b) the nucleotide sequence of SEQ ID NO:49 from nucleotide 69 to nucleotide 443;
(c) the nucleotide sequence of SEQ ID NO:49 from nucleotide 111 to nucleotide 443;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:50;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:49.
(a) the nucleotide sequence of SEQ ID NO:49;
(b) the nucleotide sequence of SEQ ID NO:49 from nucleotide 69 to nucleotide 443;
(c) the nucleotide sequence of SEQ ID NO:49 from nucleotide 111 to nucleotide 443;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd2_1 deposited under accession number ATCC 98748;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:50;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:49.
59. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:50;
(b) a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50; and (c) the amino acid sequence encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:50;
(b) a fragment of the amino acid sequence of SEQ ID NO:50, the fragment comprising eight contiguous amino acids of SEQ ID NO:50; and (c) the amino acid sequence encoded by the cDNA insert of clone vd2_1 deposited under accession number ATCC 98748;
the protein being substantially free from other mammalian proteins.
60. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:51;
(b) the nucleotide sequence of SEQ ID NO:51 from nucleotide 176 to nucleotide 1249;
(c) the nucleotide sequence of SEQ ID NO:51 from nucleotide 227 to nucleotide 1249;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:52;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:52, the fragment comprising eight contiguous amino acids of SEQ ID NO:52;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (ar(g), and that has a length that is at least 25% of the length of SEQ ID NO:51.
(a) the nucleotide sequence of SEQ ID NO:51;
(b) the nucleotide sequence of SEQ ID NO:51 from nucleotide 176 to nucleotide 1249;
(c) the nucleotide sequence of SEQ ID NO:51 from nucleotide 227 to nucleotide 1249;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd3_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:52;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:52, the fragment comprising eight contiguous amino acids of SEQ ID NO:52;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (ar(g), and that has a length that is at least 25% of the length of SEQ ID NO:51.
61. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:52;
(b) a fragment of the amino acid sequence of SEQ ID NO:52, the fragment comprising eight contiguous amino acids of SEQ ID NO:52; and (c) the amino acid sequence encoded by the cDNA insert of clone vd3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(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 vd3_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
62. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:53;
(b) the nucleotide sequence of SEQ ID NO:53 from nucleotide 94 to nucleotide 1530;
(c) the nucleotide sequence of SEQ ID NO:53 from nucleotide 145 to nucleotide 1530;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:54;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54, the fragment comprising eight contiguous amino acids of SEQ ID NO:54;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:53.
(a) the nucleotide sequence of SEQ ID NO:53;
(b) the nucleotide sequence of SEQ ID NO:53 from nucleotide 94 to nucleotide 1530;
(c) the nucleotide sequence of SEQ ID NO:53 from nucleotide 145 to nucleotide 1530;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vd4_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:54;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:54, the fragment comprising eight contiguous amino acids of SEQ ID NO:54;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:53.
63. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:54;
(b) a fragment of the amino acid sequence of SEQ ID NO:54, the fragment comprising eight contiguous amino acids of SEQ ID NO:54; and (c) the amino acid sequence encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:54;
(b) a fragment of the amino acid sequence of SEQ ID NO:54, the fragment comprising eight contiguous amino acids of SEQ ID NO:54; and (c) the amino acid sequence encoded by the cDNA insert of clone vd4_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
64. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:55;
(b) the nucleotide sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1300;
(c) the nucleotide sequence of SEQ ID NO:55 from nucleotide 182 to nucleotide 1300;
(d) the nucleotide sequence of the full-length protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:56;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56, the fragment comprising eight contiguous amino acids of SEQ ID NO:56;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:55.
(a) the nucleotide sequence of SEQ ID NO:55;
(b) the nucleotide sequence of SEQ ID NO:55 from nucleotide 71 to nucleotide 1300;
(c) the nucleotide sequence of SEQ ID NO:55 from nucleotide 182 to nucleotide 1300;
(d) the nucleotide sequence of the full-length protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone ve4_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:56;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56, the fragment comprising eight contiguous amino acids of SEQ ID NO:56;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:55.
65. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:56;
(b) a fragment of the amino acid sequence of SEQ ID NO:56, the fragment comprising eight contiguous amino acids of SEQ ID NO:56; and (c) the amino acid sequence encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:56;
(b) a fragment of the amino acid sequence of SEQ ID NO:56, the fragment comprising eight contiguous amino acids of SEQ ID NO:56; and (c) the amino acid sequence encoded by the cDNA insert of clone ve4_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
66. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:57;
(b) the nucleotide sequence of SEQ ID NO:57 from nucleotide 57 to nucleotide 785;
(c) the nucleotide sequence of SEQ ID NO:57 from nucleotide 147 to nucleotide 785;
(d) the nucleotide sequence of the full-length protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:58;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:58, the fragment comprising eight contiguous amino acids of SEQ ID NO:58;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees 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.
(a) the nucleotide sequence of SEQ ID NO:57;
(b) the nucleotide sequence of SEQ ID NO:57 from nucleotide 57 to nucleotide 785;
(c) the nucleotide sequence of SEQ ID NO:57 from nucleotide 147 to nucleotide 785;
(d) the nucleotide sequence of the full-length protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone ve8_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:58;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:58, the fragment comprising eight contiguous amino acids of SEQ ID NO:58;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:57.
67. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:58;
(b) a fragment of the amino acid sequence of SEQ ID NO:58, the fragment comprising eight contiguous amino acids of SEQ ID NO:58; and (c) the amino acid sequence encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:58;
(b) a fragment of the amino acid sequence of SEQ ID NO:58, the fragment comprising eight contiguous amino acids of SEQ ID NO:58; and (c) the amino acid sequence encoded by the cDNA insert of clone ve8_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
68. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:59;
(b) the nucleotide sequence of SEQ ID NO:59 from nucleotide 64 to nucleotide 1002;
(c) the nucleotide sequence of SEQ ID NO:59 from nucleotide 139 to nucleotide 1002;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vf1_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vf1_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:60;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:60, the fragment comprising eight contiguous amino acids of SEQ ID NO:60;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:59.
(a) the nucleotide sequence of SEQ ID NO:59;
(b) the nucleotide sequence of SEQ ID NO:59 from nucleotide 64 to nucleotide 1002;
(c) the nucleotide sequence of SEQ ID NO:59 from nucleotide 139 to nucleotide 1002;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vf1_1 deposited under accession number ATCC 98784;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
(f) the nucleotide sequence of a mature protein coding sequence of clone vf1_1 deposited under accession number ATCC 98784;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:60;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:60, the fragment comprising eight contiguous amino acids of SEQ ID NO:60;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:59.
69. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID NO:60, the fragment comprising eight contiguous amino acids of SEQ ID NO:60; and (c) the amino acid sequence encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:60;
(b) a fragment of the amino acid sequence of SEQ ID NO:60, the fragment comprising eight contiguous amino acids of SEQ ID NO:60; and (c) the amino acid sequence encoded by the cDNA insert of clone vf1_1 deposited under accession number ATCC 98784;
the protein being substantially free from other mammalian proteins.
70. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:61;
(b) the nucleotide sequence of SEQ ID NO:61 from nucleotide 588 to nucleotide 995;
(c) the nucleotide sequence of SEQ ID NO:61 from nucleotide 750 to nucleotide 995;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vh1_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vh1_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:62;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight contiguous amino acids of SEQ ID NO:62;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:61.
(a) the nucleotide sequence of SEQ ID NO:61;
(b) the nucleotide sequence of SEQ ID NO:61 from nucleotide 588 to nucleotide 995;
(c) the nucleotide sequence of SEQ ID NO:61 from nucleotide 750 to nucleotide 995;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vh1_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vh1_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:62;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight contiguous amino acids of SEQ ID NO:62;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:61.
71. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:62;
(b) a fragment of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight contiguous amino acids of SEQ ID NO:62; and (c) the amino acid sequence encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:62;
(b) a fragment of the amino acid sequence of SEQ ID NO:62, the fragment comprising eight contiguous amino acids of SEQ ID NO:62; and (c) the amino acid sequence encoded by the cDNA insert of clone vh1_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
72. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence of SEQ ID NO:63;
(b) the nucleotide sequence of SEQ ID NO:63 from nucleotide 29 to nucleotide 1369;
(c) the nucleotide sequence of SEQ ID NO:63 from nucleotide 104 to nucleotide 1369;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vi1_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vi1_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:64;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:63.
(a) the nucleotide sequence of SEQ ID NO:63;
(b) the nucleotide sequence of SEQ ID NO:63 from nucleotide 29 to nucleotide 1369;
(c) the nucleotide sequence of SEQ ID NO:63 from nucleotide 104 to nucleotide 1369;
(d) the nucleotide sequence of the full-length protein coding sequence of clone vi1_1 deposited under accession number ATCC 98804;
(e) a nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
(f) the nucleotide sequence of a mature protein coding sequence of clone vi1_1 deposited under accession number ATCC 98804;
(g) a nucleotide sequence encoding a mature protein encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
(h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO:64;
(i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64;
(j) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 65 degrees C, or 4X SSC at 42 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g);
and (k) the nucleotide sequence of a polynucleotide that hybridizes under conditions at least as stringent as 4X SSC at 50 degrees C, or 6X SSC at 40 degrees C with 50% formamide, to any one of the polynucleotides specified by (a)-(g), and that has a length that is at least 25% of the length of SEQ ID NO:63.
73. A protein comprising an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:64;
(b) a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64; and (c) the amino acid sequence encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
(a) the amino acid sequence of SEQ ID NO:64;
(b) a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising eight contiguous amino acids of SEQ ID NO:64; and (c) the amino acid sequence encoded by the cDNA insert of clone vi1_1 deposited under accession number ATCC 98804;
the protein being substantially free from other mammalian proteins.
Applications Claiming Priority (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8290498P | 1998-04-24 | 1998-04-24 | |
US60/082,904 | 1998-04-24 | ||
US8899498P | 1998-06-11 | 1998-06-11 | |
US60/088,994 | 1998-06-11 | ||
US8927898P | 1998-06-12 | 1998-06-12 | |
US60/089,278 | 1998-06-12 | ||
US9164798P | 1998-07-02 | 1998-07-02 | |
US60/091,647 | 1998-07-02 | ||
US9763998P | 1998-08-24 | 1998-08-24 | |
US60/097,639 | 1998-08-24 | ||
US09/298,102 | 1999-04-22 | ||
PCT/US1999/008504 WO1999055721A1 (en) | 1998-04-24 | 1999-04-23 | Secreted proteins and polynucleotides encoding them |
Publications (1)
Publication Number | Publication Date |
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CA2327551A1 true CA2327551A1 (en) | 1999-11-04 |
Family
ID=27536313
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002327551A Abandoned CA2327551A1 (en) | 1998-04-24 | 1999-04-23 | Secreted proteins and polynucleotides encoding them |
Country Status (4)
Country | Link |
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EP (1) | EP1075487A4 (en) |
AU (1) | AU3965299A (en) |
CA (1) | CA2327551A1 (en) |
WO (1) | WO1999055721A1 (en) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030009013A1 (en) * | 1998-12-30 | 2003-01-09 | Genentech, Inc. | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
AU4004200A (en) * | 1999-02-26 | 2000-09-14 | Zymogenetics Inc. | Mammalian alpha-helical protein, zsig83 |
AU1784201A (en) * | 1999-11-24 | 2001-06-04 | Human Genome Sciences, Inc. | Major intrinsic protein (mip)-like polynucleotides, polypeptides, and antibodies |
GB0002402D0 (en) * | 2000-02-02 | 2000-03-22 | Smithkline Beecham Biolog | Novel compounds |
WO2003002737A1 (en) * | 2001-06-27 | 2003-01-09 | Riken | Novel human topoisomerase 2α inhibitory protein and utilization thereof |
WO2003057870A1 (en) * | 2002-01-07 | 2003-07-17 | Bayer Healthcare Ag | Human phosphatidic acid phosphatase type 2-like protein |
WO2003066887A1 (en) * | 2002-02-08 | 2003-08-14 | Applera Corporation | Isolated human protease proteins, nucleic acid molecules encoding human protease proteins, and uses thereof |
MXPA05011725A (en) * | 2003-04-30 | 2006-05-17 | Johnson & Johnson | Cngh0010 specific polynucleotides, polypeptides, antibodies, compositions, methods and uses. |
US7479479B2 (en) | 2003-04-30 | 2009-01-20 | Centocor, Inc. | CNGH0010 specific polynucleotides, polypeptides, antibodies, compositions, methods and uses |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5807703A (en) * | 1996-06-17 | 1998-09-15 | Genetics Institute, Inc. | Secreted proteins and polynucleotides encoding them |
CA2296809A1 (en) * | 1997-08-01 | 1999-02-11 | Genset | 5' ests for secreted proteins identified from brain tissues |
-
1999
- 1999-04-23 AU AU39652/99A patent/AU3965299A/en not_active Abandoned
- 1999-04-23 CA CA002327551A patent/CA2327551A1/en not_active Abandoned
- 1999-04-23 WO PCT/US1999/008504 patent/WO1999055721A1/en not_active Application Discontinuation
- 1999-04-23 EP EP99922717A patent/EP1075487A4/en not_active Withdrawn
Also Published As
Publication number | Publication date |
---|---|
AU3965299A (en) | 1999-11-16 |
EP1075487A4 (en) | 2002-11-20 |
EP1075487A1 (en) | 2001-02-14 |
WO1999055721A1 (en) | 1999-11-04 |
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